Processa Pharmaceuticals Inc (PCSA) 2022 Q4 法說會逐字稿

Greetings and welcome to the Processa Pharmaceuticals year-end 2022 earnings call and corporate update. (Operator Instructions) As a reminder, this call is being recorded. It is now my pleasure to introduce Jim Stanker, Chief Financial Officer. Thank you, sir. You may begin.

歡迎參加 Processa Pharmaceuticals 2022 年底財報電話會議和公司最新動態。 （操作員說明）謹此提醒，此通話正在錄音。現在我很高興向大家介紹首席財務官 Jim Stanker。謝謝你，先生。你可以開始了。

Thank you, and welcome to Processa's 2022 year-end results and corporate update conference call. Joining me on the call today is our Chief Executive Officer, Dr. David Young.

謝謝，歡迎參加 Processa 的 2022 年年終業績和公司更新電話會議。今天與我一起參加電話會議的是我們的首席執行官 David Young 博士。

Shortly before this call, we filed our year-end Form 10-K. I will briefly touch on our published financial results, and then turn it over to Dr. Young to provide an update on our drug development activities. I want to remind everyone that a PowerPoint presentation will accompany Dr. Young's prepared remarks. To view the PowerPoint presentation, please go to the Investor Relations section on our website or to our earnings press release and click the webcast link to follow along.

在本次電話會議之前不久，我們提交了年終 10-K 表格。我將簡要介紹我們已發布的財務業績，然後將其交給楊博士，以提供我們藥物開發活動的最新情況。我想提醒大家，楊博士準備好的講話將附帶一個 PowerPoint 演示文稿。要觀看 PowerPoint 演示文稿，請訪問我們網站的投資者關係部分或我們的收益新聞稿，然後單擊網絡廣播鏈接以繼續觀看。

I'll start by reading the Safe Harbor statement. This statement is made pursuant to the Safe Harbor for forward-looking statements described in the Private Securities Litigation Reform Act of 1995. All statements made on this call with the exception of historical facts may be considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Act of 1934.

我將首先閱讀安全港聲明。本聲明是根據1995 年《私人證券訴訟改革法案》中描述的前瞻性聲明的安全港而做出的。除歷史事實外，本次電話會議中所做的所有聲明均可被視為第27A 條含義內的前瞻性聲明1933 年證券法和 1934 年證券法第 21E 條。

Although we believe expectations and assumptions reflected in these forward-looking statements are reasonable, we can make no assurances that such expectations will prove to be correct. Actual results may differ materially from those expressed or implied in forward-looking statements due to various risks and uncertainties.

儘管我們認為這些前瞻性陳述中反映的預期和假設是合理的，但我們不能保證此類預期將被證明是正確的。由於各種風險和不確定性，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。

For a discussion of such risks and uncertainties that could cause actual results to differ from those expressed or implied in the forward-looking statements, please see Risk Factors detailed in our annual report on Form 10-K.

有關可能導致實際結果與前瞻性陳述中明示或暗示的結果不同的此類風險和不確定性的討論，請參閱我們 10-K 表格年度報告中詳細說明的風險因素。

Any forward-looking statements included in this earnings call are made only as of the date of this call. We do not undertake any obligation to update or supplement any forward-looking statements to reflect subsequent knowledge, events, and circumstances.

本次財報電話會議中包含的任何前瞻性陳述僅在本次電話會議之日作出。我們不承擔更新或補充任何前瞻性陳述以反映後續知識、事件和情況的義務。

Our cash balance on December 31, 2022 was $6.5 billion. Subsequent to year end, we raised $6.4 million from the sale of 8.4 million shares of our common stock through a combination of financing vehicles, including a registered direct offering. These funds have strengthened our balance sheet, and we believe the cumulative $12.9 million will be sufficient to complete our active clinical trials and fund our operations into the third quarter of 2024.

截至 2022 年 12 月 31 日，我們的現金餘額為 65 億美元。年底後，我們通過多種融資工具（包括註冊直接發行）出售 840 萬股普通股，籌集了 640 萬美元。這些資金增強了我們的資產負債表，我們相信累計 1290 萬美元將足以完成我們正在進行的臨床試驗並為我們的運營提供資金直至 2024 年第三季度。

As a pre-revenue company, we are careful with our cash, using it to advance the drugs in our pipeline to their next value-producing milestone. We used $9.6 million during the year ended December 31, 2022, to fund our three clinical trials and operations. This represented an increase of $800,000 when compared to the $8.8 million of cash we used in 2021.

作為一家尚未盈利的公司，我們對現金非常謹慎，用它來將我們管道中的藥物推進到下一個創造價值的里程碑。截至 2022 年 12 月 31 日止的年度，我們使用了 960 萬美元來資助我們的三項臨床試驗和運營。與 2021 年我們使用的 880 萬美元現金相比，這意味著增加了 80 萬美元。

As I will explain, our operating cash flow is significantly less than our GAAP net loss, primarily due to several non-cash expenses. Our GAAP net loss for the year ended December 31, 2022, was $27.4 million or $1.70 a share compared to a net loss of $11.4 million or $0.75 per share for the same period of 2021.

正如我將解釋的那樣，我們的運營現金流明顯低於公認會計原則淨虧損，這主要是由於幾項非現金支出。截至 2022 年 12 月 31 日的年度，我們的 GAAP 淨虧損為 2740 萬美元，即每股 1.70 美元，而 2021 年同期的淨虧損為 1140 萬美元，即每股 0.75 美元。

The increase in our net loss was primarily due to a one-time non-cash impairment of an intangible asset for $7.3 million, along with increased stock-based compensation and the clinical trial costs we incurred in our active clinical trials. For the year ended December 31, 2022, we incurred $11.5 million in research and development costs, an increase of $4.6 million when compared to the same period of 2021.

我們淨虧損的增加主要是由於一項無形資產的一次性非現金減值 730 萬美元，以及股票補償的增加和我們在活躍臨床試驗中產生的臨床試驗成本。截至2022年12月31日止年度，我們的研發成本為1150萬美元，較2021年同期增加460萬美元。

During the year ended December 31, 2022, our general and administrative expenses totaled $8.8 million compared to $4.7 million for the same period in 2021. The increase was primarily due to increases in stock-based compensation and other payroll-related expenses. We rely heavily on stock-based compensation for our executive officers.

