Precigen Inc (PGEN) 2023 Q2 法說會逐字稿

Good morning, and welcome to the Precigen Second Quarter and First Half 2023 Financial Results and Business Update Call. Please note, this event is being recorded. I would like to turn the conference over to Steve Harasym, Vice President of Investor Relations.

早上好，歡迎參加 Precigen 2023 年第二季度和上半年財務業績和業務更新電話會議。請注意，此事件正在被記錄。我想將會議交給投資者關係副總裁 Steve Harasym。

Thank you, operator, and thank you for joining us today. With me are Dr. Helen Sabzevari, President and CEO of Precigen; and Harry Thomasian, our CFO. Helen will provide details on today's releases and an update on our portfolio. After which Harry will review our second quarter and first half 2023 financial results.

謝謝您，接線員，也感謝您今天加入我們。和我在一起的還有 Precigen 總裁兼首席執行官 Helen Sabzevari 博士；以及我們的首席財務官 Harry Thomasian。海倫將提供今天發布的詳細信息以及我們產品組合的更新。之後 Harry 將回顧我們 2023 年第二季度和上半年的財務業績。

Following our prepared remarks, we will open the call to Q&A. Before we begin, let me briefly review our forward-looking statement. During today's call, we will make various forward-looking statements. Investors are cautioned that our forward-looking statements are based on current expectations and are subject to risks and uncertainties that could cause actual results or outcomes to differ materially from those indicated by our forward-looking statements.

在我們準備好的發言之後，我們將開始問答環節。在開始之前，讓我簡要回顧一下我們的前瞻性聲明。在今天的電話會議中，我們將做出各種前瞻性聲明。請投資者註意，我們的前瞻性陳述基於當前的預期，並受到風險和不確定性的影響，這些風險和不確定性可能導致實際結果或結果與我們的前瞻性陳述所示的結果存在重大差異。

Please read the safe harbor statement contained in this presentation as well as risk factors contained in Precigen's most recent SEC filings for a more complete discussion of these risks and uncertainties. I will now turn the call over to Dr. Sabzevari. Helen?

請閱讀本演示文稿中包含的安全港聲明以及 Precigen 最近向 SEC 提交的文件中包含的風險因素，以更完整地討論這些風險和不確定性。我現在將把電話轉給 Sabzevari 博士。海倫？

Thank you, Steve, and thanks to all of you for joining us today. Today is a very exciting day for Precigen. And I'd like to provide you with the significant progress that we have made in the first half of this year. I will discuss 2 major topics today.

謝謝你，史蒂夫，也感謝大家今天加入我們。今天對於 Precigen 來說是非常激動人心的一天。我想向大家介紹我們今年上半年取得的重大進展。今天我將討論2個主要話題。

One is the positive regulatory developments, which we announced this morning for our lead program, PRGN-2012 in an orphan rare disease setting in RRP. And secondly, the portfolio prioritization to focus our efforts to accelerate the development of PRGN-2012 towards commercialization, while we continue advancement of our other key programs and extend our cash runways to 2025.

一是積極的監管進展，我們今天早上宣布了我們的主導項目 PRGN-2012 在 RRP 孤兒罕見病環境中的進展。其次，投資組合的優先順序是集中精力加速 PRGN-2012 的商業化開發，同時繼續推進其他關鍵項目並將現金跑道延長至 2025 年。

With that in mind, let's go to Slide #4. We have been, as you know, active in discussions with the FDA to align on a rapid regulatory path for PRGN-2012, given the high unmet need in RRP patients. but there is no approved drugs, and the only treatment options remains is recurring surgeries that are major burden for these patients. Both physically health-wise, economically.

考慮到這一點，讓我們轉到幻燈片 #4。如您所知，鑑於 RRP 患者的大量未滿足需求，我們一直在積極與 FDA 進行討論，以協調 PRGN-2012 的快速監管路徑。但目前還沒有批准的藥物，唯一的治療選擇是反复手術，這對這些患者來說是主要負擔。無論是身體健康還是經濟方面。

We are pleased to announce that the FDA has confirmed that the ongoing single-arm Phase I/II study will serve as the pivotal study to support BLA submission for an accelerated approval. At the same time, there is no additional randomized control study will be required to support accelerated approval. And we have agreement with the FDA on the endpoints from the ongoing Phase I/II study to support the BLA submission, which includes the complete response rate which is the percentage of patients with no surgical intervention required during the 12 months following the treatment. And an immunological surrogate marker for HPV-specific T cell responses, which, by the way, has been already implemented both in Phase I and Phase II.

我們很高興地宣布，FDA 已確認正在進行的單臂 I/II 期研究將作為支持 BLA 提交加速批准的關鍵研究。同時，不需要額外的隨機對照研究來支持加速批准。我們與 FDA 就正在進行的 I/II 期研究的終點達成一致，以支持 BLA 提交，其中包括完全緩解率，即治療後 12 個月內不需要手術干預的患者百分比。還有 HPV 特異性 T 細胞反應的免疫替代標記，順便說一句，該標記已在 I 期和 II 期中實施。

Precigen also has reached an agreement with the FDA that a single on confirmatory study needs to be initiated, but not completed, and that's very important prior to the submission of the BLA. At the same token, we are very thankful to the FDA, and they have even encouraged us to add and evaluate the inclusion of exploratory arm to the confirmatory study for the repeat dosing for a noncomplete responders to potentially expand the label, and we are very excited about that.

Precigen 還與 FDA 達成協議，需要啟動一項驗證性研究，但尚未完成，這在提交 BLA 之前非常重要。同樣，我們非常感謝FDA，他們甚至鼓勵我們在驗證性研究中添加和評估探索性組的納入，以對不完全反應者進行重複給藥，以潛在地擴大標籤範圍，我們非常對此感到興奮。

The ability of the ongoing Phase I/II to serve as a pivotal for accelerated approval can significantly reduce the developmental time to licensure. And you can imagine what that does that mean for our patients because now with the randomized Phase IIIs are not required here, and we can move much faster, especially as I will go through the path for the licensure for us.

正在進行的第一階段/第二階段作為加速批准的關鍵的能力可以顯著縮短獲得許可的開發時間。你可以想像這對我們的患者意味著什麼，因為現在不需要隨機的 III 期臨床試驗，我們可以更快地行動，特別是當我將為我們完成獲得許可的過程時。

To further expedite the development of PRGN-2012, we are preparing Precigen's in-house gene therapy manufacturing facility to produce drug substance for commercial launch. Why are we doing that? Simply, this allows us to maintain control of manufacturing in-house, we leverage our internal expertise and we've reduced the cost and time lines due to reduced reliance on a contract manufacturers.

為了進一步加快 PRGN-2012 的開發，我們正在準備 Precigen 的內部基因治療生產設施，以生產用於商業上市的原料藥。我們為什麼要這麼做？簡而言之，這使我們能夠保持對內部製造的控制，我們利用我們的內部專業知識，並且由於減少了對合同製造商的依賴而降低了成本和時間線。

If we look at what has happened on the -- take a moment to recognize the current status of the ongoing single-arm Phase I/II study is, as you have seen and we have reported the data, the Phase I has been completed, and the enrollment and dosing in the Phase II portion of this study is also completed.

如果我們看看發生了什麼——花點時間認識一下正在進行的單臂 I/II 期研究的當前狀態，正如您所看到的，我們已經報告了數據，I 期已經完成，本研究二期部分的入組和給藥也已完成。

Phase II patients follow-up data collection and the completion is anticipated by the second quarter of 2024. The Phase I data that we presented in January has shown 50% of our patients that they were treated at the dose level 2, have a complete response. And that means they needed no further surgery in their follow-up of 12 months.

II 期患者隨訪數據收集預計將於 2024 年第二季度完成。我們 1 月份提供的 I 期數據顯示，50% 的患者接受了 2 級劑量治療，獲得了完全緩解。這意味著他們在 12 個月的隨訪中不需要進一步手術。

And today, we are pleased to report that all complete responders from the Phase I they remain surgery-free with a minimum follow-up of 18 months and the responses are still ongoing. We are very pleased and excited about the promise of the PRGN-2012 for RRP patients who received numerous surgical procedures in absence of therapeutic in their lifetime that can be very harmful, financially burdensome to the patients and overall, the health care system.

今天，我們很高興地向大家報告，第一階段的所有完全緩解者在至少 18 個月的隨訪期內均無需接受手術，並且緩解仍在進行中。我們對 PRGN-2012 對 RRP 患者的承諾感到非常高興和興奮，這些患者一生中在缺乏治療的情況下接受了多次外科手術，這可能對患者和整個醫療保健系統造成非常有害的經濟負擔。

Getting this therapy as quickly as possible to the patients who need to relieve is our highest priority, obviously. I'd like to acknowledge at this point the tremendous effort of Precigen team and our investigators and collaborators to move the PRGN-2012 from discovery phase to recognition as a pivotal trial on a path for an accelerated approval in about 3 years, including the pandemic years.

