Abeona Therapeutics Inc (ABEO) 2024 Q1 法說會逐字稿

Good day and welcome to the Abeona Therapeutics first-quarter 2024 conference call. All participants are on a listen only mode. After management's prepared remarks, there will be a question and answer session. I would now like to turn the call over to your host, Greg Gin Vice President of Investor Relations and Corporate Communications at Abeona. Please go ahead.

美好的一天，歡迎參加 Abeona Therapeutics 2024 年第一季電話會議。所有參與者都處於只聽模式。管理階層準備好發言後，將進行問答環節。現在我想將電話轉給主持人 Abeona 投資者關係和企業傳播副總裁 Greg Gin。請繼續。

Thank you, Kelly. Good morning, and thank you for joining us on our first quarter 2024 conference call. During this call, we will refer to the press release issued this morning announcing the first quarter results, which is available on our corporate website at www.abeonatherapeutics.com.

謝謝你，凱利。早安，感謝您參加我們的 2024 年第一季電話會議。在本次電話會議中，我們將參考今天上午發布的第一季業績新聞稿，該新聞稿可在我們的公司網站 www.abeonatherapeutics.com 上查看。

I would like to note that remarks made during today's call may contain projections and forward looking statements. Forward looking statements are made pursuant to the Safe Harbor provisions of the federal securities laws. The forward-looking statements are based on current expectations and are subject to change and actual results may differ materially from those expressed or implied in the forward-looking statements.

我想指出，今天的電話會議中發表的言論可能包含預測和前瞻性陳述。前瞻性陳述是根據聯邦證券法的安全港條款做出的。前瞻性陳述基於目前的預期，可能會發生變化，實際結果可能與前瞻性陳述中明示或暗示的結果有重大差異。

Various factors that could cause actual results to differ include, but are not limited to those identified under the Risk Factors section in our Form 10-K and periodic reports filed with the SEC. These documents are available on our website at www.abeonatherapeutics.com.

可能導致實際結果有所不同的各種因素包括但不限於我們的 10-K 表格和向 SEC 提交的定期報告中風險因素部分中確定的因素。這些文件可在我們的網站 www.abeonatherapeutics.com 上取得。

On the call today with prepared remarks are Dr. Vish Seshadri, Chief Executive Officer; Dr. Madhav Vasanthavada, Chief Commercial Officer and Head of Business Development; and Joe Vazzano, Chief Financial Officer. Joining us for the Q&A session as well will be Dr. Brian Kevany, our Chief Technical Officer.

執行長 Vish Seshadri 博士在今天的電話會議上發表了事先準備好的演講； Madhav Vasanthavada 博士，首席商務長兼業務開發主管；和財務長喬·瓦扎諾。我們的技術長 Brian Kevany 博士也將參加我們的問答環節。

And with that, I'll now turn the call over to Vish Seshadri, to leave the stops.

現在，我將把電話轉給 Vish Seshadri，讓他離開車站。

Thank you, Greg. We appreciate everybody joining the call this morning. In order to continue to progress our Pz-cel program, well beyond anticipated regulatory milestones and through commercial launch, Abeona must be well capitalized. The leadership team has recently been focused on addressing our funding needs. In early May, we completed an underwritten offering with institutional investors and had raised $75 million in gross proceeds.

謝謝你，格雷格。我們感謝大家今天早上加入電話會議。為了繼續推進我們的 Pz-cel 項目，遠遠超出預期的監管里程碑並透過商業啟動，Abeona 必須資本充足。領導團隊最近一直致力於解決我們的資金需求。5 月初，我們完成了與機構投資者的承銷發行，並籌集了 7,500 萬美元的總收益。

Participants in the offering included existing and new investors who are some of the most respected blue-chip institutional healthcare investors. This was a significant development for Abeona, and we're grateful to our investors who have demonstrated their support.

此次發行的參與者包括現有和新投資者，他們都是最受尊敬的藍籌機構醫療保健投資者。這對 Abeona 來說是一個重大發展，我們感謝投資者的支持。

Importantly, financing not only has extended our cash runway into 2026, which is well beyond anticipated significant regulatory milestones and commercial launch of Pz-cel, but we believe it further validates the great potential for Pz-cels.

