Delcath Systems Inc (DCTH) 2022 Q3 法說會逐字稿

Good day, and welcome to the Delcath Systems' third-quarter 2022 financial results conference call. All participants will be in a listen-only mode. (Operator Instructions) After today's presentation, there will be an opportunity to ask questions. (Operator Instructions) Please note today's event is being recorded.

美好的一天，歡迎來到 Delcath Systems 的 2022 年第三季度財務業績電話會議。所有參與者都將處於只聽模式。 （操作員說明）在今天的演示之後，將有機會提問。 （操作員說明）請注意今天的活動正在錄製中。

I would now like to turn the conference over to David Hoffman, Delcath's General Counsel. Please go ahead.

我現在想將會議轉交給 Delcath 的總法律顧問 David Hoffman。請繼續。

Thank you. And once again, welcome to Delcath Systems' third-quarter 2022 earnings call. With me on the call are Gerard Michel, the Chief Executive Officer; Dr. Johnny John, Senior Vice President of Medical Affairs and Clinical Development; Kevin Muir, Vice President of Commercial Operations; and Anthony Dias, Vice President of Finance.

謝謝。再次歡迎來到 Delcath Systems 的 2022 年第三季度財報電話會議。與我通話的是首席執行官杰拉德·米歇爾 (Gerard Michel)；醫學事務和臨床開發高級副總裁 Johnny John 博士；商業運營副總裁 Kevin Muir；財務副總裁 Anthony Dias。

I'd like to begin the call 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 27(a) of the Securities Act of 1933 and Section 21(e) of the Securities Exchange Act of 1934.

我想通過閱讀安全港聲明開始通話。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作出的。除歷史事實外，本次電話會議上的所有聲明均可被視為前瞻性聲明1933 年證券法第 27(a) 條和 1934 年證券交易法第 21(e) 條。

Although the company believes that expectations and assumptions reflected in these forward-looking statements are reasonable, it makes no assurance that such expectations will prove to have been correct. Actual results may differ materially from those expressed or implied in forward-looking statements due to various risks and uncertainties.

儘管公司認為這些前瞻性陳述中反映的預期和假設是合理的，但不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 which could cause actual results to differ from those expressed or implied in the forward-looking statements, please see risk factors detailed in the company's annual report on Form 10-K, those contained in subsequently filed quarterly reports on Form 10-Q, as well as in other reports that the company files from time to time with the Securities and Exchange Commission.

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，請參閱公司 10-K 表格年度報告中詳述的風險因素，以及隨後提交的季度報告中包含的風險因素在 10-Q 表格以及公司不時向證券交易委員會提交的其他報告中。

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, or 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。我們不承擔任何更新或補充任何前瞻性陳述以反映後續知識、事件或情況的義務。

Now, I would like to turn the call over to Gerard Michel. Gerard, please proceed.

現在，我想把電話轉給 Gerard Michel。杰拉德，請繼續。

Thank you everyone for joining today. Delcath has had a productive third quarter of 2022 for both HEPZATO KIT, the company's product development candidate in the United States; and CHEMOSAT, the company's marketed product in Europe.

感謝大家今天的加入。 Delcath 在美國的產品開發候選產品 HEPZATO KIT 在 2022 年第三季度取得了豐碩成果；和 CHEMOSAT，該公司在歐洲銷售的產品。

In the US, we have two centers enrolled and currently treating patients under the expanded access program or EAP, with a third center enrolled and pending training. In addition, four other sites are in various stages of the startup process. And these include sites that were not involved in the FOCUS trial.

在美國，我們有兩個中心已註冊，目前正在根據擴展訪問計劃或 EAP 治療患者，第三個中心已註冊並等待培訓。此外，還有四個站點正處於啟動過程的不同階段。其中包括未參與 FOCUS 試驗的網站。

We are on track to file the HEPZATO Class 2 resubmission of the NDA to FDA by the end of December. We expect that within 30 days after the submission, the FDA will confirm receipt of the submission. And if they agree the resubmission is sufficiently complete to warrant review, establish a PDUFA date six months from the submission date.

我們有望在 12 月底之前向 FDA 提交 HEPZATO 2 類重新提交的 NDA。我們預計在提交後 30 天內，FDA 將確認收到提交的文件。如果他們同意重新提交的內容足夠完整以保證審查，請在提交日期後六個月內確定 PDUFA 日期。

As we previously reported, in the third quarter, a retrospective analysis of patients treated with CHEMOSAT in three European centers, one in the Netherlands and two in Germany between February 2014 and December 2019, was published. The analysis involved 212 PHP procedures on 101 patients. The publication reported an overall response rate of 59.4% and a disease control rate of 89.1%.

正如我們之前報導的那樣，在第三季度，對 2014 年 2 月至 2019 年 12 月期間在三個歐洲中心接受 CHEMOSAT 治療的患者進行了回顧性分析，其中一個在荷蘭，兩個在德國。該分析涉及對 101 名患者進行的 212 次 PHP 程序。該出版物報告的總體反應率為 59.4%，疾病控制率為 89.1%。

The safety analysis showed mostly grade 1-2 and self-limiting toxicity consistent with previous reports on PHP. This continues to add a path to the growing body of published research documenting the efficacy and safety of our CHEMOSAT system in the European commercial center.

