(ELDN) 2023 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to Eledon Pharmaceuticals' first-quarter 2023 earnings conference call. (Operator Instructions) This call is being recorded on Thursday, May 11, 2023. I would now like to turn the conference over to your host, Paul Little, CFO. Please go ahead.

女士們、先生們，下午好，歡迎參加 Eledon Pharmaceuticals 的 2023 年第一季度收益電話會議。 （操作員說明）此電話於 2023 年 5 月 11 日星期四進行錄音。我現在想將會議轉交給主持人、首席財務官 Paul Little。請繼續。

Good afternoon, everyone, and thank you for joining Eledon's first-quarter 2023 operating and financial results conference call. I am joined today on today's call by David-Alexandre Gros, Chief Executive Officer; and Steve Perrin, our President and Chief Scientific Officer. Jeff Bornstein, our Chief Medical Officer, is traveling today.

大家下午好，感謝您參加 Eledon 2023 年第一季度運營和財務業績電話會議。首席執行官 David-Alexandre Gros 參加了今天的電話會議；以及我們的總裁兼首席科學官 Steve Perrin。我們的首席醫療官 Jeff Bornstein 今天正在出差。

Earlier today, Eledon issued a press release announcing financial results for the first quarter ended March 31, 2023. You may access the release under the Investors tab on our company's website at eledon.com.

今天早些時候，Eledon 發布了一份新聞稿，宣布截至 2023 年 3 月 31 日的第一季度財務業績。您可以在我們公司網站 eledon.com 的“投資者”選項卡下訪問該新聞稿。

I would like to remind everyone that statements made during this conference call relating to Eledon's expected future performance, future business prospects, or future events or plans may include forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. All such forward-looking statements are intended to be subject to the Safe Harbor protection provided by the Reform Act. Actual outcomes and results could differ materially from these forecasts due to the impact of many factors beyond the control of Eledon.

我想提醒大家，本次電話會議期間發表的有關Eledon 預期未來業績、未來業務前景或未來事件或計劃的聲明可能包括1995 年《私人證券訴訟改革法案》中定義的前瞻性聲明。所有此類前瞻性聲明看似陳述的目的是受到改革法案提供的安全港保護。由於 Eledon 無法控制的許多因素的影響，實際結果和結果可能與這些預測存在重大差異。

Eledon expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of new information, future events, or otherwise. Participants are directed to the risk factors set forth in Eledon's reports filed with the US Securities and Exchange Commission.

Eledon 明確表示不承擔任何對其前瞻性陳述進行更新的義務，無論是由於新信息、未來事件還是其他原因。參與者應注意 Eledon 向美國證券交易委員會提交的報告中列出的風險因素。

Now it is my pleasure to pass the call to Eledon's CEO, Dr. David-Alexandre Gros. DA?

現在我很高興將電話轉給 Eledon 的首席執行官 David-Alexandre Gros 博士。 DA？

Thank you, Paul, and thank you all for joining us today. We began the year by announcing our primary organizational focus on our kidney transplantation program, and have since directed our resources and efforts to advance this program forward. We believe that tegoprubart, our anti-CD40 ligand antibody, can address a significant unmet need in patients undergoing kidney transplants through its potential to prevent rejection, maintain high graft function, and reduce the many toxicities associated with calcineurin inhibitors, or CNIs. We believe there is a profound urgency for new treatment options to benefit patients receiving solid organ transplants and kidneys in particular.

謝謝保羅，也感謝大家今天加入我們。今年年初，我們宣布我們的主要組織重點是腎移植計劃，此後我們投入資源和努力來推進該計劃。我們相信，我們的抗CD40 配體抗體tegoprubart 可以通過其預防排斥反應、維持高移植物功能以及減少與鈣調神經磷酸酶抑製劑(CNI) 相關的許多毒性的潛力，解決接受腎移植的患者未滿足的重大需求。我們相信，迫切需要新的治療方案來造福接受實體器官移植（尤其是腎臟移植）的患者。

According to the United Network for Organ Sharing, there are now over 25,000 annual kidney transplants in the US, the most in history, and yet the standard of care first-line chronic immunosuppression for this growing market has not changed since the approval of tacrolimus in 1994. Our goal is for tegoprubart to ultimately replace tacrolimus as the standard-of-care post-transplant immunomodulator, significantly reducing the broad number of side effects associated with that drug and thus improving graft function and survival. This in turn should result in fewer patients requiring repeat transplants, thereby freeing more kidneys to be allocated to first-time recipients and thus allowing more people to receive the kidneys that they need to live.

據器官共享聯合網絡稱，美國目前每年進行超過 25,000 例腎移植手術，創歷史新高，但自美國批准他克莫司以來，這個不斷增長的市場的一線慢性免疫抑制治療標準並未改變。 1994 年。我們的目標是替格魯巴特最終取代他克莫司作為移植後免疫調節劑的標準護理，顯著減少與該藥物相關的大量副作用，從而改善移植物功能和存活率。這反過來應該會導致需要重複移植的患者減少，從而將更多的腎臟分配給首次接受者，從而使更多的人能夠接受他們生存所需的腎臟。

At the end of March, we presented open-label data from our ongoing Phase 1b trial, evaluating tegoprubart in kidney transplantation at the World Congress of Nephrology. Our initial three participants did not show any evidence of acute rejection at measured time points, which is important since most rejection in the first year occurs within the first 90 days post-transplant. In addition, we observed strong graft function in our participants with mean eGFRs above 70 at measured time points as far out as week 31. These results were highly encouraging and suggest early clinical proof of concept for tegoprubart in this indication. And we look forward to reporting updated data from this study at a medical meeting in the latter part of the year.

3 月底，我們在世界腎髒病學大會上展示了正在進行的 1b 期試驗的開放標籤數據，該試驗評估了 tegoprubart 在腎移植中的應用。我們最初的三名參與者在測量的時間點沒有表現出任何急性排斥的證據，這一點很重要，因為第一年的大多數排斥發生在移植後的前 90 天內。此外，我們觀察到參與者俱有強大的移植功能，在第 31 週的測量時間點，平均 eGFR 超過 70。這些結果非常令人鼓舞，並表明 tegoprubart 在該適應症中的早期臨床概念證明。我們期待在今年下半年的醫學會議上報告這項研究的最新數據。

In addition to the clinical progress we made this year, we also strengthened our balance sheet through the execution of a private placement financing of up to $185 million, including $35 million upfront. Subject to achievement of our milestones, this financing will enable us to execute our kidney transplant clinical development plan, including our Phase 2 BESTOW trial in kidney transplantation.

