Biomx Inc (PHGE) 2025 Q2 法說會逐字稿

Good morning, and welcome to the BiomX second-quarter 2025 financial results and business and program update conference call. (Operator Instructions)

早安，歡迎參加 BiomX 2025 年第二季財務業績及業務及計畫更新電話會議。（操作員指示）

As a reminder, this conference call is being recorded.

提醒一下，本次電話會議正在錄音。

I would now like to turn the call over to Marina Wolfson, Chief Financial Officer of BiomX. Please proceed.

現在我想將電話轉給 BiomX 財務長 Marina Wolfson。請繼續。

Thank you, and welcome to the BiomX conference call to review the company's second quarter 2025 financial results and provide an update on our business and programs. Later today, we will file the quarterly report on Form 10-Q with the Securities and Exchange Commission.

謝謝，歡迎參加 BiomX 電話會議，回顧該公司 2025 年第二季的財務業績並提供我們的業務和計劃的最新資訊。今天晚些時候，我們將向美國證券交易委員會提交 10-Q 表季度報告。

In addition, the press release became available at 6:30 AM Eastern Time today and can be found on our website at biomx.com. A replay of this call will also be available on the Investors section of our website.

此外，新聞稿已於今日美國東部時間上午6:30發布，可在我們的網站biomx.com上查閱。本次電話會議的重播也將在我們網站的「投資者」板塊提供。

As we begin, I'd like to review the safe harbor provision. All statements on this call that are not factual historic statements may be deemed forward-looking statements. For instance, we're using forward-looking statements when we discuss on the conference call, the sufficiency of the company's cash, our pipeline, momentum and milestones, the design, recruitment, aim, expected timing, and interim and final results of our clinical trials, expected feedback from the FDA and additional regulatory agencies and results thereof, the potential benefits of our product candidates, the potential safety or efficacy or product candidates, BX004 and BX211, and the potential markets and partnering opportunities for our product candidates.

首先，我想回顧一下安全港條款。本次電話會議所有非事實歷史陳述均可視為前瞻性陳述。例如，當我們在電話會議上討論公司現金的充足性、我們的產品線、發展勢頭和里程碑、臨床試驗的設計、招募、目標、預期時間、中期和最終結果、FDA 和其他監管機構的預期反饋及其結果、我們候選產品的潛在益處、候選產品 BX004 和 BX211 的潛在安全性或有效性，以及我們都會使用前瞻性機會陳述市場和前瞻性機會。

In addition, past and current clinical results as well as compassionate use are not indicative and do not guarantee future success of our clinical trials. Except as required by law, we do not undertake to update forward-looking statements. The full Safe Harbor provisions, including risks that could cause actual results to differ from these forward-looking statements are outlined in today's press release, which as noted earlier is on our website.

此外，過去和現在的臨床結果以及同情用藥並不具有指示性，也不能保證我們未來的臨床試驗的成功。除法律要求外，我們不承擔更新前瞻性陳述的責任。完整的安全港條款，包括可能導致實際結果與這些前瞻性陳述不同的風險，均在今天的新聞稿中概述，如前所述，該新聞稿已發佈在我們的網站上。

Joining me on the call this morning is BiomX's Chief Executive Officer, Jonathan Solomon, to whom I will now turn over the call.

今天早上和我一起參加電話會議的是 BiomX 的執行長 Jonathan Solomon，我現在將電話轉給他。

Thank you, Marina and thank you all for joining BiomX second-quarter 2025 update today. The second quarter of 2025 has been a productive period for BiomX as we continue to advance our clinical programs and build scientific validation for our phage therapy platform.

謝謝你，瑪麗娜，也謝謝大家今天參加 BiomX 2025 年第二季更新。2025 年第二季度對於 BiomX 來說是富有成效的時期，因為我們繼續推進臨床計畫並為噬菌體治療平台建立科學驗證。

During the quarter, we made important progress on both our BX004 and BX211 programs and have positioned ourselves well for the upcoming milestones. Since the end of the quarter, we achieved a critical milestone with a successful initiation of patient dosing in our Phase IIb clinical trial of BX004 for cystic fibrosis patients, an important step as we advance our top line results expected in the first quarter of 2026. We also published additional data from our BX004 Phase Ib/IIa study in Nature Communications in July, providing further validation of our phage therapy platform.