顯然，盡快為需要緩解症狀的患者提供這種治療是我們的首要任務。此時此刻，我要感謝 Precigen 團隊以及我們的研究人員和合作者付出的巨大努力，將 PRGN-2012 從發現階段轉變為被認可的關鍵試驗，從而在大約 3 年內加速批准，包括大流行年。

With that in mind, if we look at the Slide #5, what I would like to highlight is what differentiates PRGN-2012 and the AdenoVerse platform from the rest. And we have -- the market and the KOL research. And we have listened to what our KOLs have been telling us that what is unique and differentiated about this molecule and this platform.

考慮到這一點，如果我們看幻燈片 #5，我想強調的是 PRGN-2012 和 AdenoVerse 平台與其他平台的區別。我們有市場和 KOL 研究。我們聽取了 KOL 的意見，告訴我們這個分子和這個平台的獨特之處和差異化之處。

As you can see in this slide, 1 thing that really stands out. It's the mechanism of action that has been seen as very promising. The physicians describe the PRGN-2012 mechanism of action as promising. And particularly, they are impressed with this molecule to generate a T cell responses that specifically targets HPV 6 and HPV 11 viral site CAR which is the root cause of RRP. And this is what is important about this therapy because it goes to the root of the problem, which is the infection in the patients that allows this recurrence of the papillomas in a very, very dangerous regions on vocal cords and trachea and even in the lungs.

正如您在這張幻燈片中看到的，有一件事情非常引人注目。這種作用機制被認為是非常有前途的。醫生們認為 PRGN-2012 的作用機制很有前景。特別是，他們對這種分子產生的 T 細胞反應印象深刻，該反應專門針對 HPV 6 和 HPV 11 病毒位點 CAR，這是 RRP 的根本原因。這就是這種療法的重要之處，因為它觸及了問題的根源，即患者體內的感染導致乳頭狀瘤在聲帶和氣管甚至肺部非常非常危險的區域復發。 。

Secondly, there is a very favorable safety data. We have shown some of the safety data from Phase I. And as you can see, and it was mentioned, the safety is the Grade 1 and Grade 2, it's flu-like vaccination. And this is extremely favorable, obviously, for the patients and there are physicians, they appreciate that tremendously. And especially that some of the patients in the future will be pediatrics and this clearly is an important factor.

其次，有非常有利的安全數據。我們已經展示了第一階段的一些安全性數據。正如你所看到的，前面提到過，安全性是1級和2級，它是類似流感的疫苗。顯然，這對於患者和醫生來說是極其有利的，他們對此非常感激。尤其是未來的一些患者將是兒科患者，這顯然是一個重要因素。

So -- and finally, the reduction in the number of surgeries. I think we have heard from our patients continuously, that's even reduction in 1 less surgery, it's fundamental to them. And now having complete responders that over 12 months and ongoing they do not require any surgery. And by the way, we have been in the most severe patient population, which they require more than 3 surgeries per year. And being able to accomplish that. So this is quite exciting, and we are really happy for the patients.

最後，手術數量的減少。我想我們不斷地收到患者的來信，甚至減少 1 次手術，這對他們來說至關重要。現在已有完全緩解者，超過 12 個月且持續，不需要任何手術。順便說一句，我們屬於最嚴重的患者群體，他們每年需要進行 3 次以上的手術。並且能夠做到這一點。所以這非常令人興奮，我們真的為患者感到高興。

And finally, this is a platform that with a very attractive route of administration. What does that mean? These vaccines have been given subcutaneously to the patients. You can imagine now the patients that they have to go continuously under surgery, now they can go to their physician basically office and receive a subcu injection very similar to a flu injection. And this is quite an accomplishment and the differentiation.

最後，這是一個具有非常有吸引力的管理途徑的平台。這意味著什麼？這些疫苗已皮下注射給患者。你可以想像現在患者必須連續接受手術，現在他們可以去他們的醫生辦公室接受與流感注射非常相似的 subcu 注射。這是一項相當大的成就和差異化。

So with that in mind, if we look at the Slide #6 and on top of this slide, what you see is the scenario that we are describing in regard to the patient. You are looking at the normal basically vocal cord throat of a normal individual. And then on the right-hand side, you are looking at what the RRP patient suffers from.

因此，考慮到這一點，如果我們查看幻燈片 #6 以及這張幻燈片的頂部，您會看到我們正在描述的有關患者的場景。您正在觀察正常人的正常聲帶喉嚨。然後在右側，您會看到 RRP 患者所遭受的痛苦。

And these patients are dependent on a surgery only continuously to remove these benign tumors. Just to be able to talk or just to be able to breathe. Can you imagine having a child that you have to do this continuously on a monthly basis take that for this kind of surgery.

這些患者只能持續依靠手術來切除這些良性腫瘤。只是為了能夠說話或只是為了能夠呼吸。你能想像有一個孩子，你必須每月連續做這樣的手術嗎？

Obviously, there are no approved therapeutics for the RRP, and this is the importance of the decision of FDA that allowing us to go for accelerated approval, which I'm thankful to the FDA in general for recognizing the need of the patients and also the innovative studies that can be addressing that need.

顯然，RRP 還沒有批准的治療方法，這就是 FDA 決定允許我們加速批准的重要性，我總體上感謝 FDA 認識到患者的需求，也感謝 FDA 的認可。可以滿足這一需求的創新研究。

As we have said, the current standard of care is repeated surgeries, and this does not affect the underlying root of this indication or this disease. Due to the chronic nature of the disease, RRP patients can undergo hundreds of surgeries during their lifetime. And this repeated surgeries, as I mentioned before, can worsen the condition of RRP as it can increase the spread of HPV virus. And can result in a significant comorbidity, including loss of vocal functions.

正如我們所說，目前的護理標準是重複手術，這不會影響這種適應症或這種疾病的根本根源。由於該疾病的慢性性質，RRP 患者一生中可能會接受數百次手術。正如我之前提到的，這種重複的手術會使 RRP 的狀況惡化，因為它會增加 HPV 病毒的傳播。並可能導致嚴重的合併症，包括發聲功能喪失。

There is a significant economic and the quality of life burden of this disease throughout the lifetime of RRP patients. And as you can see on the slide, there are -- and these are approximate numbers that in the U.S., there are 10,000, at least cases of adult and 6,000 of Juvenile and in ex U.S., there is a much larger population upwards of 60 and we really don't know the exact number of juveniles, and these are parts of the research studies that we will be doing as part of the projected market for the U.S. and ex U.S.

在 RRP 患者的一生中，這種疾病會造成重大的經濟和生活質量負擔。正如您在幻燈片上看到的那樣，這些是大約數字，在美國，至少有 10,000 例成人病例和 6,000 例青少年病例，在美國以外，人口數量要多得多，超過 60 例我們確實不知道青少年的確切數量，這些是我們將進行的研究的一部分，作為美國和美國以外的預計市場的一部分。

So with the potential now to accelerate towards becoming a commercial stage company and considering the challenging capital markets at this time. We believe that we should be laser focused on expediting the 2012 path to commercialization. By doing this, we believe that we can best position Precigen for near-term success in this current environment.

因此，現在有潛力加速成為一家商業階段的公司，並考慮到目前充滿挑戰的資本市場。我們認為，我們應該集中精力加快 2012 年的商業化進程。通過這樣做，我們相信我們可以為 Precigen 在當前環境下取得近期成功提供最佳定位。

On Slide #7, we are highlighting some of the actions that we are taking to realign our resources and pipeline. To realize a substantial savings, especially with respect to external CRO spending and the SG&A costs, compared to the original budget estimates.

在幻燈片 #7 上，我們重點介紹了我們為重新調整資源和渠道而採取的一些行動。與最初的預算估算相比，實現大幅節省，特別是在外部 CRO 支出和 SG&A 成本方面。

Harry will further expand on the cost saving measures we are taking over the past years and the current year. But just to mention what we are now focus is not only to accelerate the path for PRGN-2012 without damaging the very important other programs that we have, but also expanding our cash runway, which allows us to get to the readouts specifically and beyond by various needs.

哈里將進一步闡述我們過去幾年和今年採取的成本節約措施。但順便提一下，我們現在的重點不僅是在不損害我們擁有的非常重要的其他計劃的情況下加快PRGN-2012 的進程，而且還要擴大我們的現金跑道，這使我們能夠通過以下方式具體地獲得讀數：各種需求。

So let's go through some of these actions. We are -- first of all, reducing the cost of the clinical CRO score outside reducing the number of the sites that will be involved in various programs, as I will go through them. And definitely, we have been reducing our SG&A cost and continue to do so and Harry will highlight that.

