Prokidney Corp (PROK) 2023 Q3 法說會逐字稿

Good morning, ladies and gentlemen. And welcome to the Prokidney corporate update conference call. (Operator Instructions) As a reminder, this call is being recorded. At this time, it is now my pleasure to introduce your host, Dr. Glenn Schulman, Senior Vice President of Investor Relations. Please go ahead, sir.

早安，女士們先生們。歡迎參加 Prokidney 公司更新電話會議。 （操作員說明）謹此提醒，此通話正在錄音。此時此刻，我很高興向您介紹主持人，投資者關係資深副總裁 Glenn Schulman 博士。請繼續，先生。

Thank you, Rob. And good morning, everyone. And welcome to Prokidney's corporate update conference call. Yesterday evening after the markets closed, we issued a press release that provided several corporate updates. And then this morning, released our third quarter 2023 financial results press release and 10Q filing. Please note a replay of today's call will be available on the investors section of our website, approximately one after -- one hour after its completion.

謝謝你，羅布。大家早安。歡迎參加 Prokidney 的企業更新電話會議。昨天晚上市場收盤後，我們發布了一份新聞稿，其中提供了一些公司最新消息。今天早上，我們發布了 2023 年第三季財務業績新聞稿和 10 季報告。請注意，今天電話會議的重播將在我們網站的投資者部分提供，大約在電話會議結束後一小時後進行。

Joining us on the call this morning are Prokidney's Chairman of the Board, Pablo Legorreta; Prokidney's Co-founder and member of the Scientific Advisory Board, Dr. Tim Bertram; and Prokidney's new Chief Executive Officer, Dr. Bruce Culleton. Following some introductory comments by Pablo and Dr. Bertram, prepared remarks by Dr. Culleton on REACT 002 interim results and the clinical development program; we will open up the call for your questions. Also joining us today on the call is our Chief Financial Officer, James Coulston; and our Chief Regulatory Officer, Dr. Darin Weber.

今天早上參加我們電話會議的還有 Prokidney 董事會主席 Pablo Legorreta； Prokidney 共同創辦人兼科學顧問委員會成員 Tim Bertram 博士；以及 Prokidney 的新任執行長 Bruce Culleton 博士。在 Pablo 和 Bertram 博士進行了一些介紹性評論之後，Culleton 博士準備了關於 REACT 002 中期結果和臨床開發計劃的評論；我們將打開電話詢問您的問題。今天參加電話會議的還有我們的財務長 James Coulston；以及我們的首席監理官 Darin Weber 博士。

Before we begin, I'd just like to remind everyone that during this conference call, we will be making forward-looking statements about the company. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those forecasted. Actual results could differ materially by those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.

在開始之前，我想提醒大家，在這次電話會議中，我們將做出有關公司的前瞻性陳述。這些陳述存在風險和不確定性，可能導致實際結果與預測有重大差異。由於與公司業務相關的風險和不確定性，實際結果可能與這些前瞻性陳述中明示或暗示的結果有重大差異。

These forward-looking statements are qualified by the cautionary statements contained in today's press release, 10Q filing and our other SEC filings including our annual report on Form 10K and subsequent filings. Please also note that these forward-looking statements reflect our opinions only as of today, November 14, 2023. And except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events.

這些前瞻性陳述受到今天的新聞稿、10Q 文件和我們其他 SEC 文件（包括我們的 10K 表格年度報告和後續文件）中包含的警示性聲明的限制。另請注意，這些前瞻性陳述僅反映我們截至今天（2023 年 11 月 14 日）的觀點。 除非法律要求，否則我們明確不承擔根據新資訊或未來更新或修改這些前瞻性陳述的義務。

Turning to Slide 3. And our agenda for the call today will open with a few comments from Pablo Legorreta and Dr. Bertram hoping to provide the opening remarks and introduce our incoming CEO, Dr. Bruce Culleton, will then review the REACT Phase 2 RMCL-002 data, discuss the objectives of our Phase 3 program and conclude with our comprehensive clinical plan including milestones. Afterwards, we'll open it up -- the call for your questions. With all that, I'd like to now turn the call over to Pablo Legorreta, Prokidney's Chairman of the Board. Pablo?

轉向幻燈片 3。數據，討論我們第3 階段計劃的目標，並以包括里程碑在內的全面臨床計劃作為總結。之後，我們將打開它——詢問您的問題。儘管如此，我現在想將電話轉給 Prokidney 董事會主席 Pablo Legorreta。巴勃羅？

Thank you, Glen. And thank you all for joining. As you all may know, I partner with Tim Bertram to support his vision for the future of seek of the CKD therapy. And I believe that our renal autologous cell therapy, also known as REACT, has the potential to truly disrupt the chronic kidney disease treatment landscape.

謝謝你，格倫。感謝大家的加入。眾所周知，我與 Tim Bertram 合作支持他對 CKD 治療未來的願景。我相信我們的腎臟自體細胞療法（也稱為 REACT）有潛力真正顛覆慢性腎臟疾病的治療模式。

Before we introduce Bruce Culleton and subsequently review the promising data emerging from REACT's clinical development program, I first want to take a moment to thank Tim Bertram for all of his dedication and contributions to Prokidney. As one of the inventors of REACT, Tim has invested nearly 20 years into this technology and advanced REACT, a truly novel approach, to preserve kidney function for those with advanced chronic kidney disease from the lab and into Phase 3 human clinical development.

在我們介紹 Bruce Culleton 並隨後回顧 REACT 臨床開發計劃中出現的有希望的數據之前，我首先想花點時間感謝 Tim Bertram 對 Prokidney 的所有奉獻和貢獻。作為REACT 的發明者之一，Tim 在這項技術上投入了近20 年的時間，並推進了REACT，這是一種真正新穎的方法，可以為患有晚期慢性腎病的患者保留腎功能，從實驗室進入第三階段人體臨床開發。

During his tenure, Tim has done an impressive job shepherding this company and the REACT technology from inception into human clinical development. Tim has left Prokidney well positioned for the future. I believe I speak for everybody here at Prokidney when I say thank you, Tim, for all that you have accomplished here. While we wish him well in his future endeavors, we're very happy to say that he will be staying with us in a scientific advisory role. Again, our deepest gratitude to you, Tim and all that you have accomplished.

在他的任期內，Tim 做了令人印象深刻的工作，帶領這家公司和 REACT 技術從一開始進入人體臨床開發。 Tim 離開 Prokidney 後，為未來做好了充分的準備。我相信，當我對 Tim 所取得的一切表示感謝時，我代表 Prokidney 的每個人。雖然我們祝福他未來的事業一切順利，但我們很高興地說，他將繼續擔任我們的科學顧問。提姆，我們再次對您以及您所取得的成就表示最深切的感謝。

I would like to now briefly provide a bit of background on Bruce. And why I am, together with our Board and the Prokidney team, really excited about Bruce becoming the new CEO of Prokidney. I have known Bruce for several years. But two of Prokidney's Directors, Brian Pereira and Alan Lotvin have known him for about 20 and around 6 years respectively. Both worked closely with him. And both had suggested about a year ago that we hired him at Prokidney. Both felt that Bruce had the ideal background as nephrologist, having treated patients and having worked at various top companies in leadership roles in the renal space that he would be ideal to take Prokidney forward. So after about a year of courtship, we succeeded in hiring Bruce at Prokidney about four months ago.

我現在想簡單介紹一下布魯斯的一些背景。為什麼我、我們的董事會和 Prokidney 團隊對 Bruce 成為 Prokidney 的新任執行長感到非常興奮。我認識布魯斯好幾年了。但 Prokidney 的兩位董事 Brian Pereira 和 Alan Lotvin 分別認識他約 20 年和約 6 年。兩人都與他密切合作。大約一年前，兩人都建議我們在 Prokidney 僱用他。兩人都認為 Bruce 擁有作為腎臟病專家的理想背景，曾治療過患者，並曾在腎臟領域的多家頂級公司擔任過領導職務，因此他是推動 Prokidney 向前發展的理想人選。經過大約一年的求愛，大約四個月前，我們成功在 Prokidney 聘請了 Bruce。

I'd like now to share a few details about Bruce's background. Bruce have more than 25 years of dedication to improving the lives of patients with kidney disease. Bruce completed medical school training and training as an internist as nephrologists in Canada. He completed a fellowship in clinical as an epidemiology at the world-famous Framingham Heart Study in Massachusetts. For close to 10 years, Bruce then worked as a nephrologist and clinical researcher at the University of Calgary in Alberta, Canada. He provided direct care to patients with CKD and acted as Medical Director of the progressive kidney disease clinic.

現在我想分享一些有關布魯斯背景的細節。 Bruce 致力於改善腎臟病患者的生活超過 25 年。布魯斯在加拿大完成了醫學院培訓和腎臟病內科醫生培訓。他在世界著名的馬薩諸塞州弗雷明漢心臟研究中心完成了流行病學臨床研究。隨後，Bruce 在加拿大艾伯塔省卡加利大學擔任腎臟病學家和臨床研究員近 10 年。他為 CKD 患者提供直接護理，並擔任進行性腎臟病診所的醫療主任。

Bruce has published more than 100 scientific papers including clinical trials, epidemiology, health articles research and cost effectiveness. Bruce then moved to Chicago to join Baxter Healthcare where he spent eight years holding multiple global roles at -- all within renal including oversight of global clinical studies and medical leadership of the renal therapeutic area. After Baxter, Bruce was recruited by Alan Lotvin, one of Prokidney's director, who at the time was running CVS Caremark, the largest PBM in the country. And Vice President and General Manager of CVS Kidney Care where he provided oversight to the development of products and services for patients with kidney disease.