截至 2022 年 12 月 31 日的年度，我們的一般和管理費用總計 880 萬美元，而 2021 年同期為 470 萬美元。這一增長主要是由於股票薪酬和其他工資相關費用的增加。我們嚴重依賴高管的股票薪酬。

During 2022, the majority of our executive officers' base salary was paid out in restricted stock units. The cash portion for all six of our executive officers' base salaries was less than $600,000 with the remaining portion of their base used to acquire just a little over 390,000 shares of our common stock with a fair value of approximately $1.1 million on the day it was acquired.

2022 年，我們大部分高管的基本工資都是以限制性股票單位支付的。我們所有六名執行官的基本工資的現金部分不到 600,000 美元，他們的基本工資的其餘部分用於購買略多於 390,000 股的普通股，其公允價值約為 110 萬美元。獲得的。

Not only does this conserve our cash, but it aligns our executive team with our shareholders. In total, during the year ended December 31, 2022, we allocated $8.8 million of non-cash compensation costs between research and development, and general and administrative expense with the majority being recorded as G&A.

這不僅節省了我們的現金，而且使我們的執行團隊與股東保持一致。總的來說，在截至 2022 年 12 月 31 日的年度中，我們在研發、一般和管理費用之間分配了 880 萬美元的非現金補償成本，其中大部分記錄為一般管理費用。

This is a very exciting time for Processa as we prioritize our efforts to focus on the next-generation chemotherapy drugs in our pipeline. I will now turn the call over to our CEO, Dr. David Young, to go over our current drug pipeline and our current plans.

對於 Processa 來說，這是一個非常激動人心的時刻，因為我們優先重點關注我們管道中的下一代化療藥物。我現在將把電話轉給我們的首席執行官 David Young 博士，以審查我們當前的藥物管道和當前的計劃。

David, please go ahead.

大衛，請繼續。

Thank you, Jim. Good evening. Thank you for joining us. As Jim stated, at the end of 2022, we began to realize that it would be better for our investors if we focus on a few drugs rather than our portfolio of five drugs. In the first quarter of 2023, we announced that we would be prioritizing the development of our three oncology drugs, which we call our next-generation chemotherapy drugs.

謝謝你，吉姆。晚上好。感謝您加入我們。正如 Jim 所說，到 2022 年底，我們開始意識到，如果我們專注於幾種藥物而不是五種藥物的投資組合，對我們的投資者來說會更好。 2023年第一季度，我們宣布將優先開發三種腫瘤藥物，我們稱之為下一代化療藥物。

Slide 3, please. However, our mission has not changed. We are still developing drugs to treat patients who have no treatment or need better treatment options, but we are now focusing only on patients with cancer and our next-generation chemotherapy drugs.

請幻燈片 3。然而，我們的使命沒有改變。我們仍在開發藥物來治療無法接受治療或需要更好治療選擇的患者，但我們現在只關注癌症患者和我們的下一代化療藥物。

Next slide. It is the goal of every oncologist and the desire of every patient to be treated with the right drug at the right dose following the right treatment schedule. So often this is not the case. 30 to 50 years ago, the right drugs were only chemotherapy drugs and for metabolites that keep cancer cells from growing, dividing, and making more cancer cells.

下一張幻燈片。按照正確的治療方案、以正確的劑量接受正確的藥物治療是每位腫瘤學家的目標，也是每位患者的願望。但事實往往並非如此。 30 到 50 年前，正確的藥物只是化療藥物和阻止癌細胞生長、分裂和產生更多癌細胞的代謝物。

Even now, cancer chemotherapy drugs remain the backbone of cancer treatment, and the three of the most widely used cancer chemotherapy drugs are capecitabine, gemcitabine, and irinotecan. These three drugs are used in all types of cancers, but anywhere from 30% to 70% of the patients who start treatment has side effects requiring the patient to decrease their dose to suboptimal doses or to discontinue therapy.

即使現在，癌症化療藥物仍然是癌症治療的支柱，最廣泛使用的三種癌症化療藥物是卡培他濱、吉西他濱和伊立替康。這三種藥物用於所有類型的癌症，但開始治療的患者中有 30% 至 70% 會出現副作用，需要患者將劑量減少至次優劑量或停止治療。

And for those taking these drugs, less than 40% of patients typically have a positive response. Processa's mission is to develop the next-generation versions of these three chemotherapy drugs. We call them next generation because we have altered the drug where it is active metabolite so that it is metabolized and are distributed in the body differently than the FDA-approved drug while maintaining the same mechanism of killing cancer cells.

對於服用這些藥物的患者來說，只有不到 40% 的患者通常會出現陽性反應。 Processa 的使命是開發這三種化療藥物的下一代版本。我們稱它們為下一代，因為我們改變了藥物的活性代謝物，使其在體內的代謝和分佈與 FDA 批准的藥物不同，同時保持了相同的殺死癌細胞的機制。

These next-generation versions have already been shown in clinical and/or animal studies to have less severe side effects and fewer side effects. An improvement in the side effect profile with the next-generation chemotherapies allows a given patient to have a better quality of life when on next-generation chemotherapy, and their cancer may potentially be exposed to even more cancer-killing molecules.

這些下一代版本已經在臨床和/或動物研究中顯示出具有不太嚴重的副作用和更少的副作用。下一代化療的副作用得到改善，使接受下一代化療的患者能夠擁有更好的生活質量，並且他們的癌症可能會接觸到更多的抗癌分子。

In addition, it is likely that more patients would respond to our next-generation chemotherapy, thus providing a greater response rate than the presently used versions of each of these drugs. The question that I'm sure many of you are asking yourselves is what are these next-generation chemotherapy drugs, and why are they better than existing drugs?

此外，更多的患者可能會對我們的下一代化療產生反應，從而提供比目前使用的每種藥物更高的反應率。我相信你們很多人都在問自己的問題是這些下一代化療藥物是什麼，為什麼它們比現有藥物更好？

To answer this, let's look a little bit -- Slide Number 5. If you look at the many oncology-oriented companies, the vast majority are developing treatments for new targets or developing a new drug delivery system for an existing cancer drug.