讓我們來看看其中的一些操作。首先，除了減少參與各種項目的站點數量之外，我們還降低了臨床 CRO 評分的成本，正如我將詳細介紹的那樣。當然，我們一直在降低 SG&A 成本，並將繼續這樣做，Harry 會強調這一點。

At the same token, we are redirecting our R&D team to focus on CMC and translational clinical research activities. We have a highly productive and cross-trained teams which currently, as we speak, are involved in shifting focus in order to address the CMCN translational -- clinical translational work required to support PRGN-2012 to approval.

同樣，我們正在調整研發團隊的重點，專注於 CMC 和轉化臨床研究活動。我們擁有一支高效、經過交叉培訓的團隊，目前，正如我們所說，他們正在轉移重點，以解決 CMCN 轉化——支持 PRGN-2012 獲得批准所需的臨床轉化工作。

What does this do for us? First of all, there is no reduction in our R&D force. Secondly, this allows us to hold on to our talent without any, again, I stress that head count reduction. Furthermore, we will save time and money in trying to adjust the path. And this is very, very important for the very agile time lines that we have for the submission of the BLA.

這對我們有什麼作用？首先，我們的研發力量沒有減少。其次，這使我們能夠在沒有任何人才的情況下保留我們的人才，我再次強調減少人員數量。此外，我們將節省嘗試調整路徑的時間和金錢。這對於我們提交 BLA 的非常靈活的時間表來說非常非常重要。

In regard to our PRGN-3006 UltraCAR-T program, this remains a high priority for us. As you know, we have shown a positive data at ASH almost 30% objective response rate in AML patients that they have no other therapy in front of them, and we have received a fast track designation from FDA.

對於我們的 PRGN-3006 UltraCAR-T 項目，這仍然是我們的首要任務。如您所知，我們在 ASH 中顯示了積極的數據，AML 患者的客觀緩解率接近 30%，他們面前沒有其他治療方法，並且我們已獲得 FDA 的快速通道指定。

With that in view, this is extremely important program. We plan to maintain our 2 very productive and active sites, Moffitt and Mayo for the ongoing Phase I study for now. We plan as well to present interim Phase Ib data in 2024.

考慮到這一點，這是一個極其重要的計劃。我們計劃維持莫菲特和梅奧這兩個非常高效和活躍的研究中心，以進行目前正在進行的第一階段研究。我們還計劃在 2024 年提供 Ib 期中期數據。

There will be no initiation of new sites in the remaining part of the 2023, and we provide further updates in upcoming quarterly calls. We also have planned to give additional clarity on a site expansion in 2024. In regard to PRGN-3005, similarly, we continue our Phase Ib study enrollment at (inaudible) and as part of the cost saving measures, we plan to activate a second site under our CRADA with NCI to continue the advancement of the program without major clinical or CRO cost to us. And that's very, very important for our patients as well as for this program, which is very unique.

2023 年剩餘時間內不會啟動新站點，我們將在即將舉行的季度電話會議中提供進一步的更新。我們還計劃在 2024 年進一步明確站點擴展。同樣，對於 PRGN-3005，我們繼續在（聽不清）進行 Ib 期研究註冊，作為成本節約措施的一部分，我們計劃啟動第二個我們與NCI 合作建立了CRADA 網站，以繼續推進該計劃，而不會給我們帶來重大臨床或CRO 成本。這對於我們的患者以及這個非常獨特的項目來說都非常非常重要。

In regard to PRGN-3007, obviously, that program is an investigator initiated Phase I at Moffitt, which is ongoing and continues to move. Now in regard to what we mentioned for PRGN-2009, especially in cervical cancer, which is, by the way, on the same platform AdenoVerse platform as PRGN-2012. We are excited to announce that the plan is to activate the NCI side first, and we leverage our CRADA for the Phase II study to reduce the clinical cost for this year, and we will be giving update in early 2024 in regard to the other sites.

至於 PRGN-3007，顯然，該項目是由研究者在莫菲特發起的第一階段，該項目正在進行中並繼續推進。現在關於我們提到的 PRGN-2009，特別是宮頸癌，順便說一句，它與 PRGN-2012 位於同一平台 AdenoVerse 平台上。我們很高興地宣布，計劃首先激活 NCI 方面，我們利用 CRADA 進行 II 期研究，以降低今年的臨床成本，我們將在 2024 年初提供有關其他站點的更新。

And also, and very important. We have been in discussions with a number of parties for non-dilutive funding opportunities, which can even further extend our runway from 2025. We have begun, first of all, the process of divesting Examplar and that is important -- and I know that Harry will speak to as we divested the trends over and that has allowed us to completely pay off our convertible notes.

而且，而且非常重要。我們一直在與多方討論非稀釋性融資機會，這甚至可以從 2025 年起進一步延長我們的跑道。首先，我們已經開始剝離 Examplar 的過程，這很重要 - 我知道哈利將在我們剝離趨勢時發表講話，這使我們能夠完全還清我們的可轉換票據。

We are also in discussion and very exciting discussion in regard to our AG019 for T1D program with a number of parties, and we are planning to give our investors an update in the upcoming quarters. Furthermore, there are ongoing discussions on our UltraCAR-T programs for partnerships, and we will be addressing that.

我們還在與多方就 AG019 for T1D 計劃進行非常令人興奮的討論，我們計劃在接下來的幾個季度向投資者提供最新情況。此外，我們正在就 UltraCAR-T 合作夥伴計劃進行討論，我們將解決這個問題。

And all of this are the means of non-diluted funding opportunities that we have, along with the cash runway that currently we have to -- up to 2025 and we believe that these nondilutive fundings can extend that cash runway much further. So with that exciting update, I'm going to now turn the call over to our CFO, Harry, to discuss the financial updates and our strategy. Harry?

所有這些都是我們擁有的非稀釋融資機會的手段，以及我們目前必須擁有的現金跑道——到 2025 年，我們相信這些非稀釋資金可以進一步延長現金跑道。因此，有了這個令人興奮的更新，我現在將把電話轉給我們的首席財務官哈利，討論財務更新和我們的戰略。哈利？

Thank you, Helen. And also thank you to those participating on the call today. I'm going to speak from the notes of the information on Slide 8, just to focus those on the call. This is a momentous day for Precigen, as Helen has said earlier, combined with the announced regulatory path for PRGN-2012, we've positioned our balance sheet to provide us the cash runway to successfully transition toward a commercial stage company.

謝謝你，海倫。還要感謝今天參加電話會議的人員。我將根據幻燈片 8 上的信息註釋進行發言，只是為了將這些內容集中在電話會議上。正如Helen 早些時候所說，這對於Precigen 來說是重要的一天，結合已宣布的PRGN-2012 監管路徑，我們已經定位了我們的資產負債表，為我們提供了成功轉型為商業階段公司的現金跑道。

As you will see in our financial statements included in our 10-Q, which was filed with the SEC earlier this morning, we now retired all of our convertible notes. The retirement of these notes will save us $7 million per year in cash interest costs going forward. In addition, through the efficient early retirement of a significant portion of our convertible notes, we were able to save approximately $8.4 million in cash over the past 10 months.

正如您將在今天早上早些時候向美國證券交易委員會提交的 10-Q 財務報表中看到的那樣，我們現在已註銷所有可轉換票據。這些票據的退役將在未來每年節省 700 萬美元的現金利息成本。此外，通過高效地提前報廢大部分可轉換票據，我們在過去 10 個月中節省了約 840 萬美元的現金。

Turning now to a discussion around SG&A. Since I last -- since I started with Precigen in October of 2021, we've been laser-focused on rightsizing our SG&A costs for the company we are today. And I'm pleased to announce that on a year-to-date basis, compared to the first 6 months of 2022, our SG&A costs have decreased $5.4 million or 21%.

現在轉向圍繞SG&A 的討論。自從我上次在 2021 年 10 月加入 Precigen 以來，我們一直專注於調整我們今天的公司的 SG&A 成本。我很高興地宣布，與 2022 年前 6 個月相比，今年迄今，我們的 SG&A 成本減少了 540 萬美元，即 21%。

Just looking at the second quarter of 2023 compared to the same period last year, SG&A costs have decreased $3.4 million or 27%, showing a positive trend over the first quarter. A portion of these savings were due to past headcount reductions, which are now being realized.

僅看 2023 年第二季度，與去年同期相比，SG&A 成本就減少了 340 萬美元，即 27%，與第一季度相比呈現出積極的趨勢。這些節省的一部分是由於過去的裁員，現在正在實現。

We finished the quarter with $95.6 million in cash, cash equivalents and short and long-term investments, providing a basis for a strong forward-looking cash runway. Taking into account the reprioritization of our pipeline as Helen has laid out, the elimination of our convertible notes and continued focus on reducing SG&A expenses, we are now providing guidance on our cash runway into 2025, as Helen has previously mentioned.