Bruce 發表了 100 多篇科學論文，包括臨床試驗、流行病學、健康文章研究和成本效益。隨後，Bruce 搬到芝加哥加入 Baxter Healthcare，並在該公司工作了八年，擔任多個全球職務，所有職位均在腎臟領域，包括監督全球臨床研究和腎臟治療領域的醫療領導。在 Baxter 之後，Bruce 被 Prokidney 的董事之一艾倫·洛特文 (Alan Lotvin) 招募，當時負責營運美國最大的 PBM CVS Caremark。 CVS Kidney Care 副總裁兼總經理，負責監督腎臟病患者產品和服務的開發。

I will now pass on the call to Tim Bertram. Tim, I'm sure you have a few words that you would like to share as well.

我現在將把電話轉給蒂姆·伯特倫。提姆，我相信您也有一些話想分享。

Pablo, thank you for your support of the mission and vision of Prokidney. Since founding Prokidney, we have been focused on bringing the possibility of dialysis free-living to patients with late-stage CKD. And importantly, you have walked with us on each step of that journey. Now with mature REACT data firmly in hand, we increased the possibility for our mission to bring an advanced therapy to patients facing real potential going on to end-stage kidney failure and dialysis.

Pablo，感謝您對 Prokidney 使命和願景的支持。自成立 Prokidney 以來，我們一直致力於為晚期 CKD 患者帶來透析自由生活的可能性。重要的是，您與我們一起走過了這段旅程的每一步。現在，憑藉成熟的 REACT 數據，我們增加了為面臨末期腎衰竭和透析的真正潛力的患者提供先進治療的使命的可能性。

Bruce, I'm excited about the leadership you will bring to Prokidney. I now turn it over to you to take us forward to the next stages of our journey. And I look forward to each step that we will take.

Bruce，我對你將為 Prokidney 帶來的領導感到興奮。現在我把它交給你，帶領我們進入旅程的下一個階段。我期待著我們將採取的每一步。

Thank you for the warm welcome, Pablo and Dr. Bertram. I really want to thank Dr. Bertram for all his contributions to Prokidney and the genuine support he's provided to me over the last four months since joining the company. I also want to thank the Board of Directors for placing their trust in me at this very important time in the company's evolution. Today, it's my absolute pleasure to present exciting data from our Phase 2 RMCL-002 study. Our analysis reveal a safety profile in line with previous Phase 1 and Phase 2 REACT trials, which REACT showing a safety profile similar to that of a kidney biopsy.

感謝巴勃羅和伯特倫博士的熱情歡迎。我真的要感謝 Bertram 博士對 Prokidney 的所有貢獻，以及他加入公司後過去四個月為我提供的真誠支持。我還要感謝董事會在公司發展的這個非常重要的時刻對我的信任。今天，我非常高興地向大家展示我們 2 期 RMCL-002 研究的令人興奮的數據。我們的分析揭示了與先前的 1 期和 2 期 REACT 試驗一致的安全性，其中 REACT 顯示出與腎臟活檢相似的安全性。

The updated analysis also showed the potential to preserve kidney function in several patient groups with advanced CKD caused by Type 2 diabetes with the most notable potential benefit shown in patients who had the highest risk of kidney failure those patients with Stage 4 chronic kidney disease and severe albuminuria.

更新的分析還顯示，對於由2 型糖尿病引起的晚期CKD ​​的幾個患者群體，有可能保留腎功能，其中最顯著的潛在益處是腎衰竭風險最高的患者、患有4 期慢性腎病和嚴重腎臟病的患者。

Here are the remains a significant unmet clinical need. Based on these emerging results, we plan to update our ongoing Proact 1 Phase 3 clinical study protocol to focus on patients with higher risk of kidney failure. We will modify the EGFR enrollment range from the current range of 20 to 50 to new range of 20 to 35 milliliters per minute to focus on the most severe patients to better align with our Phase 2 results and external clinical feedback. We do not intend to modify the other Phase 3 trial Proact 2. The modification to the EGFR enrollment range in our Proact 1 Phase 3 clinical study will cause a further delay in enrollment of the study. And we expect to resume enrollment during the first half of 2024. We believe this delay is warranted because it increases our probability of overall success.

以下是尚未滿足的重大臨床需求。根據這些新出現的結果，我們計劃更新正在進行的 Proact 1 第 3 期臨床研究方案，以重點關注腎衰竭風險較高的患者。我們將把EGFR 登記範圍從目前的20 至50 毫升/分鐘修改為新的每分鐘20 至35 毫升範圍，以重點關注最嚴重的患者，以便更好地與我們的2 期結果和外部臨床反饋保持一致。我們不打算修改其他3期試驗Proact 2。我們預計在 2024 年上半年恢復招生。

We are also pausing manufacturing to address a very recent EU qualified person audit. Importantly, this pause is not due to a clinical safety event. A recent audit performed by our contracted qualified person to evaluate its readiness for release and distribution of REACT to the EU. While still in progress, identify certain deficiencies in the documentation of the quality management systems that must be addressed prior to release and distribution to EU clinical sites.

我們也暫停了生產，以應對最近的歐盟合格人員審計。重要的是，這種暫停並不是由於臨床安全事件。最近由我們簽約的合格人員進行了審計，以評估其向歐盟發布和分發 REACT 的準備。在仍在進行的過程中，確定品質管理系統文件中的某些缺陷，這些缺陷必須在發布和分發到歐盟臨床場所之前解決。

Many of these improvements to GMP systems and control activities were ongoing. But had not yet been completed at the time of the audit. We expect to resume manufacturing in the first half of 2024. Over this period, we plan to optimize our capabilities to meet EU and global standards for our Phase 3 program and future commercial manufacturing. We are implementing these manufacturing documentation improvements concurrently with the 006 pause for protocol changes. Such as we expect Proact 1 to resume and Proact 2 to commence enrollment in the first half of next year. Despite these delays, I truly believe we have a bright and exciting future ahead of us. I started Prokidney in July of this year with some degree of optimistic skepticism. Now that I deeply understand our Phase 2 data and our product, I'm definitely more optimistic about our future.

其中許多對 GMP 系統和控制活動的改進正在進行中。但截至審計時尚未完成。我們預計在 2024 年上半年恢復生產。我們正在實施這些製造文件改進，同時暫停 006 協議變更。例如我們預計Proact 1將在明年上半年恢復，Proact 2將在明年上半年開始招生。儘管有這些延誤，我堅信我們前面有一個光明和令人興奮的未來。我於今年七月帶著某種程度的樂觀懷疑態度創立了 Prokidney。現在我深入了解了我們的第二階段數據和我們的產品，我對我們的未來肯定更加樂觀。

If we can move to slide 5. Let's take a step back and review why we believe REACT is so special. As you can see, chronic kidney disease is a significant problem. While one in seven adult Americans have some degree of chronic kidney disease, there are more than 3 million Americans who have type 2 diabetes and advanced Stage 3B or Stage 4 chronic kidney disease. These are patients that have few kidney treatment options and are at very high risk of progressing to kidney failure. Within this large population, I'd note that more than 135,000 CKD patients in the US continue to progress to dialysis every year. We believe there's a substantial opportunity with our product, REACT, as we believe we can preserve kidney function to delay or eliminate time on dialysis.

如果我們可以轉到投影片 5。如您所見，慢性腎臟病是一個嚴重的問題。雖然七分之一的美國成年人患有某種程度的慢性腎病，但仍有超過 300 萬美國人患有第 2 型糖尿病和晚期 3B 期或 4 期慢性腎臟病。這些患者幾乎沒有腎臟治療選擇，且進展為腎衰竭的風險非常高。在這個龐大的人群中，我注意到美國每年有超過 135,000 名 CKD 患者繼續進行透析。我們相信我們的產品 REACT 有很大的機會，因為我們相信我們可以保留腎功能以延遲或消除透析時間。

The REACT cell therapy is different than other small molecules and biologics. And we'll walk through data this morning that will show why we believe REACT may be able to preserve kidney function and possibly provide greater benefit in high-risk CKD patients. The data will review -- we will review supports our exciting Phase 3 clinical program. And we believe it will demonstrate REACT's ability to potentially change the treatment landscape for patients with Stage 3B and Stage 4 diabetic kidney disease.

REACT 細胞療法不同於其他小分子和生物製劑。今天早上我們將瀏覽數據，這些數據將說明為什麼我們相信 REACT 可能能夠保留腎功能，並可能為高風險 CKD 患者提供更大的益處。我們將審查數據，以支持我們令人興奮的第三階段臨床計劃。我們相信，它將證明 REACT 有能力改變第 3B 期和第 4 期糖尿病腎病變患者的治療前景。

Slide 6. As Pablo mentioned, REACT is an innovative approach to preserving kidney function. It's a proprietary autologous cell therapy that's generated from a patient's own kidney cells. The patient's cells are harvested via traditional kidney biopsy, then expanded in our manufacturing facility isolating three key cell types. These expanded cells are then cryopreserved ahead of being reimplemented via a percutaneous outpatient procedure. Patients then receive reimplementation of REACT where the cells are injected back into the patient's renal cortex. In the 002 Phase 2 trial, we evaluated REACT implanted into the biopsy kidney two times six months apart. In our ongoing 007 trial and our Phase 3 program, we are evaluating one injection of REACT into each kidney or bilaterally three months apart.

投影片 6。這是一種專有的自體細胞療法，由患者自己的腎臟細胞產生。透過傳統的腎臟切片收集患者的細胞，然後在我們的生產設施中進行擴增，分離出三種關鍵的細胞類型。然後將這些擴增的細胞冷凍保存，然後透過經皮門診手術重新植入。然後患者接受 REACT 的重新實施，細胞被注射回患者的腎皮質。在 002 2 期試驗中，我們對植入活檢腎臟的 REACT 進行了兩次評估，每次間隔六個月。在我們正在進行的 007 試驗和第 3 階段計劃中，我們正在評估每側腎臟注射一次 REACT 或每側腎臟注射一次，間隔三個月。

Here on slide 7, see a robust clinical trial program with react as highlighted in this pipeline chart, we've previously published data showing REACT's potential to delay dialysis from the Phase 2 003 study in patients with Stage 4 and 5 CKD. This combined with preclinical data and data from Study002 that you'll see today, we initiated our pivotal Phase 3 program. Our Proact 1 and Proact 2 trials.