安全性分析顯示大部分為 1-2 級和自限性毒性，與之前關於 PHP 的報告一致。這繼續為越來越多的已發表研究增加了一條途徑，這些研究記錄了我們在歐洲商業中心的 CHEMOSAT 系統的有效性和安全性。

Researchers from Leiden University Medical Center in the Netherlands are making rapid progress on the randomized Phase II portion of the CHOPIN trial with approximately 50% of the planned 76 patients enrolled. Recall the goal of this combined Phase Ib randomized Phase II trial is to study the safety and potential synergistic effects of systemic immunotherapy, ipilimumab and nivolumab or ipi/nivo, when combined with Delcath's proprietary liver-targeted treatment in metastatic uveal melanoma patients.

荷蘭萊頓大學醫學中心的研究人員正在 CHOPIN 試驗的隨機 II 期部分取得快速進展，計劃招募的 76 名患者中約有 50% 入組。回想一下，這項聯合 Ib 期隨機 II 期試驗的目標是研究全身免疫療法、ipilimumab 和 nivolumab 或 ipi/nivo 與 Delcath 專有的肝靶向治療相結合對轉移性葡萄膜黑色素瘤患者的安全性和潛在協同作用。

We look forward to the completion of enrollment into this trial possibly as early as late next year given the pace of recruitment and to provide updates on the progress of the seven patients who completed the Phase Ib portion of the trial.

考慮到招募的速度，我們期待最早在明年年底完成該試驗的招募，並提供完成 Ib 期試驗的 7 名患者的最新進展。

At ASCO earlier this year, the investigators reported an ORR of 85.7% and a DCR of 100%. We expect updates on the previous and reported median progression-free survival of 22.4 months as the data matures. If similar results are seen in the current larger randomized Phase II portion of the trial and the combination continues to be well tolerated, it could represent a significant improvement over current standard of care including PHP alone.

在今年早些時候的 ASCO 上，研究人員報告了 85.7% 的 ORR 和 100% 的 DCR。隨著數據的成熟，我們預計會更新之前和報告的 22.4 個月的中位無進展生存期。如果在當前更大的隨機 II 期試驗部分中看到類似的結果，並且該組合繼續得到良好的耐受性，則它可能代表當前的護理標準（包括單獨的 PHP）的顯著改進。

While the results will be important in terms of the treatment of metastatic uveal melanoma patients, they could have relevance across multiple tumor types, where hepatic metastases are present and immunotherapy is an accepted treatment.

雖然結果對於轉移性葡萄膜黑色素瘤患者的治療很重要，但它們可能與多種腫瘤類型相關，其中存在肝轉移並且免疫療法是一種公認的治療方法。

Turning to the commercial progress of CHEMOSAT in Europe. The third quarter was the second full quarter after we resumed direct responsibility for sales, marketing, and distribution activities, which occurred on March 1, 2022. Excluding the Netherlands, where most patients are now being treated in the CHOPIN trial, our units increased 41% over the same quarter last year and increased 26% versus the second quarter.

轉向歐洲 CHEMOSAT 的商業進展。第三季度是我們於 2022 年 3 月 1 日恢復對銷售、營銷和分銷活動的直接責任後的第二個完整季度。除荷蘭外，我們的單位增加了 41 %，比去年同期增長 26%，比第二季度增長 26%。

We will continue to operate the business on a cash flow breakeven basis for the time being. But we'll make several key hires in Germany and engage with consultants to support submissions for national coverage. These submissions are reliant on the publication of the FOCUS trial results which will now occur early next year. The first submission for national coverage will be in the UK.

我們將暫時繼續在現金流盈虧平衡的基礎上經營業務。但我們將在德國招聘幾名重要人員，並與顧問合作以支持提交全國報導。這些提交取決於 FOCUS 試驗結果的公佈，該結果將於明年初公佈。第一次提交全國報導將在英國。

In late October, we agreed with medac, the previous distributor of CHEMOSAT in UK and EU, on terms to settle the party's ongoing dispute over the termination of the distribution agreement. The parties will reach a definitive settlement agreement before the end of 2022. And with this dispute behind us and the planned upcoming publication of FOCUS trial results, we are confident that Europe will become a meaningful revenue contributor to the business with EU revenues likely growing along with US commercial launch of HEPZATO if approved next year.

10 月下旬，我們與 CHEMOSAT 在英國和歐盟的前分銷商 medac 達成協議，解決雙方就終止分銷協議一直存在的爭議。雙方將在 2022 年底前達成最終和解協議。隨著這場爭端的結束以及計劃即將發布的 FOCUS 試驗結果，我們相信歐洲將成為該業務的重要收入貢獻者，歐盟收入可能會隨之增長如果明年獲得批准，將在美國商業推出 HEPZATO。

Also in October, we successfully completed a notified body audit to recertify our Queensbury, New York manufacturing facility for CHEMOSAT under the European Medical Device Regulation or MDR. While recertification even under the new MDR regulation has become routine for the company, it is important to keep in mind that our team in Queensbury has been undergoing audits for years. And I'm confident that we are well prepared for a preapproval inspection from the FDA.