重要的是，融資不僅將我們的現金跑道延長至 2026 年，這遠遠超出了 Pz-cel 預期的重大監管里程碑和商業推出，而且我們相信它進一步驗證了 Pz-cels 的巨大潛力。

We now stay resolutely focused on working with the FDA to address the CMC deficiencies noted in the CRL and making the BLA resubmission toward bringing Pz-cel to order patients as soon as possible.

我們現在堅定地專注於與 FDA 合作，解決 CRL 中指出的 CMC 缺陷，並重新提交 BLA，以盡快讓 Pz-cel 為患者訂購。

As a brief recap of our regulatory update call in late April, we received a CRL from the FDA based on the need for additional CMC information before the Pz-cel BLA can be approved. In general the information needed to satisfy the CMC requests pertains to validation requirements for certain manufacturing and release testing methods.

作為 4 月下旬監管更新電話會議的簡要回顧，我們收到了 FDA 的 CRL，因為在 Pz-cel BLA 獲得批准之前需要額外的 CMC 資訊。一般來說，滿足 CMC 要求所需的資訊涉及某些製造和發布測試方法的驗證要求。

The CRL did not identify any deficiencies related to the clinical efficacy or clinical safety data in the BLA and the FDA did not request any new clinical trials of clinical data to support the approval of Pz-cel.

CRL 沒有發現 BLA 中與臨床療效或臨床安全性數據相關的任何缺陷，FDA 也沒有要求任何新的臨床數據臨床試驗來支持 Pz-cel 的批准。

Since the update call, we have already made progress towards addressing the CMC deficiencies noted in the CRL, we have now completed the matrix in different study to validate the replication-competent retrovirus or RCR.

自從更新電話以來，我們已經在解決 CRL 中指出的 CMC 缺陷方面取得了進展，我們現在已經完成了不同研究中的矩陣，以驗證具有複製能力的逆轉錄病毒或 RCR。

We believe the outcome of this study will satisfy the agency's ask for our RCR assay validation based on our discussion with the FDA in late March. We have also completed the container closure integrity testing for the RVV and the validation reports are in place. We continue to interact with the FDA through informal meetings to gain the agency's alignment on our approach, especially on topics where interpretation of existing guidance in the context of our therapy is required.

根據我們 3 月底與 FDA 的討論，我們相信這項研究的結果將滿足該機構對我們的 RCR 檢測驗證的要求。我們也完成了 RVV 的容器密閉完整性測試，驗證報告已準備就緒。我們繼續透過非正式會議與 FDA 互動，以獲得該機構對我們的方法的一致意見，特別是在需要在我們的治療背景下解釋現有指南的主題上。

Looking ahead to the coming weeks and months, we're working on completing deliverables that would address all remaining deficiencies noted in the CRL to enable resubmission of the BLA. We anticipate completion of all these workstreams in the late Q2, early Q3 timeframe and anticipate completing the BLA resubmission in the second half of 2024.

展望未來幾週和幾個月，我們正在努力完成可交付成果，以解決 CRL 中指出的所有剩餘缺陷，以便能夠重新提交 BLA。我們預計所有這些工作流程將在第二季末、第三季初的時間範圍內完成，並預計在 2024 年下半年完成 BLA 重新提交。

We do plan to request a Type A meeting with the FDA in early Q3. The goal of this meeting would be to gain alignment with the agency on the sufficiency of our data to address the outstanding substantive and critical CMC items. As always, we will continue to be transparent with the outcomes of the meeting after completion.

我們確實計劃在第三季初請求與 FDA 舉行 A 類會議。這次會議的目標是就我們的數據是否足以解決未決的實質和關鍵 CMC 項目與該機構達成一致。一如既往，我們將在會議結束後繼續對會議結果保持透明。

I'll now turn the call over to our Chief Commercial Officer, Madhav Vasanthavada to provide an update on our commercialization readiness activities.

我現在將把電話轉給我們的商務長 Madhav Vasanthavada，以提供我們商業化準備活動的最新資訊。

Thank you, Vish. We remain confident in the potential of Pz-cel as a game-changing therapy for our patients. And our momentum towards commercial readiness continues. Because the FDA did not identify any clinical efficacy or clinical safety related issues with our BLA, our confidence in our clinical value story remains strong and so does our positioning and messaging with various stakeholders, whether they are the payers or providers, and that is huge for us.

