(ABEO) 2021 Q3 法說會逐字稿

Good morning, ladies and gentlemen. Thank you for standing by. Welcome to the Abeona Q3 2021 Earnings Call. (Operator Instructions) I would now like to turn the call over to Greg Gin, Head of Investor Relations. Please go ahead.

早上好，女士們，先生們。謝謝你的支持。歡迎參加 Abeona 2021 年第三季度財報電話會議。 （操作員說明）我現在想將電話轉給投資者關係主管 Greg Gin。請繼續。

Thank you, Kelly. Good morning, everyone. I would like to welcome and thank you for joining us on our third quarter 2021 conference call. The press release announcing the third quarter results and recent operational progress is available on our website at www.abeonatherapeutics.com.

謝謝你，凱利。大家，早安。我要歡迎並感謝您加入我們的 2021 年第三季度電話會議。宣布第三季度業績和近期運營進展的新聞稿可在我們的網站 www.abeonatherapeutics.com 上查閱。

On the call today with prepared remarks are Vish Seshadri, CEO of Abeona; and Ed Carr, CFO. After the prepared remarks, we'll host a Q&A session. We are also joined by Dr. Brian Kevany, our Chief Technical Officer.

Abeona 的首席執行官 Vish Seshadri 在今天的電話會議上準備了發言；和首席財務官 Ed Carr。在準備好的評論之後，我們將主持一個問答環節。我們的首席技術官 Brian Kevany 博士也加入了我們的行列。

Before we start, I will review our safe harbor statement. Remarks made during today's call may contain projections and forward-looking statements regarding future events. Forward-looking statements are made pursuant to the safe harbor provisions of the federal securities laws. These 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. Various factors that could cause actual results to differ include, but are not limited to, those identified under the section entitled Risk Factors in the company's annual report on Form 10-K and quarterly reports on Form 10-Q filed by the company with the SEC. These documents are available on our website at www.abeonatherapeutics.com.

在開始之前，我將回顧一下我們的安全港聲明。在今天的電話會議上發表的言論可能包含有關未來事件的預測和前瞻性陳述。前瞻性陳述是根據聯邦證券法的安全港條款作出的。這些前瞻性陳述基於當前的預期，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存在重大差異。可能導致實際結果不同的各種因素包括但不限於公司向美國證券交易委員會提交的 10-K 表格年度報告和 10-Q 表格季度報告中標題為風險因素的部分中確定的因素.這些文件可在我們的網站 www.abeonatherapeutics.com 上獲得。

And with that, I will now turn the call over to Vish.

有了這個，我現在將把電話轉給 Vish。

Thank you, Greg. Thank you, and good morning, everyone. Thank you for joining us this morning. This is my first quarterly call since transitioning to CEO about 4 weeks ago, and I'm happy to update you on our substantial progress in the third quarter and since quarter end.

謝謝你，格雷格。謝謝大家，大家早上好。感謝您今天早上加入我們。這是我自 4 週前擔任 CEO 以來的第一次季度電話會議，我很高興向您介紹我們在第三季度和季度末以來取得的重大進展。

I'm thrilled to be leading Abeona during this exciting and critical time in our life cycle. We are advancing 2 late-stage pivotal assets with rare pediatric designations, transformational potential and key anticipated milestones in the coming months, including finishing patient accrual for the EB-101 Phase III VITAL study in the first quarter of 2022 and top line data readout in the third quarter of 2022.

我很高興能在我們生命週期中這個激動人心的關鍵時刻領導 Abeona。我們正在推進 2 項具有罕見兒科指定、轉化潛力和關鍵預期里程碑的後期關鍵資產，包括在 2022 年第一季度完成 EB-101 III 期 VITAL 研究的患者招募以及在2022年第三季度。

We are continuing to work toward bringing our gene therapies as safely, effectively and quickly as possible to patients who suffer from these diseases that have no approved treatments. We have taken a big step towards that goal by recently enhancing our leadership and bench strength with gene therapy and biopharma industry veterans to prepare for 2 Biologics License Application submissions for our lead clinical program in RDEB and MPS IIIA. These hires include John Voss as Head of Quality, Carl Denny as Head of Regulatory, and Kate Imhof as Senior Director of Regulatory. All 3 bring considerable gene therapy experience with late-stage clinical and commercialized products in companies like AveXis, Sarepta Therapeutics and Cellectis.

我們將繼續努力將我們的基因療法盡可能安全、有效和快速地提供給患有這些疾病但尚未獲得批准治療的患者。我們最近向基因治療和生物製藥行業的資深人士增強了我們的領導力和板凳實力，為我們在 RDEB 和 MPS IIIA 的領先臨床項目準備 2 份生物製劑許可申請，朝著這個目標邁出了一大步。這些員工包括擔任質量主管的 John Voss、擔任監管主管的 Carl Denny 和擔任監管高級總監的 Kate Imhof。所有 3 人都為 AveXis、Sarepta Therapeutics 和 Cellectis 等公司的後期臨床和商業化產品帶來了相當多的基因治療經驗。

Now let's take a closer look at EB-101, our investigational autologous gene-corrected cell therapy that has demonstrated a high rate of instantaneous wound healing and pain reduction for 6 years, the latest follow-up time point reported after treatment of large, chronic wounds in RDEB patients in the Phase I/II study. We are anticipating similar outstanding results from our ongoing Phase III VITAL study. As a reminder, the target for the VITAL study is the treatment of approximately 35 large chronic wounds, each treated wound being paired with an untreated control wound within the same patient.

現在讓我們仔細看看 EB-101，這是我們的研究性自體基因校正細胞療法，已證明 6 年的瞬時傷口癒合率和疼痛減輕率很高，這是治療大型慢性疾病後報告的最新隨訪時間點I/II 期研究中 RDEB 患者的傷口。我們預計我們正在進行的 III 期 VITAL 研究會取得類似的出色結果。提醒一下，VITAL 研究的目標是治療大約 35 個大型慢性傷口，每個治療的傷口都與同一患者體內的一個未治療的對照傷口配對。

Large chronic wounds are the most severe and problematic wounds in RDEB. Unlike small, recurring wounds that can close spontaneously, these large chronic wounds have greater than 20-centimeter square of surface area and remain open for more than 6 months, very often for years, and cannot close themselves and are associated with severe pain that is often managed with opioids.