為了回答這個問題，讓我們稍微看一下- 第5 張幻燈片。如果你看看許多以腫瘤學為導向的公司，絕大多數都在開發新靶點的治療方法或為現有的癌症藥物開發新的藥物輸送系統。

If you look at the picture on the left, you will see that chemotherapy drugs, when administered, are first absorbed into the body, then metabolized to active cancer-killing metabolites and to metabolites that may cause side effects. They are then distributed to cancer cells and normal cells, killing cancer cells, but also causing side effects in the normal cells. And they are eliminated out of the body.

如果你看左圖，你會發現化療藥物在給藥時首先被吸收到體內，然後代謝為活性的抗癌代謝物和可能引起副作用的代謝物。然後它們分佈到癌細胞和正常細胞，殺死癌細胞，但也會對正常細胞造成副作用。並且它們會被排出體外。

What Processa has done is to take these three widely used chemotherapy treatments, capecitabine, gemcitabine, and irinotecan, and all showed how the body handles them, specifically altering how the drugs are distributed in the body or how the body metabolizes the next-generation chemotherapy drugs.

Processa所做的就是採用卡培他濱、吉西他濱和伊立替康這三種廣泛使用的化療藥物，並全部展示了身體如何處理它們，特別是改變藥物在體內的分佈方式或身體如何代謝下一代化療藥物藥物。

We have altered them in the body by either administering the drug with a second drug that alters the metabolism and the distribution, or we slightly changed the molecular structure of an approved cancer drug in order to change the metabolism or distribution of the drug. The key, however, is that we have not changed the mechanism of how the drug kills cancer cells. We only have changed how the drug is handled by the body before killing the cancer cells.

我們通過將藥物與另一種改變代謝和分佈的藥物一起給藥來改變它們在體內的情況，或者我們稍微改變已批准的抗癌藥物的分子結構，以改變藥物的代謝或分佈。然而，關鍵是我們並沒有改變藥物殺死癌細胞的機制。我們只是改變了身體在殺死癌細胞之前處理藥物的方式。

Next slide. The groundbreaking aspect of our next-generation chemotherapy is that for each drug, there are more than 200,000 cancer patients who are diagnosed with targeted cancer that each next-generation drug could be treated. And those patients would be receiving treatment with less side effects and potentially better efficacy to both increase their survival and their quality of life.

下一張幻燈片。我們下一代化療的突破性之處在於，對於每種藥物，都有超過 200,000 名癌症患者被診斷出患有每種下一代藥物可以治療的靶向癌症。這些患者將接受副作用更少、療效可能更好的治療，以提高他們的生存率和生活質量。

As you can see the bottom -- at the bottom of the slide, from a corporate and investor perspective, having these next-generation chemotherapy drugs in our pipeline helps us to be more efficient in drug development, increases the probability of FDA approval, and differentiates our products from existing products and products presently in development.

正如您可以看到的底部- 在幻燈片的底部，從企業和投資者的角度來看，將這些下一代化療藥物納入我們的產品線有助於我們提高藥物開發效率，增加FDA 批准的可能性，並且使我們的產品有別於現有產品和目前正在開發的產品。

Next slide. But it's not just our drug assets that differentiate us from other companies. It's also how we approach the development and FDA approval of these drugs. We use the Processa regulatory science approach that has been refined over the last 30 years by two of the Processa founders. In addition, more recently, the FDA has been requesting that the principles of regulatory science be used under the FDA Project Optimus oncology initiative and the related draft FDA oncology guidance.

下一張幻燈片。但我們與其他公司的區別不僅僅在於我們的藥品資產。這也是我們開發這些藥物並獲得 FDA 批准的方式。我們使用 Processa 監管科學方法，該方法在過去 30 年中由 Processa 的兩位創始人不斷完善。此外，最近，FDA 一直要求在 FDA Optimus 腫瘤學計劃和相關的 FDA 腫瘤學指南草案中使用監管科學原則。

This requires that for every NDA oncology submission, the dosage regimen and the proposed label must be justified using the principles of Project Optimus and regulatory summons. Fortunately, for us, we've used the principles of Project Optimus within our regulatory science approach for a number of other non-oncology FDA drug approvals and have already started to use the Project Optimus approach prior to the announcement by the FDA for our next-generation drugs.

這要求對於每一份 NDA 腫瘤學提交，劑量方案和擬議的標籤必須使用 Optimus 項目和監管傳票的原則來證明其合理性。幸運的是，對我們來說，我們已經在監管科學方法中使用了 Optimus 項目的原則來批准許多其他非腫瘤學 FDA 藥物，並且在 FDA 宣布我們的下一個藥物批准之前已經開始使用 Project Optimus 方法。一代藥物。

On the other hand, many other oncology companies are not experienced with the principles of Project Optimus and in fact are having to conduct additional clinical trials to justify their dosing regimens and pivotal clinical study design.

另一方面，許多其他腫瘤公司對 Optimus 項目的原理沒有經驗，事實上必須進行額外的臨床試驗來證明其給藥方案和關鍵臨床研究設計的合理性。

The combination of our pipeline of next-generation chemotherapy drugs, our regulatory science approach that already includes the principles of Project Optimus, and our experience with the principles of Project Optimus in non-oncology FDA submissions are more reasons why we can more efficiently develop each of the next-generation drugs. We have a better probability of obtaining approval, and we can differentiate each NGC from its existing counterpart therapy.

我們的下一代化療藥物管道、我們已經包含 Optimus 項目原則的監管科學方法以及我們在非腫瘤 FDA 提交中使用 Optimus 項目原則的經驗相結合，是我們能夠更有效地開發每種藥物的更多原因的下一代藥物。我們獲得批准的可能性更大，並且我們可以將每種 NGC 與其現有的對應療法區分開來。

Next slide. Let me now discuss two of our next-generation drugs and some of the results over the last three to six months. First, looking at next-generation capecitabine, to remind you, capecitabine is the oral prodrug of 5-FU and is widely used in many types of cancers, including colorectal, gastric, breast, pancreatic, and other cancers. Cumulatively, these cancers have an incident rate of greater than 200,000 new patients per year.

下一張幻燈片。現在讓我討論我們的兩種下一代藥物以及過去三到六個月的一些結果。首先看下一代卡培他濱，提醒大家，卡培他濱是5-FU的口服前藥，廣泛應用於多種癌症，包括結直腸癌、胃癌、乳腺癌、胰腺癌等。累計起來，每年這些癌症的新患者發病率超過 200,000 名。

Next-generation capecitabine is the combination treatment of PCS6422, which alters capecitabine metabolism and distribution and capecitabine itself.