在本季度，我們在 BX004 和 BX211 專案上都取得了重要進展，並為即將到來的里程碑做好了準備。自本季末以來，我們取得了一個關鍵的里程碑，在針對囊性纖維化患者的 BX004 IIb 期臨床試驗中成功啟動患者給藥，這是我們推進 2026 年第一季預期頂線表現的重要一步。我們也於 7 月在《自然通訊》上發表了 BX004 Ib/IIa 期研究的更多數據，進一步驗證了我們的噬菌體治療平台。

Let me start by reviewing the recent progress across our clinical pipeline. We launched into the second quarter with a virtual key opinion leader event to discuss the positive top line Phase II results for BX211 that were reported in March 2025. The event received resounding endorsement from key opinion leaders, physicians and industry experts highlighting the enthusiasm surrounding the strength of the data and the significant potential addressing the needs of patients living with diabetic foot osteomyelitis or DFO.

首先，我來回顧一下我們臨床流程的最新進展。我們在第二季度啟動了一場虛擬關鍵意見領袖活動，討論 2025 年 3 月報告的 BX211 第二階段的積極頂線結果。這項活動得到了關鍵意見領袖、醫生和行業專家的強烈支持，強調了人們對數據強度的熱情以及滿足糖尿病足骨髓炎或 DFO 患者需求的巨大潛力。

To recap, those March results demonstrated that BX211 was safe and well tolerated and produced sustained and statistically significant percent area reduction in ulcer size with a p-value of 0.046 at week 12 and 0.052 at week 13. We saw separation from placebo starting at week 7, with a difference greater than 40% by week 10.

總結一下，3 月的結果表明，BX211 是安全的，耐受性良好，並且潰瘍面積百分比持續減少，具有統計學意義，第 12 週的 p 值為 0.046，第 13 週的 p 值為 0.052。我們從第 7 週開始看到與安慰劑的差異，到第 10 週差異超過 40%。

The results showed statistically significant improvement in both ulcer death at week 13 in patients with ulcer death, defined as bone at baseline with a p-value of 0.048, reducing the expansion of ulcer area with a p-value of 0.017 compared to placebo.

結果顯示，與安慰劑組相比，潰瘍死亡（定義為基線時的骨骼）患者在第 13 週的潰瘍死亡率均有統計學顯著改善（p 值為 0.048），潰瘍面積擴大減少（p 值為 0.017）。

As background on the significance of this program, DFO is an extremely challenging indication with substantial unmet patient need. Each year, there are approximately 160,000 lower limb amputations in diabetic patients in the US alone with 85% estimated to be caused either by DFO or diabetic foot infections. No therapeutics have been improved in the United States, specifically for the treatment of DFO in over 20 years.

作為該計劃重要性的背景，DFO 是一個極具挑戰性的適應症，有大量未滿足的患者需求。光是在美國，每年就有大約 16 萬名糖尿病患者下肢截肢，其中 85% 估計是由 DFO 或糖尿病足感染引起的。20 多年來，美國的治療方法一直沒有改進，特別是針對 DFO 的治療。

Following the positive Phase II results, we are now engaged in continued discussion with the U.S. Defense Health Agency, a key financer and supporter driving the development of BX211 program. And in parallel, we're currently planning for BX211 registrational study, pending discussion and feedback from the FDA.

在第二階段取得積極成果之後，我們目前正在與美國國防衛生局（推動 BX211 計畫發展的主要資助者和支持者）繼續進行討論。同時，我們目前正在計劃 BX211 註冊研究，等待 FDA 的討論和回饋。

The second quarter also marked with continuous advancement for our Phase IIb trial of BX004, which included the successful initiation of patient dosing in this Phase IIb trial, a critical milestone for our cystic fibrosis or CF program, aligning with our timeline of expected top line results from the Phase IIb results in the first quarter of 2026.

第二季度，我們的 BX004 IIb 期試驗也取得了持續進展，其中包括成功啟動該 IIb 期試驗的患者給藥，這是我們囊性纖維化或 CF 計畫的一個重要里程碑，與我們預期的 2026 年第一季度 IIb 期試驗頂線結果的時間表一致。

We are encouraged by the high level of enthusiasm for enrollment in the Phase IIb CF trial across the board for both patients and investigators driven by the strength of a prior Phase Ib/IIa data in which 14.3% of patient cleared infections completely after 10 days of treatment.

令我們感到鼓舞的是，患者和研究人員對參加 IIb 期 CF 試驗的熱情很高，這得益於先前 Ib/IIa 期數據的強勁表現，其中 14.3% 的患者在接受 10 天的治療後完全清除了感染。

The design of the Phase IIb trial of BX004 for the treatment of patients with cystic fibrosis infection associated with Pseudomonas aeruginosa is designed as a randomized, double-blind, placebo-controlled multicenter study in approximately 60 cystic fibrosis patients with chronic pseudomonas aeruginosa infections.