本季度結束時，我們擁有 9560 萬美元的現金、現金等價物以及短期和長期投資，為強大的前瞻性現金跑道奠定了基礎。考慮到 Helen 所規劃的管道優先順序調整、取消可轉換票據以及繼續專注於減少 SG&A 費用，正如 Helen 之前提到的，我們現在正在為 2025 年的現金跑道提供指導。

This extended cash runway is important for our shareholders as it gives us a runway well beyond the pivotal Phase II data readout of PRGN-2012 in 2024 and provides us with substantial amount of time to obtain additional funding via nondilutive methods. I will now turn the call over to the operator for Q&A. Pete?

這條延長的現金跑道對我們的股東很重要，因為它為我們提供了一條遠遠超出2024 年PRGN-2012 關鍵第二階段數據讀出的跑道，並為我們提供了大量時間通過非稀釋方法獲得額外資金。我現在將把電話轉給接線員進行問答。皮特？

(Operator Instructions) And the first question comes from Jason Butler with JMP Securities.

（操作員說明）第一個問題來自 JMP 證券的 Jason Butler。

Congrats on the progress. A couple on PRGN-2012. Just was there any discussion with FDA about the magnitude of benefit and a complete response rate you would need to show in the Phase II portion to support accelerated approval and then can you just remind us what the patient population baseline characteristics in the Phase II portion look like versus Phase I? And then I have a follow-up.

祝賀取得的進展。 PRGN-2012 上的一對夫婦。是否與 FDA 討論過您需要在 II 期部分中顯示的獲益程度和完整反應率以支持加速批准，然後您能否提醒我們 II 期部分中的患者群體基線特徵是什麼樣的就像第一階段一樣？然後我有一個後續行動。

Sure. Thank you, Jason. So in regard, obviously, we have had discussions in regard with complete responses. And we are happy that the FDA has agreed with our endpoints, as I mentioned, as far as the complete responders with a follow-up of 12 months. And the current design of a combination of a Phase I, Phase II data for being considered as pivotal for accelerated approval.

當然。謝謝你，傑森。因此，顯然，我們已經就完整的答復進行了討論。我們很高興 FDA 同意我們的終點，正如我提到的，就完全緩解者而言，並進行了 12 個月的隨訪。而目前設計的一期、二期數據的組合被認為是加速審批的關鍵。

One of the things that we are very, very thankful and grateful to the FDA leadership is the fact that recognition that our Phase II is the exact same design as our Phase I in the same patient population, which are basically minimum of 3 surgeries and above. And both of Phase I and II have enrolled patients with the same characteristics.

我們非常非常感謝 FDA 領導層的一件事是，我們認識到我們的 II 期試驗與 I 期試驗在相同患者群體中的設計完全相同，基本上至少進行 3 次及以上手術。 I期和II期均招募了具有相同特徵的患者。

We have the same endpoints. And this is part of the reason that the FDA also has confirmed that we can combine the results from our dose level 2 of Phase I and the Phase II, which is all dose level 2 together. Also, what is also very exciting and in part of the discussions that we have had with the FDA the possibility to have additional on 1 dose are not necessarily part of the confirmatory, it can be additional that we can expand the label by going to, first of all, patients that they have less than 3 surgeries, obviously, as little as 1 surgery even per year and also for repeat dosing.

我們有相同的端點。這也是 FDA 也確認我們可以將第一階段和第二階段的劑量水平 2 的結果結合起來的部分原因，即所有劑量水平 2 在一起。此外，非常令人興奮的是，在我們與 FDA 進行的部分討論中，增加 1 劑劑量的可能性並不一定是確認的一部分，我們還可以通過以下方式擴展標籤：首先，患者的手術次數少於3 次，顯然，即使每年也只有1 次手術，而且還需要重複給藥。

One thing that we clearly showed in our data presentation in January, we have the overall 83% response rate in this patient population. 50% of our patients had the complete responses and 33% of our patients reduced the number of surgeries. And FDA definitely recognizes the mechanism of action here and the value of the immunological enhancement of the T-cell against the HPV, and has actually encouraged us to have another arm added that we can address those partial responders by repeat dosing, which we are very thankful for that.

我們在 1 月份的數據演示中清楚地表明了一件事，我們在該患者群體中的總體緩解率為 83%。 50% 的患者獲得完全緩解，33% 的患者減少了手術次數。 FDA 肯定認識到這裡的作用機制以及 T 細胞針對 HPV 的免疫增強的價值，並且實際上鼓勵我們添加另一條手臂，我們可以通過重複給藥來解決那些部分反應者的問題，我們非常希望這樣做。對此表示感謝。

And I think it's excellent for the future expansion of the label of this drug product. So yes, we have had discussion and yes we have the agreement. And by the way, as I mentioned, and I will mention again, the end points for a Phase I and Phase II and what we have confirmed with the FDA are the same end points.

我認為這對於該藥品標籤的未來擴展非常有用。所以，是的，我們進行了討論，並且達成了協議。順便說一句，正如我提到的，我將再次提到，第一階段和第二階段的終點與我們向 FDA 確認的終點是相同的。

Great. And then how should we think about repeat dosing in terms of how the timing after the first dose. Would you wait as long as 12 months? Or could you actually give a second dose earlier given that in some of your complete responses, at least you were seeing it within the 6- to 12-week time frame?

偉大的。然後我們應該如何考慮第一次給藥後的重複給藥時間。你願意等12個月嗎？或者考慮到在您的一些完整反應中，至少您在 6 至 12 週的時間範圍內看到了它，您實際上可以提前註射第二劑嗎？

Yes. Excellent question. Definitely, this is something that currently we are discussing with our investigators for this. As you can imagine, the ones that they are depending on the number of the surgeries. If patients are not complete to responders, obviously, they might, after finishing the course, which, by the way, the course of the treatment here is for vaccination for treatment.

是的。很好的問題。當然，這是我們目前正在與我們的調查人員討論的事情。正如您可以想像的那樣，它們取決於手術的數量。如果患者對反應不完全，顯然，他們可能會在完成療程後，順便說一下，這裡的治療過程是疫苗接種治療。

And once that is finished, you can imagine if the patient requires a surgery 2 months later or so, then this is something that we can, obviously, it's not a complete responder, and it will be at this point is considered partial responder or a nonresponder.

一旦完成，你可以想像如果病人在2個月左右之後需要手術，那麼這是我們可以做的事情，顯然，它不是一個完全的反應者，並且在這一點上它會被認為是部分反應者或一個無反應者。

And with that, we can design various aspects. And then we can also look at the number of different patient population. This is all in discussions with our investigators. And obviously, as we design those arms, we will be going back to the FDA and also seek further guidance through our breakthrough designation, which is extremely valuable and important to us because it allows us to have a continuous dialogue in a very rapid fashion with the FDA a number of things, and this would be part of it.

這樣，我們就可以設計各個方面。然後我們還可以看看不同患者群體的數量。這一切都在與我們的調查人員討論中。顯然，當我們設計這些武器時，我們將回到 FDA 並通過我們的突破性指定尋求進一步的指導，這對我們來說非常有價值和重要，因為它使我們能夠以非常快速的方式與FDA 做了很多事情，這將是其中的一部分。

So we are looking forward to that. But then again, I want to stress, this is not part of the confirmatory. This is optional for us, and it's actually -- it's encouraging that the FDA sees the positive results of this that would like us to and encourages us to even go for an extended repeat dosing.

所以我們對此充滿期待。但我想再次強調，這不是確認的一部分。這對我們來說是可選的，實際上，令人鼓舞的是 FDA 看到了這一積極結果，希望我們這樣做，甚至鼓勵我們延長重複給藥時間。

And the next question comes from Jennifer Kim with Cantor Fitzgerald.

下一個問題來自詹妮弗·金和坎托·菲茨杰拉德。

And congrats on a lot of good progress this quarter, especially with 2012. Maybe to start off on 2012, is there a way we should think about the time line between the positive phase or if there's positive Phase II data in the second quarter starting the confirmatory study and then BLA submission. And I know you just said that the exploratory arms aren't required for BLA submission, but would you want to submit something on that point in conjunction with the submission? Or what is your thinking currently? And I have a few more after.

祝賀本季度取得了很多良好進展，尤其是 2012 年。也許從 2012 年開始，我們是否應該考慮積極階段之間的時間線，或者第二季度是否有積極的第二階段數據開始驗證性研究，然後提交BLA。我知道您剛才說過 BLA 提交不需要探索性武器，但是您想在提交的同時提交有關這一點的內容嗎？或者說你目前的想法是什麼？之後我還有一些。

Yes. Obviously, we are laser focused first on getting our -- all of the ducks in a row and moving towards the BLA submission. As you know, and we have mentioned and that's why it's one of the exciting thought. The Phase I/II their single arm is an open label, it's not randomized. And as the data comes in, we have the data and clearly, we can assort the preparation.