下一代卡培他濱是 PCS6422 的聯合治療，它改變卡培他濱的代謝和分佈以及卡培他濱本身。

Next slide. This slide is a summary of the data to date from our Phase 1b next-generation capecitabine clinical trial. I would like to point out a few items on the slide. First, we found that next-generation capecitabine alters the metabolism distribution of capecitabine.

下一張幻燈片。這張幻燈片是我們 1b 期下一代卡培他濱臨床試驗迄今為止數據的摘要。我想指出幻燈片上的一些內容。首先，我們發現下一代卡培他濱改變了卡培他濱的代謝分佈。

Second, in the last column of the table, next-generation capecitabine at all doses evaluated so far does not cause any adverse events from the metabolite called catabolites This is important to note, since 50% to 70% of the patients receiving the present capecitabine have adverse events from catabolites.

其次，在表的最後一列中，迄今為止評估的所有劑量的下一代卡培他濱不會因稱為分解代謝物的代謝物引起任何不良事件。這一點值得注意，因為接受本卡培他濱治療的患者中有50% 至70%有分解代謝物引起的不良事件。

Third, we have identified drug exposure levels that cause dose-limiting toxicities, abbreviated as DLT, and exposure levels that do not cause DLT. Fourth, we will be meeting with FDA in mid-April to discuss the Phase 2b safety efficacy trial and which regimens or exposure level should be used our implementation of Project Optimus.

第三，我們確定了導致劑量限制性毒性（縮寫為 DLT）的藥物暴露水平和不導致 DLT 的暴露水平。第四，我們將於 4 月中旬與 FDA 會面，討論 2b 期安全有效性試驗，以及我們實施 Optimus 項目時應使用哪些方案或暴露水平。

And lastly, our goal is to initiate the Phase 2b trial in the second half of 2023, performance interim analysis mid-2024, and complete enrollment by the end of 2024.

最後，我們的目標是在 2023 年下半年啟動 2b 期試驗，在 2024 年中期進行性能中期分析，並在 2024 年底完成入組。

Now let's look at our next-generation irinotecan drug. Next slide. Again, there are more than 200,000 patients per year who are diagnosed with the types of cancers that irinotecan is used for. Next slide. We wanted to determine if Project Optimus was important for this drug. In other words, do we need to do a dose-ranging clinical study evaluating response versus dose to determine an FDA-approvable dose as recommended by Project Optimus?

現在讓我們來看看我們的下一代伊立替康藥物。下一張幻燈片。同樣，每年有超過 200,000 名患者被診斷患有伊立替康所治療的癌症類型。下一張幻燈片。我們想確定擎天柱計劃對於這種藥物是否重要。換句話說，我們是否需要進行劑量範圍臨床研究來評估反應與劑量的關係，以確定 FDA 批准的 Optimus 項目推薦的劑量？

What we have analyzed from our cancer animal models is that the response exposure relationships for irinotecan and next-generation irinotecan are different. Looking at the left figure, if we decrease the dose from the maximum tolerated dose or the MTD to 50% of the MTD for next-generation irinotecan, the adverse events decrease, which is the red line. But the efficacy, which is the blue line, remains about the same.

我們從癌症動物模型中分析發現，伊立替康和下一代伊立替康的反應暴露關係是不同的。看左圖，如果我們將下一代伊立替康的劑量從最大耐受劑量或MTD減少到MTD的50%，不良事件就會減少，也就是紅線。但功效（即藍線）保持大致相同。

For irinotecan, however, in the figure on the right, decreasing the dose to 50% of the MTD results in a decrease in both the adverse events and the efficacy.

然而，對於伊立替康，如右圖所示，將劑量減少至 MTD 的 50% 會導致不良事件和療效均下降。

We concluded that besides now being an FDA requirement for oncology drugs, the principles of Project Optimus need to be used for next-generation irinotecan because the justification of their dosage regimen for approval needs to evaluate the adverse event exposure and the efficacy exposure relationships, which do not appear to follow a parallel path for next-generation irinotecan.

我們的結論是，除了現在 FDA 對腫瘤藥物的要求外，下一代伊立替康還需要採用 Project Optimus 的原則，因為其劑量方案批准的合理性需要評估不良事件暴露和療效暴露關係，這似乎沒有遵循下一代伊立替康的平行路徑。

Next slide. In the last three slides, I would like to briefly provide an overview of what we have accomplished in 2022 and what we plan to accomplish in 2023. This slide describes what we've accomplished in 2022. Let me just briefly point to three key accomplishments in 2022 for our next-generation drugs.

下一張幻燈片。在最後三張幻燈片中，我想簡要概述我們在2022 年取得的成就以及我們計劃在2023 年實現的目標。這張幻燈片描述了我們在2022 年取得的成就。讓我簡單指出三項關鍵成就2022 年我們的下一代藥物。

First, we determined what next-generation capecitabine drug exposure levels would cause dose-limiting side effects and what exposure levels will not. Second, we have defined the 2b-targeted cancer populations for next-generation gemcitabine. And third, we have determined that next-generation irinotecan adverse event exposure and efficacy exposure relationships do not follow the similar pattern.

首先，我們確定哪些下一代卡培他濱藥物暴露水平會導致劑量限制性副作用，哪些暴露水平不會。其次，我們定義了下一代吉西他濱的 2b 靶向癌症人群。第三，我們確定下一代伊立替康不良事件暴露和療效暴露關係並不遵循類似的模式。

For our non-oncology drugs, which we hope to [outlicense] or find a partner, we've completed the Phase 2a 12852 gastroparesis trial in which 12852 had a positive effect on gastric emptying rate and a larger effect in placebo and improving gastroparesis symptoms.

對於我們希望[獲得許可]或尋找合作夥伴的非腫瘤藥物，我們已經完成了2a 期12852 胃輕癱試驗，其中12852 對胃排空率有積極作用，並且對安慰劑和改善胃輕癱症狀有更大作用。

And for 499, we discontinued the trial due to enrollment difficulties, which is different from the published literature prior to starting the study. We are now evaluating other indications with larger populations for future licensees or partners.