謝謝你，維什。我們對 Pz-cel 作為一種改變患者療法的潛力充滿信心。我們的商業準備勢頭仍在繼續。由於FDA 沒有發現我們的BLA 有任何臨床療效或臨床安全性相關問題，因此我們對我們的臨床價值故事仍然充滿信心，我們對各個利益相關者的定位和資訊傳遞也同樣如此，無論他們是付款人還是提供者，這是巨大的為了我們。

In speaking with physicians at our targeted treatment sites as well as with patient groups like DEBRA and EBRP that has continued enthusiasm for the value of Pz-cel. We hear from physicians, including prominent physicians in the EB space about the need for using complementary treatment modalities for DEB patients.

在與我們目標治療地點的醫生以及 DEBRA 和 EBRP 等患者團體交談時，他們對 Pz-cel 的價值始終充滿熱情。我們從醫生（包括 EB 領域的知名醫生）那裡了解到，需要對 DEB 患者使用補充治療方式。

Pz-cel, if approved, would be the only therapy, which in clinical trials has addressed large body surface areas, including toughest to treat wounds and demonstrated wound healing and pain reduction with years of durability after a single application. These aspects of Pz-cel would make it a highly differentiated and clinically meaningful for RDEB patients.

Pz-cel 如果獲得批准，將是唯一的療法，在臨床試驗中，該療法已解決了大面積的身體表面積，包括最難治療的傷口，並顯示出傷口癒合和疼痛減輕，單次使用後可保持多年的耐久性。Pz-cel 的這些方面將使其對 RDEB 患者俱有高度差異化和臨床意義。

In light of the updated BLA time line, our launch strategy now is to focus on prioritizing activities that we can front load with payers through the payer discussions with the goal of having better access and faster access upon approval.

根據更新的 BLA 時間表，我們現在的啟動策略是重點關注我們可以透過付款人討論與付款人預先加載的活動的優先級，目標是在批准後獲得更好的訪問和更快的訪問。

We will also focus on exchanging scientific data with ED physician community through various forums to strengthen Pz-cel medical awareness. In that regard of scientific exchange, our abstract discussing 11 years of safety profile from long-term follow up of Pz-cel has been accepted as a late-breaker for presentation at this week's Society for Investigative Dermatology SID annual meeting in Dallas.

我們還將透過各種論壇重點與 ED 醫生社群交流科學數據，以加強 Pz-cel 醫療意識。在這方面的科學交流方面，我們討論 Pz-cel 11 年長期追蹤安全性的摘要已被接受為遲到者，將在本週達拉斯舉行的皮膚病研究學會 SID 年會上進行介紹。

With more than 11 years of safety in the earliest treated patient Pz-cel would have upon its potential approval, one of the longest durations of safety follow-up available for gene therapies. Besides disseminating scientific data, as we wait for regulatory approval, we will also be generating new clinical data that could also benefit payer discussions.

Pz-cel 在最早接受治療的患者中具有超過 11 年的安全性，一旦獲得批准，將成為基因療法中持續時間最長的安全追蹤之一。除了傳播科學數據外，在等待監管部門批准的過程中，我們還將產生新的臨床數據，這也有利於付款人的討論。

You may recall we have an active Phase 3b study that is currently enrolling new and previously treated RDEB patients where we have treated four patients to date, all of whom have elected to come back as a repeat Pz-cel patients for their previously untreated wounds.

您可能還記得我們有一項活躍的3b 期研究，目前正在招募新的和之前接受過治療的RDEB 患者，迄今為止我們已經治療了4 名患者，他們都選擇作為重複Pz-cel 患者回來治療他們之前未經治療的傷口。

This study also allowed treating patients that have received or are currently receiving the recently approved treatments for Dystrophic EB and generating such data will help us shape better access policies for Pz-cel post-approval.

這項研究還允許治療已經接受或正在接受最近批准的營養不良 EB 治療的患者，產生此類數據將幫助我們制定批准後更好的 Pz-cel 准入政策。

Speaking of payer discussions, we have had nearly a dozen one-on-one engagements with commercial payers through preapproval information exchange since the last time we spoke and payers continue to be impressed with the clinical value story of Pz-cel and the unmet need it can address, which is encouraging from coverage and access perspective.