是的。顯然，我們首先專注於讓所有的事情都井然有序，並向 BLA 提交邁進。如您所知，我們已經提到過，這就是為什麼它是令人興奮的想法之一。他們的單臂 I/II 期是開放標籤，不是隨機的。隨著數據的到來，我們有了數據，並且顯然我們可以對準備工作進行分類。

We also have a plan through our breakthrough designation to move and ask for a rolling BLA, and this is part of our strategy so further rapid. And finally, the last is as we mentioned, our Phase II follow-up will be done by the second quarter of 2024.

我們還制定了一項計劃，通過我們的突破性指定來推動並要求滾動 BLA，這是我們進一步快速戰略的一部分。最後，正如我們提到的，我們的第二階段後續工作將在 2024 年第二季度完成。

So we have all the intention to be prepared and move as fast as we can for the submission of our BLA. In regard to the confirmatory trial, clearly our confirmatory trial and part of the agreement is going to be, again, a single-arm trial, very similar to what we have done and that has to be just initiated, and we are already in the process of that.

因此，我們全力做好準備並儘快提交 BLA。關於確認性試驗，顯然我們的確認性試驗和協議的一部分將再次成為單臂試驗，與我們所做的非常相似，而且必須剛剛啟動，而且我們已經處於的過程。

As you can imagine, there is really not that much discussion around the design of this or what needs to be done. As far as the on -- for the extension of the label and inclusion of the patients with the lower burden of the disease or for the repeat dosing, this is something that currently we are discussing and of the design.

正如您可以想像的那樣，關於此設計或需要做什麼的討論實際上並沒有太多。至於標籤的擴展和納入疾病負擔較低的患者或重複給藥，這是我們目前正在討論和設計的事情。

Clearly, we will see how that can be done. But the first priority for us is to put the confirmatory in, initiate that as we submit the BLA because it's every -- intention for us to submit the BLA, as soon as possible as we know that these patients have no other options, and we are looking forward to get this to the commercial path as soon as possible.

顯然，我們將看看如何做到這一點。但我們的首要任務是在我們提交 BLA 時開始確認，因為我們的目的是盡快提交 BLA，因為我們知道這些患者沒有其他選擇，而且我們期待盡快將其推向商業化道路。

Okay. Wonderful. And as you look at the 18-month follow-up data and these complete responders and you're considering the ability for redosing, how does all of that play into your current thinking about pricing?

好的。精彩的。當您查看 18 個月的隨訪數據和這些完整的響應者並考慮重做的能力時，所有這些對您當前的定價想法有何影響？

So yes, we are receiving the data, and we see the data as it goes, number one, since there are still complete responders and they are in response, they have not required any redosing. So obviously, that's very exciting, and we are very, very happy for the patients.

所以，是的，我們正在接收數據，並且我們會看到數據的變化，第一，因為仍然有完整的響應者並且他們正在響應，所以他們不需要任何重做。顯然，這非常令人興奮，我們為患者感到非常非常高興。

In regard to the patients that are partial responders, and we are designing the arm to address the repeat dosing, this is something that we will be addressing and we will report on what the design would be in the upcoming months. And we will further discuss about the market and pricing at that point.

對於部分反應的患者，我們正在設計手臂來解決重複給藥問題，這是我們將要解決的問題，我們將在未來幾個月內報告設計內容。屆時我們將進一步討論市場和定價。

Okay. Great. And my last question, just on your discussions with parties for nondilutive opportunities, I think, 2 that you -- or 2 focuses that you mentioned were AG019 and then the UltraCAR-T platform. I guess when you're talking about these discussions, what type of framework are you working under? Is this more like a research and development collaboration? Or is it something where -- just trying to understand what the upfront in terms might be to you guys?

好的。偉大的。我的最後一個問題，關於您與各方就非稀釋性機會進行的討論，我認為，您提到的 2 個焦點是 AG019，然後是 UltraCAR-T 平台。我想當你談論這些討論時，你在什麼類型的框架下工作？這更像是研發合作嗎？或者只是想了解一下前期對你們來說可能意味著什麼？

Absolutely. So in regards to the AG019, as you know, we have had the Phase II data -- positive Phase II data and our group has also prepared for the Phase III and manufacturing -- commercial manufacturing. However, we have refrained from entering to the Phase III because of the prioritization of the program and the cash requirement that the program had.

絕對地。所以關於 AG019，正如你所知，我們已經有了第二階段的數據——積極的第二階段數據，我們的團隊也為第三階段和製造——商業製造做好了準備。然而，由於該計劃的優先順序和該計劃的現金需求，我們沒有進入第三階段。

In the past 1.5 years, it has become very clear in the field that, especially with the approval of some of the antibodies for the antibody pembrolizumab for Type 1B. And actually in conjunction with the data that we have shown both as a monotherapy and in combination that is actually superior into that treatment.

在過去的 1.5 年裡，這一點在該領域已經變得非常清楚，特別是隨著 1B 型抗體 pembrolizumab 的一些抗體獲得批准。實際上，結合我們所顯示的單一療法和聯合療法的數據，實際上優於該療法。

The AG019 has become a center of attention. We are in discussion with a number of parties. And this discussion is not about the research development, I would say, on the level of AG019 for sure. And it's required -- talking about partnerships. In regard to the UltraCAR-T, similarly in view of some of the data, especially on the AML that we have shown and the potential in solid tumors, we are in discussion with a number of parties that it's taking into consideration, various type of collaboration or partnership that addresses research and clinical. And we will be reporting hopefully in the near future on those.

AG019成為了人們關注的焦點。我們正在與多方進行討論。我想說，這次討論肯定不是關於 AG019 水平的研究進展。這是必需的——談論夥伴關係。關於 UltraCAR-T，同樣考慮到一些數據，特別是我們已經展示的 AML 以及實體瘤的潛力，我們正在與它正在考慮的許多各方進行討論，各種類型的解決研究和臨床問題的合作或夥伴關係。我們將在不久的將來滿懷希望地報告這些內容。

And finally, I think maybe I can add this even though you didn't ask it, Jennifer. We are also very excited about now the -- we have started the progress on divestiture of our subsidiary Exemplar. And I think this will be also very important in providing a non-dilutive cash to extend our runway from 2025 to further.

最後，我想也許我可以補充這一點，即使你沒有問，詹妮弗。我們現在也非常興奮——我們已經開始剝離我們的子公司 Exemplar。我認為這對於提供非稀釋性現金以將我們的跑道從 2025 年延伸到更遠也非常重要。

So those are all the means that by now extending our cash run rate to 2025, not only we get our data readouts, but also it allows declaration of these discussions that we have with various partners to come to hopefully reality, and that will even further extend our cash run rate.

因此，這些都是現在將我們的現金運行率延長到 2025 年的所有方法，我們不僅可以獲得數據讀數，而且還可以宣布我們與各個合作夥伴進行的這些討論有望成為現實，這將進一步提高我們的現金運行率。

And the next question comes from Arthur He with H.C. Wainright.

下一個問題來自 Arthur He 和 H.C.溫賴特。

There is a technical difficulty, I apologize if the question has been asked before. So regarding the 2012 program, I'm just curious, from your perspective, regarding the efficacy data endpoint, what is kind of efficacy you think is the approval threshold and what kind of data you think is more commercially favorable?

存在技術困難，如果之前已經提出過這個問題，我深表歉意。那麼關於2012年的計劃，我只是好奇，從您的角度來看，關於功效數據終點，您認為什麼樣的功效是審批門檻以及您認為什麼樣的數據更有商業優勢？

I think from a perspective of commercially favorable, as you can see, there is nothing there. There is no other therapeutic and from that currently exists for this patient, except number of surgeries over and over and over again in the last time of this. And if you can imagine that if you have this disease from childhood, it means a lifetime of surgeries and challenges with this.

我認為從商業有利的角度來看，正如你所看到的，那裡什麼也沒有。除了上次一次又一次的手術之外，目前對該患者沒有其他治療方法。如果你能想像，如果你從小就患有這種疾病，那就意味著一生都需要接受手術和挑戰。

So in that regard, we hope to be the first therapeutic on the market for this disease on patient population. In regard to the efficacy, as we have said, we have currently shown what as far as 50% of our patients from Phase I is they are a complete responder. And one thing that we have discussed with FDN is very clear that surgeries alone doesn't lead to the regression of these patients.

因此，在這方面，我們希望成為市場上第一個針對患者群體的這種疾病的治療方法。至於療效，正如我們所說，我們目前已經證明，第一階段的患者中有 50% 是完全緩解的。我們與 FDN 討論過的一件事非常明確，僅靠手術並不會導致這些患者的病情消退。

And because if it was, then all the years that these patients had the surgeries, they should have been cured by now, which unfortunately, that is not the case. And therefore, we have the automatic regression, it's not there. But even if you consider that it's going to be above 10%, you will be benefiting this patient population, but we are currently standing at 50% response rates with it.