大型慢性傷口是 RDEB 中最嚴重和問題最嚴重的傷口。與可以自發閉合的小型、反復出現的傷口不同，這些大型慢性傷口的表面積超過 20 平方厘米，並保持開放超過 6 個月，通常長達數年，並且無法自行閉合，並伴有嚴重的疼痛，即經常用阿片類藥物治療。

I am very pleased to report that since the last earnings call we have continued to treat patients, and we are close to accruing the VITAL study. We have identified and are scheduling treatment for the final patients and anticipate treating them by first quarter of 2022. We therefore expect top line study results in the third quarter of 2022 upon completing the 24-week follow-up for the last patient treated.

我很高興地報告，自上次財報電話會議以來，我們一直在繼續治療患者，並且我們即將完成 VITAL 研究。我們已經確定並正在為最終患者安排治療，並預計在 2022 年第一季度之前對他們進行治療。因此，我們預計在完成對最後一名接受治療的患者的 24 週隨訪後，將在 2022 年第三季度獲得一線研究結果。

The anticipated timing for BLA filing is year-end 2022 to early 2023. As previously mentioned, UMass Memorial Medical Center, the second clinical site in the VITAL study, is now active and prescreening the patients.

BLA 申報的預計時間是 2022 年底至 2023 年初。如前所述，VITAL 研究中的第二個臨床中心 UMass 紀念醫學中心現在正在積極進行患者的預篩查。

Turning to EB-101 manufacturing. As a reminder, we are a non-CDMO-dependent company. We've manufactured the drug product for the Phase III VITAL study at our Cleveland facility. We have made significant progress in updating the module 3 of the IND with information pertaining to manufacture of EB-101 in-house. We have also been advancing process characterization work and other CMC activities to support a BLA filing for EB-101. We believe that bringing manufacturing and critical analytical assays for our assets in-house at Abeona is a key strategic advantage in the cell and gene therapy space.

轉向 EB-101 製造。提醒一下，我們是一家不依賴 CDMO 的公司。我們已經在克利夫蘭工廠生產了用於 III 期 VITAL 研究的藥物產品。我們在更新 IND 模塊 3 方面取得了重大進展，其中包含有關內部製造 EB-101 的信息。我們還一直在推進流程表徵工作和其他 CMC 活動，以支持 EB-101 的 BLA 申請。我們相信，在 Abeona 內部為我們的資產帶來製造和關鍵分析分析是細胞和基因治療領域的關鍵戰略優勢。

Let's turn to our adeno-associated virus platform and our second clinical program, ABO-102, investigational therapy for Sanfilippo syndrome Type A or MPS IIIA. In the previous earnings call, we reported that we aligned with the FDA on the definition of the primary end point for the pivotal Transpher A study to enable registration. The primary end point is a neurocognitive assessment using raw score of Bayley scale for infant and toddler development, BSITD, and the Kaufman Assessment battery for children, KABC2, for children who attain a developmental age of 42 months.

讓我們轉向我們的腺相關病毒平台和我們的第二個臨床項目 ABO-102，這是針對 Sanfilippo 綜合徵 A 型或 MPS IIIA 的研究性治療。在之前的財報電話會議中，我們報告說，我們與 FDA 在關鍵 Transpher A 研究的主要終點定義上保持一致，以實現註冊。主要終點是使用貝利嬰幼兒發育量表原始分數 BSITD 和考夫曼兒童評估電池 KABC2 對發育年齡為 42 個月的兒童進行神經認知評估。

We have since submitted an amended trial protocol reflecting the agreed-upon end points. We have collaborated with experts in the MPS IIIA to finalize a statistical analysis plan, or SAP, which we are scheduled to discuss with the FDA in the first quarter of 2022 through the RMAT mechanism. As a reminder, we have already treated 10 patients with ABO-102 in the therapeutic dose cohort. The preservation of neurocognitive development is evaluated over a period of up to 5 years. Therefore, depending on the primary analysis methodology and the neurocognitive performance observed in the more recently dosed patients, we anticipate top line results from Transpher A anywhere between the fourth quarter of 2022 and second quarter of 2023.

此後，我們提交了一份修改後的試驗方案，反映了商定的終點。我們已與 MPS IIIA 的專家合作，最終確定了一項統計分析計劃或 SAP，我們計劃在 2022 年第一季度通過 RMAT 機制與 FDA 討論該計劃。提醒一下，我們已經在治療劑量組中用 ABO-102 治療了 10 名患者。在長達 5 年的時間內評估神經認知發育的保存情況。因此，根據主要分析方法和在最近給藥的患者中觀察到的神經認知表現，我們預計 Transpher A 在 2022 年第四季度至 2023 年第二季度之間的任何時間都可以獲得頂級結果。

We are excited about the safety and magnitude of benefit seen with ABO-102 in children treated early in age at the therapeutic dose for whom we have reported unprecedented trends in disease-specific biomarkers, preservation of neurocognitive development as well as anatomical development using brain MRI, which was presented at the International Symposium on MPS and Related Diseases in the third quarter 2021. The MRI data shows increased gray matter, corpus callosum and amygdala volumes in the brain in 3 young patients with MPS IIIA treated at 24 months or before and at 2 years post treatment as compared to afflicted patients without treatment, which is consistent with the preservation of neurocognitive development that we have previously reported.

我們對 ABO-102 在兒童早期以治療劑量治療的安全性和益處感到興奮，在 2021 年第三季度 MPS 及相關疾病國際研討會上發表。MRI 數據顯示，在 24 個月或之前和在與未治療的患者相比，治療後 2 年，這與我們之前報導的神經認知發育的保存一致。

While the triangulation of results from biomarker, neurocognitive development and brain MRI builds clinical conviction about the treatment effect of ABO-102, this will be important also from a regulatory approval standpoint as the FDA has indicated that they will consider all kinds of clinical data points holistically in regulatory decision-making.