說到付款人討論，自上次我們發言以來，我們已經透過預先批准資訊交換與商業付款人進行了近十幾次一對一的接觸，付款人繼續對Pz-cel 的臨床價值故事和未滿足的需求印象深刻可以解決，從覆蓋範圍和訪問的角度來看，這是令人鼓舞的。

Lastly, from site onboarding standpoint, we are continuing to work with our initial network of 5 to 7 high-volume EB centers and are taking advantage of the regulatory time to refine and strengthen launch readiness and building a high-touch patient services program. We want to make sure that sites will be ready to treat as soon as possible for PD cell approval. And we'll keep you updated on progress.

最後，從現場啟動的角度來看，我們將繼續與由 5 到 7 個大容量 EB 中心組成的初始網路合作，並利用監管時間完善和加強啟動準備工作，並建立高接觸性患者服務計畫。我們希望確保這些場所能夠盡快做好治療準備，以獲得 PD 細胞的批准。我們將隨時向您通報最新進展。

With that, I'll now hand the call over to our Chief Financial Officer, Joe Vazzano, to discuss our financial results.

現在，我將把電話轉交給我們的財務長喬·瓦扎諾 (Joe Vazzano)，討論我們的財務表現。

Thanks, Madhav. I would like to remind everyone that you can find additional details on our financial results for the three months ended March 31 2024, and our most recent Form 10-Q, which is available on our website.

謝謝，馬達夫。我想提醒大家，您可以在我們的網站上找到有關我們截至 2024 年 3 月 31 日的三個月財務業績以及最新的 10-Q 表格的更多詳細資訊。

Starting with the financial resources on our balance sheet, we had cash, cash equivalents, restricted cash and short-term investments of $62.7 million as of March 31 2024, as compared to $52.6 million as of December 31 2023.

從資產負債表上的財務資源開始，截至 2024 年 3 月 31 日，我們的現金、現金等價物、限制性現金和短期投資為 6,270 萬美元，而截至 2023 年 12 月 31 日為 5,260 萬美元。

Net cash used in operating activities was $14.5 million for the three months ended March 31, 2024. Based on our current operating plan and assumptions with our existing cash resources also including the credit facility and combined with the gross proceeds from our recent $75 million equity offering, we estimate we have sufficient financial resources to fund operations into 2026.

截至 2024 年 3 月 31 日的三個月，經營活動使用的現金淨額為 1,450 萬美元。根據我們目前的營運計畫和對現有現金資源（包括信貸額度）的假設，再加上我們最近 7,500 萬美元股票發行的總收益，我們估計我們有足夠的財務資源為 2026 年的營運提供資金。

Our cash runway assumptions do not account for any potential revenue from commercial sales of Pz-cel or proceeds from the sale of a priority review voucher or PRV, if awarded by the FDA. I'll remind you that Pz-cel has been granted rare pediatric disease designation by the FDA. So upon its potential approval, we believe that we are eligible to receive a PRV.

我們的現金跑道假設並未考慮 Pz-cel 商業銷售的任何潛在收入或優先審查憑證或 PRV（如果 FDA 授予）銷售收益。我要提醒您的是，Pz-cel 已被 FDA 授予罕見兒科疾病資格。因此，一旦獲得批准，我們相信我們有資格獲得 PRV。

Research and development expenses were $7.2 million for the three months ended March 312024, compared to $8 million for the three months ended March 31 2023. Our spend on general and administrative activities was $7.1 million for the three months ended March 31, 2024, compared to $4 million for the three months ended March 31 2023.

截至2024年3月31日止三個月的研發費用為720萬美元，截至2023年3月31日止三個月的研發費用為800萬美元。截至2024年3月31日的三個月，我們的一般和行政活動支出為710萬美元，而截至2023年3月31日的三個月為400萬美元。

Net loss was $31.6 million for the first quarter of 2024 or $1.16 loss per common share is important to note that the net loss in the first quarter of 2024 included a noncash loss of $17.3 million related to the change in fair value of warrant liabilities. These warrants are required to be classified as liability and remeasured at fair market value each reporting period.

2024 年第一季的淨虧損為3,160 萬美元，即每股普通股虧損1.16 美元，值得注意的是，2024 年第一季的淨虧損包括與認股權證負債公允價值變動相關的1,730 萬美元非現金虧損。這些認股權證需要歸類為負債，並在每個報告期間以公平市價重新計量。

Net loss in the first quarter of 2023 was $9.1 million or $0.54 loss per common share.

2023 年第一季的淨虧損為 910 萬美元，即每股普通股虧損 0.54 美元。

With that, operator, please open the Q&A session.