同樣在 10 月，我們成功完成了公告機構審核，根據歐洲醫療器械法規或 MDR 重新認證了我們位於紐約昆斯伯里的 CHEMOSAT 製造工廠。雖然即使在新的 MDR 法規下重新認證也已成為公司的例行公事，但請務必記住，我們在昆斯伯里的團隊多年來一直在接受審計。我相信我們已經為 FDA 的預批准檢查做好了充分準備。

Finally, we continue to lay the foundation for the planned commercialization of HEPZATO. During the third quarter, we held an advisory board in the United States with interventional radiologists and anesthesiologists to gain further insight into the way treating facilities will utilize HEPZATO, if approved, within their continuum of care.

最後，我們繼續為計劃中的 HEPZATO 商業化奠定基礎。在第三季度，我們在美國與介入放射科醫生和麻醉師舉行了一個諮詢委員會，以進一步了解治療設施將在其連續護理中使用 HEPZATO 的方式（如果獲得批准）。

We have solidified our market access plans and are confident that for Medicare patients, HEPZATO will primarily be reimbursed using pass-through status, initially with a miscellaneous [ZIP] code before being assigned our unique ZIP code. We are carefully watching Immunocore's progress and noticed that in their first full quarter, they obtained a unique ZIP code and booked $20 million in revenue from US KIMMTRAK sales despite being restricted to less than 50% of the patient population given their mechanism of action.

我們已經鞏固了我們的市場准入計劃，並相信對於 Medicare 患者， HEPZATO 將主要使用直通狀態進行報銷，最初使用雜項 [ZIP] 代碼，然後再分配我們獨特的郵政編碼。我們正在仔細觀察 Immunocore 的進展，並註意到在他們的第一個完整季度中，他們獲得了一個獨特的郵政編碼，並從美國 KIMMTRAK 銷售中獲得了 2000 萬美元的收入，儘管鑑於其作用機制，僅限於不到 50% 的患者群體。

Based on publicly available information, in the US, KIMMTRAK is priced at a level which equates to approximately $925,000 per patient based on the average duration of therapy reported for their pivotal trial. An equivalent price for the HEPZATO KIT would be somewhere between $150,000 to $225,000 per kit depending upon whether the price is based on a nine-month duration of therapy or six kits, or four HEPZATO treatments over six months, the mean number of treatments from the FOCUS trial.

根據公開信息，在美國，根據關鍵試驗報告的平均治療持續時間，KIMMTRAK 在美國的定價水平相當於每位患者約 925,000 美元。 HEPZATO KIT 的等效價格在每套 150,000 美元至 225,000 美元之間，具體取決於價格是基於九個月的治療時間還是六套，或者六個月內四次 HEPZATO 治療，平均治療次數焦點試驗。

While it is premature to finalize the price, this dynamic is important for investors to understand as we approach commercialization next year. We believe that the ultra-orphan pricing dynamic combined with a very focused set of treating centers we will support and the growing number of EAP sites will translate into rapid revenue growth, a short runway to becoming cash flow positive, and very strong operating margins.

雖然現在確定價格還為時過早，但隨著我們明年接近商業化，這種動態對投資者來說很重要。我們相信，超孤兒定價動態與我們將支持的一組非常集中的治療中心以及 EAP 站點數量的增加將轉化為快速的收入增長，短期內變為正現金流，以及非常強勁的營業利潤率。

Obviously, there is much to get done between now and launch. But the commercial potential for this first indication and the value it represents is clear.

顯然，從現在到發布之間還有很多工作要做。但是，這第一個適應症的商業潛力及其所代表的價值是顯而易見的。

I look forward to taking questions. But first, we'll turn the call over to Tony to review the financials. Tony?

我期待著回答問題。但首先，我們會把電話轉給托尼審查財務狀況。托尼？

Thank you, Gerard. Product revenues for the three months ended September 30, 2022 was approximately $906,000 compared to $395,000 for the prior quarter from the sales of CHEMOSAT in Europe. Revenues increased 129% over the same period last year, primarily because we're now booking all European revenue after the termination of the medac distribution agreement versus a royalty and a revenue share.

謝謝你，杰拉德。截至 2022 年 9 月 30 日止三個月的產品收入約為 906,000 美元，而上一季度來自 CHEMOSAT 在歐洲的銷售收入為 395,000 美元。收入比去年同期增長了 129%，這主要是因為我們現在在 medac 分銷協議終止後計入所有歐洲收入，而不是特許權使用費和收入分成。

Research and development expenses for the quarter increased to $4 million compared to $3 million in the prior quarter primarily due to higher professional service costs relating to the preparation for our NDA submission by the end of this year. Selling, general, and administrative expenses for the quarter were approximately $4.5 million compared to $4 million in the prior-year quarter. The increase was primarily due to recording an estimated $1.2 million for the settlement of the medac litigation, offset by lower share-based compensation expense of $800,000.