雖然生物標誌物、神經認知發育和腦部 MRI 結果的三角測量建立了對 ABO-102治療效果的臨床信念，但從監管批准的角度來看，這也很重要，因為 FDA 表示他們將考慮各種臨床數據點全面參與監管決策。

We have previously sourced the ABO-102 drug product from Nationwide Children's Hospital. Earlier this year, we commenced activities to be able to manufacture ABO-102 at our Cleveland facility. We are on track to complete manufacturing of 6 GMP lots of ABO-102 this year using animal-free materials. We expect analytical comparability studies to establish equivalence of Abeona-produced drug product with that sourced from Nationwide Children's Hospital in the first half of 2022 using the battery of tests as instructed by the FDA for ABO-102.

我們之前從 Nationwide Children's Hospital 採購了 ABO-102藥物產品。今年早些時候，我們開始了能夠在克利夫蘭工廠生產 ABO-102 的活動。我們有望在今年使用無動物材料完成 6 批 GMP 批次的 ABO-102 的生產。我們預計分析可比性研究將在 2022 年上半年使用 FDA 對 ABO-102 指示的一系列測試確定 Abeona 生產的藥品與來自全國兒童醫院的藥品的等效性。

Additionally, in preparation for commercial supply of ABO-102, we have initiated the construction of a 12,000 square foot commercial AAV manufacturing facility at our Cleveland site. This facility will also have the capacity to support other AAV programs, including our preclinical ocular programs in the future.

此外，為準備 ABO-102 的商業供應，我們已開始在克利夫蘭工廠建設 12,000 平方英尺的商業 AAV 製造設施。該設施還將有能力支持其他 AAV 項目，包括我們未來的臨床前眼科項目。

Let's move on to a brief update on our third clinical program, the ABO-101 Transpher B study in Sanfilippo Type B or MPS IIIB. As we first mentioned on the second quarter call, we have closed enrollment in the Transpher B study and are following patients treated in the study and under the compassionate use program in Germany for safety and efficacy of ABO-101. As reported earlier, biomarker and safety data look encouraging. We look forward to seeing 2-year neurocognitive data to assess efficacy of ABO-101 in the second half of 2022.

讓我們繼續簡要介紹我們的第三個臨床項目，即 Sanfilippo B 型或 MPS IIIB 中的 ABO-101 Transpher B 研究。正如我們在第二季度電話會議上首次提到的那樣，我們已經結束了 Transpher B 研究的註冊，並正在跟踪在研究中接受治療的患者以及在德國的同情使用計劃下 ABO-101的安全性和有效性。如前所述，生物標誌物和安全數據看起來令人鼓舞。我們期待在 2022 年下半年看到 2 年的神經認知數據來評估 ABO-101 的療效。

I will now briefly turn to our preclinical programs. While we are currently focused on rare diseases in our clinical programs, we intend to address larger areas of unmet medical need, and our preclinical programs are investigating novel AAV capsids in 5 undisclosed ophthalmic conditions with estimated U.S. prevalence ranging from 5,000 to 15,000 patients. We previously shared data from nonhuman primates to determine optimal routes of administration with different novel capsids.

我現在將簡要介紹我們的臨床前計劃。雖然我們目前在臨床項目中專注於罕見疾病，但我們打算解決更大的未滿足醫療需求領域，我們的臨床前項目正在研究 5 種未公開的眼科疾病中的新型 AAV 衣殼，估計美國患病率從 5,000 到 15,000 名患者。我們之前共享了來自非人類靈長類動物的數據，以確定不同新型衣殼的最佳給藥途徑。

Subsequently, we have made significant progress in generating mouse models for 3 indications, prepared the genetic constructs, produced the vectors with appropriate capsid and develop assays to measure efficacy in the preclinical setting. We are encouraged by gene expression levels with our constructs in in vitro studies. We're expanding the model mouse colonies and have already started dosing animals. We expect animal proof-of-concept data by mid-2022 and pre-IND meetings with the FDA in late 2022.

隨後，我們在為 3 種適應症生成小鼠模型、製備基因構建體、生產具有適當衣殼的載體以及開髮用於在臨床前環境中測量療效的測定法方面取得了重大進展。我們對體外研究中構建體的基因表達水平感到鼓舞。我們正在擴大模型小鼠群體，並且已經開始對動物進行給藥。我們預計到 2022 年中期將提供動物概念驗證數據，並在 2022 年末與 FDA 舉行 IND 前會議。

Before I request Ed to review our financial results, I want to briefly comment on our formal settlement with REGENXBIO, which resolves our previously disclosed dispute over an arbitration award. The settlement provides for payments by Abeona over a 3-year period and, importantly, raises certain downside scenarios that could have made it challenging to make it to our next inflection points. With the arbitration uncertainty behind us, we are focused on completing the registration-enabling studies and submitting BLA filings for both EB-101 and ABO-102 to deliver these therapies to patients in need as quickly as we can. With that, I now turn over the call to Ed.

在我要求 Ed 審查我們的財務業績之前，我想簡要評論一下我們與 REGENXBIO 的正式和解，這解決了我們之前披露的關於仲裁裁決的爭議。該和解協議規定 Abeona 在 3 年內付款，重要的是，提出了某些不利情景，這些情景可能使我們難以進入下一個拐點。由於仲裁的不確定性已經過去，我們專注於完成註冊授權研究並提交 EB-101 和 ABO-102 的 BLA 文件，以盡快將這些療法提供給有需要的患者。有了這個，我現在把電話轉給 Ed。

Thank you, Vish. I would like to remind everyone that the Form 10-Q is available on our website, which is where you can get additional details on our financial results for the 3 and 9 months ended September 30, 2021.

謝謝你，維什。我想提醒大家，我們的網站上提供了 10-Q 表格，您可以在該網站上獲得有關我們截至 2021 年 9 月 30 日的 3 個月和 9 個月財務業績的更多詳細信息。

Starting with the financial reasons on our balance sheet, we had cash, cash equivalents and short-term investments of $67 million as of September 30, 2021. Net cash used in operating activities was $10.3 million for the third quarter of 2021. As part of the settlement with REGENXBIO, we have agreed to make payments to REGENXBIO of $20 million in the fourth quarter of 2021, $5 million in November 2022 and $5 million no later than November 2024. As Vish mentioned, this settlement allows us to eliminate ongoing legal expenses, deployment of resources and risks related to the dispute.