BX004 用於治療與銅綠假單胞菌相關的囊性纖維化感染患者的 IIb 期試驗設計為一項隨機、雙盲、安慰劑對照的多中心研究，在約 60 名患有慢性銅綠假單胞菌感染的囊性纖維化患者中進行。

Patients in the trial will be randomized at a 2:1 ratio to receive either BX004 or placebo via inhalation twice daily for eight weeks. The trial is designed to measure multiple efficacy endpoints, including reduction in bacterial burden, improvement in lung function and enhanced quality of life as measured by patient questionnaires.

試驗中的患者將以 2:1 的比例隨機分配接受 BX004 或安慰劑吸入治療，每天兩次，持續八週。該試驗旨在測量多種療效終點，包括透過患者問卷測量的細菌負擔減少、肺功能改善和生活品質提高。

In July, we published in a highly acclaimed nature communication publication. The paper included new findings from our Phase Ib/IIa trial, showcasing previously unreported antimicrobial efficacy data that demonstrated BX004 achieving a substantially greater improvement of approximately 500 fold. That's a 2.7 log reduction in bacterial reduction compared to placebo in CF patients. Importantly, the data also highlights no bacterial resistance to BX004 emerged during the trial. The article also details our innovative approach to large-scale data analysis in order to optimize bacteria phage cocktails.

7月份，我們在備受好評的《自然通訊》刊物上發表了文章。該論文包含了我們 Ib/IIa 期試驗的新發現，展示了先前未報告的抗菌功效數據，顯示 BX004 實現了約 500 倍的顯著改善。與 CF 患者的安慰劑相比，細菌數量減少了 2.7 個對數。重要的是，數據還強調在試驗期間沒有出現對 BX004 的細菌抗藥性。文章也詳細介紹了我們為優化細菌噬菌體混合物而採用的大規模數據分析創新方法。

We believe that this publication in one of the highly prestigious scientific journals, represents an important validation for our phage platform and methodology from broader scientific community. We continue to press forward with the execution of the BX004 trial.

我們相信，這篇發表在享有盛譽的科學期刊之一上的文章代表了更廣泛的科學界對我們的噬菌體平台和方法的重要認可。我們將繼續推進BX004試驗的執行。

And in parallel, we expect to receive feedback from the US FDA regarding the potential investigation and use of real-world evidence linking material reduction to clinical outcomes during the second half of 2025, bring us closer to addressing the urgent unmet need of patients with pseudomonas aeruginosa, CF infections sooner.

同時，我們預計將在 2025 年下半年收到美國 FDA 關於將材料減少與臨床結果聯繫起來的潛在調查和真實世界證據的反饋，使我們更接近更快地解決銅綠假單胞菌、CF 感染患者的迫切未滿足需求。

The combined progress across our clinical pipeline during the second quarter, in addition to recent achievement in July, reinforces our approach and gives us strong momentum as we advance towards our next milestones.

我們第二季臨床管線的綜合進展，加上 7 月的最新成就，強化了我們的方法，並為我們邁向下一個里程碑提供了強勁動力。

I'd like to now pass you on to Marina to review our second quarter 2025 financial results.

現在，我想請瑪麗娜 (Marina) 來審查我們 2025 年第二季的財務業績。

Thank you, Jonathan. As a reminder, the financial information for the company's second quarter 2025 is available in the press release that we issued earlier today as well as in more detail in our Form 10-Q, which we will file later today.

謝謝你，喬納森。提醒一下，該公司 2025 年第二季的財務資訊可在我們今天早些時候發布的新聞稿中找到，更詳細的資訊可在我們今天稍後提交的 10-Q 表中找到。

I will now proceed with the highlights of our second quarter financial results. Cash balance and restricted cash as of June 30, 2025, were $15.2 million compared to $18 million as of December 31, 2024. The decrease was primarily due to net cash used in operating activities. We estimate that our cash, cash equivalents and restricted cash are sufficient to fund our operations into the first quarter of 2026.

現在我將繼續介紹我們第二季財務表現的要點。截至 2025 年 6 月 30 日的現金餘額和受限現金為 1,520 萬美元，而截至 2024 年 12 月 31 日的現金餘額和受限現金為 1,800 萬美元。減少的主要原因是經營活動所用的淨現金。我們估計，我們的現金、現金等價物和受限現金足以支持我們到 2026 年第一季的營運。

Research and development expenses net were $5 million for the second quarter of 2025 compared to $6.9 million for the second quarter of 2024. The decrease was primarily driven by reduced salary expenses from workforce reductions, lower rent expenses following 2024 right-of-use asset impairment accounting and increased grant funding from the Medical Technology Enterprise Consortium and the Israel Innovation Authority. This was partially offset by higher expenses from initiating the Phase IIb clinical trial for CF product candidate, BX004.