因為如果是的話，那麼這些患者接受手術的這些年來，他們現在應該已經治癒了，但不幸的是，事實並非如此。因此，我們有自動回歸，但它不存在。但即使您認為它會超過 10%，您也會使該患者群體受益，但我們目前的響應率為 50%。

So we are very excited. And by the way, this is a very deep response. Not only we have completed our 12 months of a response. But as I mentioned, from a Phase I our patients' responses, the complete responses are ongoing, and none of them have required any surgeries.

所以我們非常興奮。順便說一句，這是一個非常深刻的回應。我們不僅完成了 12 個月的響應。但正如我所提到的，從我們患者的第一階段反應來看，完全反應正在進行中，而且他們都不需要任何手術。

Yes. And just to go a little bit deeper regarding the study. During your transition with FDA, did they put any color for the pre-existing level of the antibody to the vector as a screening requirement for the patient. And also, did they make a requirement for monitoring the antibody raised in the body upon their treatment?

是的。只是為了更深入地了解這項研究。在您向 FDA 過渡期間，他們是否將任何顏色來表示載體中預先存在的抗體水平，作為對患者的篩查要求。還有，他們有沒有要求監測治療時體內產生的抗體？

We already had -- actually in our design, we already had immunological readouts, which included both neutralizing antibodies as well as HPV-specific T cells. And actually, FDA very much appreciated that and recognized the importance of these readouts in conjunction with the mechanism of action that we are showing.

實際上，在我們的設計中，我們已經有了免疫讀數，其中包括中和抗體以及 HPV 特異性 T 細胞。事實上，FDA 非常讚賞這一點，並認識到這些讀數與我們所展示的作用機制相結合的重要性。

And one thing I should remind everyone in regard to the AdenoVerse platform, again, that as we have shown in previous data, both in regards to PRGN-2012, but PRGN-2009. And even in healthy volunteers, there is no prior or very little pre immunity to the gorilla Adenoviruses. And this is the uniqueness of this platform.

關於 AdenoVerse 平台，我應該再次提醒大家一件事，正如我們在之前的數據中所顯示的那樣，既涉及 PRGN-2012，也涉及 PRGN-2009。即使在健康的志願者中，也沒有或很少有對大猩猩腺病毒的預免疫力。這就是這個平台的獨特之處。

One other thing that in the data with PRGN-2012, we showed in January is that upon repeat dosing, you would not see increases in a neutralizing antibody or if there is a slight increase, then it comes down. And therefore, you will not have the issues that you're having with Ad5 and other viruses, which basically limits you to giving this only once or at best that you can give twice.

我們在一月份展示的 PRGN-2012 數據中的另一件事是，重複給藥後，您不會看到中和抗體增加，或者如果有輕微增加，則它會下降。因此，您不會遇到 Ad5 和其他病毒所遇到的問題，這基本上限制您只能提供一次或最多可以提供兩次。

And we have shown now that data extensively for various drug products that has used the AdenoVerse platform, both PRGN-2012 and 2009. And similarly, I will remind everyone that we have shown HPV-specific T cells from our Phase I PRGN-2012 as well as Phase I in PRGN-2009, which, in those setting the patients that they had HPV cancers, for instance, upon repeat dosing on a monthly basis.

我們現在已經廣泛展示了使用 AdenoVerse 平台的各種藥品的數據，包括 PRGN-2012 和 2009。同樣，我要提醒大家，我們已經將來自第一階段 PRGN-2012 的 HPV 特異性 T 細胞展示為以及PRGN -2009 的第一階段，例如，在那些患有HPV 癌症的患者中，每月重複給藥。

We have shown that you can keep enhancing the T-cell responses over the year, for instance, that the patients have been on treatment. And again, this is part of the differentiation of the mechanism of action of this platform versus all the other Ad5s, retroviruses and other platform that exists there.

我們已經證明，您可以在一年中不斷增強 T 細胞反應，例如，患者一直在接受治療。再說一遍，這是該平台作用機制與所有其他 Ad5、逆轉錄病毒和其他現有平台的區別的一部分。

That's great. And if I may, I can -- if I may ask a last question. So regarding the market outside the U.S., what's your current strategy for that?

那太棒了。如果可以的話，我可以——如果我可以問最後一個問題。那麼對於美國以外的市場，你們目前的策略是什麼？

As we just have confirmed with the FDA, we are moving rapidly with the discussions with the EMA at the same token with the U.K. and also with Japan currently, to basically position PRGN-2012 as a drug product and also on a path for licensure there.

正如我們剛剛向 FDA 確認的那樣，我們正在迅速與 EMA 進行討論，同樣，目前還與英國和日本進行討論，基本上將 PRGN-2012 定位為藥品，並正在那裡獲得許可。

And the next question comes from Ben Burnett with Stifel.

下一個問題來自 Ben Burnett 和 Stifel。

And I will throw in my congrats on the progress this quarter. I would ask, sticking with PRGN 2012, in the past, you provided efficacy on a number of different endpoints in addition to the 12-month CR rate. I guess what is kind of the totality of the data that the FDA is going to look at? Are they -- are they focused on those other endpoints that you've shown? And I guess maybe how focused are they on durability versus response rate?

我將對本季度的進展表示祝賀。我想問的是，堅持 PRGN 2012，過去，除了 12 個月 CR 率之外，你們還提供了許多不同終點的療效。我想 FDA 將要查看的數據總量是多少？他們是否專注於您所展示的其他端點？我想也許他們對耐用性與響應率的關注程度如何？

I think very good question. First of all, the part of the endpoints that we put forward, which was very meaningful was, we didn't go for a reduction in a number of surgeries. But we went for upfront and we provided was that no surgeries required, and we made that for 12 months, which is quite a long period of time. It was not for 3 months or 6 months.

我認為非常好的問題。首先，我們提出的終點中非常有意義的部分是，我們並沒有追求減少手術數量。但我們預先提出了不需要手術的要求，我們做了 12 個月，這是相當長的一段時間。不是3個月或6個月。

And one other thing that we did, which I believe it was seen as a very positive point, was we went to a very severe patient population, which they required 3 surgeries and higher. So all those elements together, it not only shows the durability of the immune response, especially now that we continue, obviously, following all of our patients.

我們做的另一件事，我認為這被視為非常積極的一點，是我們接觸了非常嚴重的患者群體，他們需要 3 次手術或更多。因此，所有這些因素加在一起，它不僅顯示了免疫反應的持久性，特別是現在我們顯然繼續跟踪所有患者。

And especially with our responders, we are showing they are well past 12 months, and they continue to be in full response. So that speaks to the durability of that response, that 12-month follow-up and beyond. On the other hand, the fact that we showed a mechanism of action associated with this.

特別是對於我們的響應者，我們表明他們已經過去 12 個月了，並且他們繼續做出充分的響應。因此，這說明了該響應、12 個月及以後的後續行動的持久性。另一方面，我們展示了與此相關的作用機制。

And I think this is again, was appreciated by the FDA leadership because clearly, we have clinical data from the patients that are in full response that they have generated a specific HPV 6 and 11 responses and obviously, this is due to the treatment as this patient did not have these responses prior to entering to the trial. So I think that has become very, very important.

我認為這再次得到了 FDA 領導層的讚賞，因為顯然，我們有來自完全緩解的患者的臨床數據，他們已經產生了特定的 HPV 6 和 11 反應，顯然，這是由於治療所致患者在進入試驗之前沒有這些反應。所以我認為這已經變得非常非常重要。

And the fact that the mechanism of action, it relates to the ability to redose with the AdenoVerse platform. Again, that's a huge differentiation and difference between us and others because with this you allow now to give a number of, in this case, is the course of 4 over 85 days. And by the way, it's subcutaneously given.

事實上，其作用機制與 AdenoVerse 平台重新劑量的能力有關。再說一遍，這是我們和其他人之間的巨大差異，因為有了這個，您現在可以給出一些數字，在這種情況下，是 85 天的 4 個過程。順便說一句，它是皮下注射的。

And it allows, obviously, without having increase neutralizing antibodies or tremendously increased neutralizing antibodies, which will hinder the -- usually the T-cells, and we don't see that at all opposite. It allows all of that to be considered as the uniqueness of this product and also the FDA confirmation for accepting the endpoints that we had plus the immunological markers that we have currently have put in the trials and they are [solved].