從我們資產負債表上的財務原因開始，截至 2021 年 9 月 30 日，我們的現金、現金等價物和短期投資為 6700 萬美元。2021 年第三季度用於經營活動的現金淨額為 1030 萬美元。與 REGENXBIO 達成和解後，我們同意在 2021 年第四季度向 REGENXBIO 支付 2000 萬美元，2022 年 11 月支付 500 萬美元，不遲於 2024 年 11 月支付 500 萬美元。正如 Vish 所說，這項和解使我們能夠消除持續的法律費用、資源部署和與爭議相關的風險。

With our existing financial resources, we are continuing to drive our lead programs toward key milestones. Based on our existing cash, cash equivalents and short-term investments, our ability to access additional financial resources and our financial flexibility to reduce operating expenses, if required, we believe that we have sufficient resources to fund operations through at least the next 12 months. To further strengthen the balance sheet and prepare for BLA filings, commercial launch readiness and the AAV facility build-out that Vish mentioned, we are exploring various options, including strategic partnering of pipeline assets and nondilutive funding.

憑藉我們現有的財務資源，我們將繼續推動我們的領先計劃朝著關鍵里程碑邁進。根據我們現有的現金、現金等價物和短期投資、我們獲得額外財務資源的能力以及我們在必要時減少運營費用的財務靈活性，我們相信我們有足夠的資源來為至少未來 12 個月的運營提供資金.為了進一步加強資產負債表並為 BLA 申報、商業發射準備和 Vish 提到的 AAV 設施擴建做準備，我們正在探索各種選擇，包括管道資產的戰略合作和非稀釋性資金。

Turning to research and development activities in the third quarter of 2021, we spent $8 million, which is consistent with the $8 million spent in the third quarter of 2020. Our spend on general and administrative activities was $6.1 million in the third quarter of 2021 compared to $4.4 million spent in the third quarter of 2020.

談到 2021 年第三季度的研發活動，我們花費了 800 萬美元，與 2020 年第三季度的 800 萬美元一致。與 2021 年第三季度相比，我們在一般和行政活動上的支出為 610 萬美元到 2020 年第三季度的支出為 440 萬美元。

General and administrative expenses include the cost of personnel not working directly on clinical and preclinical activities as well as professional fees, insurance, rent and office expenses. The increase in general and administrative expenses in the third quarter of 2021 results primarily from increased stock-based compensation and professional fees, partially offset by decreased salary and related costs.

一般和行政費用包括不直接從事臨床和臨床前活動的人員成本以及專業費用、保險、租金和辦公費用。 2021 年第三季度一般和管理費用的增加主要是由於股票薪酬和專業費用增加，部分被工資和相關成本的減少所抵消。

Gain on settlement with (inaudible) licensor was $6.7 million in the third quarter of 2021 as compared to 0 in the same period of 2020 and resulted from the accounting for the settlement agreement with REGENXBIO. The PPP, or Paycheck Protection Program, loan forgiveness income was $1.8 million in the third quarter of 2021 as compared to 0 in the same period of 2020 as a result of receiving the SBA or Small Business Administration's forgiveness of our PPP loan in July 2021.

2021 年第三季度與（聽不清）許可方的和解收益為 670 萬美元，而 2020 年同期為 0，這是由於與 REGENXBIO 達成和解協議的會計結果。由於在 2021 年 7 月獲得 SBA 或小企業管理局對我們的 PPP 貸款的寬恕，2021 年第三季度 PPP 或薪資保護計劃的貸款減免收入為 180 萬美元，而 2020 年同期為 0。

With that, I'll turn the call over to the operator to commence the Q&A session. Operator?

有了這個，我將把電話轉給接線員開始問答環節。操作員？

Certainly. (Operator Instructions) Your first question is coming from Maury Raycroft with Jefferies.

當然。 （操作員說明）您的第一個問題來自傑富瑞的 Maury Raycroft。

First, I wanted to ask on the press release that came out this morning on ABO-102 and the ICIEM conference. I guess maybe if you could just talk a little bit more about what you're going to be presenting at the conference, and how this is -- how this factors into the big picture plan for 102.

首先，我想問一下今天上午發布的關於 ABO-102 和 ICIEM 會議的新聞稿。我想也許你能多談談你將在會議上展示的內容，以及這是如何 - 這如何影響 102 的總體規劃。

Absolutely. Thank you, Maury, for the question. I will take this one. The data that we are presenting at ICIEM, the important part of the data is really the correlation that we see between Bayley scoring and Mullen. These are 2 different scales that are used in neurocognitive assessment.

絕對地。謝謝你，莫里，你的問題。我會拿這個。我們在 ICIEM 上展示的數據，數據的重要部分實際上是我們在 Bayley 評分和 Mullen 之間看到的相關性。這是用於神經認知評估的 2 個不同的量表。

What we have shared in the past, the data from the Transpher A study in terms of developmental age equivalent and the wonderful results that we've seen for the first 3-dose children are all based on the Mullen scores, but we've been collecting Bayley as well. So the common question that arises is how will the neurocognitive assessment look when you switch over to a Bayley, which is now what's been agreed with the FDA as our primary end point for the study.

我們過去分享的，Transpher A 研究中關於發育年齡當量的數據以及我們在前 3 劑兒童中看到的精彩結果都是基於 Mullen 分數，但我們一直也收集貝利。因此，出現的常見問題是，當您切換到 Bayley 時，神經認知評估將如何看待，這現在是 FDA 同意作為我們研究的主要終點的內容。

So the data that shows correlation between Bayley and Mullen that we will be presenting at ICIEM shows that those scores are correlated at approximately 95% correlation. And therefore, what it implies is that you should almost expect similar results if you put our Bayley scores instead of Mullen in the current ongoing Transpher A study. I hope that answers this question, Maury. Happy to clarify if you have any other follow-ups on that.

因此，我們將在 ICIEM 上展示的顯示 Bayley 和 Mullen 之間相關性的數據表明，這些分數的相關性約為 95%。因此，這意味著如果您在當前正在進行的 Transpher A 研究中使用我們的 Bayley 分數而不是 Mullen，您幾乎應該期待類似的結果。我希望能回答這個問題，莫里。很高興澄清您是否對此有任何其他後續行動。

Yes, that helps the answer. And so it seems like this is going to be an important update that would likely go right into the filing for this program and help, I guess, align -- make sure that the end points are aligned for one.