對於 499 例，我們由於入組困難而停止了試驗，這與開始研究之前發表的文獻不同。我們現在正在為未來的被許可人或合作夥伴評估更多人群的其他適應症。

Next slide. The major milestones we expect to achieve in 2023 are: For next-generation capecitabine, we expect to meet with FDA in mid-April to discuss the Phase 2b safety efficacy trial with interim analysis and next-development steps; we expect to complete the Phase 1b trial to refine our understanding of the adverse event exposure relationship; and lastly, we hope to initiate the Phase 2b study sites in 2023 -- at the end of 2023, with the goal to have our interim analysis mid-2024 and complete enrollment in 2024.

下一張幻燈片。我們預計在 2023 年實現的主要里程碑是： 對於下一代卡培他濱，我們預計於 4 月中旬與 FDA 會面，討論 2b 期安全有效性試驗以及中期分析和下一步開發步驟；我們期望完成 1b 期試驗，以加深我們對不良事件暴露關係的理解；最後，我們希望在 2023 年（即 2023 年底）啟動 2b 期研究中心，目標是在 2024 年中期進行中期分析，並在 2024 年完成入組。

For next-generation gemcitabine, we expect to meet with FDA in mid-2023 on the Phase 2b safety efficacy trial and next development steps with the goal to submit a Phase 2b protocol to the IND in the fourth quarter of 2023 and initiate the trial in 2024.

對於下一代吉西他濱，我們預計將於 2023 年中期與 FDA 就 2b 期安全功效試驗和後續開發步驟進行會面，目標是在 2023 年第四季度向 IND 提交 2b 期方案，並於 2023 年啟動試驗。 2024年。

For next-generation irinotecan, we hope to initiate the IND-enabling studies in 2023 with the goal to complete studies by the end of 2024.

對於下一代伊立替康，我們希望在2023年啟動IND研究，目標是在2024年底完成研究。

Regarding licensing or partnering our drugs, we are now working on licensing or partnering our non-oncology drugs. But we would also consider monetizing one or more of our next-generation chemotherapy drugs.

關於我們的藥物的許可或合作，我們現在正在致力於非腫瘤藥物的許可或合作。但我們也會考慮將一種或多種下一代化療藥物貨幣化。

Corporately, we are expanding our visibility and public presence, including social media, by engaging an IR/PR group as well as planning to communicate more with our investors. We also plan to interact more with the oncology community, including key opinion leaders and patient advocacy groups.

在企業方面，我們正在通過與投資者關係/公關小組合作以及計劃與投資者進行更多溝通來擴大我們的知名度和公眾影響力，包括社交媒體。我們還計劃與腫瘤學界進行更多互動，包括關鍵意見領袖和患者倡導團體。

Next slide. This last slide summarizes some of the material in the previous slides. Before we end my part of the earnings call, I thought I would address a few questions that we received from investors. The first one I'd like to address is we've been asked, why develop next-generation chemotherapy instead of finding a new oncology treatment?

下一張幻燈片。最後一張幻燈片總結了前面幻燈片中的一些材料。在結束財報電話會議之前，我想先回答投資者提出的一些問題。我想解決的第一個問題是我們被問到，為什麼要開發下一代化療而不是尋找新的腫瘤治療方法？

As I stated when discussing the slides, our next-generation chemotherapy drugs represent a better treatment for cancer patients that will improve their survival and quality of life. These drugs are not new because they kill the cancer in the same way as the presently approved drugs. But new -- they are new because they provide less side effects. They are handled by the body differently, and it should provide a better benefit risk profile for approval.

正如我在討論幻燈片時所說，我們的下一代化療藥物為癌症患者提供了更好的治療方法，將提高他們的生存率和生活質量。這些藥物並不新鮮，因為它們殺死癌症的方式與目前批准的藥物相同。但新的——它們是新的，因為它們提供的副作用更少。機構對它們的處理方式不同，應該提供更好的利益風險概況以供批准。

With these drugs and the implementation of our regulatory science approach, including the principles of Project Optimus, these next-generation chemotherapy drugs can be more efficiently developed, have a greater probability of approval, and will be better treatment options than the existing FDA-approved drugs.

通過這些藥物以及我們監管科學方法（包括Optimus計劃的原則）的實施，這些下一代化療藥物可以更有效地開發，獲得批准的可能性更大，並且將是比現有FDA批准的更好的治療選擇藥物。

A second question [that we have been] asked is what steps are you taking to enhance shareholder value? We've implemented a number of strategies to increase shareholder value, and we are in the process of launching more. These have included increasing Processa visibility by bringing on the IR/PR group to improve everything from our website to the number and quality of our presentations to include -- increase our presence on social media.

[我們]被問到的第二個問題是，你們正在採取哪些措施來提高股東價值？我們已經實施了多項提高股東價值的戰略，並且正在推出更多戰略。其中包括通過引入 IR/PR 團隊來改進從我們的網站到演示文稿的數量和質量的所有內容，包括提高我們在社交媒體上的影響力，從而提高 Processa 的知名度。

We're also reaching out more to the oncology community, as I said, both physicians and patients, to make sure that Processa and our next-generation chemotherapy drugs are better known. And finally, we are working with FDA to hopefully expedite development and make the development process as efficient as possible.

正如我所說，我們還更多地接觸腫瘤學界，包括醫生和患者，以確保 Processa 和我們的下一代化療藥物得到更好的了解。最後，我們正在與 FDA 合作，希望能夠加快開發速度，並使開發過程盡可能高效。

The last -- well, not last -- question I'd like to address is we've been asked, why have the members of the C-suite not purchased shares recently? Some of the C-suite and Board were involved in the $6 million raise earlier this year that Jim mentioned. Unfortunately, during most of the first quarter of 2023, we have all been blacked out, which has made any type of Processa stock purchase impossible. Hopefully, that will change in the near future.

我想解決的最後一個——好吧，不是最後一個——問題是我們被問到，為什麼最高管理層的成員最近沒有購買股票？ Jim 提到，今年早些時候，一些最高管理層和董事會參與了 600 萬美元的融資。不幸的是，在 2023 年第一季度的大部分時間裡，我們都處於停電狀態，這使得任何類型的 Processa 股票購買都變得不可能。希望這種情況在不久的將來會改變。

I want to close by saying that my management team and I are keenly aware of the underperformance of our stock in recent months. As noted earlier, this remains an equity play for all of us involved. While displeased with our current valuation, we are focused on doing those things which we believe are all in our collective best interest and have the potential to create substantial value for Processa and its investors.