除了今年取得的臨床進展外，我們還通過執行高達 1.85 億美元的私募融資（其中包括 3500 萬美元的預付款）來加強我們的資產負債表。根據我們的里程碑的實現，這筆融資將使我們能夠執行我們的腎移植臨床開發計劃，包括我們的腎移植 2 期 BESTOW 試驗。

We were particularly proud to have this financing co-led by one of our historical investors, BVF Partners, as well as by new investor, Armistice Capital. Of note, Sanofi, the global pharmaceutical company, also participated in the financing, as did a number of private individuals and families that believe in Eledon's missions and have done so and invested in our company since our early days. With the financing completed, we are now laser-focused on execution. We continue to enroll our Phase 1b trial, in which we have now enrolled six participants and expect to initiate our Phase 2 BESTOW trial midyear.

我們特別自豪的是，這筆融資由我們的歷史投資者之一 BVF Partners 以及新投資者 Armistice Capital 共同牽頭。值得注意的是，全球製藥公司賽諾菲也參與了融資，許多相信 Eledon 使命的個人和家庭也參與了融資，並從公司成立之初就開始投資我們公司。融資完成後，我們現在專注於執行。我們繼續招募 1b 期試驗，目前已招募了 6 名參與者，並預計在年中啟動 2 期 BESTOW 試驗。

With that, I would now like to hand over the call to Steve Perrin, our President and Chief Scientific Officer, to provide more details on our development programs. Steve?

現在，我想將電話轉交給我們的總裁兼首席科學官 Steve Perrin，以提供有關我們開發計劃的更多詳細信息。史蒂夫？

Thank you, DA. I'd like to begin by touching upon the opportunity we see in kidney transplantation and why we made the decision to focus our resources on the development of tegoprubart for this indication. Kidney transplantation is a growing space which has had limited innovation in decades. The National Kidney Foundation estimates that 660,000 people live with kidney failure in the United States. And out of those are over 100,000 people on the kidney transplant waiting list, with about 5,000 individuals dying annually while waiting for a transplant.

謝謝你，DA。首先，我想談談我們在腎移植方面看到的機會，以及為什麼我們決定將資源集中在針對該適應症的 tegoprubart 的開發上。腎移植是一個不斷發展的領域，幾十年來創新有限。國家腎臟基金會估計，美國有 66 萬人患有腎衰竭。其中有超過 100,000 人在腎移植等待名單上，每年約有 5,000 人在等待移植期間死亡。

Since the average deceased donor-transplanted kidney only functions for an average of 10 to 12 years, and the mean age of transplantation is 50 years old, most patients will require multiple kidney transplants if they are to live a normal lifespan. Therefore, the need has never been greater to pursue a new treatment option that can prolong the functional life of a transplanted kidney. That is our goal. And we believe this can be achieved with tegoprubart, allowing transplanted kidneys to last the duration of recipients' lives and thereby freeing up precious kidneys so that a greater percentage of patients on the waiting list can receive a kidney.

由於死者供體移植的腎臟平均只能發揮10至12年的功能，而移植的平均年齡為50歲，因此大多數患者如果要過上正常的壽命，就需要進行多次腎移植。因此，現在迫切需要尋求一種可以延長移植腎功能壽命的新治療方案。這就是我們的目標。我們相信，tegoprubart 可以實現這一目標，讓移植的腎臟能夠持續到接受者的一生，從而釋放寶貴的腎臟，從而使等待名單上更大比例的患者可以獲得腎臟。

As DA mentioned, we reported open-label data from our ongoing Phase 1b kidney transplant study at the World Congress of Nephrology in March. At the time of data submission, three patients have been enrolled in the trial, which has sites enrolling in Canada, Australia, and the UK.

正如 DA 提到的，我們在 3 月份的世界腎髒病大會上報告了正在進行的 1b 期腎移植研究的開放標籤數據。截至提交數據時，已有三名患者參加了該試驗，試驗地點位於加拿大、澳大利亞和英國。

To evaluate signals of clinical efficacy, we reported the estimated glomerular filtration rate, or eGFR, of each patient at specified time points. From large retrospective studies conducted in transplant recipients taking CNIs, we know that a 50th percentile eGFR falls around 50 during the first year post transplant. 12-month eGFR has been shown to be the most significant single predictor of future graft failure, and as eGFR values decrease, the risk of graft failure and hospitalization increases exponentially.

為了評估臨床療效的信號，我們報告了每位患者在特定時間點的估計腎小球濾過率（eGFR）。通過對服用 CNI 的移植受者進行的大型回顧性研究，我們知道，移植後第一年，第 50 個百分位的 eGFR 下降到 50 左右。 12 個月 eGFR 已被證明是未來移植失敗最重要的單一預測因子​​，隨著 eGFR 值降低，移植失敗和住院的風險呈指數增加。

Importantly, studies have shown that the 12-month eGFR is correlated with eGFR value seen as early as 90 days. And thus, we believe that the eGFR data we shared at 90 days is highly relevant and potentially predictive in determining graft function and outcome. At the time of our data submission for the conference, we had three subjects enrolled in the trial. Results from the first three participants demonstrated no incidence of acute rejection at 56, 167, and 232 days, respectively. Graft function was very good in all three participants, with the participants having eGFRs of 54, 85, and 77 at the latest available time point of 49, 154, and 217 days, respectively.

重要的是，研究表明 12 個月的 eGFR 與最早在 90 天觀察到的 eGFR 值相關。因此，我們相信我們在 90 天分享的 eGFR 數據在確定移植物功能和結果方面具有高度相關性和潛在預測性。在我們向會議提交數據時，我們有三名受試者參加了試驗。前三名參與者的結果分別表明在 56 天、167 天和 232 天時沒有發生急性排斥反應。所有三名參與者的移植物功能都非常好，參與者在最新可用時間點 49、154 和 217 天的 eGFR 分別為 54、85 和 77。

Given the correlation between eGFR levels at 90 days and 12 months, we feel encouraged by these early results and their potential to translate into longer-term graft functionality. Long-term graft function is critical, but not the only part of meaningful outcomes we are looking for in kidney transplant recipients. The current standard-of-care calcineurin inhibitors help preserve graft survival. But they are also associated with significant side effects such as hypertension, dyslipidemia, new onset of diabetes, and tremors. Moreover, research shows that 10-year post transplant, almost all transplanted kidneys will demonstrate evidence of CNI-induced nephrotoxicity. We believe, based on the evidence generated to date, that tegoprubart has the potential to reduce or even potentially eliminate these side effects while also providing improved graft function.