是的，這有助於回答。所以看起來這將是一個重要的更新，很可能會直接進入該程序的文件中，並幫助，我猜，對齊——確保端點對齊。

Yes. Yes.

是的。是的。

Got it. Okay. And then I also wanted to ask a question on EB-101 for RDEB. You noted -- you mentioned that you were opening up this other site on the East Coast, UMass med school. Just wanted to see how recruiting is going there. And if you can provide any more perspective into enrollment for the study?

知道了。好的。然後我還想問一個關於 RDEB 的 EB-101 的問題。你注意到了——你提到你正在東海岸開設另一個站點，麻省大學醫學院。只是想看看那裡的招聘情況如何。如果你能提供更多關於入學的觀點？

Sure. Thanks for that question, Maury. As we previously shared, we have activated the UMass site now, and they are actively prescreening patients. So we can expect patients to be treated there at any given point in time. We're definitely seeing more interest from patients who would not travel to the Stanford site because it would take from the East Coast a 5-hour journey, and that's something that's prohibited for many patients from participating.

當然。謝謝你的問題，莫里。正如我們之前分享的那樣，我們現在已經激活了 UMass 網站，他們正在積極對患者進行預篩查。因此，我們可以期望患者在任何給定時間點都在那裡接受治療。我們肯定會看到那些不願前往斯坦福醫院的患者更感興趣，因為從東海岸出發需要 5 小時的路程，而這對許多患者來說是被禁止的。

And we would like to stress the fact that we already shared this, we have identified the patients that we need, the last final patient that we need to complete accrual in the VITAL study. Most importantly, in getting patients treated at UMass, we have done a lot of work transferring the knowledge from Stanford so that UMass is fully up to speed with all the protocols and procedures. Because the way of treating EB-101 product for the patient has a lot of intricacies, and we wanted to make sure that nothing is missed in that tech transfer. So that's what has taken this time, but we are very confident that UMass is an equally competent site that can apply EB-101, and they are actively screening patients.

我們想強調一個事實，我們已經分享了這一點，我們已經確定了我們需要的患者，我們需要在 VITAL 研究中完成招募的最後一位患者。最重要的是，在讓患者在 UMass 接受治療方面，我們做了大量工作，從斯坦福大學轉移知識，以便 UMass 完全掌握所有協議和程序。因為為患者治療 EB-101 產品的方式有很多錯綜複雜的地方，我們希望確保在技術轉讓中不會遺漏任何東西。所以這就是這次所花費的時間，但我們非常有信心 UMass 是一個同樣有能力申請 EB-101 的網站，他們正在積極篩查患者。

Your next question is coming from Ram Selvaraju with H.C. Wainwright.

您的下一個問題來自 Ram Selvaraju 和 H.C.溫賴特。

This is [Mas] on for Ram. So firstly, just regarding the enrollment for the Phase III VITAL study for EB-101. Is there a significant reason you changed guidance on completion of enrollment from the end of this year to Q1 2022?

這是 Ram 的 [Mas]。首先，關於 EB-101 的 III 期 VITAL 研究的註冊。您是否有重要原因將完成註冊的指導從今年年底更改為 2022 年第一季度？

Thanks for the question, Ram. The short answer is, no, it's not a significant change in the timing. And it has nothing to do patient availability for the study or patients' interest in participating. We have a lot of patients who are interested. It's more a matter of logistics and experimental design.

謝謝你的問題，拉姆。簡短的回答是，不，這不是時間上的重大變化。並且它與研究的患者可用性或患者參與的興趣無關。我們有很多感興趣的患者。這更多的是物流和實驗設計的問題。

As you would think, in commercial setting, any large, chronic wound is absolutely appropriate for treatment of EB-101. But in our study, we have to randomize intrapatient wounds to have symmetry in the body. So if you have a wound in the upper right arm, you want a wound that is a controlled wound in the upper left arm, which puts some artificial constraints on who are the most appropriate patients. And that's one factor which is unique to the clinical trial. You will not see that in the commercial setting. So that's one.

如您所想，在商業環境中，任何大型慢性傷口都絕對適合治療 EB-101。但在我們的研究中，我們必須隨機分配患者體內的傷口以使其在體內具有對稱性。因此，如果您的右上臂有傷口，您希望左上臂的傷口是受控傷口，這會人為地限制誰是最合適的患者。這是臨床試驗獨有的因素之一。你不會在商業環境中看到這一點。所以這是一個。

And second is we have the patients identified. It's a matter of scheduling, and it's also a matter of -- we have an annual routine cGMP shutdown that happens in the last half of December. And at that time, we cannot manufacture, and this is something that we do every year. If you missed an interim biopsy date by end of November, the next available stock -- slot goes to mid-January. So that is the primary reason why that spilled over to quarter 1 2022. And we're very confident that we're going to be accrued in quarter 1.

其次，我們已經確定了患者。這是一個日程安排的問題，也是一個問題——我們在 12 月下半月進行了年度例行 cGMP 關閉。那時，我們無法製造，這是我們每年都在做的事情。如果您在 11 月底之前錯過了臨時活檢日期，則下一個可用庫存 - 插槽將轉到 1 月中旬。因此，這就是為什麼會溢出到 2022 年第一季度的主要原因。我們非常有信心，我們將在第一季度累積。

Okay. I appreciate the clarification. And then regarding the neurological assessments for the Phase I/II AV-101 study for MPS IIIB, has there been any current hindrance due to the ongoing pandemic for this assessment?

好的。我很欣賞澄清。然後關於 MPS IIIB 的 I/II 期 AV-101 研究的神經學評估，由於該評估的持續大流行，目前是否有任何障礙？

Thanks for the question, Ram. There is no specific hindrance for MPS IIIB neurocognitive assessments due to the pandemic per se which is any different from the MPS IIIA program. As you -- as we've previously shared, for the MPS IIIB program, the timing of when we will have meaningful neurocognitive assessment requires that follow-up period. And that's what leads us to -- based on the 7 patients that have been dosed already, that meaningful time will be in the second half of 2022, where we would have a 2-year follow-up for at least 4 or 5 patients. So that's the time we can really make meaningful assessments of the MPS IIIB patients.