本季度的研發費用從上一季度的 300 萬美元增加到 400 萬美元，這主要是由於與準備今年年底提交 NDA 相關的專業服務成本增加。本季度的銷售、一般和管理費用約為 450 萬美元，而去年同期為 400 萬美元。增加的主要原因是記錄了估計的 120 萬美元用於解決 medac 訴訟，被較低的 800,000 美元的基於股份的補償費用所抵消。

Other expenses increased $730,000 from $420,000 due to a full quarter of interest expense and amortization related to our debt financing during the third quarter of 2022. The company recorded a net loss for the three months ended September 30, 2022 of $8.5 million, $0.92 per share basic and diluted, compared to a net loss of $7.1 million, $0.94 per share basic and diluted, for the same period in 2021.

由於 2022 年第三季度與我們的債務融資相關的整個季度的利息支出和攤銷，其他費用從 420,000 美元增加了 730,000 美元。公司錄得截至 2022 年 9 月 30 日止三個月的淨虧損 850 萬美元，每股虧損 0.92 美元基本和稀釋後的淨虧損為 710 萬美元，2021 年同期基本和稀釋後每股虧損 0.94 美元。

On September 30, 2022, the company had cash, cash equivalents, and restricted cash totaling $14 million as compared to cash, cash equivalents, and restricted cash totaling $27 million on December 31, 2021. During the three months ended September 30, 2022 and September 30, 2021, we used $5.2 million and $4.9 million, respectively, of our cash in our operating activities.

截至 2022 年 9 月 30 日，公司擁有現金、現金等價物和受限制現金總額為 1400 萬美元，而 2021 年 12 月 31 日的現金、現金等價物和受限制現金總額為 2700 萬美元。截至 2022 年 9 月 30 日的三個月和2021 年 9 月 30 日，我們在經營活動中分別使用了 520 萬美元和 490 萬美元的現金。

On July 20, 2022, we closed a private placement for $5 million issuance and sale of 690,954 shares of common stock and 566,751 pre-funded warrants to purchase common stock to certain investors. Each share of common stock was sold at a price per share of $3.98. And the pre-funded warrants were sold at a price of $3.97 pre-funded warrant.

2022 年 7 月 20 日，我們完成了 500 萬美元的私募，向某些投資者發行和出售 690,954 股普通股和 566,751 股預注認股權證，以購買普通股。每股普通股以每股 3.98 美元的價格出售。預注權證以3.97美元的價格出售預注權證。

The pre-funded warrants have an exercise price of a $0.01 per share of common stock and are immediately exercisable. Delcath received gross proceeds from the private placement of approximately $5 million before deducting offering expenses.

預注資認股權證的行權價為每股普通股 0.01 美元，可立即行權。在扣除發行費用之前，Delcath 從私募中獲得的總收益約為 500 萬美元。

That concludes my financial remarks. I'll ask the operator to open the phone lines for Q&A. Can you please check for questions?

我的財務評論到此結束。我會請接線員開通問答電話。你能檢查一下問題嗎？

Yes, sir. Absolutely. We will now begin the question-and-answer session. (Operator Instructions) Marie Thibault, BTIG.

是的先生。絕對地。我們現在開始問答環節。 （操作員說明）BTIG 的 Marie Thibault。

Hey. Good morning, everyone. This is Sam Eiber on for Marie. Thanks for taking the questions here. Maybe if I can ask with my first question here any updates or color on maybe what's happening behind the scenes here at the CROs? Maybe what's left that's needed before getting this resubmission before the end of the year? Thanks.

嘿。大家，早安。這是瑪麗的山姆艾伯。感謝您在這裡提出問題。也許如果我可以在這裡問我的第一個問題，關於 CRO 幕後發生的事情的任何更新或顏色？也許在年底前重新提交之前還需要什麼？謝謝。

Sure. The primary thing at this point is medical writing. We have about 98% of the data from our key CRO, a little bit more to get out of them. But really right now, the gating item is medical writing.

當然。此時最主要的是醫學寫作。我們有大約 98% 的數據來自我們的關鍵 CRO，還有一點需要從中獲取。但實際上現在，門控項目是醫學寫作。

And I would say we're well down the path. It will be towards the very end of December. If it slips, it will slip slightly, a week or so. But I'm confident we're very close to getting it filed. And I don't see any major issues in getting it done at this point.

我會說我們已經走在了這條道路上。這將是在 12 月底。滑的話就稍微滑點，一個星期左右。但我相信我們已經非常接近歸檔了。在這一點上，我沒有看到完成它的任何重大問題。

Okay. Very good. Thanks for answering that. And then maybe on the EAP sites here. I might have missed this in the prepared remarks, but maybe how many treatments have been done or scheduled at this point so far? And maybe how are some of those early learnings there, informing maybe the referral pathway for when you potentially do get FDA approval here?

好的。非常好。謝謝你的回答。然後可能在此處的 EAP 站點上。我可能在準備好的評論中錯過了這一點，但也許到目前為止已經完成或安排了多少治療？也許那裡的一些早期學習如何，可能會告知您何時可能在這裡獲得 FDA 批准的轉介途徑？

Johnny, can you answer that in terms of how many treatments we've done to date?

約翰尼，你能根據迄今為止我們做過多少次治療來回答這個問題嗎？

Sure, Gerard. So to date, we have seven treatments. There is actually a treatment occurring today at the Moffitt Cancer Center, so that would be the eighth.