鑑於 90 天和 12 個月的 eGFR 水平之間的相關性，我們對這些早期結果及其轉化為長期移植物功能的潛力感到鼓舞。長期移植物功能至關重要，但這並不是我們在腎移植受者中尋找的有意義結果的唯一部分。目前的護理標準鈣調神經磷酸酶抑製劑有助於保持移植物存活。但它們也與顯著的副作用有關，例如高血壓、血脂異常、新發糖尿病和震顫。此外，研究表明，移植後 10 年，幾乎所有移植的腎臟都會表現出 CNI 誘導的腎毒性的證據。我們相信，根據迄今為止產生的證據，tegoprubart 有潛力減少甚至可能消除這些副作用，同時還可以改善移植物功能。

Turning to the safety results we observed in the study, we're among the three participants tegoprubart showed good tolerability, especially among a difficult-to-treat population. None of the participants experienced acute rejection, and there was no evidence of new-onset diabetes after transplant or any impact on glucose levels in two participants without diabetes at baseline. One participant was discontinued from the study on day 55 after developing BK viremia, a common occurrence following a kidney transplant, which occurs in 20% or more of transplant recipients.

談到我們在研究中觀察到的安全性結果，我們是三名參與者之一，tegoprubart 顯示出良好的耐受性，特別是在難以治療的人群中。沒有參與者經歷急性排斥反應，也沒有證據表明移植後新發糖尿病，也沒有證據表明基線時沒有糖尿病的兩名參與者的血糖水平受到任何影響。一名參與者在出現 BK 病毒血症後於第 55 天停止研究，BK 病毒血症是腎移植後常見的情況，20% 或更多的移植受者會出現這種情況。

An additional participant elected to discontinue from the study after 33 weeks, reporting mild alopecia and mild insomnia, which the investigator did not attribute to tegoprubart. The adverse events continued once the patient was switched from tegoprubart to CNIs. We continue to make progress with this ongoing trial and have since enrolled an additional two participants who both remain on study. We expect to report updated data at a medical conference later this year.

另一位參與者在 33 週後選擇終止研究，報告有輕度脫髮和輕度失眠，但研究者並未將其歸因於替戈普魯巴特。當患者從替戈普魯巴特轉為 CNI 後，不良事件仍在繼續。我們繼續在這項正在進行的試驗中取得進展，並且此後又招募了兩名仍在研究中的參與者。我們預計將在今年晚些時候的醫學會議上報告最新數據。

Building off our results from the ongoing Phase 1b trial, we remain on track to initiate our randomized open-label Phase 2 BESTOW study to assess the safety and efficacy of tegoprubart compared to tacrolimus and the preservation of allograft function after kidney transplantation. 120 participants will be randomized one to one to receive either tegoprubart every 21 days or twice-daily oral tacrolimus. The primary endpoint will compare the mean eGFR at 12 months for participants receiving tegoprubart versus tacrolimus. Secondary objectives will include safety and tolerability, participants in graft survival, biopsy-proven acute rejection, and the incidence of new-onset diabetes mellitus after transplant.

基於正在進行的1b 期試驗的結果，我們仍在啟動隨機開放標籤2 期BESTOW 研究，以評估替戈普魯巴特與他克莫司相比的安全性和有效性以及腎移植後同種異體移植物功能的保存。 120 名參與者將被一對一隨機分配，接受每 21 天一次的替戈普魯巴特治療或每天兩次口服他克莫司治療。主要終點將比較接受替戈普魯巴特與他克莫司的參與者在 12 個月時的平均 eGFR。次要目標包括安全性和耐受性、移植物存活的參與者、活檢證實的急性排斥反應以及移植後新發糖尿病的發生率。

I'd like to conclude by briefly covering our IgAN program. We're following our announcement to de-prioritize the program at the beginning of the year. We continue to collect safety data from the patients previously enrolled to provide additional insight into tegoprubart's safety profile. The data we presented at WCN from 16 patients in the high dose cohort of 10 mgs per kg every three weeks showed tegoprubart to be safe and well tolerated with no serious nor severe adverse events reported and no early discontinuations.

最後我想簡要介紹一下我們的 IgAN 計劃。我們正在遵循我們在年初宣布取消該計劃優先級的公告。我們繼續從之前入組的患者那裡收集安全數據，以提供對 tegoprubart 安全狀況的更多了解。我們在 WCN 上提供的每三週 10 毫克/公斤高劑量隊列中 16 名患者的數據顯示，tegoprubart 是安全的且耐受性良好，沒有報告嚴重或嚴重不良事件，也沒有早期停藥的情況。

Four participants had completed at least 24 weeks on treatment, and five others completed at least 12 weeks. We are encouraged by the safety profile tegoprubart continues to display, and to date, we have now dosed approximately 100 human subjects across multiple disease indications. Given the deprioritization of the IgAN program, and having now generated key safety insights in this population, we are now winding down all IgAN study activities at our sites, and we anticipate winding down the vast majority of our IgAN activity and spend in the second quarter of 2023.

4 名參與者完成了至少 24 週的治療，另外 5 名參與者完成了至少 12 週的治療。 tegoprubart 持續展現的安全性讓我們深受鼓舞，迄今為止，我們已對大約 100 名患有多種疾病適應症的人類受試者進行了給藥。鑑於 IgAN 計劃的優先級被取消，並且現在已經對該人群產生了關鍵的安全見解，我們現在正在逐步結束我們站點的所有 IgAN 研究活動，我們預計將在第二季度逐步結束大部分 IgAN 活動和支出2023 年。

With that, I'd now like to turn the call over to Paul for the financial update.

現在，我想將電話轉給保羅，了解最新的財務情況。

Thank you, Steve. The company reported a net loss of $10.8 million or $0.75 per share for the three months ended March 31, 2023, compared to a net loss of $9.9 million or $0.69 per share for the same period in 2022. Research and development expenses were $8.1 million for the three months ended March 31, 2023, compared to $6.6 million for the comparable period in 2022, an increase of $1.5 million. The increase is primarily due to higher clinical development expenses, primarily with external CROs of $2.1 million and an increase in personnel costs due to increased headcount. The increase was partially offset by decreases in stock-based compensation, manufacturing, and consulting expenses.

謝謝你，史蒂夫。該公司報告稱，截至2023 年3 月31 日的三個月淨虧損為1080 萬美元，即每股0.75 美元，而2022 年同期淨虧損為990 萬美元，即每股0.69 美元。研發費用為810萬美元。截至 2023 年 3 月 31 日的三個月，與 2022 年同期的 660 萬美元相比，增加了 150 萬美元。這一增長主要是由於臨床開發費用增加（主要是外部 CRO 的費用為 210 萬美元）以及由於人員數量增加而導致的人員成本增加。這一增長被股票薪酬、製造和諮詢費用的減少部分抵消。

General and administrative expenses were $3 million for the three months ended March 31, 2023, compared to $3.2 million for the comparable period in 2022, a decrease of $200,000. The decrease was primarily result -- primarily related to the lower stock-based compensation costs.