最後，我想說的是，我和我的管理團隊都敏銳地意識到我們的股票近幾個月表現不佳。如前所述，對於我們所有參與者來說，這仍然是一場公平的遊戲。雖然對我們目前的估值感到不滿意，但我們專注於做那些我們認為符合我們集體最佳利益並有潛力為 Processa 及其投資者創造巨大價值的事情。

Operator, I'd like to hand it to you.

接線員，我想把它交給你。

(Operator Instructions) François Brisebois, Oppenheimer.

（操作員說明）François Brisebois，Oppenheimer。

[It's Dan on for Frank]. Thanks for taking the question. Just -- if I could start with more of a broad-level question, given the alignment of the trials to Project Optimus, just wondering how we should be thinking about dosage levels, given that the dosage is going to be optimized for efficacy and safety, and it can vary from patient to patient? And how should we be thinking about that?

[由丹代替弗蘭克]。感謝您提出問題。只是——考慮到試驗與擎天計劃的一致性，我是否可以從一個更廣泛的問題開始，只是想知道我們應該如何考慮劑量水平，因為劑量將針對功效和安全性進行優化，並且它可能因患者而異？我們應該如何思考這個問題？

And related to that, if you could add some color on what the goals are for the upcoming mid-April meeting with the FDA, that would be great. Thanks.

與此相關的是，如果您能為即將舉行的 4 月中旬 FDA 會議的目標添加一些色彩，那就太好了。謝謝。

Okay. Thanks for joining us. Can you hear me? Can everybody hear me okay, I hope?

好的。感謝您加入我們。你能聽到我嗎？我希望每個人都能聽到我的聲音嗎？

Yes.

是的。

Okay. So let me first -- let me go to the last question first. The goals for the meeting with FDA mid-April are to actually discuss their view of Project Optimus, given our next-generation capecitabine and then come to an agreement and negotiate out what would be the best dosage regimen or designs to put into the Project Optimus Phase 2b trial.

好的。首先讓我——讓我先回答最後一個問題。 4 月中旬與 FDA 會議的目標是實際討論他們對 Optimus 項目的看法，考慮到我們的下一代卡培他濱，然後達成協議並協商出適合 Project Optimus 的最佳劑量方案或設計2b 期試驗。

Since we use Project Optimus in other types of drugs, we know how to do it. But we wanted to hear from the oncology group because this is new to them, their thoughts and their approach that they want to take. We'll then take that together and discuss it with them, come up with an agreement with them, and then be able to move forward. So that's the real design and -- the design of the study as well as the dosage regimen.

由於我們在其他類型的藥物中使用了 Project Optimus，因此我們知道如何去做。但我們想听聽腫瘤學小組的意見，因為這對他們、他們的想法和他們想要採取的方法來說都是新的。然後我們將與他們一起討論這個問題，與他們達成協議，然後才能繼續前進。這就是真正的設計——研究的設計以及劑量方案。

Your first question, could you remind me what the first question was? I apologize.

你的第一個問題，你能提醒我第一個問題是什麼嗎？我道歉。

Just in terms of how -- since it's not an MTD trial, how we should be thinking about dosage levels across patients going to be optimized for --

只是就如何——因為這不是 MTD 試驗，我們應該如何考慮患者的劑量水平進行優化——

Yes. So what we're going to be doing is -- what we have done in our Phase 1b trial is we've been monitoring the exposure of the drug to each of the patients. You have to remember that this is a drug interaction situation where one drug alters the metabolism of capecitabine. 6422 alters the metabolism of capecitabine, which then alters also the distribution, all right?

是的。所以我們要做的是——我們在 1b 期試驗中所做的是，我們一直在監測每位患者的藥物暴露情況。您必須記住，這是一種藥物相互作用的情況，其中一種藥物會改變卡培他濱的代謝。 6422 改變卡培他濱的代謝，從而改變分佈，好嗎？

So what's important is to know that how is it altering? Is it altering? As you said, there may be an individual patient that alters differently than another patient. And all these things are going to be monitored in patients so that by the end of the Phase 2b trial, we'll have a better idea of what the design of the Phase 3 trial should be.

那麼重要的是要知道它是如何改變的？是在改變嗎？正如您所說，個別患者的變化可能與其他患者不同。所有這些事情都將在患者身上進行監測，以便在 2b 期試驗結束時，我們將更好地了解 3 期試驗的設計應該是什麼。

We're already getting that initial information in our Phase 1b trial, but we need to get to the efficacy side, which would be in the Phase 2b trial, then we'll be able to design the Phase 3.

我們已經在 1b 期試驗中獲得了初步信息，但我們需要了解功效方面，這將在 2b 期試驗中進行，然後我們才能設計 3 期試驗。

Great. And just a quick one from another one. How are you thinking about indications for the next-gen capecitabine program? Is that patients who would be otherwise be prescribed capecitabine or across indications?

偉大的。這只是另一篇的快速一篇。您如何看待下一代卡培他濱項目的適應症？這些患者是否會接受卡培他濱治療或跨適應症治療？

Right now, we're going to be looking at patients who would typically be prescribed capecitabine. But we do not think that that will be the end result. We think the types of patients, the targeted population, is much broader. And we also believe that the targeted population will be on metastatic colorectal cancer. It's also pancreatic cancer, other types of cancers. This is just the first step to get to the end.

現在，我們將研究通常服用卡培他濱的患者。但我們認為這不會是最終結果。我們認為患者的類型、目標人群要廣泛得多。我們還相信目標人群將是轉移性結直腸癌。這也是胰腺癌和其他類型的癌症。這只是到達終點的第一步。

Great. Thank you for taking my questions.

偉大的。感謝您回答我的問題。

Thank you.

謝謝。

(Operator Instructions) Naz Rahman, Maxim Group.

（操作員說明）Naz Rahman，Maxim 集團。

Hi, guys. Thanks for taking my question. I have a few, actually. I'll just start on your next-gen capecitabine product. Recently, you announced you're enrolling the 300-milligram patient cohort. And you said that you expect to complete enrollment by mid-2023. Could you comment on what gives you confidence in completing one by mid-2023? And when can we expect to see data from that cohort?