顯然，它允許在不增加中和抗體或極大增加中和抗體的情況下，這會阻礙——通常是T細胞，而我們完全沒有看到相反的情況。它使所有這些都可以被視為該產品的獨特性，並且 FDA 確認接受我們擁有的終點以及我們目前已投入試驗的免疫標記物，並且它們已[解決]。

Okay. Excellent. That's very helpful. And I would also like to ask a question around this repeat dosing, which I think is really interesting. I guess do you have a sense at this point, like how many patients would kind of constitute a relevant database to adjudicated efficacy of repeat dosing? And I'm assuming would a repeat dosing just be the 4 dose course as -- or would you maybe modify that course in patients that you're redosing.

好的。出色的。這非常有幫助。我還想問一個關於重複給藥的問題，我認為這非常有趣。我想您現在是否有這樣的感覺，比如有多少患者會構成一個相關數據庫來判定重複給藥的療效？我假設重複給藥只是 4 劑量療程，或者您可能會修改正在重新給藥的患者的療程。

Yes. I think that, that's a discussion that we have with our investigators. Clearly, you can think of various scenarios for repeat dosing that patients, for instance, after a period of when -- if they require surgery and becomes obvious that they are not full responders, then they can receive another course or you can imagine also a situation that these patients received single doses throughout because again, because of uniqueness of this platform.

是的。我認為這是我們與調查人員進行的討論。顯然，你可以想到重複給藥的各種情況，例如，在一段時間後，如果他們需要手術並且明顯表明他們不是完全反應者，那麼他們可以接受另一個療程，或者你也可以想像一個療程由於該平台的獨特性，這些患者始終接受單劑量的情況。

And the fact that you can give it in a repeated fashion as we have done for PRGN-2009 on a monthly base, and we have had patients on the trial that they receive this over 2 years, and we had complete responders that similarly, they went to very deep responses for over a year after receiving the vaccination with PRGN-2009.

事實上，你可以像我們在 PRGN-2009 中每月所做的那樣，以重複的方式給予它，並且我們已經有患者接受了超過 2 年的試驗，並且我們有完全的反應者，同樣，他們在接受PRGN-2009 疫苗接種後一年多的時間裡，我們產生了非常深刻的反應。

This also can become another scenario that you can be doing on a monthly basis or every 3 months. And this is the discussions that we have based on the immunological readouts, and we will be designing appropriate arms to address exactly that factor for repeat dosing to address the full population.

這也可以成為您可以每月或每 3 個月執行一次的另一個場景。這是我們基於免疫學讀數進行的討論，我們將設計適當的武器來準確解決重複給藥的因素，以解決整個人群的問題。

And you can imagine also this is PRGN-2012, clearly, it's extremely important in this RRP. And for us, it's very, very important to address the whole patient population if we can, and we will do that as we also will go into the pediatric population.

你也可以想像這是PRGN-2012，顯然，它在這個RRP中極其重要。對我們來說，如果可以的話，解決整個患者群體是非常非常重要的，我們將這樣做，因為我們也將進入兒科群體。

Okay. Fantastic. And if I could just maybe squeeze one more just a clarification question obviously. The updated cash runway, which, by the way, great to hear about the cash runway and obviously, congrats on now fully retiring the remaining debt.

好的。極好的。如果我可以再擠出一個顯然只是一個澄清問題。更新的現金跑道，順便說一句，很高興聽到現金跑道，顯然，祝賀現在完全償還了剩餘的債務。

Is the updated cash runway include costs associated with this expansion repeat dosing cohort and the confirmatory study? Or is that separate?

更新後的現金跑道是否包括與擴大重複給藥隊列和驗證性研究相關的成本？或者說那是分開的？

It does include Ben. It does include some of that. Not to the specificities, as Helen had said, we're still needing to design that. But there is contemplation of those costs.

它確實包括本。它確實包括其中一些。正如海倫所說，我們仍然需要設計它，而不是具體細節。但人們正在考慮這些成本。

Yes. Then I can also say that it does include the confirmatory because, again, our confirmatory is a single arm. I want to remind everyone, it's not a randomized control Phase III will be a single arm with a similar exact design as we have done with the Phase I or Phase II.

是的。然後我也可以說它確實包括確認，因為我們的確認是單臂。我想提醒大家，這不是隨機對照，第三階段將是一個具有與我們在第一階段或第二階段所做的類似精確設計的單臂。

The expanded arms is something that we will be discussed, but that does not have to be initiated projects to BLA, and we can initiate those arms at the later point after the design. So -- for the purposes of the costs and our runway, we have considered part of our manufacturing.

擴展臂是我們將討論的問題，但這不必向 BLA 啟動項目，我們可以在設計後的稍後時間啟動這些臂。因此，出於成本和跑道的目的，我們考慮了製造的一部分。

As you can see that we are switching our own manufacturing by reprioritizing our own manufacturing facility to address some of the costs, and it does take into account the initiation of the confirmatory trial.

正如您所看到的，我們正在通過重新調整我們自己的製造設施的優先順序來改變我們自己的製造，以解決一些成本，並且它確實考慮到了驗證性試驗的啟動。

And the next question comes from Brian Cheng with JPMorgan.

下一個問題來自摩根大通的 Brian Cheng。

From your discussion -- have they talked about how long of a safety follow-up do you need in the ongoing study before filing? And then on the preparation work for filing, can you talk about whether there are any additional preclinical work that you need to tee up between now and filing that you have to work on? And then I have a couple of follow-ups.

從你們的討論來看——他們是否談到了在提交申請之前，你們在正在進行的研究中需要多長時間的安全隨訪？然後關於備案的準備工作，您能談談從現在到備案之間您是否還需要準備一些額外的臨床前工作？然後我有一些後續行動。

So in regards to the safety profile, it's similar to the endpoints that we have for efficacy, 1-year safety follow-ups -- of course, and we have -- we will be following these patients regardless as they move on. So those are part of the endpoints.

因此，就安全性而言，它與我們對療效、1 年安全性隨訪的終點類似——當然，我們也有——我們將跟踪這些患者，無論他們是否繼續前進。所以這些是端點的一部分。

And as we have mentioned and I will repeat, this product -- drug product has a very favorable safety profile in all of the patients that we have treated very, very similar and very favorable. As far as -- in regard to the preclinical discussions, obviously, the preclinical work has been already taken place prior to us going to a Phase I, Phase II, what obviously is as part of any BLA submission, we have to meet all the criteria that the FDA is asking for.

正如我們已經提到的，我將重複一遍，該產品 - 藥品在我們治療過的所有患者中具有非常有利的安全性，非常相似且非常有利。就臨床前討論而言，顯然，在我們進入第一階段、第二階段之前，臨床前工作已經開始，這顯然是任何 BLA 提交的一部分，我們必須滿足所有要求FDA 要求的標準。

This is part of a typical of submission for the BLA, which includes obviously, the Phase II data has to be similar and to what we have seen up to this point. It has to meet the clinical end point. We also are in discussion with the FDA for a manufacturing comparability and using our commercial material in our manufacturing in the confirmatory trial. So those discussions are ongoing.

這是 BLA 典型提交的一部分，其中顯然包括第二階段數據必須與我們迄今為止所看到的數據相似。它必須滿足臨床終點。我們還正在與 FDA 討論製造可比性，並在驗證性試驗的製造中使用我們的商業材料。所以這些討論正在進行中。

And when we submit our BLA, of course, it has to have all those components in for the rapid review and approval, which we are hoping that we will moving towards that very rapid.

當然，當我們提交 BLA 時，它必須包含所有這些組件以供快速審查和批准，我們希望我們能夠非常迅速地朝著這一目標邁進。

Okay. And then on the manufacturing front, can you elaborate on your commercial readiness? What's needed specifically to prepare on the CMC side and at the time of your anticipated launch, what is the capacity that we should anticipate?

好的。然後在製造方面，您能詳細說明一下您的商業準備情況嗎？ CMC 方面需要具體準備什麼，以及在預期啟動時，我們應該預期的容量是多少？

So we have evaluated our own manufacturing facility, which, by the way, provided all of the GMP material that was used in this trials even during the pandemic time, as you can imagine, because we started the trial of PRGN-2012 on April, I believe of 2021. So you can imagine our manufacturing had prepared that during the ongoing pandemic, which was very important because at that point, all of the external manufacturing, they were shut down and no one could prepare anything.

所以我們評估了我們自己的生產設施，順便說一句，即使在大流行期間，它也提供了本次試驗中使用的所有GMP 材料，正如你可以想像的，因為我們在4 月份開始了PRGN-2012的試驗，我相信 2021 年。所以你可以想像我們的製造業在持續的大流行期間已經做好了準備，這非常重要，因為那時所有外部製造業都被關閉，沒有人可以準備任何東西。

So that's one of the importance, as I mentioned, why we have decided to move the commercial manufacturing to our own facility and make our facility commercially basically ready for this past and for the licensure path. We will be moving on our material for the commercial material as we speak. Our teams are working on various aspects of comparability and also production.