截至 2023 年 3 月 31 日的三個月，一般及行政費用為 300 萬美元，而 2022 年同期為 320 萬美元，減少了 20 萬美元。下降的主要原因是基於股票的薪酬成本降低。

Earlier this month, we announced the entry into a definitive securities purchase agreement with select healthcare investors that will provide up to $185 million in gross proceeds through a private placement. The purchase agreement included an initial upfront financing of $35 million; an additional aggregate financing up to $105 million, subject to achieving clinical development milestones, volume, weighted share price levels, and trading volume conditions; plus up to $45 million upon the full exercise of warrants being issued in connection with the agreement. The financing was led by BVF Partners and Armistice Capital and includes participation from new and existing investors, including the global pharmaceutical company Sanofi. Eledon ended the first quarter with approximately $46.5 million in cash and cash equivalents.

本月早些時候，我們宣布與精選的醫療保健投資者簽訂最終證券購買協議，該協議將通過私募提供高達 1.85 億美元的總收益。購買協議包括 3500 萬美元的初始預付款；額外融資總額高達 1.05 億美元，具體取決於臨床開發里程碑、數量、加權股價水平和交易量條件的實現；加上根據協議發行的認股權證完全行使後高達 4500 萬美元。此次融資由 BVF Partners 和 Armistice Capital 牽頭，新老投資者也參與其中，其中包括全球製藥公司賽諾菲 (Sanofi)。 Eledon 第一季度末現金及現金等價物約為 4650 萬美元。

With that financial update, I'll turn the call back over to DA.

更新財務信息後，我會將電話轉回給 DA。

Thanks, Paul. I am proud of the progress that Eledon has made in the early part of 2023 and feel we are now well positioned to make significant strides in our evaluation of tegoprubart as a potential much-needed replacement for CNIs in kidney transplantation. We are highly encouraged by the data generated to date in our ongoing Phase 1b study and look forward to both its continued enrollment and to providing a clinical update later in the year.

謝謝，保羅。我對 Eledon 在 2023 年初取得的進展感到自豪，並認為我們現在處於有利地位，可以在評估 tegoprubart 作為腎移植中急需的 CNI 潛在替代品方面取得重大進展。我們對正在進行的 1b 期研究迄今為止生成的數據感到非常鼓舞，並期待繼續入組並在今年晚些時候提供臨床更新。

Finally, following our financing, we now have a well-capitalized path to launch and execute our Phase 2 BESTOW trial while we continue to report data from the open-label Phase 1b study in parallel.

最後，在融資之後，我們現在擁有了一條資本充足的途徑來啟動和執行我們的 2 期 BESTOW 試驗，同時我們繼續並行報告開放標籤 1b 期研究的數據。

Operator, please begin the Q&A session.

接線員，請開始問答環節。

Thank you. (Operator Instructions) Pete Stavropoulos, Cantor Fitzgerald.

謝謝。 （操作員指令）Pete Stavropoulos、Cantor Fitzgerald。

Hi, DA, Steven, and Paul. Want to congratulate you on your successful financing and happy to see that the tego kidney transplant program is moving forward.

嗨，DA、史蒂文和保羅。祝賀您成功融資，並很高興看到 Tego 腎移植項目正在取得進展。

So one of your investors stood out at me when I saw the press release for the financing, which was Sanofi. It's a well-established -- it has a well-established kidney transplant franchise, so well versed in the space. Can you provide any color on those interactions? And what do you think drew them -- drew this company to invest in this molecule and program? Do you think it was the totality of the data generated with tego to date across all programs? Or was it kidney-specific data?

因此，當我看到融資新聞稿時，你們的一位投資者（賽諾菲）引起了我的注意。它是一家成熟的公司——它擁有完善的腎移植專營權，非常熟悉這個領域。您能為這些互動提供一些顏色嗎？你認為是什麼吸引了他們——吸引這家公司投資這個分子和項目？您認為這是迄今為止所有程序中使用 tego 生成的數據的總和嗎？或者是腎臟特定的數據？

Hey, Pete. Thanks for the question. In terms of Sanofi, we obviously appreciate having them as a new investor. As you mentioned, they know the space quite well. They've also had said in the past that in terms of the way they viewed their interactions or their development in the space, they were not looking at kidney transplantation. I think they looked at us and saw a good investment opportunity. This was an investment that came, though in the same way as other investors. So Sanofi did not get any type of rights beyond -- or in any way different from what other investors received in this financing.

嘿，皮特。謝謝你的提問。就賽諾菲而言，我們顯然很高興他們成為新投資者。正如您提到的，他們非常了解這個領域。他們過去還曾表示，就他們在該領域的互動或發展的看法而言，他們並沒有考慮腎移植。我認為他們看到了我們並看到了一個很好的投資機會。這是一筆投資，儘管方式與其他投資者相同。因此，賽諾菲沒有獲得任何超出或與其他投資者在本次融資中獲得的權利不同的權利。

All right. Thank you. So I have a couple of questions on the BESTOW study. The data presented for tego at the kidney transplantation World Congress of Nephrology, there was one patient who had BK viremia. Can you sort of touch on how common BK viremia is in kidney transplant? And how is it going to be handled in the BESTOW study? Will it be up to the investigator to withdraw the patient from the study? Or will there be some type of protocol in place?

好的。謝謝。我對 BESTOW 研究有幾個問題。在腎移植世界腎髒病大會上為tego提供的數據顯示，有一名患者患有BK病毒血症。您能談談 BK 病毒血症在腎移植中有多常見嗎？ BESTOW 研究將如何處理這一問題？研究者是否有權讓患者退出研究？或者是否會制定某種類型的協議？

Thanks for the question, Pete. Steve, I'll turn that over to you.

謝謝你的提問，皮特。史蒂夫，我會把它交給你。

Yes, BK viremia, Pete, is -- it's a great question. BK viremia is pretty common. It's common across all polypharmacy that is associated with the prevention of transplant rejection that occurs in 10% to 20% of studies. And it does vary from site to site, country to country, and it does vary regimen to regimen.

是的，BK 病毒血症，Pete，是——這是一個很好的問題。 BK 病毒血症很常見。在所有與預防移植排斥相關的多重用藥中都很常見，在 10% 到 20% 的研究中發生這種情況。它確實因地點、國家和國家而異，而且治療方案也不同。

The standard practice for dealing with the viral load with BK viremia is to wean people off the immunosuppressant drugs that are required to prevent rejection, and that's done at the discretion of the PI depending upon viral load. And then there's this balance between letting the immune system of the transplanted individual fight back the viral load while still trying to protect the organ from rejection. And obviously, that is up to the investigator on a site-by-site basis on how they want to manage that.

處理 BK 病毒血症病毒載量的標準做法是讓人們停止使用防止排斥反應所需的免疫抑製藥物，這是由 PI 根據病毒載量自行決定的。然後，在讓移植個體的免疫系統抵抗病毒載量的同時仍試圖保護器官免受排斥之間存在著這種平衡。顯然，這取決於調查員想要如何管理每個站點。

Okay. I mean, I don't know if you've disclosed, but is there opportunity to sort of wean off of tego and then sort of put them back on as time progresses?