謝謝你的問題，拉姆。由於大流行本身，MPS IIIB 神經認知評估沒有具體的障礙，這與 MPS IIIA 計劃有任何不同。正如您 - 正如我們之前分享的那樣，對於 MPS IIIB 計劃，我們何時進行有意義的神經認知評估需要隨訪期。這就是讓我們得出結論的原因——根據已經給藥的 7 名患者，有意義的時間將在 2022 年下半年，屆時我們將對至少 4 或 5 名患者進行為期 2 年的隨訪。因此，我們可以真正對 MPS IIIB 患者進行有意義的評估。

Okay. And then just finally, shifting to your gene therapy pipeline. The MPS III space is relatively crowded. What do you think differentiates your AAV-based therapies? And in light of your AAV manufacturing facility, do you anticipate any kind of clear, competitive advantage arising from this? And if you have any plans to monetize your manufacturing facility or leverage it in some way?

好的。最後，轉向您的基因治療管道。 MPS III 空間相對擁擠。您認為您的基於 AAV 的療法有何不同？鑑於您的 AAV 製造設施，您是否預計會由此產生任何明顯的競爭優勢？如果您有任何計劃將您的製造設施貨幣化或以某種方式利用它？

Yes. Thanks for that question, Ram. I will have to correct you on one point here. The MPS IIIA and MPS IIIB space is not crowded. We currently have nothing that works in this disease. There is no standard of care. There's no treatment at all. And the -- our programs are the most advanced. And anything that is still in development is at least 5 to 7 years away. We have only seen preclinical or clinical preliminary biomarker clinical data and ecto-systemic data, not anything to do with central nervous system. So we believe that this is unique there.

是的。謝謝你的問題，拉姆。我將不得不在這裡糾正你的一點。 MPS IIIA 和 MPS IIIB 空間並不擁擠。我們目前沒有任何東西對這種疾病有效。沒有護理標準。根本沒有治療。而且——我們的程序是最先進的。任何仍在開發中的東西至少還需要 5 到 7 年的時間。我們只看到臨床前或臨床初步生物標誌物臨床數據和外系統數據，與中樞神經系統無關。所以我們相信這是獨一無二的。

And the second part of your question, which had to do with manufacturing preparedness for -- we are -- we've made a strategic choice here. We don't want to be at the mercy of a CDMO. We want to be a non-CDMO-dependent company, which is why -- and even as we wait for our products to get approved, there are patients that are lined up for these therapies. Which is why in our latest protocol amendments, we're making provisions for patients to be -- continue to be treated in Transpher A, even though we've gotten the necessary accrual done for an efficacy analysis for registrational purposes.

你問題的第二部分，這與製造準備有關——我們是——我們在這裡做出了戰略選擇。我們不想任由 CDMO 擺佈。我們希望成為一家不依賴 CDMO 的公司，這就是為什麼——即使在我們等待我們的產品獲得批准的時候，也有患者在排隊接受這些療法。這就是為什麼在我們最新的協議修正案中，我們為患者做出規定——繼續在 Transpher A 中接受治療，即使我們已經為註冊目的進行了療效分析所需的應計工作。

So we don't want to lose any time, and these patients are waiting, which is why we've already started work on building out our AAV facility. And it also has to do with when EB-101 goes -- launches commercially, our current facility will become a single-source, single-product facility, which means we cannot any longer manufacture MPS IIIA ABO-102 product there. Which is why we've already started to construct this new facility, and we want to be in time to be able to dose patients in need.

所以我們不想浪費任何時間，而這些患者正在等待，這就是為什麼我們已經開始建設我們的 AAV 設施的原因。它還與 EB-101 何時上市有關——商業推出時，我們目前的設施將成為單一來源、單一產品的設施，這意味著我們不能再在那裡生產 MPS IIIA ABO-102 產品。這就是為什麼我們已經開始建造這個新設施，並且我們希望能夠及時為有需要的患者提供劑量。

The next question is coming from Mani Foroohar with SVB Leerink.

下一個問題來自 Mani Foroohar 和 SVB Leerink。

I guess a couple of questions around how you're thinking about strategic alternatives versus sort of strategy on managing the balance sheet. Obviously, you mentioned some investments you have to make around the transition from you being a single-sourced manufacturing to product manufacturing. Can you give us some exactly where your approximate cash funnel will be as you hit some of the key catalysts that you're talking about in terms of the EB program and the gene therapy and the AAV program?

我想有幾個問題是關於你如何考慮戰略選擇與管理資產負債表的戰略。顯然，您提到了從單一來源製造到產品製造的過渡，您必須進行一些投資。當您遇到一些您正在談論的 EB 計劃、基因治療和 AAV 計劃方面的關鍵催化劑時，您能否準確地告訴我們您的大致現金漏斗在哪裡？

And then secondarily, in the second question, as you think about potentially out-licensing or partnering some of these assets, should we view the entire AAV platform as a single asset? Is it operationally even possible to license these programs and assets out for different recipients? Like how should we think about the partner-able quantum of your AAV programs?

其次，在第二個問題中，當您考慮可能對其中一些資產進行許可或合作時，我們是否應該將整個 AAV 平台視為單一資產？在操作上甚至可以將這些程序和資產許可給不同的接收者嗎？比如我們應該如何考慮您的 AAV 程序的合作夥伴數量？

Yes. So first, we'll take the first question, Mani, and thank you for that. Ed will be addressing your question that relates to cash balance and our build-out coming up to the next milestones. Ed?

是的。首先，我們將回答第一個問題，Mani，謝謝你。 Ed 將解決您與現金餘額和我們即將到來的下一個里程碑有關的問題。埃德?

Yes, sure. Sure, yes. Yes. I mean as you know, there's $67 million on the balance sheet at the end of September. So just looking forward, as we mentioned in my prepared remarks, I think we have enough cash. I'm confident we have enough cash and financial flexibility, access to resources to get to the key milestone next year, which is the Phase III VITAL study readout. That would be a key inflection point for us. But there's also some other key inflection points as we think about that, even before we have the MPS IIIA top line data hopefully. I hope, assuming the magnitude of effect is still there for late 2022, early '23. You've got BLA filings, BLA approval. So I think there's a really healthy pipeline of inflection points as we look forward.