當然，杰拉德。所以到目前為止，我們有七種治療方法。事實上，今天莫菲特癌症中心正在進行治療，所以這將是第八次。

In terms of your question on learnings, we're using the learnings from our European experience and the FOCUS trial in the training and the conduct of EAP. So it's still a little bit early. We're carefully monitoring the safety of these patients. And we don't see any concerns with the adverse events so far that have been reported.

關於您關於學習的問題，我們正在使用從我們的歐洲經驗和 FOCUS 試驗中學到的知識來培訓和實施 EAP。所以現在還有點早。我們正在仔細監測這些患者的安全。到目前為止，我們對已報告的不良事件沒有任何擔憂。

And Kevin --

還有凱文——

Sorry, go ahead.

對不起，繼續。

Kevin, it might be worth you noting what -- you've noticed some really interesting referral patterns going into market, I think?

凱文，可能值得你注意什麼——我認為你已經註意到一些非常有趣的推薦模式進入市場？

Yes. We've seen some patients being referred to Moffitt Cancer Center and using HEPZATO as a first-line treatment in the theory being that it stabilized the disease and preserved liver function before treatment with KIMMTRAK. So it's an interesting dynamic that we've seen here of sequencing these treatments in combination to extend -- better preserve the liver function in anticipation of treating with KIMMTRAK or tebentafusp.

是的。我們已經看到一些患者被轉介到 Moffitt 癌症中心並使用 HEPZATO 作為一線治療，理論上它在使用 KIMMTRAK 治療之前穩定了疾病並保留了肝功能。因此，我們在這裡看到了一個有趣的動態，將這些治療組合起來進行排序，以更好地保護肝功能，以期使用 KIMMTRAK 或 tebentafusp 進行治療。

Sam, what's interesting with this concept, although obvious, it's not something that we've driven at this point, because obviously we're not approved. But this seems to be -- it's one specific doctor, but he was a very active, I believe active in the trial.

山姆，這個概念有什麼有趣的地方，雖然很明顯，但我們目前還沒有推動它，因為顯然我們沒有得到批准。但這似乎是一位特定的醫生，但他非常活躍，我相信他在試驗中很活躍。

And he is now steering his -- it's only I think N equals two at this point, if I have it correct. But he's steering his HLA -- the patients with the appropriate HLA phenotype to Moffitt to get treated first and then move on to KIMMTRAK.

他現在正在操縱他的——我只是認為此時 N 等於二，如果我沒記錯的話。但他正在引導他的 HLA——具有適當 HLA 表型的患者先到 Moffitt 接受治療，然後再轉向 KIMMTRAK。

So as I've said before, I don't view that KIMMTRAK as a competitor. I think it's a win-win for patients and that they're both out there. And doctors will figure out a way to use them best in a combined fashion.

因此，正如我之前所說，我不認為 KIMMTRAK 是競爭對手。我認為這對患者來說是雙贏的，而且他們都在那裡。醫生將想出一種以組合方式最好地使用它們的方法。

It makes sense. Thanks for taking the questions.

這說得通。感謝您提出問題。

Scott Henry, ROTH Capital.

斯科特·亨利，羅斯資本。

Thank you and good morning. I guess just starting on the FDA process. First, do you think there's any risk to it being a six-month review? It would seem likely given the indication. And any thoughts on whether they'd be a panel as well as do you have any planned meetings prior to the filing? Thank you.

謝謝你，早上好。我想剛剛開始 FDA 流程。首先，您認為進行為期六個月的審核是否存在任何風險？鑑於指示，這似乎很可能。關於他們是否會成為專家組的任何想法，以及在提交之前您是否有任何計劃的會議？謝謝。

Yeah. In terms of risk of it being a six-month review, we're trying to make sure that the package is as complete as possible. And quite frankly, we've been focused on making it very easy to navigate. If you take everything given to you as some of the writers -- some, especially the non-clinical writers, they give it to you, it can be [barrier] to navigate.

是的。就六個月審核的風險而言，我們正在努力確保該包盡可能完整。坦率地說，我們一直專注於讓導航變得非常容易。如果你接受一些作家給你的一切——一些，尤其是非臨床作家，他們把它給你，這可能是導航的[障礙]。

So we're trying to make it -- and there is a fair amount you can do as easy as possible to navigate and review. The second thing in our favor is that's not a particularly large filing. The drug has a long history behind it admittedly, but it's not a very large filing being a single trial that we're submitting. But the FDA, we all know they are overworked, and they have kicked some things down the road. So we're hopeful and we're doing everything we can on our end to avoid that.

所以我們正在努力做到這一點——您可以盡可能輕鬆地瀏覽和查看相當多的內容。對我們有利的第二件事是，這不是一個特別大的申請。誠然，該藥物背後有著悠久的歷史，但作為我們提交的單一試驗，這並不是一個非常大的申請。但是 FDA，我們都知道他們工作過度了，他們已經取消了一些東西。所以我們充滿希望，我們正在盡我們所能避免這種情況。

In terms of any meetings scheduled with them, none at this particular time. And in terms of advisory, I think it's probably as likely as not. But we will, of course, be prepping for it as if we have 100% certainty that it will happen. Obviously, there'll never be enough time to prepare if you wait for the notes.