好的。我的意思是，我不知道你是否已經透露了，但是是否有機會擺脫 Tego，然後隨著時間的推移又重新使用它們？

So being an antibody, typically the administration, as you know, is every three weeks. And so if somebody's viral load creeps up shortly after dosing, the investigator has a period of time where they could try to manage other immunosuppressants to see if they can manage viral load and get it back down prior to the next infusion. There is some flexibility on if you wanted to delay the next infusion of tegoprubart a little bit. But as we know with biologics, you don't want to pause an infusion for too long due to increased risk of anti-drug antibody responses. Again, we'd be in close dialogue with PIs if that's the route that they'd choose to take and we would give them guidance based on what we know from our preclinical and clinical data to date on how to manage that.

因此，如您所知，作為抗體，通常每三週給藥一次。因此，如果某人的病毒載量在給藥後不久就開始上升，研究人員可以在一段時間內嘗試使用其他免疫抑製劑，看看是否可以控制病毒載量並在下一次輸注之前將病毒載量降下來。如果您想稍微推遲下一次泰戈普魯巴特的輸注，可以靈活選擇。但正如我們所知，對於生物製劑，您不希望暫停輸注太長時間，因為抗藥物抗體反應的風險增加。同樣，如果 PI 選擇採取這種路線，我們將與他們進行密切對話，並且我們將根據迄今為止從臨床前和臨床數據中了解到的信息，為他們提供如何管理的指導。

Great. Thank you for that. Another question again on the BESTOW study. One of the goals will be to reduce steroid use. And there will be steroid tapering, from my understanding, until they're completely removed from each of the patients' treatment regimens. Can you just talk a bit about the clinical benefit? It may be still on these patients, tapering them off? And how do you plan to capture that benefit?

偉大的。謝謝你。又一個關於 BESTOW 研究的問題。目標之一是減少類固醇的使用。根據我的理解，類固醇將會逐漸減少，直到它們完全從每個患者的治療方案中去除。您能簡單談談臨床益處嗎？它可能仍在這些患者身上，逐漸減少？您打算如何獲得這種好處？

DA, do you want me to take that one?

DA，你想讓我拿那個嗎？

Sure.

當然。

The steroids, Pete, as you point out, another great question, is the primary difference between our Phase 1b study and the Phase 2 BESTOW study, where in the BESTOW study, they will start weaning participants off steroids fairly quickly after transplant and they will be off steroids by six months. This is not an uncommon practice. Many sites globally do a complete steroid taper. And there is variability among sites that do that.

類固醇，Pete，正如你所指出的，另一個重要問題是我們的1b 期研究和2 期BESTOW 研究之間的主要區別，在BESTOW 研究中，他們將在移植後相當快地開始讓參與者戒掉類固醇，並且他們將六個月前停止使用類固醇。這並不是一種罕見的做法。全球許多網站都進行了徹底的類固醇逐漸減量。這樣做的網站之間存在差異。

The biggest thing that's beneficial here to patients is, again, the side effects of steroids can be significant. And so getting patients off as many of the immunosuppressant drugs in a cocktail is critically important for managing side effects. And so we think it's a potentially great upside. But we feel that with tegoprubart on board, we can completely wean people off of steroids in a fairly rapid manner by six months.

對患者來說最大的好處是，類固醇的副作用可能很嚴重。因此，讓患者戒掉盡可能多的免疫抑製劑混合物對於控制副作用至關重要。因此我們認為這是一個潛在的巨大優勢。但我們認為，有了 tegoprubart，我們可以在六個月內以相當快的速度讓人們完全戒掉類固醇。

As you know, nobody -- people don't like to be on steroids -- it's DA. People don't like to be on steroids long term. They've got just impacts in terms of blood sugar control, moods, ability to sleep, potential hair loss. So, removing -- if we're able to allow people to taper completely off steroids, that would be another win on top of removing the CNIs for patients.

如你所知，沒有人——人們不喜歡使用類固醇——而是 DA。人們不喜歡長期服用類固醇。它們只會對血糖控制、情緒、睡眠能力和潛在的脫髮產生影響。因此，如果我們能夠讓人們完全減少類固醇的使用，那將是除了為患者取消 CNI 之外的另一個勝利。

In terms of the clinical study, any secondary or exploratory endpoints that you're going to use to sort of capture that benefit?

就臨床研究而言，您將使用任何次要或探索性終點來獲得這種益處？

(multiple speakers) Go ahead, DA, I'm sorry.

（多個發言者）請繼續，DA，對不起。

No, no, go. You can go.

不，不，走吧。你可以走了。

I don't think, Pete, there's any exploratory endpoints that specifically deal with the tapering of steroids. But obviously to be captured as part of the safety profile of tego much like in our other studies.

皮特，我認為沒有任何探索性終點專門針對類固醇的逐漸減少。但顯然要作為 tego 安全概況的一部分，就像我們的其他研究一樣。

Okay. Thank you very much.

好的。非常感謝。

We're going to look at removing steroids from both arms. So it would be comparative. But in terms of the steroid-specific side effects, one would see the benefits if one compared the data at historicals.

我們將考慮從雙臂上去除類固醇。所以才會有比較。但就類固醇特異性副作用而言，如果將歷史數據進行比較，人們就會看到好處。

All right. Thank you very much. And again, congratulations on the financing and all the progress.

好的。非常感謝。再次祝賀融資和所有進展。

Thank you, Pete.

謝謝你，皮特。

Thomas Smith, SVB Securites.

托馬斯·史密斯，SVB 證券公司。

Hey, guys, good afternoon. Thanks for taking the questions and congrats on all the progress. A couple of questions on our end. I guess first on the Phase 1b study, you mentioned that you've enrolled six patients to date and you're targeting a medical meeting later this year for an update. Just wondering if you can elaborate on some of the venues you're considering, and just walk through sort of your expectations in terms of how many patients and amount of follow-up you think you could have by then.

嘿，伙計們，下午好。感謝您提出問題並祝賀所有的進展。我們有幾個問題。我想首先在 1b 期研究中，您提到迄今為止您已經招募了 6 名患者，並且您計劃在今年晚些時候召開一次醫學會議以獲取最新信息。只是想知道您是否可以詳細說明您正在考慮的一些場所，並簡單介紹一下您對屆時可能有多少患者和隨訪量的期望。

Thanks, Tom. It's DA. So we'll look for a medical meeting towards the end of the year. There are a number of kidney meetings for this, including Kidney Week, where we might be able to present. Since we already have six patients, as we just mentioned. Even without counting potential new patients that come into the study, that would mean that all of the patients would have over 90 days -- would most probably have over 90 days on drug by that point. So would go from somewhere in the 90-day timeframe all the way out to a year or so.