正如我所提到的，這就是為什麼我們決定將商業製造轉移到我們自己的工廠，並使我們的工廠基本上為過去和許可路徑做好商業準備的重要性之一。在我們發言的同時，我們將繼續討論商業材料。我們的團隊正在研究可比性和生產的各個方面。

Since we have produced our GMP material ourselves and the processes are minimally switched, we hope that we have a very good comparability profile for manufacturing, which will be obviously presented to the FDA, and we anticipate that we will be ready to launch from our commercial facility here after the approval of our BLA. I should mention that especially within the patient population that is in U.S.

由於我們自己生產 GMP 材料，並且工藝轉換最少，我們希望我們的製造具有非常好的可比性，這將明顯地提交給 FDA，並且我們預計我們將準備好從我們的商業產品推出經我們的BLA 批准後，我們​​將在此處設立設施。我應該提到這一點，尤其是在美國的患者群體中。

We believe our commercial facility has the capability to produce enough doses for that. And also, obviously, after the approval and during this process, -- we are also looking at further expansion. So with that, we believe that we can be -- our facility will be sufficient for production of the doses that is needed in U.S.

我們相信我們的商業設施有能力為此生產足夠的劑量。而且，顯然，在獲得批准之後以及在此過程中，我們也在考慮進一步擴張。因此，我們相信我們可以——我們的設施將足以生產美國所需的劑量。

Great. If I can squeeze in the last one, that would be great. Just one on your overall thinking around the entire R&D portfolio. As you mentioned that there are multiple potential partnerships and divesting opportunities that you currently have on the table. And given that you have a cash runway out to 2025, can you talk about how should we think of how the R&D portfolio will evolve over the next 12 months? And what are the factors that you will take when you think about what to prioritize and what to partner off?

偉大的。如果我能擠進最後一張那就太好了。請談談您對整個研發組合的整體思考。正如您提到的，您目前有多種潛在的合作夥伴關係和剝離機會。鑑於您有到 2025 年的現金跑道，您能否談談我們應該如何考慮未來 12 個月內研發組合將如何發展？當您考慮優先考慮什麼以及合作什麼時，您會考慮哪些因素？

Thanks. So very clear. I think as far as immediate partnership is very clear that -- and we had announced this previously on AG019 because we believe that this is something that -- it's very exciting.

謝謝。所以非常清楚。我認為就直接合作夥伴關係而言，我們已經在 AG019 上宣布了這一點，因為我們相信這是非常令人興奮的。

However, Precigen does not have the cash requirements to go to extended Phase III with this asset, and this is why we have the very active discussions with a number of parties around AG019.

然而，Precigen 沒有足夠的現金需求來使用該資產進行第三階段擴展，這就是為什麼我們與許多各方圍繞 AG019 進行了非常積極的討論。

In regards to our UltraCAR-Ts, as I mentioned, especially the PRGN-3005 because it's much -- it's more advanced and from the objective responses. It has the fast track and path to perhaps a rapid regulatory strategy for the AML patients that we anticipate that the 2 sites, the Moffitt and Mayo Clinic have done an excellent job in recruiting and they will continue to do that, especially in this half of the year.

至於我們的 UltraCAR-T，正如我提到的，特別是 PRGN-3005，因為它更先進，而且來自客觀的反應。它為 AML 患者提供了快速通道和快速監管策略，我們預計莫菲特和梅奧診所這兩個中心在招募方面做得非常出色，他們將繼續這樣做，特別是在今年下半年。那一年。

So we will be having the data for a Phase Ib in minimum the interim data for 2024. Again, this position us -- and not only from a regulatory path, and the decisions that has to be made for perhaps a rapid move in that direction, but also in our discussions with the groups that are right now are interested in the program and in advancement of the program towards the commercialization.

因此，我們將獲得 Ib 階段的數據，至少是 2024 年的中期數據。同樣，這不僅是從監管路徑出發，而且是為了朝這個方向快速前進而必須做出的決定，而且還包括我們與目前對該計劃感興趣並推動該計劃走向商業化的團體的討論。

The priority of the portfolio, I want to stress this, and I know Harry has stressed. We have now really minimized the costs of SG&A. We have minimized to the limit the extraneous CRO costs by not opening some of the sites, as we all know, in developed -- drug development, one of the heaviest cost is your sites that you are initiating and it requires a large cash by not doing that in an immediate fashion.

作品集的優先級，我想強調這一點，我知道哈利也強調過。我們現在確實最大限度地降低了 SG&A 成本。我們通過不開放某些站點，將額外的 CRO 成本降至最低，眾所周知，在發達國家的藥物開發中，最沉重的成本之一是您正在啟動的站點，它需要大量現金立即這樣做。

We are saving to get to the readout of our PRGN-2012, which is, as I mentioned, the decision of the FDA why it's so important to us is because it eliminated requirement of the Phase III, which you can imagine and appreciate, it would have taken another 3 or 4 years just to get to the point of data.

我們正在節省資金以獲取 PRGN-2012 的讀數，正如我所提到的，FDA 的決定為什麼它對我們如此重要，因為它消除了 III 期的要求，您可以想像並理解這一點，它僅僅需要3到4 年的時間才能得到數據。

And right now, we are basically -- first of all, we are seeing our data from Phase II as we speak because it's an open side. And secondly, we will finish the complete follow-up, which is the endpoint of 12 months that FDA has agreed with, by the second quarter of 2024.

現在，我們基本上——首先，我們正在看到第二階段的數據，因為它是開放的。其次，我們將在 2024 年第二季度之前完成完整的隨訪，這是 FDA 同意的 12 個月的終點。

So our cash runway is well beyond that and it allows us to have our readout and move with our BLA submission. From a non-dilutive fashion, definitely, the discussions that we have is very productive and ongoing. And our hope is that will extend our cash runway beyond 2025.

因此，我們的現金跑道遠遠超出了這一範圍，它使我們能夠讀出並隨著 BLA 提交而移動。當然，從非稀釋的角度來看，我們的討論非常富有成效並且持續進行。我們希望這能夠將我們的現金跑道延伸到 2025 年以後。

One other thing that I have to say, and I'm grateful to the team at Precigen for dedication that they have shown. And what we have done, which is not typical to a lot of other companies is our R&D because of the knowledge and especially in -- on the side of asset development, immunological -- immunology and clinical, they have pivoted that they have taken a lot of the responsibilities on that side, which we do not need to now hire a tremendous force, retrain, lose time in order to move rapidly towards the commercialization. And I think that's another strength that Precigen has and obviously, we are utilizing.

我還要說的另一件事是，我感謝 Precigen 團隊所表現出的奉獻精神。我們所做的，對於許多其他公司來說並不典型的是我們的研發，因為我們的知識，特別是在資產開發、免疫學、免疫學和臨床方面，他們已經轉向，他們已經採取了這方面的很多責任，我們現在不需要雇傭巨大的力量，重新培訓，浪費時間來快速走向商業化。我認為這是 Precigen 擁有的另一個優勢，顯然我們正在利用。

And this concludes the question-and-answer session. I would like to turn the floor to Dr. Sabzevari for any closing comments.

問答環節到此結束。我想請 Sabzevari 博士徵求結束意見。

Thank you. First of all, I would like to thank you for joining us today. I want to extend our thanks to the patients for participating in clinical trials, our investigators for their dedication and commitment working on studying new therapies for our unmet needs and to the team at Precigen, who have worked so hard over the last several years.

謝謝。首先，我要感謝您今天加入我們。我要感謝參與臨床試驗的患者，感謝我們的研究人員致力於研究新療法來滿足我們未滿足的需求，感謝他們的奉獻和承諾，感謝 Precigen 的團隊，他們在過去幾年中辛勤工作。

As we have discussed today, we believe the PRGN-2012 has a paradigm-changing potential. And with today's announcement of the FDA alignment on a path to an accelerated approval request for our ongoing Phase I/II study. This is an important milestone that brings us a step closer in our transition to a commercial stage company and in realizing our vision of bringing life-changing therapies to patients with unmet medical need.

正如我們今天所討論的，我們相信 PRGN-2012 具有改變範式的潛力。隨著今天 FDA 宣布，我們將加速批准我們正在進行的 I/II 期研究的請求。這是一個重要的里程碑，使我們在向商業階段公司的過渡以及實現為醫療需求未得到滿足的患者提供改變生活的療法的願景方面又邁進了一步。

Given that the Phase I/II is fully enrolled and serves as pivotal, this sets us up potentially to bring a life-changing first therapeutic option for RRP patients who have been waiting for decades for such an option. Thank you again. And now I return it to operator.

鑑於 I/II 期已完全入組並發揮關鍵作用，這使我們有可能為幾十年來一直等待這種選擇的 RRP 患者帶來改變生活的第一個治療選擇。再次感謝你。現在我把它還給操作員。

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.

謝謝。會議現已結束。感謝您參加今天的演講。您現在可以斷開線路。