那麼，操作員，請開啟問答環節。

(Operator Instructions)

（操作員說明）

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑弗里斯。

Hi, good morning and congrats on the progress, and thanks for taking my question. I was going to ask just a clarification one for the BLA submission time line change to second versus third quarter. Is there anything anymore behind that? Or is it just a softening of timeline just to make sure that you get everything in on time or any more prospective there that you can add?

你好，早安，恭喜你取得的進展，感謝你提出我的問題。我只想要求澄清 BLA 提交時間軸更改為第二季與第三季。這後面還有東西嗎？或者這只是時間安排的軟化，只是為了確保您按時完成所有內容，或者您​​可以添加更多的前景？

Hi, Maury. Good morning. Thanks for the question. Clearly really the latter, we're still on track. And so the resubmission in quarter three is very much our plan. Just the softening of the language is second half of 2024 is to accommodate external uncertainties like when the FDA grant us a meeting because we do want to be doubly terribly sure that we have squared off all the questions that they've asked us during the CRL and that we've satisfied those.

嗨，莫里。早安.謝謝你的提問。顯然是後者，我們仍然走在正軌上。因此，第三季的重新提交正是我們的計劃。只是在 2024 年下半年軟化語言是為了適應外部不確定性，例如 FDA 批准我們召開一次會議，因為我們確實希望更加確定我們已經解決了他們在 CRL 期間向我們提出的所有問題我們已經滿足了這些要求。

As I said, our plan is to actually validate them with the FDA before we make the resubmission. So there's no surprise. So just to give, if it's on the borderline of a last day of Q3 versus beginning of Q4, we want to keep that broadly as second half. But there is no material change in our thinking of how and rigorously we're looking to complete the work that we need to do as discussed in the previous conference call after we announced the CRL. Hope that addresses your questions.

正如我所說，我們的計劃是在重新提交之前向 FDA 實際驗證它們。所以這並不奇怪。因此，如果它位於第三季最後一天與第四季開始的邊界，我們希望將其大致保留為下半年。但我們對於如何、嚴格地完成我們在宣布 CRL 後的電話會議中討論的需要做的工作的想法沒有發生重大變化。希望能解決您的問題。

Yes, that's helpful. In some for the cell-based identity assay, and can you talk a little bit more about just alignment on that assay with FDA due to the novel nature of that assay and maybe talk about the progress that's made there and the plan to make sure that there is alignment with FDA going into the BLA?

是的，這很有幫助。在一些基於細胞的身份測定中，由於該測定的新穎性，您能否更多地談談該測定與 FDA 的一致性，也許可以談談在那裡取得的進展以及確保的計劃BLA 是否與FDA 保持一致？

Sure. Thanks for that question. So the cell-based identity assay really looks at what's the cell composition of our product. And we are continuing to gain alignment with the FDA through our informal meetings with the agency. We have a fairly good understanding on what is required to be done to address the sensitivity and specificity.

當然。謝謝你提出這個問題。因此，基於細胞的身份測定真正著眼於我們產品的細胞組成。我們將透過與 FDA 的非正式會議繼續與該機構保持一致。我們對需要採取哪些措施來解決敏感性和特異性有相當好的了解。

So we have made those proposals and the agency has indicated that our approach seems fairly straightforward and that this will be a review issue with the data that we generate. So we are confident that we'll be able to provide the necessary data based on the feasibility runs that we've done so far in identifying markers that are specific to keratinocytes.

因此，我們提出了這些建議，而該機構表示我們的方法似乎相當簡單，這將是對我們產生的數據的審查問題。因此，我們有信心能夠根據迄今為止在鑑定角質形成細胞特異性標記物方面所做的可行性運行提供必要的數據。

Just as a reminder, our product is primarily keratinocytes. So you need to have an antibody that can detect keratinocytes and is not binding to other site types of cells that you may find in this environment, and we're able to deliver that kind of specificity and sensitivity. So we're fairly confident that we'll be we'll have the identity assay in place by the time we do the resubmission.