謝謝，湯姆。是達。因此，我們將尋求在年底召開一次醫學會議。為此有許多腎臟會議，包括腎臟週，我們也許可以在其中進行展示。正如我們剛才提到的，因為我們已經有六名患者。即使不計算進入研究的潛在新患者，這也意味著所有患者都將有超過 90 天的時間——到那時很可能有超過 90 天的藥物治療時間。因此，時間範圍可以從 90 天一直延長到一年左右。

Okay. Got it. That makes sense. And then, maybe just following up on the Sanofi investment. I understand they are pursuing solid organ transplant at this point for their CD40 ligand frexalimab But maybe if you could just remind us of the differences between tego and frexalimab. And then just thinking a little bit bigger picture, just wondering if you could comment on sort of the broader strategic interest in the space and how you're thinking about partnership or other business development opportunities at this point?

好的。知道了。這就說得通了。然後，也許只是跟進賽諾菲的投資。我知道他們目前正在為其 CD40 配體 frexalimab 尋求實體器官移植但也許您能提醒我們 tego 和 frexalimab 之間的差異。然後想一下更大的前景，只是想知道您是否可以評論該領域更廣泛的戰略利益，以及您目前如何考慮合作夥伴關係或其他業務發展機會？

Sure. So the two molecules or anti -- both ourselves and Sanofi have an anti-CD40 ligand. And in that, we're using a full antibody approach. And so, the two molecules are probably, if you looked at the broader competitive landscape, the two that are the most similar. The difference has really been around strategy and where we've -- each company has chosen to focus. We've now chosen to focus on transplant. Sanofi's focus has been on larger population indications, including Sjogren's. They're running trials in MS, and they've discussed the rheumatoid arthritis before. So that is the difference in terms of the approach that we're taking.

當然。因此，這兩個分子或抗 - 我們自己和賽諾菲都有一個抗 CD40 配體。在這方面，我們使用的是完整的抗體方法。因此，如果你著眼於更廣泛的競爭格局，這兩種分子可能是最相似的兩種。差異實際上在於戰略以及我們——每家公司都選擇關注的領域。我們現在選擇專注於移植。賽諾菲的重點是更大的人群適應症，包括乾燥綜合症。他們正在開展多發性硬化症試驗，之前也討論過類風濕性關節炎。這就是我們所採取的方法的差異。

Did I -- is there a second part to the question?

我是否——這個問題還有第二部分嗎？

Yes, that's helpful. I was just wondering if you could comment on sort of the broader strategic interest in the space and how you're thinking about business development or partnership opportunities at this point?

是的，這很有幫助。我只是想知道您是否可以評論一下該領域更廣泛的戰略利益，以及您目前如何考慮業務發展或合作機會？

Yes. So in terms of broad interest in the space, I think there are a lot of companies that are interested in the broader immunology space. It's become one of -- a key area of focus for both smaller biotechs as well as large pharma. From our perspective today in terms of business development, we are not looking to in-license. That wasn't one of the reasons why we did the deal. And we now have the capital we need if we hit our milestones to be able to take this drug and develop it all the way through to getting a Phase 2 data and beyond. So that's very much what we are going to be focused on, which is executing our trials and continuing to generate data with tegoprubart.

是的。因此，就該領域的廣泛興趣而言，我認為有很多公司對更廣泛的免疫學領域感興趣。它已成為小型生物技術公司和大型製藥公司關注的關鍵領域之一。從我們今天的業務發展角度來看，我們並不打算獲得許可。這不是我們達成這筆交易的原因之一。如果我們達到里程碑，能夠使用這種藥物並一直開發到獲得第二階段數據及以後，我們現在擁有所需的資金。這就是我們將要關注的重點，即執行我們的試驗並繼續使用 tegoprubart 生成數據。

Got it. That makes sense to me. All right, guys. I appreciate you taking the questions, and congrats again on the progress.

知道了。這對我來說很有意義。好吧，伙計們。感謝您提出問題，並再次祝賀我們取得的進展。

Thank you. Appreciate it, Tom.

謝謝。很感激，湯姆。

Thank you, Tom.

謝謝你，湯姆。

Rami Katkhuda, LifeSci Capital.

Rami Katkhuda，生命科學資本。

Thanks for taking my questions as well. And congrats on the update. A couple of quick ones from me. I guess first up, are you guys using the iBox Scoring System in the BESTOW study?

也感謝您回答我的問題。並祝賀更新。我的一些快速的。我想首先，你們在 BESTOW 研究中使用 iBox 評分系統嗎？

Yes, that's being evaluated as an exploratory endpoint. (multiple speakers)

是的，這正在作為探索性終點進行評估。 （多個發言者）

Great question, Rami. We're obviously really excited that agencies are starting to look at alternative endpoints, like iBox, which can be really transformational as far as helping to assess early-stage clinical trial development and the ability to estimate long-term graft function and survival. So a great question.

好問題，拉米。我們顯然非常興奮各機構開始尋找替代終點，例如 iBox，它可以真正實現變革，有助於評估早期臨床試驗的發展以及估計長期移植物功能和生存的能力。這是一個很好的問題。

And Rami, just to add to what Steve said, we're doing it as part of our collaboration with CareDx. So if you remember, we announced a collaboration with CareDx, and that covers a number of biomarkers and algorithms, including iBox.

Rami，我想補充一下 Steve 所說的，我們這樣做是與 CareDx 合作的一部分。如果您還記得的話，我們宣布了與 CareDx 的合作，涵蓋了許多生物標記物和算法，包括 iBox。

Got it. Makes sense. And then going off a previous question, with the recent regulatory successes in the ALS field can you touch upon potential routes to make [paths to] continued development of tego in that indication?

知道了。說得通。然後繼續前一個問題，隨著最近 ALS 領域監管的成功，您能否談談在該適應症中繼續開發 tego 的潛在途徑？

So right now, this financing is going to allow us to advance tegoprubart in transplantation. And that's what we are primarily focusing on. We'll continue to look for other ways to potentially finance tegoprubart in ALS as we've said before. And we believe in order to advance tegoprubart in ALS, what we would like to do is a trial that would be well designed and does have the best possible chance of success.

所以現在，這筆融資將使我們能夠推進替戈普魯巴特的移植。這就是我們主要關注的問題。正如我們之前所說，我們將繼續尋找其他可能為 ALS 治療中的 tegoprubart 提供資金的方式。我們相信，為了推進 tegoprubart 在 ALS 中的應用，我們想做的是一項設計良好且成功機會最大的試驗。

To do a smaller trial, potentially one that would require less money, we don't think would help fundamentally answer the question of whether tegoprubart would work in ALS, and as such, wouldn't be the best solution for patients and for the field. So we're focused on transplant. We'll continue to look at ways to advance tegoprubart in ALS. And if we do so, we do it in a way to have a trial that would be substantially set to truly be able to answer the question of how well tegoprubart is working in that indication.