在幻燈片7 上，可以看到一個強大的React 臨床試驗計劃，如該流程圖中突出顯示的那樣，我們之前發布的數據顯示REACT 有可能延遲2 003 期研究中4 期和5 期CKD ​​患者的透析。結合您今天將看到的臨床前數據和 Study002 的數據，我們啟動了關鍵的第 3 階段計劃。我們的 Proact 1 和 Proact 2 試驗。

Today, we'll be focusing on data from our 002 study that is near completion. And how this data informs our Proact 1 and Proact 2 Phase 3 trials. Further, I'd like to point out that our 007 program, which is different from 002, as mentioned earlier, will also be helpful in providing us confidence in our Phase 3 program. I'll touch on the 007 study and related milestones much later in the presentation.

今天，我們將重點放在即將完成的 002 研究的數據。以及這些數據如何為我們的 Proact 1 和 Proact 2 第 3 期試驗提供資訊。此外，我想指出的是，我們的007計劃與前面提到的002不同，也將有助於增強我們對第三階段計劃的信心。我將在稍後的演示中談到 007 研究和相關里程碑。

For additional context, let me share with you a framework for the classification of chronic kidney disease. The foundation of this work started over 20 years ago by the National Kidney Foundation. I'm humbled to have played a very small role in that work. For the first time, it provided standard definitions for CKD and an approach to risk stratification. This general approach is now used globally and is accepted by guideline committees around the world.

為了了解更多背景信息，讓我與您分享一個慢性腎臟病分類框架。這項工作的基礎是 20 多年前由國家腎臟基金會發起的。我很榮幸在這項工作中扮演了一個很小的角色。它首次提供了 CKD 的標準定義和風險分層方法。這種通用方法現已在全球範圍內使用，並被世界各地的指導委員會所接受。

If you look at the heat map, the rows represent kidney disease function. And the columns represent kidney injury. Together, they predict the risk of kidney failure as shown in the different colors. As a company, we are focused in the highest risk area. Patients who have moderate to high kidney injury in moderate to severe decrease in their kidney function. This is an area where we believe is distinctly different from where many small molecules and biologics operate as shown here with the dashed oval lines.

如果你看一下熱圖，行代表腎臟疾病的功能。柱子代表腎損傷。它們共同預測腎衰竭的風險，如不同顏色所示。作為一家公司，我們專注於風險最高的領域。中度至重度腎損傷患者的腎功能中度至重度下降。我們認為這個領域與許多小分子和生物製劑的運作領域明顯不同，如橢圓虛線所示。

Today, clinical priorities for patients with Stage 4 kidney disease, G4 on this chart, are largely focused on treating comorbidities, such as anemia or abnormalities in mineral metabolism, and preparing patients for dialysis or kidney transplantation. We also know that payers acknowledge a specific pain point with Stage 4 chronic kidney disease. They know these patients have the highest risk to progress to kidney failure and the need for dialysis. As I stated earlier, this is a goal of Prokidney to reduce or eliminate time in dialysis, which is life-altering for patients and their care partners. And cost payers between $110,000 to $240,000 per patient per year.

如今，4 期腎臟病（圖表中的 G4）患者的臨床重點主要集中在治療合併症，例如貧血或礦物質代謝異常，以及為患者做好透析或腎臟移植的準備。我們也知道，付款人承認第四階段慢性腎臟病的一個特定痛點。他們知道這些患者進展為腎衰竭並需要透析的風險最高。正如我之前所說，Prokidney 的目標是減少或消除透析時間，這將改變患者及其照護夥伴的生活。每位患者每年花費 11 萬至 24 萬美元。

On Slide 9, further focus our focus -- to further support our focus on these high-risk patients, we took a look at the several landmark CKD studies that have been published over the last several years. Here's a selection of them. Of note, three papers use SGLT2 inhibitors. All published in the New England Journal of Medicine. The paper using selective MRA as well as the baseline paper using GLP-1. As you can see in all these landmark papers, there is very little focus on patients with Stage 4 chronic kidney disease. And that's where our focus is.

在投影片 9 上，進一步聚焦我們的焦點——為了進一步支持我們對這些高風險患者的關注，我們回顧了過去幾年發表的幾項具有里程碑意義的 CKD 研究。以下是其中的一些選擇。值得注意的是，三篇論文使用了 SGLT2 抑制劑。全部發表在《新英格蘭醫學雜誌》。使用選擇性 MRA 的論文以及使用 GLP-1 的基線論文。正如您在所有這些具有里程碑意義的論文中所看到的，很少有人關注第四期慢性腎病患者。這就是我們的重點。

On Slide 10, we go into more detail on one of these published studies specifically the study that looked at the SGLT2 data versus placebo that was published a couple of years ago again in the New England Journal of Medicine. And there are three key points here that I want to draw your attention to.

在投影片10 上，我們更詳細地介紹了其中一項已發表的研究，特別是幾年前在《新英格蘭醫學雜誌》上再次發表的一項研究，該研究考察了SGLT2 數據與安慰劑的比較。這裡我想提請大家注意三個要點。

The first is although these new SGLT2 inhibitors are a step forward, patients still lose kidney function. And this is shown on the right-hand panel of this slide, which looks at change in estimated glomerular filtration rate over time. This is also the same efficacy measure in our Phase 2 study that I will present shortly.

首先，雖然這些新的 SGLT2 抑制劑向前邁出了一步，但患者仍然喪失腎功能。這顯示在這張投影片的右側面板上，它觀察了估計腎小球濾過率隨時間的變化。這也是我即將介紹的第二階段研究中相同的療效衡量標準。

The second point, also in the right-hand panel, is the fact that patients who are treated with SGLT2 inhibitors or Ace inhibitors or angiotensin receptor blockers for that matter, there is an initial short term abrupt decline in kidney function. And it takes 12 months for the eGFR to actually catch up to placebo. And then another 6-12 months before separation of the SGLT2 inhibitor from placebo. My point here is that it takes some time for patients on these agents to see a benefit in kidney function.

第二點（也在右側圖中）是這樣的事實：接受 SGLT2 抑制劑或 Ace 抑制劑或血管緊張素受體阻斷劑治療的患者，腎功能最初會出現短期突然下降。 eGFR 需要 12 個月才能真正趕上安慰劑。然後又過了 6-12 個月，才將 SGLT2 抑制劑與安慰劑分開。我的觀點是，服用這些藥物的患者需要一段時間才能看到腎功能的改善。

The last point is that even after two years, there's only a very small difference in EGFR between patients treated with DAPA and placebo. Less than 1ml per minute per year. Please keep this number in mind as we present our 002 results today. Despite this very small improvement, a reduction in clinical events is still observed and as shown on the left panel. Like our Phase 3 program, these patients were randomized to receive an investigational product for placebo. Patients were then followed over time to determine any difference in the occurrence of the composite end point.

最後一點是，即使兩年後，接受 DAPA 和安慰劑治療的患者之間 EGFR 的差異也非常小。每年每分鐘少於 1 毫升。當我們今天展示 002 結果時，請記住這個數字。儘管改善很小，但仍觀察到臨床事件減少，如左圖所示。與我們的第三階段計劃一樣，這些患者被隨機接受安慰劑的研究產品。然後隨時間推移對患者進行隨訪，以確定複合終點發生的任何差異。

In this case, a 50% decline in EGFR, incidence of kidney failure or incidence of cardiovascular kidney death. While this blue line shows that DAPA reduces those events versus placebo, it's important to recognize that these events on DAPA -- the patients on DAPA still had events -- still ended up on dialysis and still succumb to their disease. In fact, 19 patients need to be treated with DAPA to prevent one primary outcome event. Highlighting the fact that there remains a big unmet need in this population. Now that we've clearly articulated the opportunity for Prokidney, let's walk through the latest update of our Phase 2 RMCL-002 clinical trials.

在這種情況下，EGFR 下降 50%，腎衰竭發生率或心血管腎死亡發生率。雖然這條藍線表明 DAPA 與安慰劑相比減少了這些事件，但重要的是要認識到 DAPA 上的這些事件（使用 DAPA 的患者仍然有事件）仍然最終接受透析並仍然死於疾病。事實上，19 名患者需要接受 DAPA 治療以預防一項主要結局事件。強調這一人群仍然存在大量未滿足的需求。現在我們已經清楚地闡明了 Prokidney 的機會，讓我們來看看 2 期 RMCL-002 臨床試驗的最新更新。

On Slide 12, we believe the data in-hand demonstrat the potential for preservation of kidney function in diabetic patients with advanced chronic kidney disease. REACT's benefit was most notably observed in the sickest patients. Those who had Stage 4 CKD with a high UACR or severe kidney injury. Consistent with previous study data, REACT was well tolerated and continues to demonstrate a safety profile in line with the traditional kidney biopsy. With this updated data in mind, we are modifying one of our Phase 3 pivotal trials proact 1 study to focus more closely on patients with the highest risk of kidney failure. Patients who have late Stage 3B and Stage 4 CKD with an EGFR between 20 and 35mls per minute.

在投影片 12 上，我們相信現有數據證明了患有晚期慢性腎病的糖尿病患者保留腎功能的潛力。 REACT 的益處在病情最嚴重的患者中最為明顯。患有 4 期 CKD 且 UACR 高或嚴重腎損傷的患者。與先前的研究數據一致，REACT 具有良好的耐受性，並且繼續表現出與傳統腎臟活檢一致的安全性。考慮到這些最新數據，我們正在修改一項 3 期關鍵試驗 proact 1 研究，以更密切地關注腎衰竭風險最高的患者。患有 3B 期晚期和 4 期 CKD 且 EGFR 濃度在每分鐘 20 至 35 毫升之間的患者。

Let's revisit the design of RMCL-002 study, which is fully enrolled and near completion. Patients with CKD caused by diabetes were randomized after kidney biopsy to one of two treatment arms. The active treatment arm or the deferred treatment arm. Active group patients received two REACT injections. The first, as soon as REACT was available, and again approximately six months later. Follow-up visits were scheduled every three months after the second REACT injection until 24 months after the second injection when the study ended free subject.