嗨，大家好。感謝您提出我的問題。其實我有幾個。我將開始介紹你們的下一代卡培他濱產品。最近，您宣布將招募 300 毫克的患者隊列。您表示預計在 2023 年中期完成註冊。您能否評論一下是什麼讓您有信心在 2023 年中期完成一項任務？我們什麼時候可以看到該隊列的數據？

Well, so for the 300-milligram group, we already have some patients enrolled. We have been pushing the sites to enroll more quicker. And so, we're pretty confident we'll have it done in the next month or two, all right?

嗯，對於 300 毫克組，我們已經招募了一些患者。我們一直在推動網站更快地註冊。因此，我們非常有信心在接下來的一兩個月內完成它，好嗎？

The question then becomes do we go to the next cohort, or should we be going to the next cohort after that? We won't know that until we see the doses or the safety profile from the dose that we're presently on. We're still going to the FDA, though, in mid-April because regardless of having it, we know that one of the dosing regimens that FDA will want us to take into the Phase 2b will be that MTD -- will be that MTD dose.

那麼問題就變成了我們是否應該進入下一個隊列，或者我們應該在那之後進入下一個隊列？在我們看到劑量或我們目前使用的劑量的安全性之前，我們不會知道這一點。不過，我們仍然會在 4 月中旬向 FDA 提交申請，因為無論是否有它，我們都知道 FDA 希望我們進入 2b 期的給藥方案之一將是 MTD——將是 MTD劑量。

And so, we will be using that. So it doesn't prevent us from meeting the FDA -- with the FDA. It doesn't prevent us from initiating things in terms of protocols and getting CROs selected. It doesn't prevent us from doing all that. But we won't know the exact dose or the exact dosage regimen until we get to that MTD, which, again, we project it will be in mid-year.

因此，我們將使用它。所以這並不妨礙我們與 FDA 會面。這並不妨礙我們在協議方面啟動一些事情並選擇 CRO。它並不妨礙我們做這一切。但在我們達到 MTD 之前，我們不會知道確切的劑量或確切的劑量方案，我們再次預計這將在年中進行。

Got it. And on that Phase 2b protocol that you plan to discuss with the FDA, could you provide some potential color in what you expect the Phase 2b or what are you thinking the Phase 2b might look like in terms of study design?

知道了。關於您計劃與 FDA 討論的 2b 期協議，您能否提供一些您對 2b 期的預期的潛在色彩，或者您認為 2b 期在研究設計方面可能會是什麼樣子？

Yes, I prefer not to discuss that right now until we negotiate a little bit more and discuss it with the FDA. But it's going to be a more typical efficacy safety study, where we're looking, of course, at efficacy and safety. We are going to be talking about probably anywhere from three to four groups with different dosing regimens and potentially a control group with the established dose.

是的，我現在不想討論這個問題，直到我們進行更多談判並與 FDA 討論。但這將是一項更典型的功效安全性研究，我們當然會關注功效和安全性。我們將討論可能有三到四個具有不同給藥方案的組，以及可能具有既定劑量的對照組。

So again, we are proposing something to the FDA and trying to figure out how what how they're thinking about Project Optimus. And based on what they share, we'll be able to figure out how they're thinking about it a little bit more and then be able to tweak our study to -- not only the needs of getting into Phase 3, but also fit the needs of the answers and questions that FDA might have.

我們再次向 FDA 提出一些建議，並試圖了解他們對 Optimus 項目的看法。根據他們分享的內容，我們將能夠進一步了解他們的想法，然後能夠調整我們的研究，不僅滿足進入第三階段的需求，而且適合FDA 可能需要的答案和問題。

Got it. And I'm going to shift gears a little to on 3117, a few questions here. Previously, you mentioned that you guys are developing a macro molecule assay. Have you on completed work on that, and what might it look like? Is it like blood based or biopsy based, and are you still working on this project?

知道了。我將稍微轉向一下 3117，這裡有幾個問題。之前，您提到你們正在開發一種大分子檢測方法。你已經完成了這方面的工作嗎？它會是什麼樣子？是基於血液還是基於活檢，您還在從事這個項目嗎？

Yes, we are still working on it. But if you think about how biomarkers are evaluated at FDA, identifying a potential biomarker is the first step. That's all the analytical procedures, et cetera. That's the step we're at right now. The next step in the biomarker work is that you have to prove there really is a biomarker. So our hope is that we will have the analytical part done.

是的，我們仍在努力。但如果您考慮 FDA 如何評估生物標誌物，那麼第一步就是確定潛在的生物標誌物。這就是所有的分析程序等等。這就是我們現在正在進行的步驟。生物標誌物工作的下一步是必須證明確實存在生物標誌物。所以我們希望能夠完成分析部分。

And then, at the end of the year, we'll be able to submit the protocol to the IND for a Phase 2b trial. And that Phase 2b trial will be the one that says, is it really a biomarker? Even though the analytical is done, you have to prove biologically and clinically it is a biomarker. So that will be done also at the same time in the Phase 2b trial.

然後，在今年年底，我們將能夠將方案提交給 IND 進行 2b 期試驗。 2b 期試驗將說明，它真的是一種生物標誌物嗎？即使分析完成，您也必須在生物學和臨床上證明它是一種生物標誌物。因此，這也將在 2b 階段試驗中同時進行。

So we're not using it. We're not going to be using the biomarker to say these are the only patients to study. We cannot do that because we don't know it's a biomarker because there hasn't been a study yet. So that's the Phase 2b study. We're looking at efficacy, safety, as well as determining if this analytical measurement of a macro molecule is really a biomarker.

所以我們不使用它。我們不會使用生物標誌物來表明這些患者是唯一需要研究的患者。我們不能這樣做，因為我們不知道它是一個生物標誌物，因為還沒有研究。這就是 2b 期研究。我們正在研究功效、安全性，並確定這種大分子的分析測量是否真的是生物標誌物。

Got it. And the biomarkers you're evaluating, are they blood based or biopsy based?

知道了。您正在評估的生物標誌物是基於血液還是基於活檢？

I can't comment on that right now.

我現在無法對此發表評論。

Okay.

好的。

Because there may be some intellectual property things that we're dealing with [and things] -- so I can't comment on that right now.