進行一項規模較小的試驗（可能需要較少的資金），我們認為這無助於從根本上回答tegoprubart 是否適用於ALS 的問題，因此，對於患者和該領域來說，這不是最好的解決方案。所以我們的重點是移植。我們將繼續尋找在 ALS 中推進 tegoprubart 的方法。如果我們這樣做，我們將進行一項試驗，該試驗將在很大程度上真正能夠回答 tegoprubart 在該適應症中的效果如何的問題。

Got it. Thanks so much.

知道了。非常感謝。

Vernon Bernardino, H.C. Wainwright.

弗農·伯納迪諾，H.C.溫賴特。

Hi, DA, Steve, and Paul. Good afternoon and thanks for taking my questions. Congrats on bolstering the balance sheet. And I appreciate the presentation on the kidney transplant. This question is less more to do with that data -- and apologize for the music, so hopefully you can hear me well enough -- and perhaps more to do with a study with tegoprubart in IgAN.

嗨，DA、史蒂夫和保羅。下午好，感謝您提出我的問題。祝賀資產負債表得到改善。我很欣賞關於腎移植的介紹。這個問題與這些數據關係不大——並對音樂表示歉意，所以希望你能聽清楚我的意思——也許更多與 IgAN 中 tegoprubart 的研究有關。

Given what you perhaps see as side effects, biomarkers that are looked at, and perhaps endpoints you're considering for, again, less severe with a kidney transplant, but perhaps a future study with -- in IgAN. Is there anything that is informing you that targeting anti-CD40 ligand as a strategy to perhaps replace calcineurin inhibitors is informing you that targeting anti-CD40 ligand is working?

考慮到您可能認為的副作用、所觀察的生物標誌物以及您可能正在考慮的終點，再次強調，腎移植的嚴重程度較低，但未來可能會在 IgAN 中進行研究。是否有任何信息告訴您，靶向抗 CD40 配體作為可能替代鈣調神經磷酸酶抑製劑的策略正在告訴您，靶向抗 CD40 配體正在發揮作用？

Because as you know, with the calcineurin inhibitors, you've seen that as dose goes up, so does side effects, so does efficacy, except for perhaps a bit of an exception that we've seen [but not performed]. So just wondering if anything there you're seeing so far? And I know that patients -- the number of patients have been low so far, so you don't have a concrete idea about how to answer this question. Just wondering if there's something you're seeing now that's perhaps informing you of future study and whether targeting anti-CD40 ligand is turning out as you expect? Sorry for the long preamble.

因為如您所知，對於鈣調神經磷酸酶抑製劑，您已經看到隨著劑量的增加，副作用也會增加，療效也會增加，除了我們已經看到的[但未執行]的一些例外情況。所以只是想知道到目前為止你看到了什麼嗎？我知道患者——到目前為止，患者數量很少，所以你不知道如何回答這個問題。只是想知道您現在所看到的是否有一些東西可能會告訴您未來的研究以及靶向抗 CD40 配體的結果是否如您所期望的那樣？很抱歉序言太長。

Vernon, thank you for the question. Steve, I'll turn that over to you to talk about what we're seeing or what we've seen in terms of biomarkers as well as how you interpret the data that we've generated to date with regards to tegoprubart's efficacy.

弗農，謝謝你的提問。史蒂夫，我將把這個問題交給你來談談我們所看到的或我們在生物標誌物方面所看到的，以及你如何解釋我們迄今為止生成的有關 tegoprubart 功效的數據。

Sure, DA. Great question, Vernon. Thank you for that question. We've actually gleaned an amazing amount of data from very diverse indications to date in a very short period of time as you know. We demonstrated very robust target engagement in our ALS study, showing that we knock down both T and B cell markers of target engagement in a very dose proportional way. That translated into functional decreases and over 20 pro-inflammatory markers that sit downstream of co-stimulatory signaling. So again, very good functional data showing that tegoprubart modulated the immune system in that study. And it did so in a very rapid way after the first infusion, which was quite exciting.

當然，DA。好問題，弗農。謝謝你提出這個問題。正如您所知，我們實際上已經在很短的時間內從非常不同的適應症中收集到了大量數據。我們在 ALS 研究中展示了非常強大的靶點參與，表明我們以非常劑量成比例的方式敲低了靶點參與的 T 和 B 細胞標記物。這轉化為功能下降和位於共刺激信號下游的 20 多種促炎標記物。再次，非常好的功能數據表明，替戈普魯巴特在該研究中調節了免疫系統。在第一次輸注後，它以非常快的速度完成，這非常令人興奮。

Globally across all of our indications, the safety profile of tego continues to look very exciting and very encouraging. We haven't seen any serious adverse events in any of our studies. And these are patient population, as you just suggested, that -- these patients in transplant and ALS are very sick and yet the drug has shown a very good safety profile at this point and very predictable pharmacokinetics as well. So that opens up an opportunity, when you kind of summarize all of that data in total, that as we have hypothesized in general, going back over 30 years of data, that blocking this pathway really has an opportunity in multiple autoimmune indications as well as in the transplant indications that we're pursuing.

在全球範圍內，在我們所有的適應症中，tego 的安全性仍然看起來非常令人興奮和鼓舞。我們的任何研究中都沒有發現任何嚴重的不良事件。正如您剛才所建議的，這些患者群體是接受移植和 ALS 治療的患者，病情非常嚴重，但該藥物目前已顯示出非常好的安全性，並且藥代動力學也非常可預測。因此，當你總結所有這些數據時，這就打開了一個機會，正如我們一般假設的那樣，回顧 30 多年的數據，阻斷這條通路確實有機會治療多種自身免疫適應症以及在我們正在尋求的移植適應症中。

Do you plan to present any, even if it's preclinical data, that continues to validate the approach?

您是否計劃提供任何繼續驗證該方法的數據，即使是臨床前數據？

I mean, in the preclinical side, we have multiple collaborations going on both with allograft transplant experiments as well as in the xeno transplant space. As we've mentioned, we have a collaboration with eGenesis that's ongoing. So we anticipate that as we continue to execute on those primate studies, both on allograft and xenograft, that we will present them at some point at scientific conferences.

我的意思是，在臨床前方面，我們在同種異體移植實驗以及異種移植領域進行了多次合作。正如我們所提到的，我們與 eGenesis 的合作正在進行中。因此，我們預計，隨著我們繼續進行這些靈長類動物研究，無論是同種異體移植還是異種移植，我們將在某個時候在科學會議上展示它們。

Perfect. And I'm glad to see we have a bolstered balance sheet, and looking forward to more data. Thanks again for taking my questions.

完美的。我很高興看到我們的資產負債表得到了加強，並期待更多數據。再次感謝您回答我的問題。

Thanks, Vernon.