提醒一下，我們的產品主要是角質形成細胞。因此，您需要一種能夠檢測角質形成細胞並且不與您在這種環境中可能發現的其他位點類型的細胞結合的抗體，我們能夠提供這種特異性和敏感性。因此，我們相當有信心，在重新提交時我們將完成身份分析。

Got it. Okay. And then maybe last question for you said a late-breaking abstract, given there seems to be at least a numerical difference in SEC where there is no SEC treated sites, but SEC non-treated sites and where you don't see this with [vajuvec]. Have you discussed with KOLs and potentially FDA whether prevention of SESCC. could be included in the label? And how should we think about this in respect to demographics for patients who may be at higher risk of SEC.

知道了。好的。然後也許你的最後一個問題說了一個最新的摘要，因為 SEC 中似乎至少存在數字差異，其中沒有 SEC 處理的站點，但 SEC 未處理的站點，並且你看不到這一點[瓦尤韋克]。您是否與 KOL 以及潛在的 FDA 討論過是否預防 SECC。可以包含在標籤中嗎？我們應該如何考慮可能面臨 SEC 較高風險的患者的人口統計。

Thanks for that question, Maury, wonderful question. Naturally, we've been giving a lot of thought to this. What we do know is in order to get a label claim that Pz-cel would it will be a preventative measure to you know, to avoid SEC's happening is it's a little too premature to have that level of data to date. But the early indications of our data that are definitely encouraging. It is probably going to be a longer term effort on our part to demonstrate that clinically.

謝謝你提出這個問題，莫里，這是一個很好的問題。當然，我們對此進行了很多思考。我們所知道的是，為了獲得標籤聲稱 Pz-cel 將是一種預防措施，為了避免 SEC 的發生，目前擁有該水平的數據還為時過早。但我們數據的早期跡象絕對令人鼓舞。我們可能需要長期努力才能在臨床上證明這一點。

However, what we do know from published literature is that large chronic wounds are the originating areas where you typically see squamous cell carcinomas. And so to treat those types of wounds is high priority from a patient risk perspective, and that is well known aligned and agreed upon by the medical community. So we will still prioritize treating those patients at high-risk. But whether our label can include a claim like that, it's a TBD, but it may require additional data generation for the future, but we're definitely looking into that.

然而，我們從已發表的文獻中確實知道，大的慢性傷口是鱗狀細胞癌的起源區域。因此，從患者風險的角度來看，治療這些類型的傷口是重中之重，這是眾所周知的，並且得到了醫學界的一致同意。所以我們還是會優先治療那些高風險的病人。但我們的標籤是否可以包含這樣的聲明，還有待確定，但未來可能需要產生額外的數據，但我們肯定會對此進行研究。

Got it. Okay. Thanks. I'll hop back in the queue.

知道了。好的。謝謝。我會跳回到隊列中。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

Hi, good morning, everybody. Thanks for taking the question. Great to see that a lot of new investors are taking a look at the company and I wanted to ask two key questions that we've been getting from a lot of some of these newer investors. I guess, first, can you remind us about the importance of understanding the endpoints that you looked at in the Phase 3 trial relative to the size of the wounds that you treated? And then also looking at, at least 15% will really only 75% wound healing. How do we understand that? And these data are very important relative to just understanding the complete healing. Thank you.

嗨，大家早安。感謝您提出問題。很高興看到許多新投資者正在關注這家公司，我想問我們從許多新投資者那裡得到的兩個關鍵問題。我想，首先，您能否提醒我們了解您在第 3 階段試驗中觀察的終點相對於您治療的傷口大小的重要性？然後再看看，至少15%的傷口真正癒合的只有75%。我們如何理解這一點？這些數據對於理解完整的治癒來說非常重要。謝謝。

Good morning, Christian, and thanks so much for that question. We often tend to forget those nuances, right? So it's important to remind ourselves the endpoints of the study as well as the types of wounds that we have treated in our pivotal study as well as the Phase 1/2a with Pz-cel, we treated the toughest to treat wounds.

早安，克里斯蒂安，非常感謝你提出這個問題。我們常常容易忘記這些細微差別，對嗎？因此，重要的是要提醒自己研究的終點以及我們在關鍵研究以及 Pz-cel 的 1/2a 期中治療的傷口類型，我們治療了最難治療的傷口。

And when I say that there are two dimensions to that. One is the wound size, but the minimum loan size required was 20 centimeters squared. but there are some loans that run into hundreds of centimeters squared where you needed to quilt like apply multiple graft, multiple pz-cel sheets in that area. And that is something that we often forget. So that is a size aspect of our rules.