就與他們安排的任何會議而言，在這個特定時間沒有。就諮詢而言，我認為這很有可能。但我們當然會為此做好準備，就好像我們有 100% 的把握它會發生一樣。顯然，如果您等待筆記，將永遠沒有足夠的時間來準備。

Okay, great. And then with regards to the European revenue trends. Certainly, good sequential growth from 2Q to 3Q. Should we expect continued sequential growth? Or will it be lumpy?

好的，太好了。然後是關於歐洲收入趨勢。當然，從第二季度到第三季度的連續增長良好。我們應該期待持續的連續增長嗎？還是會結塊？

Yes. These are still fairly small numbers. So by definition, when you have small numbers, it can be very lumpy at times. Most of this revenue is coming from Germany and the UK.

是的。這些仍然是相當小的數字。所以根據定義，當你有小數字時，它有時會非常不穩定。大部分收入來自德國和英國。

In the UK, we have a rep. We hired one little bit before getting the product back, actually converted an MSL to a rep. And in Germany actually, it's all referrals on their own. Basically, the product's been on autopilot for years. I think some of that growth is definitely due to our efforts; I think its lumpiness is probably in order.

在英國，我們有代表。我們在取回產品之前僱用了一點，實際上將 MSL 轉換為代表。實際上在德國，這都是他們自己推薦的。基本上，該產品多年來一直處於自動駕駛狀態。我認為部分增長肯定歸功於我們的努力；我認為它的塊狀可能是有序的。

I think what will really drive revenue in the short term is us hiring a rep in Germany to help improve referral patterns. As I mentioned a second ago, it's all on autopilot. And then longer term, what will really drive revenue will be UK reimbursements. We'll probably focus on France at some point as the next market given the burden of disease. When the CHOPIN trial winds down, we'll get that back online.

我認為在短期內真正推動收入的是我們在德國聘請代表以幫助改善推薦模式。正如我剛才提到的，一切都在自動駕駛儀上。從長遠來看，真正推動收入增長的將是英國的報銷。考慮到疾病負擔，我們可能會在某個時候將重點放在法國作為下一個市場。當肖邦試驗結束時，我們會把它重新上線。

But I think the focus probably is the last dynamic. When that gets published, I think that will help a tremendous amount. But as is always the case, it's a matter of getting reimbursement in each individual market. That will take a number of years. So steady growth. But we need to get those reimbursement submissions in.

但我認為焦點可能是最後一個動力。當它發佈時，我認為這將有很大幫助。但與往常一樣，這是在每個單獨的市場獲得報銷的問題。這將需要數年時間。所以穩定增長。但我們需要提交這些報銷申請。

Okay. Great. And final question just with regards to the EAP sites. Eight procedures seems like a pretty good number. I guess how should we think about the volume per se? Is this like a once-a-week-type procedure? I guess one, does it go -- yeah, I imagine it goes up, the volume goes up significantly once the product is approved.

好的。偉大的。最後一個問題是關於 EAP 站點的。八個程序似乎是一個相當不錯的數字。我想我們應該如何考慮體積本身？這像是每週一次的程序嗎？我猜一個，它會不會 - 是的，我想它會上升，一旦產品獲得批准，數量就會顯著增加。

But just in general, how do you think about -- and obviously there are higher volume and lower volume. But on average, how do you think about volume per site as far as number of patients post-approval based on what you've learned so far? Just any color there would be helpful. Thank you.

但總的來說，你如何看待 - 顯然有更高的音量和更低的音量。但平均而言，根據您目前所了解的情況，就批准後的患者數量而言，您如何看待每個站點的數量？任何顏色都會有幫助。謝謝。

Yeah. That's a great question, and we've been obviously focused on that ourselves. And I think it will vary, not surprisingly, dramatically by sites. I think an average of one a week per site is probably a reasonable effort after some period after launch.

是的。這是一個很好的問題，顯然我們自己也一直在關注這個問題。而且我認為它會因網站而異，這並不奇怪。我認為在啟動後的一段時間後，每個站點平均每週一個可能是合理的努力。

In terms of getting the sites to that level prior to launch, the EAP, we have to make an effort with our MSL. We have one right now to drive patients, inform clinicians about the sites, and referral patterns in a compliant manner, of course.

就在發布之前讓站點達到該級別 EAP 而言，我們必須在 MSL 方面做出努力。當然，我們現在有一個可以驅動患者，以合規的方式告知臨床醫生有關站點和轉診模式的信息。

Could we get it up to one a week prior to that? That probably would be a reach given our current resources. But I think the demand is certainly there. We're able to communicate it. But again, we're being very careful as to how hard we hit the accelerator.

我們可以在那之前一周最多得到一個嗎？鑑於我們目前的資源，這可能是一個範圍。但我認為需求肯定存在。我們能夠傳達它。但同樣，我們對加速器的力度非常小心。

I think that I've said this before, just trying to harbinger our resources at the moment. But I think post-launch, I think one a week is feasible. And I think we probably could get up to maybe as high as 20 sites over time within perhaps two years post-launch. But we're hopeful that we'll have seven sites up and running at launch and probably well under one a week at that point but moving towards that.