讓我們重新審視 RMCL-002 研究的設計，該研究已全部入組且即將完成。糖尿病引起的 CKD 患者在腎臟切片後被隨機分配至兩個治療組之一。積極治療組或延期治療組。活躍組患者接受兩次 REACT 注射。第一次是 REACT 推出後，大約六個月後又是一次。第二次 REACT 注射後每三個月安排一次隨訪，直至第二次注射後 24 個月，研究結束自由受試者。

Deferred group patients receive standard of care for the first 12 months after randomization. At the 12-month mark, they were eligible to receive the first of two REACT injections with the second injection administered six months after the first. Follow-up visits also occurred every three months for 12 months following the second injection. Notably, the biopsy and the two injections were performed in the same kidney. This differs from our Phase 3 studies, which I'll explain later.

延遲組患者在隨機分組後的前 12 個月內接受標準護理。在 12 個月時，他們有資格接受兩次 REACT 注射中的第一次，第二次注射是在第一次注射後六個月進行的。第二次注射後的 12 個月內，每三個月進行一次追蹤。值得注意的是，活檢和兩次注射是在同一個腎臟中進行的。這與我們的第三階段研究不同，我將在稍後解釋。

Please also note that we still have 13 participants who will receive their last kidney function measurement and their end of study visits this year. Given that these patients have already had 18 or more months of follow-up, we do not believe our results will materially change upon study completion. Finally, it's worth noting that we received RMAT designation partially based upon early data from this study. And our Phase 3 study program was designed and initiated before completion of this Phase 2 study.

另請注意，我們仍有 13 位參與者將在今年接受最後一次腎功能測量和研究結束訪視。鑑於這些患者已經接受了 18 個月或更長時間的隨訪，我們認為研究完成後我們的結果不會發生重大變化。最後，值得注意的是，我們獲得 RMAT 頭銜部分是基於這項研究的早期數據。我們的第三階段研究計劃是在第二階段研究完成之前設計和啟動的。

As the Phase 2 trial, the study objectives were focused on the safety and efficacy of two REACT injection six months apart and delivered into the biopsy kidney using a percutaneous approach. Study endpoints included procedural and REACT related adverse events along with change in kidney function as assessed by change in estimated glomerular filtration rate or EGFR.

作為第 2 期試驗，研究目標集中在兩次 REACT 注射的安全性和有效性，兩次 REACT 注射相隔六個月，並使用經皮方法注射到活檢腎臟。研究終點包括手術和 REACT 相關的不良事件，以及透過估計腎小球濾過率或 EGFR 的變化來評估的腎功能變化。

On Slide 15, we show the characteristics and demographics of the 002 study population. There were well-balanced with patients with high-risk CKD comprising a significant portion of both treatment groups. In fact, 43% of all enrolled subjects had Stage 4 chronic kidney disease. The average baseline EGFR was 33.9 and 31.8mls per minute. And UACR of 740 and 598 milligrams per gram in the active and deferred arm respectively.

在投影片 15 上，我們展示了 002 研究族群的特徵和人口統計。兩個治療組中都有很大一部分患有高風險 CKD 的患者比例良好。事實上，所有登記受試者中有 43% 患有第四期慢性腎臟病。平均基線 EGFR 為每分鐘 33.9 和 31.8 毫升。主動組和延遲組的 UACR 分別為 740 毫克/克和 598 毫克/克。

On slide 16, we described the number of subjects in our analysis at different time points. 20 subjects dropped out of the analysis for protocol related reasons including in an earlier protocol version that followed patients for a shorter period of time. New comorbidities that prevented injection with REACT. And our protocol design that limited REACT injections to patients with an EGFR of 20mls per minute or more.

在投影片 16 上，我們描述了不同時間點分析的受試者數量。 20 名受試者因方案相關原因退出分析，其中包括早期方案版本中追蹤患者時間較短的情況。阻礙 REACT 注射的新併發症。我們的方案設計將 REACT 注射限制為 EGFR 為每分鐘 20 毫升或更多的患者。

The rates of dropouts due to dialysis and death were typical for this high-risk co-morbid population. All patients are expected to complete study visits by end of this year with final safety and efficacy results anticipated in the first half of next year. The safety of REACT remains a significant focus for us as we understand the highest risk CKD patient population often has multiple comorbidities and tend to be older patients on many medications. The biopsy and REACT injections continue to be well tolerated. And we are pleased to report that there are no significant REACT related serious adverse events. Procedure-related events occurred in 6 of 83 REACT patients and are consistent with published reports of events observed during kidney biopsies, which are commonly done to assess and diagnosed CKD.

由於透析和死亡而導致的退出率對於這種高風險共病族群來說是典型的。預計所有患者將在今年年底前完成研究訪問，最終的安全性和有效性結果預計將在明年上半年公佈。 REACT 的安全性仍然是我們關注的重點，因為我們了解風險最高的 CKD 患者群體通常有多種合併症，並且往往是服用許多藥物的老年患者。活檢和 REACT 注射的耐受性仍然良好。我們很高興地報告，沒有發生與 REACT 相關的嚴重不良事件。 83 名 REACT 患者中有 6 名發生了手術相關事件，這與已發表的腎臟活檢期間觀察到的事件報告一致，腎臟活檢通常用於評估和診斷 CKD。

As we move on to efficacy data in the 002 update, this slide shows the average EGFR in patients randomized to the active and deferred groups. Patients in the active group, as shown on the blue dotted line, showed no clinically meaningful decline in average EGFR out to 30 months. Overall, the change in average EGFR in this active group were 90% of patients had grade Stage 3B and Stage 4 CKD was accumulative minus 3.2 mils at 30 months. Patients in the deferred group that only receive standard of care had a decrease of minus 3.4 mils after just 12 months. The reduction over 12 months for this deferred group is in range of what we would expect for patients with advanced diabetic chronic kidney disease.

當我們繼續討論 002 更新中的療效數據時，這張投影片顯示了隨機分配到活躍組和延遲組的患者的平均 EGFR。如藍色虛線所示，活躍組患者在 30 個月內平均 EGFR 並沒有出現有臨床意義的下降。總體而言，該活性組中 90% 的患者的平均 EGFR 變化為 3B 級，而 4 期 CKD 在 30 個月時累積為負 3.2 mil。僅接受標準護理的延遲組患者僅 12 個月後就減少了 -3.4 mil。此延遲組 12 個月內的減少量在我們對晚期糖尿病慢性腎臟病患者的預期範圍內。

As we move to the next slide, please look again at this deferred group of patients on standard of care. Here on the left side of this graph is the deferred group again as they received standard of care. And then 34 of these patients receive REACT at month 12 and again at month 18. They're followed out to 12 months after their second injection.

當我們轉到下一張投影片時，請再次查看這組延遲接受標準護理的患者。該圖的左側再次是延遲組，因為他們接受了標準護理。然後，其中 34 名患者在第 12 個月接受 REACT，並在第 18 個月再次接受 REACT。

As stated on the previous slide, patients in the deferred group who received standard of care showed a minus 3.4ml decline in average EGFR over 12 months. But after a REACT injection, their average EGFR decline was only 0.2 over the next 18 months. We feel confident that stabilization of EGFR after REACT injection in this high-risk population reflects the potential for preservation of EGFR in patients with diabetic chronic kidney disease. And it's one reason why we feel excited and confident in our Phase 3 program.

如上一張投影片所述，接受標準護理的延遲組患者在 12 個月內平均 EGFR 下降了 -3.4ml。但注射 REACT 後，在接下來的 18 個月內，他們的 EGFR 平均下降僅為 0.2。我們相信，在這一高風險族群中註射 REACT 後 EGFR 的穩定反映了糖尿病慢性腎病患者保留 EGFR 的潛力。這也是我們對第三階段計畫感到興奮和充滿信心的原因之一。

The next two slides are post-hoc analysis of the 73 patients that received at least one REACT injection. The first slide here looks at average EGFR over time in two groups of patients. We divided these patients into those who had no decline in their individual EGFR slope over 18 months, and those who had an individual EGFR slope of less than zero. What we found was 27 of 73 patients. Impressive 37% of all participants had no or minimal decline in their kidney function over the course of 30 months of follow-up. As you can see in the gray box on the right, the change in average EGFR in this group was only 0.5mls. Notably, 56% of these patients had Stage 4 chronic kidney disease.

接下來的兩張投影片是對至少接受過一次 REACT 注射的 73 名患者的事後分析。第一張投影片顯示了兩組患者隨時間變化的平均 EGFR。我們將這些患者分為 18 個月內個別 EGFR 斜率沒有下降的患者和個別 EGFR 斜率小於零的患者。我們發現的是 73 名患者中的 27 名。令人印象深刻的是，在 30 個月的追蹤過程中，所有參與者中 37% 的腎功能沒有出現或僅有輕微下降。如右側灰色框中所見，該組中平均 EGFR 的變化僅為 0.5ml。值得注意的是，其中 56% 的患者患有第四期慢性腎臟病。

On slide 21, we show a -- we perform a very similar analysis, but more rigorously, we look at change from baseline kidney function in the same two groups. The graph looks very similar to the previous slide. At each time point, we present the average change in EGFR from baseline instead of the average EGFR at different time points. We present this over to 30 months of follow-up after first injection. Again, 37% of all subjects injected had minimal or no change in their kidney function from baseline over this period of time.

在投影片 21 上，我們展示了——我們進行了非常相似的分析，但更嚴格的是，我們觀察了相同兩組中腎功能基線的變化。該圖看起來與上一張投影片非常相似。在每個時間點，我們呈現 EGFR 相對於基線的平均變化，而不是不同時間點的平均 EGFR。我們在首次注射後 30 個月的隨訪中展示了這一點。同樣，在這段時間內，所有接受注射的受試者中有 37% 的腎功能與基線相比變化很小或沒有變化。

If we move to slide 22, here we highlight the CKD Stage 4 patients with severe Class 3 -- Class A3 albuminuria. On the left, we have 13 patients meeting this criteria who are in the active group. And as it turns out, 13 patients in the deferred receiving standard of care also met these criteria. In this left panel, over 12 months, the average change from baseline in EGFR in the active patient group was minus 1.6. In contrast, the average change in EGFR in the standard of care group was minus six.