當我說這有兩個維度。一是傷口大小，但要求的最小貸款大小是20平方公分。但有些貸款的面積達到數百平方厘米，您需要在該區域應用多個移植物、多個 pz-cel 床單。這是我們經常忘記的事情。這是我們規則的一個規模面向。

The second is the chronicity of chronic wounds are definitely different from what we are hearing from these experts. They're different type of wounds and compared to the recurrent wounds and they cannot self-heal themselves. You will -- if you look at our complete wound healing rate, zero, zero chronic wounds ever completely healed in our study. So that tells you that the wound type of cells that we're treating is very different here. And so that's one thing.

其次，慢性傷口的慢性程度與我們從這些專家那裡聽到的肯定不同。與復發性傷口相比，它們是不同類型的傷口，並且無法自我療癒。如果你看看我們的傷口完全癒合率，你會發現，在我們的研究中，零、零的慢性傷口完全癒合。這告訴你，我們正在治療的細胞傷口類型非常不同。這是一回事。

The second is, of course, the other primary endpoint that we're looking at is a pain reduction but I'll come to that later. Why do we have 50% wound healing and not 100% wound healing infact. In VITAL we've looked at all three levels of wound healing, 50%, 75% and complete, which is 100% wound healing.

當然，第二個是我們正在研究的另一個主要終點是減輕疼痛，但我稍後會談到這一點。事實上，為什麼我們的傷口癒合率為 50%，而不是 100%。在 VITAL 中，我們研究了傷口癒合的所有三個等級：50%、75% 和完全（即 100% 傷口癒合）。

And in all those three aspects, we have shown that there is a highly statistically significant difference in the healing rates, what we see with Pz-cel versus the control. It's important to note that for these types of sizes of wounds, even at 50% wound healing leads to a very significant outcome for the patient when you look at their quality of life and their pain reductions.

在所有這三個方面，我們已經證明 Pz-cel 與對照組的治癒率存在高度統計顯著差異。值得注意的是，對於這些類型的傷口大小，即使傷口癒合率為 50%，當您觀察患者的生活品質和疼痛減輕情況時，也會為患者帶來非常顯著的結果。

But I would say I would emphasize that two thirds of the wound, 67% showed even greater than 75% wound healing. And the way we score for 100% wound healing is extremely stringent in the case of the VITAL study, which is if there is even a small patch of crusted area, you cannot you cannot obviously pick on that crust and see the wound healed underneath that so when you have that element of doubt, it was not scored as a completely healed wound, even though the rest of the wound was completely healed.

但我要強調的是，三分之二的傷口（67%）顯示出甚至超過 75% 的傷口癒合。在 VITAL 研究中，我們對 100% 傷口癒合的評分方式非常嚴格，即使有一小塊結痂區域，你也不能明顯地挑起結痂並看到下面的傷口癒合。時，即使傷口的其餘部分已完全癒合，也不會將其視為完全癒合的傷口。

And therefore, when you cannot verify that under the crust on the or even if there is a microscopic dot a red dot on the wound, we wouldn't score that that as a completely healed room. So these are some of the nuances that you asked is when you look at numbers there.

因此，當你無法驗證傷口上的痂下，或即使傷口上有一個微小的紅點，我們也不會認為這是一個完全癒合的房間。這些是您在查看數字時所詢問的一些細微差別。

But regardless when you look at our, you know, the one pictures speak volumes of how the differences between heat treated, heal wound versus, on the control rooms. So that is also further corroborated by our second clinical endpoint, which is pain reduction, where we found that there is significant patient-reported outcome.

但無論如何，當你看我們的照片時，你知道，這些照片充分說明了熱處理、癒合傷口與控制室之間的差異。因此，我們的第二個臨床終點（即疼痛減輕）也進一步證實了這一點，我們發現患者報告的結果顯著。

That is ultimately what is important, and when we use when we look at wounds that started with a high pain score of 6 or worse on a 10 point scale. The mean reduction in pain was 5.7. So that basically underscores how much of a alleviation of pain therapy is able to offer to these patients in addition to purely the wound healing aspect of it. I hope I addressed your question. If not, please do ask me further details. I'm happy to address that in person.