我想我之前已經說過，只是想預示一下我們目前的資源。但我認為發布後，我認為每週一個是可行的。而且我認為我們可能會在發布後的兩年內隨著時間的推移增加多達 20 個站點。但我們希望在啟動時我們將有 7 個站點啟動並運行，並且可能在那個時候每周少於一個，但正在朝著這個目標邁進。

Okay, great. That's helpful. Thank you for taking the questions.

好的，太好了。這很有幫助。感謝您提出問題。

Yale Jen, Laidlaw & Company.

Yale Jen, Laidlaw & Company。

Good morning, and thanks for taking the questions. Gerard, I remember that there's -- for the FOCUS study in terms of the final survival data, that potentially could be available I believe by May of next year. If that's the case, would you need to further submit that data to the agency for the approval? Or that's not relevant for that process?

早上好，感謝您提出問題。杰拉德，我記得對於最終生存數據的 FOCUS 研究，我相信可能會在明年 5 月之前提供。如果是這樣，您是否需要進一步將該數據提交給該機構以供批准？或者這與該過程無關？

Yeah. The primary endpoint of the trial is objective response rate. So there won't be any need to update the data. But the data we're submitting to the FDA is a slight update since the last update we've given publicly.

是的。試驗的主要終點是客觀反應率。所以不需要更新數據。但我們提交給 FDA 的數據自上次公開更新以來略有更新。

And in regular filings, if there's an abstract or something that we publish with a further update, that will go into the FDA, so they would be informed. But it wouldn't be a significant update. So short answer is no. It's not necessary. It's not part of the process, but they will be kept informed.

在定期提交的文件中，如果有摘要或我們發布的進一步更新的內容，這些內容將提交給 FDA，以便他們得到通知。但這不會是一個重大更新。所以簡短的回答是否定的。這不是必需的。這不是流程的一部分，但他們會隨時了解情況。

Okay. Great. That's very helpful. Just two more quick ones. First, a housekeeping question. Based on the expenses, operating expenses, should we anticipate that going down further sequentially compared to the third quarter or the fourth quarter? Or how should we think about that?

好的。偉大的。這很有幫助。再快兩個。首先，一個家政問題。根據費用、運營費用，我們是否應該預計與第三季度或第四季度相比會進一步下降？或者我們應該如何考慮？

I think it's in there. They're about on a steady state for the next two quarters.

我認為它在裡面。在接下來的兩個季度中，他們將處於穩定狀態。

Okay. Great. And maybe the last question here is that once the FDA accepts the application, I assume a month after it was submitted, could you tell us the procedure or the process in terms of the FDA facility inspection and possible timeline of that? So that's probably the last piece for the agency in the process to complete their work.

好的。偉大的。也許這裡的最後一個問題是，一旦 FDA 接受了申請，我假設在提交申請一個月後，你能告訴我們 FDA 設施檢查的程序或過程以及可能的時間表嗎？因此，這可能是該機構完成其工作的最後一步。

Yeah. There's no formal, cut and dry. It's always -- but I would expect four to six weeks prior to the PDUFA date. Then, scheduling a preapproval inspection.

是的。沒有正式的、千篇一律的。它總是——但我希望在 PDUFA 日期之前四到六週。然後，安排預批准檢查。

Okay. Great. That's very helpful. And congrats on all the progress and look forward you, guys, filing the things before end of the year.

好的。偉大的。這很有幫助。祝賀所有的進展，期待你們，伙計們，在年底前提交文件。

Thanks, Yale.

謝謝，耶魯。

Bill Maughan, Canaccord Genuity.

Bill Maughan，Canaccord Genuity。

Hey. Good morning. And thanks for taking the question. So after a recent FDA advisory committee for another oncology product in a small orphan population, there's a little bit more of a renewed focus on what the FDA is expecting to prove efficacy in a single-arm trial in a small population. So I was just hoping you could hit the highlights again.

嘿。早上好。感謝您提出這個問題。因此，在最近 FDA 諮詢委員會針對小孤兒人群中的另一種腫瘤產品進行諮詢後，人們重新關注 FDA 期望在小人群中進行的單臂試驗中證明療效的東西。所以我只是希望你能再次成為亮點。

I know you've gone through it before. But in terms of what the FDA expected or required of your pivotal data, specifically as you can, what they needed to see to prove efficacy. And any -- to the extent that you were able to compare that to results outside of your trial, the suitability of that comparison, and how satisfied the FDA will be that HEPZATO is achieving the level of response needed for approval.

我知道你以前經歷過。但就 FDA 對你的關鍵數據的期望或要求而言，特別是你可以，他們需要看到什麼來證明療效。以及任何——只要你能夠將其與你的試驗之外的結果進行比較，這種比較的適用性，以及 FDA 對 HEPZATO 達到批准所需的響應水平的滿意程度。

Sure. Well, I think the first thing, it is a single-arm trial. And what the FDA stated to us when we were discussing with them turning this into a single-arm trial is they wanted to see a clinically meaningful objective response rate that had a clinically meaningful duration of response.

當然。好吧，我認為首先是單臂試驗。當我們與 FDA 討論將其轉變為單臂試驗時，FDA 對我們說的是，他們希望看到具有臨床意義的客觀反應率，以及具有臨床意義的反應持續時間。

Picking up that second one, duration response, because that's the simplest. They asked us to do a follow up for at least six months to demonstrate that the duration of the response was meaningful. And we actually had was a 14-month duration. And that is frankly hitting the ball out of the park in terms of durations. So we know we're on very, very solid ground there.