如果我們轉到投影片 22，這裡我們將重點放在患有嚴重 3 級（A3 級蛋白尿）的 CKD 4 期患者。在左邊，我們有 13 位符合此標準的患者屬於活躍組。事實證明，13 名接受延期治療的患者也符合這些標準。在左圖中，12 個月內，活躍患者組 EGFR 相對於基線的平均變化為 -1.6。相較之下，標準治療組的 EGFR 平均變化為負六。

The same standard of care group is also reflected in the bottom line on the right panel. As we've previously described, these same patients then received REACT. Their EGFR baseline was reset at the time of REACT injection and their change from this new baseline is reflected in the top line on the right panel. Their average change from baseline after REACT injection was essentially zero compared to minus six mils for the 12 months before REACT injection.

相同的護理組標準也反映在右側面板的底線。正如我們之前所描述的，這些患者隨後接受了 REACT。他們的 EGFR 基線在 REACT 注射時重置，並且他們相對於新基線的變化反映在右側面板的頂行中。注射 REACT 後，其與基線的平均變化基本上為零，而注射 REACT 前 12 個月的平均變化為負 6 密耳。

As you could see in these subgroup analyses of high-risk Stage 4 CKD patients, treatment with REACT was associated with the stabilization of kidney function as assessed by change in EGFR over a one-year period. We feel this data strongly supports REACT having its biggest impact on the highest risk CKD subpopulation. We believe the data in hand demonstrate REACT's potential for the preservation of kidney function in Type 2 diabetic patients with advanced kidney disease.

正如您在這些高風險 4 期 CKD 患者的亞組分析中所看到的，REACT 治療與透過一年內 EGFR 變化評估的腎功能穩定相關。我們認為這些數據強烈支持 REACT 對最高風險 CKD 亞群的影響最大。我們相信現有的數據證明了 REACT 在患有晚期腎病的 2 型糖尿病患者中保留腎功能的潛力。

REACT's benefit was observed for up to 30 months, most notable in the sickest patients, those who had Stage 4 chronic kidney disease with a high UACR. Consistent with previous study data, REACT was well tolerated and continues to demonstrate a safety profile in line with the kidney biopsy. With this updated data in mind, we will be modifying one of our Phase 3 pivotal trials, the proact 1 trial, to enrich the number of patients with the highest risk of kidney failure.

REACT 的益處可觀察長達 30 個月，對於病情最嚴重的患者（患有 4 期慢性腎病且 UACR 較高的患者）最為顯著。與先前的研究數據一致，REACT 具有良好的耐受性，並繼續證明其安全性與腎臟活檢相符。考慮到這些更新的數據，我們將修改我們的一項 3 期關鍵試驗，即 proact 1 試驗，以豐富腎衰竭風險最高的患者數量。

In light of the data we've shared today, our first REACT Phase 3 pivotal trial designated proact 1 is being modified to include the following as shown in the box at the bottom of the slide. Focusing on Stage 3b and 4 by limiting the range of EGFR for eligibility between 20 and 35 mls per minute. This is a change from our previous design of 20 to 50 mls per minute. We're limiting the range of UACR for eligibility to 300 to 5,000 for patients with an EGFR between 30 and 35. And these are patients who are likely to become a Stage 4 patient in short order. We're updating our standard of care expectations giving the changing CKD treatment landscape, and we're increasing enrollment for an additional 600 incremental patients. There are approximately 50 patients who've already been enrolled that meet the updated protocol requirements.

根據我們今天分享的數據，我們的第一個 REACT 第 3 階段關鍵試驗指定的 proact 1 正在修改，以包括幻燈片底部框中所示的以下內容。透過將 EGFR 的合格範圍限制在每分鐘 20 至 35 毫升之間，重點關注第 3b 和第 4 期。這與我們之前每分鐘 20 至 50 毫升的設計有所不同。對於 EGFR 介於 30 至 35 之間的患者，我們將 UACR 資格範圍限制為 300 至 5,000。我們正在更新我們的護理期望標準，以適應不斷變化的 CKD 治療環境，並且我們正在增加 600 名新增患者的入組人數。約有 50 名患者已入組，且符合更新後的方案要求。

The second REACT Phase 3 pivotal trial designated proact 2, which is enrolling patients -- which will be enrolling patients primarily outside of the United States, is not anticipated to have any further modifications at this time. The trial is already designed to include advanced CKD patients who have an EGFR between 20 and 44 and in UACR greater than 300. We are allowing the study to proceed with an upper EGFR inclusion threshold that is higher than our 006 study to help us with future product labeling and addressable market size.

第二項 REACT 3 期關鍵試驗指定為 proact 2，該試驗正在招募患者，主要招募美國境外的患者，預計目前不會有任何進一步的修改。該試驗已設計為包括 EGFR 在 20 至 44 之間且 UACR 大於 300 的晚期 CKD 患者。 。

Finally, on slide 26, we show our clinical study accomplishments for 2023 and updated milestones for 2024 and beyond. We reported today the encouraging, updated interim Phase 2 results from 002, which continues to show REACT's potential to preserve kidney function with the notable activity observed in those diabetic patients with Stage 4 CKD. As discussed, the last patient visits for this study will be completed by end of this year, and we look forward to presenting full results in the first half of 2024.

最後，在投影片 26 上，我們展示了 2023 年的臨床研究成就以及 2024 年及以後的更新里程碑。我們今天報告了 002 令人鼓舞的、更新的中期 2 期結果，該結果繼續表明 REACT 具有保護腎功能的潛力，並且在患有 4 期 CKD 的糖尿病患者中觀察到了顯著的活性。如同所討論的，這項研究的最後一次病患訪視將於今年底完成，我們期待在 2024 年上半年公佈完整結果。

Looking forward, the Phase 2 007 clinical trial was fully enrolled earlier this year. The study was conducted to provide some insight into our Phase 3 development program. Importantly, these diabetic patients with Stage 3 and 4 CKD are being treated with our commercial-ready, cryopreserved formulation of REACT with patients receiving REACT injections bilaterally, with the second injection three months after the first, in the contralateral kidney. This mirrors our approach in our Phase 3 program.

展望未來，2007期臨床試驗已於今年稍早全面入組。進行這項研究是為了深入了解我們的第三階段開發計劃。重要的是，這些患有3 期和4 期CKD ​​的糖尿病患者正在接受我們的商用冷凍保存REACT 製劑治療，患者接受雙側REACT 注射，第二次注射在第一次注射後三個月，在對側腎臟注射。這反映了我們在第三階段計劃中的方法。

We anticipate reporting interim results from this study around mid-2024, with the final study results anticipated in the first half of 2025. For proact 1 and proact 2, our two registrational Phase 3 studies, we are implementing changes as discussed earlier to proact 1 only, focusing the EGFR range to 20 to 35 mls per minute. The modification to the EGFR enrollment range to our proact 1 Phase 3 study will cause the delay in enrollment of this study, and we expect to resume enrollment during the first half of next year. We believe this delay is warranted as it increases our ability to recruit patients and our overall probability of success.

我們預計在2024 年中期左右報告這項研究的中期結果，最終研究結果預計在2025 年上半年公佈。討論的變更僅將 EGFR 範圍集中到每分鐘 20 至 35 毫升。我們的 proact 1 3 期研究對 EGFR 入組範圍的修改將導致該研究的入組延遲，我們預計在明年上半年恢復入組。我們認為這種延遲是合理的，因為它提高了我們招募患者的能力和整體成功的可能性。

We are also pausing manufacturing to address the very recent EU-qualified person audit. Importantly, this pause is not due to a clinical safety event. Our recent audit performed by our contracted qualified person to evaluate its readiness for release and distribution of REACT to the EU, while still in progress, identified certain deficiencies in the documentation of the quality management systems that must be addressed prior to release and distribution of product for EU clinical site. Many of these improvements to GMP systems and control activities were ongoing before the audit, but had not yet been completed at the time of the audit.

我們也暫停了生產，以應對最近的歐盟合格人員審核。重要的是，這種暫停並不是由於臨床安全事件。我們最近由簽約合格人員進行的審計，旨在評估其向歐盟發布和分發REACT 的準備情況，雖然仍在進行中，但發現了品質管理系統文件中的某些缺陷，必須在產品發布和分發之前解決這些缺陷適用於歐盟臨床站點。許多 GMP 系統和控制活動的改進在審計前正在進行，但在審計時尚未完成。

We expect to resume manufacturing in the first half of 2024. Over this period, we plan to optimize our capabilities to meet EU and global standards for our Phase 3 program and future commercial manufacturing. We are implementing these manufacturing and documentation improvements concurrently with the 006 study pause because protocol changes such that we expect proact 1 to resume and proact 2 to commence enrollment in the first half of 2024. We anticipate completion of both studies in 2027.

我們預計在 2024 年上半年恢復生產。我們在006 研究暫停的同時實施這些製造和文件改進，因為協議發生了變化，我們預計proact 1 將在2024 年上半年恢復，proact 2 將在2024 年上半年開始入組。將於2027 年完成。

As Pablo mentioned during his opening remarks, this is a very exciting time here at ProKidney, building upon what Dr. Bertram and the team have done to bring REACT forward as a truly novel cell therapeutic approach to preserving kidney function. I am excited to lead ProKidney through this next phase. The team is focused on getting our global Phase 3 program back on track and enrolling patients and resolving the issues raised by the QP auditor.