這才是最重要的，當我們使用時，當我們觀察開始疼痛評分為 6 分或更差（10 分制）的傷口時。疼痛平均減輕 5.7 度。因此，這基本上強調了除了純粹的傷口癒合方面之外，疼痛治療還能為這些患者提供多少緩解效果。我希望我回答了你的問題。如果沒有，請向我詢問更多詳情。我很高興親自解決這個問題。

You did. Certainly.

你做到了。當然。

I just wanted to add --

我只是想添加--

Go ahead.

前進。

I just wanted to add to what Vish said in terms of our baseline characteristics besides numbers the average duration of loans that are opening are widely to remind was five years with some of the ones that had never closed for up to 21 years.

我只是想補充 Vish 所說的基本特徵，除了數字之外，廣泛提醒人們注意的是，貸款的平均期限為 5 年，其中一些貸款長達 21 年從未關閉。

So these are the types of loans that had hardened and especially in adult patients, when you have these chronic wounds that have not healed with other treatment modalities, we have been able to show, most of our patients invited were adult patients, and we have been able to show these kinds of data with them.

因此，這些類型的貸款已經硬化，尤其是在成年患者中，當您有這些慢性傷口尚未通過其他治療方式治愈時，我們已經能夠證明，我們邀請的大多數患者都是成年患者，我們有能夠用它們顯示這些類型的數據。

So I think that is pretty profound knowing that these loans have until the next six months, we are able to show this kind of wound closures.

所以我認為這是非常深刻的，因為知道這些貸款在接下來的六個月之前，我們能夠展示這種傷口閉合的情況。

Okay. Thank you. And then an often for rare diseases, I know you've done things like genetic modeling to understand what the actual patient pool sizes, but also with rare diseases, new therapies come online, others enter late-stage development. We start to increase in some of the patients that are identified. So as you guys are doing a lot of diligence with KOL preparing for potential approval, I'm curious if you've heard any commentary about the market size and if there's been any change in the last few years with all the development in the space?

好的。謝謝。然後，對於罕見疾病，我知道您已經做了諸如基因建模之類的事情來了解實際患者池的規模，而且對於罕見疾病，新療法上線，其他療法進入後期開發。我們開始增加一些已確診的患者。因此，當你們與 KOL 一起做大量的盡職調查以準備潛在的批准時，我很好奇你們是否聽說過有關市場規模的任何評論，以及過去幾年該領域的所有發展是否有任何變化？

Go ahead, Madhav.

繼續吧，馬達夫。

I think what we are definitely hearing is an increase in genetic testing panel and collecting more biopsies, especially with, as you said, similar to other rare diseases as more therapies come on market. A, the misclassification that has been happening in the EB space. We heard one of the reports from DEBRA that as high as 75% of EB patients were misclassified.

我認為我們肯定聽到的是基因檢測小組的增加和收集更多的活檢，特別是正如你所說，隨著更多的療法上市，與其他罕見疾病類似。A，EB 領域中發生的錯誤分類。我們聽到 DEBRA 的一份報告稱，高達 75% 的 EB 患者被錯誤分類。

We hope that that kind of misclassification, that there is an accurate diagnosis that happens, but definitely on the on the right track with major genetic testing. And it is that certainly advocacy from physicians to be able to test no sooner and earlier on.

我們希望這種錯誤分類能夠發生，但透過主要的基因檢測絕對走在正確的軌道上。醫生肯定提倡儘早進行檢測。

Okay. Thanks very much.

好的。非常感謝。

There appear to be no further questions in queue. I would now like to turn the call back over to Vish Seshadri for any closing remarks.

隊列中似乎沒有其他問題了。現在我想將電話轉回給 Vish Seshadri，讓其發表結束語。

Thank you, Kelly, and thank you all for joining us today. In closing, we remain committed to bringing Pz-cel to patients with our RDEB as quickly as possible. I firmly believe we will get there.

謝謝你，凱利，也謝謝大家今天加入我們。最後，我們仍然致力於盡快將 Pz-cel 帶給 RDEB 患者。我堅信我們會到達那裡。

Thank you, everyone, for joining us today for today's business update. With that, we'll talk to you again soon. Thank you.

感謝大家今天加入我們今天的業務更新。這樣，我們很快就會再次與您交談。謝謝。

Thank you, everyone. This does conclude today's conference call. You may disconnect your phone lines at this time, and have a wonderful day. Thank you for your participation.

謝謝大家。今天的電話會議到此結束。此時您可以斷開電話線，度過美好的一天。感謝您的參與。