是的，當然。當然，是的。是的。我的意思是，如你所知，9 月底的資產負債表上有 6700 萬美元。因此，正如我們在準備好的講話中提到的那樣，展望未來，我認為我們有足夠的現金。我相信我們有足夠的現金和財務靈活性，可以獲得資源來實現明年的關鍵里程碑，即 III 期 VITAL 研究讀數。這對我們來說將是一個關鍵的轉折點。但在我們考慮到這一點時，還有一些其他關鍵的拐點，甚至在我們有希望獲得 MPS IIIA 頂線數據之前。我希望，假設 2022 年末 23 年初的影響仍然存在。你有 BLA 文件，BLA 批准。因此，我認為在我們期待的過程中，有一個非常健康的拐點管道。

So the one that we are obviously most myopic on is getting to this Phase III EB VITAL readout in Q3 of 2022. So that's how I would answer that question. Hopefully, that's helpful.

因此，我們顯然最短視的一個是在 2022 年第三季度進行第三階段 EB VITAL 讀數。這就是我回答這個問題的方式。希望這會有所幫助。

Thank you, Ed. On the second part of your question, Mani, which is the quanta for out-licensing. It's a little premature to give a definitive answer. But as you see, there is a whole portfolio or a spectrum of different potential partners for out-licensing, and their goals can be different: some that will be interested in the platform as a whole, some that will be interested in late-stage assets where they have the ability to commercialize in certain geographies. Depending on -- and we've seen all those different shades of strategic positions of our potential partners, and we're open to all different types of arrangements. And that's all I could say right now.

謝謝你，埃德。關於你的問題的第二部分，Mani，這是向外許可的數量。現在給出明確的答案還為時過早。但正如你所見，有一個完整的投資組合或一系列不同的潛在合作夥伴進行外包，他們的目標可能不同：一些對整個平台感興趣，一些對後期感興趣他們有能力在某些地區進行商業化的資產。取決於 - 我們已經看到了我們潛在合作夥伴的所有這些不同的戰略地位，我們對所有不同類型的安排持開放態度。這就是我現在能說的。

But our platform applies to multiple therapeutic areas as well. As you know, our preclinical programs are in the ocular space. So there could be players that are specifically interested in ocular programs. And our -- the MPS IIIA and IIIB are more in the neurological, neuropsychiatric kind of marketplace, and there are specific players that are interested in those types of assets. So we are in a position to develop quanta or packets as and how these conversations ensue.

但我們的平台也適用於多個治療領域。如您所知，我們的臨床前計劃是在眼部空間中進行的。所以可能會有玩家對視覺程序特別感興趣。而我們的 MPS IIIA 和 IIIB 更多地出現在神經、神經精神病學的市場中，並且有一些特定的參與者對這些類型的資產感興趣。因此，我們有能力開發量子或數據包，以及這些對話是如何進行的。

Your next question is coming from Kristen Kluska with Cantor Fitzgerald.

您的下一個問題來自克里斯汀·克魯斯卡（Kristen Kluska）和康托·菲茨杰拉德（Cantor Fitzgerald）。

The first one I have is on EB-101. Wondering if you think this data top line readout next year could include any longer-term findings beyond the 6-month end point since some of these patients were enrolled early on ahead of the pandemic. And then could you speak to the importance of your durability data from both this trial, and then, of course, the Phase I/II trial when potentially filing for BLA given the FDA's stance and focus on the effects across cell and gene therapies and durability?

我的第一個是EB-101。想知道您是否認為明年的這一數據頂線讀數可能包括超過 6 個月終點的任何長期發現，因為其中一些患者在大流行之前就已入組。然後你能談談你的耐久性數據的重要性，從這個試驗，當然，考慮到 FDA 的立場和關注跨細胞和基因療法的影響以及耐久性，當可能申請 BLA 時的 I / II 期試驗?

Thank you, Kristen, for the question. First off, it's a very important question that you raised, the durability and the long-term benefit that we offer to patients. The regulatory requirement is a 6-month time point. So what you will see in a regulatory package is going to be 6 months from treatment, and what is the level of wound healing and the pain reduction that we see, right?

謝謝你，克里斯汀，這個問題。首先，您提出了一個非常重要的問題，即我們為患者提供的持久性和長期利益。監管要求是 6 個月的時間點。因此，您將在監管包中看到治療後的 6 個月，我們看到的傷口癒合和疼痛減輕程度如何，對嗎？

However, the long-term follow-up data that we have presented from our Phase I/II study, so far, tell us that there's a lot more value proposition than the regulatory hurdle. We have seen up to 6 years of data. And a patient that had 80% of the wounds treated at 6 years, showing 80% of the wounds showing greater than 75% closure, which is very significant, and also the pain reduction sustaining that way. So this is going to help us completely build out the value proposition and be appropriately pricing our assets and commensurate with the value that we provide to patients.

然而，到目前為止，我們從 I/II 期研究中提供的長期後續數據告訴我們，除了監管障礙之外，還有更多的價值主張。我們已經看到了長達 6 年的數據。一位患者在 6 年內治療了 80% 的傷口，顯示 80% 的傷口顯示大於 75% 的閉合，這是非常重要的，並且以這種方式持續減輕疼痛。因此，這將幫助我們完全建立價值主張，並適當地為我們的資產定價，並與我們為患者提供的價值相稱。

And to your question about whether Phase III data will also have similar, there will be some patients that have longer-term follow-up 2, 3 years out, that we will continue to publish and report on as the study continues.

對於您關於 III 期數據是否也會有類似的問題，將會有一些患者進行 2、3 年的長期隨訪，隨著研究的繼續，我們將繼續發表和報告。

What is important is to recognize what both the Phase I/II and the Phase III, the patients are being followed for a period of 15 years. So this is going to be a continuous data update over time, showing the durability of our therapies. So I hope that gives you a good sense to the full value proposition of the drug, more than just the regulatory end point that we're looking at to get the product into the market.

重要的是要認識到 I/II 期和 III 期患者的隨訪時間為 15 年。因此，隨著時間的推移，這將是一個持續的數據更新，顯示我們療法的持久性。因此，我希望這能讓您對藥物的全部價值主張有一個很好的認識，而不僅僅是我們正在考慮將產品推向市場的監管終點。

Okay, appreciate that. And then I had a question regarding the potential and exploration of strategic partnerships. So understand that your late-stage pipeline is rare disease focus and that the ophthalmology pipeline, while not disclosed, you have indicated that some of these indications are a little bit larger. So wondering if we should be thinking -- or if the company is evaluating things on a geography basis. So perhaps are there certain regions where these diseases are more impacted?