正如Pablo 在開幕致詞中提到的那樣，這是ProKidney 非常激動人心的時刻，它建立在Bertram 博士和團隊為將REACT 作為一種真正新穎的細胞治療方法來保護腎功能所做的努力的基礎上。我很高興能夠帶領 ProKidney 度過下一階段。團隊致力於讓我們的全球第 3 階段計畫重回正軌、招募患者並解決 QP 審核員提出的問題。

Lastly, we are fortunate to be well capitalized well into 2025. And in the interim, we have a couple of potential financing catalysts.

最後，我們很幸運能夠在 2025 年之前擁有充足的資本。

With that review, I'd now like to open up the call to your questions.

經過上述審查，我現在想開始回答您的問題。

(Operator Instructions) Yigal Nochomovitz, Citi.

（操作員指令）Yigal Nochomovitz，花旗銀行。

Hi, everyone. Thank you very much for taking the questions. I had a bunch in no particular order. First of all, for the patients that were already enrolled in proact 1 above 35 from 35 to 50, are they -- what happens to them? Are they included or not in the analysis? And then secondly, regarding the delay in the enrollment for proact 1, obviously, you're already enrolling 20 to 35 EGFR anyway, even though you've lowered the upper bound down to 35 from 50. So I'm just wondering if you could explain a little more detail why that would further delay per se, given that that range was already open for enrollment. And then I think at the end, you mentioned that both studies are completing in 2027. Could you comment on whether there will still be interim analyses, I believe originally, the proact 1 interim was scheduled for the end of 2024. Thanks.

大家好。非常感謝您接受提問。我有一堆，沒有特定的順序。首先，對於那些已經在 35 歲以上參加 proact 1 的患者，從 35 歲到 50 歲，他們會發生什麼事？它們是否包含在分析中？其次，關於 proact 1 註冊的延遲，顯然，無論如何，您已經註冊了 20 至 35 EGFR，即使您已將上限從 50 降低到 35。 所以我只是想知道您是否可以更詳細地解釋為什麼這本身會進一步延遲，因為該範圍已經開放註冊。然後我想最後，您提到這兩項研究將於 2027 年完成。

Thanks, Yigal, for your questions. I'll address them in order. We do have patients already enrolled, as he noted in study 006 that may not meet the inclusion criteria that we're moving forward with. We will obviously continue to follow those patients and they'll be treated as per protocol, and we'll be part of a final analysis set that we submit to the FDA. And as for why we are delaying enrollment in this study while we execute on enriching our program with patients with a higher risk of CKD. Really, there's twofold here. The first response is we do want to ensure, as we complete the changes and modifications in the protocol, that these patients that we really do truly enrich and don't enroll any further subjects who may be outside of those criteria.

謝謝伊格爾的提問。我將按順序解決它們。正如他在研究 006 中指出的那樣，我們確實已經招募了患者，這些患者可能不符合我們正在推進的納入標準。顯然，我們將繼續追蹤這些患者，他們將按照方案接受治療，我們將成為提交給 FDA 的最終分析集的一部分。至於為什麼我們要延後這項研究的入組，同時我們要豐富 CKD 風險較高患者的項目。確實，這裡有雙重性。第一個回應是，當我們完成方案中的更改和修改時，我們確實希望確保我們真正豐富的這些患者，並且不會招募任何可能超出這些標準的進一步受試者。

The second is as you did hear, we're pausing manufacturing to improve our systems and for all the reasons that I've outlined. And in pausing that manufacturing, we're also pausing the Phase 3 006 study over that same period of time.

第二個是正如您所聽到的，我們正在暫停生產以改進我們的系統，原因我已經概述了。在暫停生產的同時，我們也暫停了同一時間段的 3 006 期研究。

And then finally, I think from a question around interim data, we will complete our studies in 2027. We've previously communicated to you that we would perform an interim analysis, I think in 2024. We haven't committed just yet on when we'll perform an interim analysis for our Phase 3 program now that we're performing this modification, but we will get back to you in the future with timing and a decision around that interim analysis.

最後，我認為，從有關中期數據的問題來看，我們將在2027 年完成我們的研究。完成既然我們正在執行此修改，我們將為我們的第 3 階段計劃進行中期分析，但我們將在未來回复您有關中期分析的時間安排和決定。

Okay, thanks.

好的，謝謝。

A couple of additional comments to Bruce's excellent answers. One is if you modify entry criteria in a study you have to refile with FDA. So that's why we're actually doing this right. And it's going to take a little bit of time, not much, but it will take a little time and we as we said, we hope to resume next year.

對布魯斯出色答案的一些補充評論。其中之一是，如果您修改了研究中的進入標準，則必須向 FDA 重新提交文件。這就是為什麼我們實際上正在做正確的事情。這將需要一點時間，而不是很多，但這需要一點時間，正如我們所說，我們希望明年恢復。

The other thing that I think is really important to mention is that focusing the patients in the study to the sicker patients, 20 to 35, is beneficial on many fronts. As you saw from the data, what's really remarkable is that we have data that is telling us about 23 out of the 73 injected patients, which is close to 30, have preservation of function. And this are the highest risk patients where you never see those kinds of evolution or preservation of function. But the other thing that's exciting about concentrating the study in that patient population is that what we have seen as we're talking to the sites and patients is that there's huge interest among the commission three patients to enroll patients with this kind of disease, because there's no alternative. When you go and talk to them about enrolling patients that have, for example, 3a, which we had a few, it's harder to get them excited about it. But when you tell them, the study is going to focus on patients that are 3 -- Stage 4, and a little bit of Stage 3b from 30 to 35, there's a big interest in that. So it's going to accelerate the enrollment of the trial for us by doing, making the change to the enrollment criteria.

我認為真正值得一提的另一件事是，將研究中的患者重點放在病情較重的患者（20 歲至 35 歲）上，這在許多方面都是有益的。正如您從數據中看到的，真正值得注意的是，我們的數據告訴我們，在 73 名註射患者中，約有 23 名（接近 30 名）保留了功能。這是風險最高的患者，你永遠看不到這種演化或功能的保留。但是，將研究集中在該患者群體中的另一件令人興奮的事情是，當我們與這些地點和患者交談時，我們看到的是，委託三名患者對招募患有此類疾病的患者表現出極大的興趣，因為沒有其他選擇。當你去和他們談論招募患有 3a 的患者時，我們有一些，很難讓他們對此感到興奮。但當你告訴他們，這項研究將重點關注 3-4 階段的患者，以及一些 30 歲至 35 歲的 3b 階段患者，他們對此很感興趣。因此，它將透過改變註冊標準來加速我們試驗的註冊。

Published one more thing on that. Having cared for patients and stay close to patients for kidney patients for my whole professional career. There's also a -- when patients reach EGFR of 30 around that period of time, that's also period when patients are being told a lot about preparing for dialysis. And that's when those discussions become very meaningful and patients do look for options and we do have an option for patients to enter into a clinical study where there's a possibility that they may receive some benefit.

就此還發表了一件事。在我的整個職業生涯中，我一直在照顧腎臟病患者並與患者保持密切聯繫。還有一個——當患者在那段時間左右達到 EGFR 30 時，也是患者被告知許多有關準備透析的時期。那時，這些討論變得非常有意義，患者確實在尋找選擇，我們確實可以讓患者選擇參與臨床研究，他們有可能從中受益。

Right.

正確的。

Thanks very much. And then, just a quick follow-up. You have had or have had not had the discussion with FDA with respect to the slight modification to the enrollment criteria for proact 1. And then secondly, I take your point regarding the retaining the 44 at the higher end for the proact 2 to maintain optionality in the commercial setting, but I do wonder how much of an internal debate there was with regard to just aligning both and having them both be 20 to 35 to maximize the probability of success for proact 2, as you outlined Pablo, that is the most interesting in terms of enrollment, kinetics, and likely, clinical benefit. Thanks.

非常感謝。然後，進行快速跟進。您已經或沒有與 FDA 討論過對 proact 1 的註冊標準進行輕微修改。兩者對齊並讓它們都為20 到35 以最大限度地提高proact 2 成功的可能性，有多少內部爭論，正如您概述的Pablo 那樣，這是最重要的在入組、動力學和可能的臨床獲益方面很有趣。謝謝。

So I'll address your second question first, Yigal, if I could. First, we believe, based upon the data that we see, that REACT works across multiple different patient groups. And so, we do believe that even including those patients up to an EGFR 44, we might see a possible benefit. So we didn't want to include them for the reasons that were outlined.

所以，如果可以的話，我會先解決你的第二個問題，Yigal。首先，根據我們看到的數據，我們相信 REACT 適用於多個不同的患者群體。因此，我們確實相信，即使將 EGFR 達到 44 的患者納入其中，我們也可能會看到可能的益處。因此，出於上述原因，我們不想將它們包括在內。

And then second, from an FDA perspective, we do not see our change, our modification to the study, 006 study, as being a significant modification and we plan to submit a notification letter to the FDA. We based upon our regulatory feedback internally, we do not believe that this will require an in-person or specific meeting to discuss this modifications. We think it's a lower risk and can be managed with a letter.

其次，從 FDA 的角度來看，我們不認為我們的改變、對 006 研究的修改是重大修改，我們計劃向 F​​DA 提交通知信。根據我們內部的監管回饋，我們認為不需要親自或專門的會議來討論此修改。我們認為風險較低，可以透過信件進行管理。

Understood. Thank you so much for taking the questions.

明白了。非常感謝您提出問題。

Your welcome.

別客氣。

Justin Zelin, BTIG.

賈斯汀·澤林，BTIG。

Hi, team. Congrats on the data here, and thanks for taking my questions. I just want to hear your latest thoughts on the durability of effects of the treatment and how does that fall into your thinking about potential redosing after two years? And I have some follow-ups.

大家好。恭喜這裡的數據，並感謝您提出我的問題。我只是想聽聽您對治療效果持久性的最新想法，以及您對兩年後可能再次接受治療的想法有何影響？我還有一些後續行動。

Thanks, Justin, for your question. The data that we have that we showed you today, there's a suggestion, but keep in mind that's Phase 2 data and we don't have a control group out to 24, 18 or 24 months. There's a suggestion that some benefit may tail off towards the end. We can't be confident about the durability of REACT based upon this data. We do think we'll see with a parallel control group in our Phase 3 program, we'll get more insights from that program on the durability of REACT. And it's quite likely that we may need to redose at some point 18 to 24 months after first injection, but more to come on that, Justin, in the future.