選擇第二個，持續時間響應，因為這是最簡單的。他們要求我們進行至少六個月的跟進，以證明響應的持續時間是有意義的。我們實際上有 14 個月的持續時間。坦率地說，就持續時間而言，這是將球擊出公園。所以我們知道我們在那裡的基礎非常非常堅實。

In terms of objective response rate, that's a little harder to point to something specific the FDA has said to us. Now we did tell them that we were powering the (inaudible) trials to show a meaningful improvement based on the meta-analysis of immuno-oncology agents. And we had -- our lower bound needed to beat 8.3% on that. Our lower bound was 26.4%, so obviously, we're well over that hurdle.

就客觀回應率而言，要指出 FDA 對我們說的具體內容有點困難。現在我們確實告訴他們，我們正在推動（聽不清）試驗，以顯示基於免疫腫瘤藥物薈萃分析的有意義的改進。我們有——我們的下限需要超過 8.3%。我們的下限是 26.4%，所以很明顯，我們已經遠遠超過了這個障礙。

Now, the FDA might decide that that in itself isn't adequate. And we, of course, will input in terms of evidence, in terms of a comparison. So we have other things we can pull upon, which some are quite obvious. I think the most compelling one is to look at OS.

現在，FDA 可能會認為這本身是不夠的。當然，我們會根據證據和比較來輸入。所以我們還有其他可以利用的東西，其中一些是非常明顯的。我認為最引人注目的是看操作系統。

Our OS is fairly similar to what tebentafusp showed. And we had sicker patients in terms of -- we had first, second, third-line patients. We have a variety of parameters that we can compare to and will, based on their published data that demonstrates that our patients were further along in the disease process. Yet we came in within spitting distance of their overall OS.

我們的操作系統與 tebentafusp 展示的非常相似。我們有更嚴重的患者——我們有一線、二線和三線患者。根據他們公佈的數據，我們有多種參數可以比較，我們將比較這些參數，這些數據表明我們的患者在疾病過程中走得更遠。然而，我們與他們的整體操作系統相差無幾。

And then if we look at one-year OS, they were I believe 77% -- we were at 77%, excuse me, survival for a year. They were at 73%. So we have a number of things we can point to. We look at our older survival data, pre-KIMMTRAK, HEPZATO publication we're well, well over.

然後，如果我們看一下一年的操作系統，我相信他們是 77%——我們當時是 77%，對不起，存活了一年。他們是73%。所以我們有很多事情可以指出。我們查看我們較早的生存數據，在 KIMMTRAK 之前，HEPZATO 出版物我們已經很好，很好。

Usually, it's not over. It's well under a year in terms of survival. So that's well in our favor as well. So I think with our overall OS, we said 19.25 months last time we gave an update, but that was versus the BAC-level stuff. Now, we have 14.5 months.

通常，它還沒有結束。就生存而言，還不到一年。所以這也對我們有利。所以我認為對於我們的整體操作系統，我們上次提供更新時說是 19.25 個月，但那是與 BAC 級別的東西相比。現在，我們有 14.5 個月。

We have that delta. That OS continues to mature. So it's definitely not the final number. And it compares reasonably favorably with KIMMTRAK.

我們有那個三角洲。該操作系統繼續成熟。所以這絕對不是最終數字。它與 KIMMTRAK 相比相當有利。

We have the meta-analysis in terms of ORR, objective response rate. And our response rates are head to shoulders above anything else out there. Most response rates are single digit and then the duration 14 months. So taken in totality, I think we're in great shape.

我們根據 ORR（客觀緩解率）進行了薈萃分析。我們的回复率比其他任何東西都高。大多數回复率是個位數，然後是 14 個月的持續時間。總的來說，我認為我們的狀態很好。

I think the last thing I would mention is although we haven't published this, I have stated qualitatively our response rates or category of response rates, whether or not you are complete responder, a partial response, or progressive disease, that all correlates with survival quite cleanly. So therefore, we can show that the response rate, the ORR is meaningful in terms of OS, which isn't always the case for all classes of therapy. So that's an important component as well.

我想我最後要提到的是，雖然我們還沒有發表這個，但我已經定性地說明了我們的反應率或反應率類別，無論你是完全反應者、部分反應者還是進行性疾病，都與生存的相當乾淨。因此，我們可以證明反應率，ORR 在 OS 方面是有意義的，這並不總是適用於所有類別的治療。所以這也是一個重要的組成部分。

I've thrown a lot at you. But I think we have a lot at our disposal. So I just want to make sure I was complete with that.

我向你扔了很多東西。但我認為我們有很多可以支配的。所以我只想確保我已經完成了。

Absolutely. I appreciate the thorough answer. Thank you.

絕對地。我感謝徹底的回答。謝謝。

Thank you. And ladies and gentlemen, this concludes our question-and-answer session and today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.

謝謝。女士們，先生們，我們的問答環節和今天的電話會議到此結束。感謝大家出席今天的演講。您現在可以斷開線路並度過美好的一天。