謝謝，弗農。

(Operator Instructions) Matt Kaplan, Ladenburg Thalmann.

（操作員說明）Matt Kaplan、Ladenburg Thalmann。

Well, hi, this is Raymond in for Matt. Thanks for taking our question and congrats on all the progress. I guess the question I was thinking, I was reading -- I read this recent New York Times article about transplantation, very compelling. And I was wondering, how are doctors and patients responding to the initial data in your renal transplantation program? Is that potentially building more awareness for your Phase 2 trial? And I have another question.

嗯，嗨，這是雷蒙德代替馬特。感謝您提出我們的問題並祝賀我們取得的所有進展。我想我正在思考、正在閱讀的問題——我最近讀了《紐約時報》關於移植的這篇文章，非常引人注目。我想知道，醫生和患者對你們腎移植計劃的初始數據有何反應？這是否有可能提高您對第二階段試驗的認識？我還有另一個問題。

Thank you. That is a wonderful opinion piece that was published in the New York Times, and I encourage really everyone on the call if you haven't had a chance to read it to do so.

謝謝。這是發表在《紐約時報》上的一篇精彩的評論文章，如果您還沒有機會閱讀它，我真的鼓勵參加電話會議的每個人都這樣做。

Steve, let me turn it over to you in terms of awareness, the need, and the receptivity that physicians that you've been talking to have had to our data.

史蒂夫，讓我從與您交談過的醫生對我們數據的認識、需求和接受度方面向您轉達。

Yes, sure. Thanks, DA. And a great question, I agree. The receptivity has been absolutely amazing. I mean, there's a long history, as we know, of blocking this pathway, going back 25 to 30 years, with many different antibodies in preclinical models in particular. But the field was set back in the early 2000s with the first-generation antibodies. And yet to this day, blocking this pathway, and blocking CD40 ligand in particular, has been the most potent way to prevent transplant rejection. It was also a very, very potent strategy to ameliorate autoimmune diseases in multiple different models.

是的，當然。謝謝，DA。這是一個很好的問題，我同意。接受度絕對是驚人的。我的意思是，據我們所知，阻斷這一途徑已有很長的歷史，可以追溯到 25 到 30 年前，特別是在臨床前模型中使用了許多不同的抗體。但該領域在 2000 年代初因第一代抗體而倒退。然而直到今天，阻斷這一途徑，特別是阻斷 CD40 配體，仍然是預防移植排斥的最有效方法。這也是一種在多種不同模型中改善自身免疫性疾病的非常非常有效的策略。

So the second-generation antibody, tegoprubart, that we now have clinical data for us has really generated an incredible amount of excitement as we've reached out to potential sites for the BESTOW study and doing feasibility. And the PIs have been very impressed with the eGFR data that we have to date, albeit on a handful of patients. But folks have been very excited because of the opportunity to reengage this pathway after so many years.

因此，我們現在擁有的第二代抗體 tegoprubart 的臨床數據確實產生了令人難以置信的興奮，因為我們已經接觸到了 BESTOW 研究的潛在地點並進行了可行性研究。 PI 對我們迄今為止掌握的 eGFR 數據印象深刻，儘管只針對少數患者。但人們非常興奮，因為多年後有機會重新走上這條道路。

Yes, that's great. Thanks for all that color. I guess just one other question. It might be too early to say, but with the kind of impressive data you had so far and thinking about the BESTOW trial, does the magnitude and duration of any potential [EDR] benefit over (inaudible) might potentially dictate the path forward clinically or regulatory?

是的，那太好了。感謝所有這些顏色。我想還有一個問題。現在說可能還為時過早，但根據您迄今為止獲得的令人印象深刻的數據並考慮BESTOW 試驗，任何潛在[EDR] 獲益的程度和持續時間（聽不清）是否可能決定臨床或未來的發展方向監管？

Yes. So we obviously would want to show a -- we're looking at eGFR, and this is a superiority study. So we're going to want to see a statistically superior delta in terms of eGFR versus standard of care. And the larger that delta, the better. I would note that even small deltas in eGFR can make a difference clinically. So for example, we know that as early as six months, a 10-point delta in eGFR means an 11% delta in the chance of a patient being -- of a post-transplant patient being hospitalized. Similarly, the lower the eGFR, the more likely the patients are to be hospitalized multiple times.

是的。因此，我們顯然想要展示——我們正在研究 eGFR，這是一項優勢研究。因此，我們希望看到 eGFR 與標準護理相比具有統計學上的優越性。增量越大越好。我要指出的是，即使 eGFR 的變化很小，也會在臨床上產生影響。例如，我們知道，早在六個月內，eGFR 變化 10 點就意味著移植後患者住院的可能性增加了 11%。同樣，eGFR 越低，患者多次住院的可能性就越大。

And finally of course, eGFR is associated with the risk of graft failure. So the lower the eGFR, the higher the risk of that kidney being lost. And that graft, that increase is almost exponential, pretty much exponential. One to one has an eGFR that goes below 50 or 55, which is the mean eGFR in post -- in the year post transplant. So if we would be able to move the needle in those patients by even only 10 points, that would be very meaningful since we're looking at an exponential increase in terms of risk. Steve?

最後，當然，eGFR 與移植失敗的風險相關。因此，eGFR 越低，失去腎臟的風險就越高。而這種移植，這種增長幾乎是指數級的，幾乎是指數級的。一對一的 eGFR 低於 50 或 55，這是移植後一年的平均 eGFR。因此，如果我們能夠將這些患者的治療效果提高哪怕只有 10 個百分點，那也將非常有意義，因為我們面臨的風險呈指數級增長。史蒂夫？

I appreciate it.

我很感激。

I was going to see if Steve wanted to add anything.

我想看看史蒂夫是否想補充什麼。

No. Yes, I agree. I mean, even small differences in eGFR based on very large retrospective studies can really impact long-term graft function and survival. So, even smaller differences will be very, very important.

不，是的，我同意。我的意思是，即使是基於大規模回顧性研究的 eGFR 的微小差異也會真正影響長期移植物功能和生存。因此，即使是更小的差異也將非常非常重要。

Thanks for that. Congrats on all the progress.

感謝那。祝賀所有的進步。

Thank you.

謝謝。

And there are no further questions at this time. I will turn the call back over to Mr. Gros for closing remarks.

目前沒有其他問題。我將把電話轉回給格羅斯先生做總結髮言。

Thank you for your assistance, operator. And thank you all for joining us today on this call. Have a great evening.

感謝您的幫助，接線員。感謝大家今天參加我們的電話會議。祝您度過一個美好的夜晚。

Ladies and gentlemen, this concludes your conference call for today. We thank you for joining, and you may now disconnect your lines.

女士們、先生們，今天的電話會議到此結束。我們感謝您的加入，您現在可以斷開線路了。