謝謝賈斯汀的提問。我們今天向您展示的數據有一個建議，但請記住，這是第 2 階段的數據，我們沒有 24、18 或 24 個月的對照組。有人建議，一些好處可能在年底逐漸減弱。根據這些數據，我們無法對 REACT 的持久性充滿信心。我們確實認為，我們將在第三階段計劃中看到一個平行對照組，我們將從該計劃中獲得有關 REACT 耐久性的更多見解。我們很可能需要在第一次注射後 18 到 24 個月的某個時間點重新註射藥物，但賈斯汀，未來還會有更多注射。

Great. And if I could ask, it looks like you had 27 patients here for preservation of EGFR. Of those 27, do you have the data as far as whether they fit into that new enrollment criteria of 20 to 35 passage for CKD?

偉大的。如果我可以問的話，看起來你們這裡有 27 位病人需要保存 EGFR。在這 27 名患者中，您是否有關於他們是否符合 20 至 35 名 CKD 患者的新入組標準的數據？

Yes, Justin, I think 56% of those are in Stage 4. And I don't have the data off hand on how many of those are in the 3b category of 30 to 35, but it's already a majority of patients already included in that group. We can follow up with you on that question.

是的，賈斯汀，我認為其中 56% 處於第 4 階段。我們可以就這個問題與您聯絡。

But it's 23 of the 73 that actually are Stage 4, with the -- no ACR greater than 300 that are actually pretty stable. Some of those you see maybe a slight decline, but relative to the similar group and the standard of care, which declined by six points, it's actually quite impressive.

但這 73 個中的 23 個實際上是第 4 階段，沒有 ACR 大於 300，實際上相當穩定。您看到的其中一些可能略有下降，但相對於類似的群體和護理標準（下降了六個百分點），這實際上是相當令人印象深刻的。

Great. Thanks for taking my questions.

偉大的。感謝您回答我的問題。

Thanks, Justin.

謝謝，賈斯汀。

Kelly Shi, Jefferies.

施凱莉，傑弗里斯。

Hi. This is Clara for Kelly. Thanks for taking my question. For the two pivotal Phase 3 trial enrolled with, as you mentioned, the CKD pivotal landscape is evolving. So would you expect more patients having received attributes such as GLP-1 become -- before coming to REACT cell therapy. What kind of GLP-1 drug impact would have on REACT's activity for kidney preservation Thank you.

你好。這是凱莉的克拉拉。感謝您提出我的問題。正如您所提到的，對於兩個關鍵的 3 期試驗來說，CKD 的關鍵景觀正在不斷發展。因此，您是否期望更多的患者在接受 REACT 細胞療法之前就已經接受了 GLP-1 等特性？什麼樣的 GLP-1 藥物會對 REACT 的腎臟保存活性產生影響謝謝。

Thanks for the question, Clara. I understand you're asking about our Phase 3 program and the changing CKD landscape, including GLP-1. We will -- so several points on that. So the first is from a study perspective, we will be -- we think it's extremely important for us to ensure that standard of care, as defined by clinical practice guidelines, is instituted across both arms of those studies. And we're working to make sure that that will happen.

謝謝你的提問，克拉拉。我知道您在詢問我們的第 3 階段計劃和不斷變化的 CKD 格局，包括 GLP-1。我們會——關於這一點有幾點。因此，第一個是從研究的角度來看，我們認為，確保在這些研究的兩個分支中製定臨床實踐指南所定義的護理標準對我們來說極為重要。我們正在努力確保這一切都能實現。

The second is with regards to the GLP-1 effect within the chronic kidney disease space. We do understand, based upon published data, that the FLOW study, which I think some of you may be familiar with, the percent of patients with Stage 4 kidney disease included in the FLOW study was a small amount compared to the rest of the CKD subjects in that study. It's -- noticed the FLOW study was stopped early for efficacy, and it's hard for me to comment on what that actually means at this point, we do know that GLP-1 do have a favorable cardiovascular event profile on, but we'll have to wait until that data is actually published for me to have a more educated answer to your question. Thanks, Clara.

第二個是關於 GLP-1 在慢性腎臟疾病領域中的作用。根據已發表的數據，我們確實了解 FLOW 研究（我想你們中的一些人可能很熟悉），與其他 CKD 患者相比，FLOW 研究中納入的 4 期腎病患者的百分比很小該研究中的主題。注意到 FLOW 研究因療效而提前停止，我很難評論這實際上意味著什麼，我們確實知道 GLP-1 確實具有有利的心血管事件特徵，但我們會等到這些數據真正發布後，我才能對你的問題有一個更有根據的答案。謝謝，克拉拉。

Okay, got it. Thank you.

好的，明白了。謝謝。

Jonathan Miller, Evercore.

喬納森·米勒，Evercore。

Thanks, guys. Let's start maybe with some housekeeping. How many patients that are already enrolled aren't meeting the new criteria? I just wanted to get a sense for how many folks you enrolled in total that are going to be in the final analysis of the FDA, but maybe not on the primary endpoint.

謝謝，夥計們。讓我們從一些家事服務開始。有多少已入組的患者不符合新標準？我只是想了解您總共招募了多少人將參與 FDA 的最終分析，但可能不會參與主要終點。

And then secondly, I would love to probe a little bit deeper into the assertion that it's the Stage 4 patients that are getting the most benefit. I noticed that none of the presented analyses directly compare the benefit patients are getting to the severity at baseline. You're pulling out that subgroup. So I guess I'm looking at the entire deferred cohort and seems like they also see stabilization, similar stabilization at that Stage 4 cohort. So I'd love to dive a little bit deeper into what's underlying the assertion that Stage 4 is getting the most benefit.

其次，我想更深入探討第四階段患者獲得最大益處的論點。我注意到所提出的分析都沒有直接比較患者在基線時的嚴重程度所獲得的益處。你正在抽出那個小組。所以我想我正在關注整個延期隊列，似乎他們也看到了穩定，在第四階段隊列中類似的穩定。因此，我很想更深入地探討第四階段獲得最大利益的論點背後的原因。

Thanks for your questions, Jonathan. I'm sure you can appreciate that our 006 or proact 1 study is an ongoing Phase 3 program. And we are not analyzing that data on a day-to-day basis because of the nature of it being a Phase 3 program. We're also blinded, as you know, to the treatment groups. What I can say is that based upon the information we can have access to, that we've enrolled over 80 subjects and we believe that approximately 50 of those subjects will meet our new inclusion criteria.

謝謝你的提問，喬納森。我相信您會理解我們的 006 或 proact 1 研究是一個正在進行的第 3 階段計劃。我們不會每天分析這些數據，因為它是第三階段計劃的性質。如您所知，我們對治療組也視而不見。我能說的是，根據我們可以獲得的信息，我們已經招募了 80 多名受試者，我們相信其中大約 50 名受試者將符合我們新的納入標準。

And then, Jonathan, on your other question, you rightly do point out that we see a very impressive stabilization, preservation of EGFR in patients who were crossed over and receive REACT for out to 18 months in that group after their first REACT injection. We believe react works in different subgroups, but the focus on Stage 4 moving forward and down, we have tortured this data, if you like, inside out. And we're very confident in our decision that we want to move forward with this Stage 4 and advanced 3b population for proact 1.

然後，喬納森，關於你的另一個問題，你正確地指出，我們在第一次REACT 注射後交叉接受REACT 治療長達18 個月的患者中，我們看到了非常令人印象深刻的EGFR 穩定和保存。我們相信 React 在不同的子群組中都有效，但重點是第四階段的向前和向下移動，如果你願意的話，我們已經從裡到外地折磨了這些數據。我們對我們的決定非常有信心，我們希望推進第 4 階段和高級 3b 人群的 proact 1。

And part of it is based upon the data that you saw here today. Part of it is based upon clinical feedback, which Pablo mentioned around nephrologists recognizing that these patients are on a slippery slope to dialysis, and we need an option for these patients. Part of it is for the lack of better word, some desperation from patients to not having other options within this group. And finally, having worked at CVS and sitting close to Aetna and understanding how payers think about this space and also understanding how other CMOs in other large health plans think about this space. They clearly say that Stage 4 kidney disease is their pain point. And so it's for all those reasons we're refocusing our proact 1 study.

其中一部分是基於您今天在這裡看到的數據。其中一部分是基於臨床回饋，巴勃羅在腎臟科醫生周圍提到，認識到這些患者正處於透析的滑坡上，我們需要為這些患者提供一個選擇。部分原因是缺乏更好的措辭，患者對這群人沒有其他選擇感到絕望。最後，我曾在 CVS 工作過，與 Aetna 關係密切，了解付款人如何看待這個領域，也了解其他大型健康計劃中的其他 CMO 如何看待這個領域。他們明確表示，第四階段腎臟疾病是他們的痛點。因此，基於所有這些原因，我們重新調整了 proact 1 研究的重點。

Actually, when they talk about the different stages, what we hear is that patients that are in Stage 3a and 3b are patients that cost less than the premiums they collect. But it completely changes when you get into Stage 4, where actually the premiums that get paid do not cover the cost of Stage 4 patients, so it creates an opportunity for us. But I think the other key thing is that we feel confident that we're going to actually enroll quicker but also hit events quicker because this page 4 patient are having events much more quickly than other patients. But the data is quite interesting because we do see some good responses from, not only the Stage 4 patients, but a bunch of the other patients in the study also.

實際上，當他們談論不同階段時，我們聽到的是處於 3a 和 3b 階段的患者的費用低於他們收取的保費。但當你進入第四階段時，情況就完全改變了，實際上支付的保費並不能涵蓋第四階段患者的費用，所以這為我們創造了機會。但我認為另一個關鍵的事情是，我們有信心我們實際上會更快地註冊，而且也會更快地參加活動，因為這位第 4 頁的患者比其他患者更快地參加活動。但這些數據非常有趣，因為我們確實看到了一些良好的反應，不僅來自第四階段患者，而且來自研究中的其他許多患者。

Yeah.