好的，感激不盡。然後我有一個關於戰略夥伴關係的潛力和探索的問題。因此，請了解您的後期管道是罕見病重點，而眼科管道雖然沒有披露，但您已經表示其中一些適應症更大一些。所以想知道我們是否應該考慮 - 或者公司是否在地理基礎上評估事物。那麼，也許在某些地區這些疾病受到的影響更大？

And then also separately, looking at the earlier pipeline, the AIM capsid library. Could you discuss some areas that could be attractive for somebody to evaluate, including perhaps how some of these capsids could address some of the limitations that are currently observed in AAV-based gene therapies?

然後也分別查看早期的管道，AIM 衣殼庫。您能否討論一些可能吸引某人評估的領域，包括這些衣殼如何解決目前在基於 AAV 的基因療法中觀察到的一些限制？

Absolutely. So there's at least 2 parts to the question, Kristen. First, let me talk about the strategic partnerships and your question about geographic prevalence of some of the diseases that we are more mature in development. We -- our goal is to have these therapies commercialized in every geography. We currently don't, for MPS IIIA as well as EB, we do not have any variations on a per population basis, the incidence levels of these diseases being very different in different geographies.

絕對地。所以這個問題至少有兩個部分，克里斯汀。首先，讓我談談戰略合作夥伴關係以及您對我們在發展中較為成熟的一些疾病的地理流行程度的問題。我們——我們的目標是讓這些療法在每個地區商業化。我們目前沒有，對於 MPS IIIA 和 EB，我們在每個人群的基礎上沒有任何差異，這些疾病的發病率水平在不同的地區非常不同。

These are genetic disorders that happen in all different parts of the world. Our initial focus for launches, of course, are U.S. and Europe focused. But our goals are completely to expand beyond that to other geographies, including Asia Pacific and everywhere there's a need. And this is where we are looking at potential strategic partners that have more experience in those more emerging kind of markets. And there is -- I mean we do know that there are -- there is interest in those types of geographic expansions where our data could be very useful.

這些是發生在世界各地的遺傳疾病。當然，我們最初的發布重點是美國和歐洲。但我們的目標是完全超越這一點，擴展到其他地區，包括亞太地區以及任何有需要的地方。這就是我們正在尋找在那些新興市場擁有更多經驗的潛在戰略合作夥伴的地方。還有——我的意思是我們確實知道——人們對那些我們的數據可能非常有用的地理擴張類型感興趣。

So the short answer is yes, but it's not based on how much prevalence there is in certain geographies. It's just based on we're going about this a little bit of sequential way.

所以簡短的回答是肯定的，但這並不是基於某些地區的流行程度。它只是基於我們將採用這種順序的方式。

The second part that you brought up is our AIM capsid library, and how that could differentiate. Part of the beauty of the AIM capsid library is the tropism. So we have knowledge of what types of capsids have a preferential tropism for different types of tissues. And that's something that's going to be very helpful in addressing some of the current challenges.

您提出的第二部分是我們的 AIM 衣殼庫，以及它如何區分。 AIM 衣殼庫的部分優點在於其向性。因此，我們知道哪些類型的衣殼對不同類型的組織具有優先趨向性。這對於解決當前的一些挑戰非常有幫助。

Because as you know, immunological responses to AAV-based therapies is a big hindrance to optimizing the therapeutic effect of our drug. By engineering capsids that can have tissue tropism, you're partly circumventing that. And this is definitely part of the value proposition that we come with our proprietary capsids, number one.

因為如您所知，對基於 AAV 的療法的免疫反應是優化我們藥物治療效果的一大障礙。通過設計具有組織趨向性的衣殼，您可以部分規避這一點。這絕對是我們的專有衣殼價值主張的一部分，第一。

The second is beyond just the AIM capsids, we are also looking at how to circumvent other types of limitations in AAV-based therapies. For example, the size of the genes that you can package. You cannot put more than 4 kilobase sites into an AAV capsid. And here is where we are developing other methodologies where you could have recombination-based. At ARVO, we presented new data on recombination-based techniques where you can have larger genes, for example ABCA4, delivered and -- to the patients. And this is something that, beyond just the capsid engineering, that we're focusing on overcoming some of the limitations of gene therapy as such. I hope that gives you some flavor as to where we're likely to be differentiated and advance our knowledge, Kristen.

第二個不僅僅是 AIM 衣殼，我們還在研究如何規避基於 AAV 的療法中的其他類型的限制。例如，您可以包裝的基因的大小。您不能將超過 4 kb 的位點放入 AAV 衣殼中。在這裡，我們正在開發其他可以基於重組的方法。在 ARVO，我們展示了基於重組技術的新數據，您可以將更大的基因（例如 ABCA4）交付給患者。除了衣殼工程之外，我們還專注於克服基因治療本身的一些限制。 Kristen，我希望這能讓您了解我們可能在哪些方面與眾不同並提升我們的知識。

There appears to be no further questions in queue at this time. I'd like to turn the floor back over to Vish for any closing remarks.

目前隊列中似乎沒有其他問題。我想把發言權轉回給 Vish 來做任何結束語。

Thank you very much. I have full conviction about the transformative value that Abeona's lead assets can deliver to patients. We're focused on our road map and making progress through disciplined execution. Our current leadership team is stronger than ever, especially with some important recent additions geared towards BLA readiness. I want to thank our shareholders and our stakeholders who have listened to this call, and we'll talk to you on the fourth quarter call. Thank you.

非常感謝。我完全相信 Abeona 的領先資產可以為患者帶來的變革價值。我們專注於我們的路線圖，並通過嚴格執行取得進展。我們目前的領導團隊比以往任何時候都更強大，尤其是最近增加了一些旨在為 BLA 做好準備的重要人員。我要感謝聽取了這次電話會議的股東和利益相關者，我們將在第四季度電話會議上與您交談。謝謝你。

Thank you, ladies and gentlemen. 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.

謝謝你們，女士們，先生們。這確實結束了今天的電話會議。你可以在這個時候斷開你的電話線，並有一個美好的一天。感謝您的參與。