因為我們正在處理一些知識產權問題，所以我現在無法對此發表評論。

Got it. And I guess my last question is on 11T irinotecan. You mentioned that you obviously see a better risk benefit profile at a 50% dose. But could you give more color on what the dosing regimen might look like? Does that mean, for example, you provide like 50% or even lower dose and increase the dosing frequency to reduce the incidents of AEs? Or are you dosing at the same volume and intervals just with a better formulation? Could just provide more color surrounding that?

知道了。我想我的最後一個問題是關於 11T 伊立替康。您提到，您顯然會在 50% 的劑量下看到更好的風險收益狀況。但是您能否對給藥方案進行更多說明？例如，這是否意味著您提供 50% 甚至更低的劑量並增加給藥頻率以減少 AE 事件？或者您是否以相同的體積和間隔給藥，只是採用了更好的配方？可以在周圍提供更多顏色嗎？

Yes. So right now, what we've done is we've kept the dosing regimen, the timing of the dose, the same. And the only thing we've done is change the actual amount that's been dosed, all right, in terms of the active molecule. But we have to remember, this is not a formulation change.

是的。所以現在，我們所做的就是保持給藥方案、給藥時間相同。我們所做的唯一一件事就是改變活性分子的實際劑量。但我們必須記住，這不是公式的改變。

So the formulation of these things don't make a difference. But the key to this is this is a prodrug. So what we've done is we've taken the active molecule of irinotecan, which is SN-38, and we've hooked on some other molecules onto it. And those other molecules preferentially put the drug into the membrane of the cancer cells over normal cells.

所以這些東西的表述並沒有什麼區別。但關鍵是這是一種前藥。因此，我們所做的就是採用伊立替康的活性分子 SN-38，並在其上附加一些其他分子。與正常細胞相比，這些其他分子優先將藥物放入癌細胞膜中。

So it's like -- I don't want to call it -- it's like a transporter, or in some way just loads up the drug into the cancer cells versus normal cells. And so, we have a different balance between how much the cancer cells get this SN-38 versus normal cells compared to irinotecan, where you have a different balance. So what we're really doing is the prodrug that makes this drug be attracted into the membrane of cancer cells.

所以它就像——我不想這麼稱呼它——它就像一個轉運蛋白，或者以某種方式將藥物裝載到癌細胞而不是正常細胞中。因此，與伊立替康相比，癌細胞與正常細胞獲得 SN-38 的量之間存在不同的平衡，在這種情況下，我們有不同的平衡。所以我們真正做的是使這種藥物被吸引到癌細胞膜上的前藥。

That actually raised two questions from me. So it sounds like that your 11T, it sounds like it's more selective. Do you have any numbers surrounding selectivity of 11T versus regular irinotecan? And also, is it also more bioavailable?

這實際上向我提出了兩個問題。所以聽起來你的11T，聽起來更有選擇性。您是否有關於 11T 與常規伊立替康選擇性的數據？而且，它的生物利用度是否也更高？

We do have numbers. I can't share those right now, but we'll be putting something out on that in the near future. But in terms of -- the administration is parenteral administration, if not oral administration. So the bioavailability is pretty much the same.

我們確實有數字。我現在無法分享這些內容，但我們會在不久的將來發布一些內容。但就給藥而言，即使不是口服給藥，也是腸胃外給藥。所以生物利用度幾乎相同。

But again, I won't -- I can't comment. There is a difference in the cancer to tissue ratio of irinotecan versus next-generation irinotecan. There is definitely a difference, a big difference. But I just can't say the number right now at this time.

但我再說一遍，我不會——我無法發表評論。伊立替康與下一代伊立替康的癌症與組織比率存在差異。肯定是有區別的，而且是很大的區別。但現在我還不能說出這個數字。

Got it. So I just have one last question, if you don't mind. Is it possible for you to comment on what you think the Phase 2B for 6422 and Phase 2b for 3117 might cost?

知道了。如果你不介意的話，我只有最後一個問題。您能否評論一下您認為 6422 的 2B 階段和 3117 的 2b 階段的成本可能是多少？

That's hard for us to do right now because a lot of it depends on the discussion and negotiations with the FDA. Of course, if they want four arms and they want a bigger study, that's going to be more expensive. If it's only two or three arms and not having a normal control, for example, it would be less expensive.

我們現在很難做到這一點，因為這很大程度上取決於與 FDA 的討論和談判。當然，如果他們想要四隻手臂並且想要進行更大規模的研究，那就會更昂貴。例如，如果只有兩個或三個手臂並且沒有正常的控制，那麼它會更便宜。

I really can't say because it depends on how we finalize the design, which we won't know until after we meet [NATCO] for next-generation capecitabine.

我真的不能說，因為這取決於我們如何最終確定設計，直到我們與[NATCO]會面討論下一代卡培他濱之後我們才會知道這一點。

For next-generation gemcitabine, it's a little different. What we are going to be looking at, we are meeting with the FDA also mid-year in that. And what we are going to be looking at is the alternative types of pancreatic cancers that we should be targeting this drug to.

對於下一代吉西他濱來說，情況有些不同。我們將在年中與 FDA 舉行會議，討論我們將要關注的問題。我們將關注的是我們應該將這種藥物瞄準的其他類型的胰腺癌。

And so, a lot of that it will, again, will depend on where we think the FDA will want us to go, where the market is for this drug in terms of type of pancreatic cancer, or in terms of what stage of pancreatic cancer, or surgical/nonsurgical. So there's always nuances of pancreatic cancer that we have to discuss with the FDA and then evaluate from a market as well as drug development timeframe, as well as costs, which is about to go.

因此，這在很大程度上將再次取決於我們認為 FDA 希望我們走向何方，就胰腺癌類型或胰腺癌的哪個階段而言，該藥物的市場在哪裡，或手術/非手術。因此，我們必須與 FDA 討論胰腺癌的細微差別，然後從市場、藥物開發時間表以及即將過去的成本進行評估。

Got it. Thanks for taking all my questions.

知道了。感謝您回答我所有的問題。

Thanks, Naz.

謝謝，納茲。

(Operator Instructions) Okay. We have no further questions in queue.

（操作員指示）好的。我們沒有其他問題了。

We have reached the end of the question-and-answer session. This concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation.

我們的問答環節已經結束。今天的會議到此結束，此時您可以掛斷電話了。感謝您的參與。

Thank you.

謝謝。