是的。

Thank you, Jonathan.

謝謝你，喬納森。

(Operator Instructions) Jason Gerberry, Bank of America.

（操作員指示）Jason Gerberry，美國銀行。

Hey, guys, thanks for taking my question. If I heard you right, for proact 1, you've enrolled 50 out of a target 600. I just wanted to confirm that. And it sounds like you think even with the new enrichment criteria that won't slow enrollment, it actually will speed enrollment. And then just a follow-up on the question about interim. Just to make sure, is it more a question of when not if we get an interim? I'm ultimately wondering, you talked about multiple financeable catalyst before your cash runs out. What do you think are financeable catalyst if you don't offer it in an interim before the cash runs out? thanks.

嘿，夥計們，謝謝你提出我的問題。如果我沒聽錯的話，對於 proact 1，您已經註冊了目標 600 人中的 50 人。聽起來您認為即使新的豐富標準不會減慢註冊速度，它實際上也會加快註冊速度。然後是關於臨時問題的後續行動。只是為了確定一下，這更多的是什麼時候的問題，而不是我們是否得到臨時的問題？我最終想知道，在你的現金用完之前，你談到了多種可融資的催化劑。如果您不在現金耗盡之前臨時提供，您認為什麼是可融資的催化劑？謝謝。

Thanks, Jason. Just for clarity, we've enrolled over 80 people in proact 1. Not 50, we think there's about 50 that meet our new inclusion criteria. And second is we believe we have multiple financing catalysts. Notably, our study 007, which is as stated earlier, diabetic patients who are biopsied, injected into the biopsy kidney and then three months later, injected into the contralateral kidney with our commercial product. We think that mirrors more closely our Phase 3 program and we're going to be happy to share with you an interim look at that data in mid 2024.

謝謝，傑森。為清楚起見，我們在 proact 1 中招募了超過 80 人。其次，我們相信我們有多種融資催化劑。值得注意的是，我們的研究007，如前所述，糖尿病患者進行活檢，注射到活檢腎臟中，然後三個月後，用我們的商業產品注射到對側腎臟。我們認為這更能反映我們的第 3 階段計劃，我們很樂意在 2024 年中期與您分享該數據的中期數據。

We think that will offer a potential catalyst and final data for that, we believe, in the first half of 2025. We'll also bring to you final results of 002 in the first half of next year. So we'll have multiple opportunities to present, publicly, data from several different studies in the next couple of years.

我們認為，這將為 2025 年上半年提供潛在的催化劑和最終數據。因此，在接下來的幾年中，我們將有多次機會公開展示幾項不同研究的數據。

With regards to the interim analysis, I can give you some insight into how we're thinking about it, but decisions haven't been made and we will share with you the decision in the future. But we received some feedback, I received some feedback in someone that's led a global SGLT2 inhibitor trial who essentially said, you may want to think about an early IA in case the benefit is even bigger than what you expect. But I want to make it clear to everyone then when we do an IA, all we will get from our safety committee is a letter that says continue to move forward or not. We're not able to share with you any analysis at that interim analysis, given the Phase 3 nature of the program and the endpoints that were chosen within this Phase 3 program are the eventual endpoints that will be adjudicated for FDA approval.

關於中期分析，我可以跟大家介紹我們的想法，但目前還沒做出決定，我們會在未來與大家分享這個決定。但我們收到了一些回饋，我收到了一些領導全球 SGLT2 抑制劑試驗的人的回饋，他基本上說，你可能需要考慮早期 IA，以防效益比你預期的更大。但我想向大家明確表示，當我們進行 IA 時，我們從安全委員會得到的只是一封信，表明是否繼續前進。鑑於該計劃的第 3 階段性質，以及在此第 3 階段計劃中選擇的終點是將被判定為 FDA 批准的最終終點，我們無法與您分享該中期分析的任何分析。

And if I could just ask one follow-up here. You mentioned, that the 80 versus the 50 so does your -- do you need to have 600 patients that meet the new inclusion criteria? Or is that adjusted to 570 patients that have to meet the new inclusion criteria?

如果我可以在這裡問一個後續問題。您提到，80 名患者與 50 名患者之間的情況也是如此，您是否需要 600 名患者符合新的納入標準？或是否調整為必須符合新納入標準的 570 名患者？

Jason, we're targeting 600 new incremental patients.

Jason，我們的目標是增加 600 名新患者。

Okay.

好的。

Thank you.

謝謝。

One topic that hasn't been discussed that I think is worth just mentioning so that everyone understands what's going on here is that proact 2 is not changed and are the enrollment criteria is 20 to 44, which really will have all of the Stage 3b range from 30 to 44. And what we see as positive of having the other study, the other Phase 3 was that range of enrollment criteria of 20 to 44 is that it will give us the possibility of actually having a broader label, right? Because it's going to have a lot of Phase 3b patients. So I think by having the two studies with slightly different ranges of enrollment criteria. We see that as beneficial.

有一個尚未討論但我認為值得一提的話題，以便每個人都了解這裡發生的事情，即 proact 2 沒有改變，並且入學標準是 20 到 44，這實際上將包含所有第 3b 階段的範圍從30到44。 我們認為進行另一項研究（另一項第3 階段）的積極之處在於，20 到44 的入學標準範圍將使我們有可能真正擁有更廣泛的標籤，對吧？因為它將有很多 3b 期患者。所以我認為這兩項研究的入學標準範圍略有不同。我們認為這是有益的。

Thank you. At this time, we have reached the end of the question-and-answer session, and I'll now turn the call over to Dr. Bruce Culleton for closing remarks.

謝謝。現在，我們的問答環節已經結束，我現在將電話轉交給 Bruce Culleton 博士做總結發言。

Bruce, before you do that, I'd just like to share with all of you a perspective I have on what's going on here, I've been investing in Life Sciences for about three decades. And one of the things that I've seen over and over again in my history, investing in so many different drugs in so many therapeutic areas is this view of how many patients get benefit when you have a product and what has been a common theme in my investment history is, and I can reflect back and look at our investments in TNF inhibitors, in Crohn's psoriasis, in multiple sclerosis, and many, many other areas. And when I see in those cases that -- it's super hard, just things that are very difficult to treat for more than half of the patients to get benefit. It just doesn't happen.

布魯斯，在你這樣做之前，我想與大家分享我對這裡正在發生的事情的看法，我已經投資生命科學大約三十年了。在我的歷史中，我一次又一次地看到，在如此多的治療領域投資如此多的不同藥物，就是這樣一種觀點：當你擁有一種產品時，有多少患者會受益，以及什麼是共同的主題在我的投資歷史中，我可以回顧並審視我們在 TNF 抑制劑、克隆氏牛皮癬、多發性硬化症以及許多其他領域的投資。當我在這些病例中看到——這非常困難，只是很難讓一半以上的患者受益。它就是不會發生。

Take cancer for example, that's actually even lower. 20% and 25% of patients responding and we get excited, a certain we get very excited. So when you see situation where a meaningful number of patients is doing well, I get very excited and I think what's great about what we're seeing here is exactly that when I got involved with ProKidney, at the time, what I was hoping was that about a third of patients would respond and that we would actually slow the decline, which at the time it was somewhere in the five point of EGFR per year untreated patients and the SGLT2s showed about four points of decline per year, when treated with SGLT2s. And at Royalty Pharma, we actually looked at several of those drugs and actually have a royalty in one of them, but -- and royalties and DPP-4 inhibitors. So it's a space that we follow closely.

以癌症為例，這個數字其實更低。 20% 和 25% 的患者做出了反應，我們感到興奮，有的我們感到非常興奮。因此，當你看到大量患者表現良好的情況時，我感到非常興奮，我認為我們在這裡看到的偉大之處正是當我參與 ProKidney 時，當時我所希望的是大約三分之一的患者會做出反應，而且我們實際上會減緩下降速度，當時未經治療的患者的EGFR 下降速度約為每年5 個點，而當接受SGLT2 治療時，SGLT2 每年顯示約4 個點下降。在Royalty Pharma，我們實際上研究了其中幾種藥物，並且實際上對其中一種藥物收取了特許權使用費，但是——還有特許權使用費和DPP-4抑製劑。所以這是我們密切關注的一個空間。

But what's really exciting of what we're seeing today with REACT is not only a slowdown of the decline in function, but a preservation of function, which is really unique and unprecedented. And I think from that perspective, I think what we're seeing today in a small trial, 80 patients, but it's a good number of patients, is this preservation of function, which is unprecedented and I'll stop there and pass it back to you, Bruce.

但我們今天看到的 REACT 真正令人興奮的不僅是功能衰退的減緩，而且是功能的保留，這確實是獨一無二的、前所未有的。我認為從這個角度來看，我認為我們今天在一項小型試驗中看到的，80 名患者，但患者數量很大，是這種功能的保留，這是前所未有的，我會停在那裡並將其傳回給你，布魯斯。

Thanks, Pablo. I'd like to just thank everyone for joining today and your insightful questions. I'm sure you can tell that I'm excited to lead ProKidney during this next phase of its development. A final thank you to Dr. Bertram, for everything that you've done, Tim, for the last 20 years, to get us to where we are today. And for everyone on the call, I look forward to our future interactions. Thank you.

謝謝，巴勃羅。我只想感謝大家今天的加入以及你們富有洞察力的問題。我相信您可以看出，我很高興能夠領導 ProKidney 的下一階段的發展。最後感謝 Bertram 博士，感謝你在過去 20 年所做的一切，讓我們取得了今天的成就。對於通話中的每個人，我期待著我們未來的互動。謝謝。

This will conclude today's conference. You may disconnect your lines at this time. We thank you for your participation.

今天的會議到此結束。此時您可以斷開線路。我們感謝您的參與。