2025 年第二季研發費用淨額為 500 萬美元，而 2024 年第二季為 690 萬美元。下降的主要原因是裁員導致的工資支出減少、2024 年使用權資產減損會計後的租金支出降低以及醫療技術企業聯盟和以色列創新局增加的撥款。這部分被啟動 CF 候選產品 BX004 的 IIb 期臨床試驗所產生的更高成本所抵銷。

General and administrative expenses were $2.4 million for the second quarter of 2025 compared to $2.8 million for the second quarter of 2024. The decrease was primarily attributed to a reduction in legal and other professional service fees, partially offset by increased share-based compensation expenses.

2025 年第二季的一般及行政費用為 240 萬美元，而 2024 年第二季為 280 萬美元。下降的主要原因是法律和其他專業服務費用的減少，但被股權激勵費用的增加部分抵消。

Net loss was $6 million for the second quarter of 2025 compared to income of $4.5 million for the second quarter of 2024. The decrease was mainly due to the change in the fair value of warrants issued as part of the company's March 2024 financing. Net cash used in operating activities for the 6 months ended June 30, 2025, was $14.8 million compared to $22.6 million for the same period in 2024.

2025 年第二季淨虧損為 600 萬美元，而 2024 年第二季營收為 450 萬美元。下降的主因是公司2024年3月融資中發行的認股權證的公允價值發生了變化。截至 2025 年 6 月 30 日的 6 個月內，經營活動所用淨現金為 1,480 萬美元，而 2024 年同期為 2,260 萬美元。

I'll now return the call to Jonathan for his closing remarks.

我現在將電話回撥給喬納森，請他作最後發言。

Thanks, Marina. The second quarter of 2025 was a productive period for BiomX as we advance our clinical programs and build momentum for upcoming milestones. Since the end of the quarter, we have achieved important milestones, including the successful initiation of our BX004 Phase IIb trial and the publication of our data in Nature Communications, which we believe provides important scientific validation of our phage therapy platform from the global research community.

謝謝，瑪麗娜。2025 年第二季是 BiomX 的豐收時期，我們推進了臨床計畫並為即將到來的里程碑積蓄動力。自本季末以來，我們取得了重要的里程碑，包括成功啟動 BX004 IIb 期試驗以及在《自然通訊》上發表我們的數據，我們相信這為我們的噬菌體治療平台提供了來自全球研究界的重要科學驗證。

With multiple value-creating catalysts ahead, including FDA feedback on our real-world evidence approach in the second half of 2025, ongoing collaboration discussion with the U.S. Defense Health Agency and BX004 Phase IIb top line results expected in the first quarter of 2026, we continue to advance our potentially life-changing therapeutics. We appreciate the continued support of our shareholders and look forward to updating you on our progress.

隨著未來多個創造價值的催化劑的出現，包括 FDA 在 2025 年下半年對我們的真實世界證據方法的反饋、與美國國防衛生局的持續合作討論以及預計在 2026 年第一季度公佈的 BX004 IIb 期頂線結果，我們將繼續推進可能改變生活的治療方法。我們感謝股東的持續支持，並期待向您通報我們的進展。

Thanks again to all who joined the call this morning. And with that, we'd like to open to questions.

再次感謝今天早上參加電話會議的所有人。有了這些，我們願意回答大家的提問。

(Operator Instructions) Joe Pantginis, H.C. Wainwright.

（操作員指示）Joe Pantginis、H.C. Wainwright。

I have a couple, but I wanted to start with a bit of a macro question first regarding bacteria phage. So for the 004 study, you mentioned significant interest in the study. You have the Phase II data for 211. So I was just curious, based on the positive clinical data that you've delivered as well as others in the space, have you seen a relative inflection with regard to site and physician interest, with regard to wanting to be in the studies?

我有幾個問題，但我想先從一個有關細菌噬菌體的宏觀問題開始。對於 004 研究，您提到了人們對該研究的極大興趣。您有 211 的第二階段資料。所以我只是好奇，根據您以及該領域其他人提供的積極臨床數據，您是否看到在研究地點和醫生興趣方面，對於想要參與研究的相對變化？

Joe, and I look forward to meeting you face-to-face in New York pretty soon on the conference. And you're hitting the nail on the head. I think we've seen -- in the past, you remember all our conversation, right? The previous CF studies took a while to recruit. Now sites are excited, patients are excited, physicians are excited. So it does seem very different. And again, I think it's our prior data. I think it's a data that others have generated. So I think there's excitement around efficacy.

喬，我期待很快在紐約的會議上與您見面。你說得一針見血。我想我們已經見過——在過去，你記得我們所有的談話，對嗎？先前的 CF 研究需要一段時間才能招募到患者。現在，診所很興奮，患者很興奮，醫生也很興奮。所以它看起來確實非常不同。再次強調，我認為這是我們之前的數據。我認為這是其他人產生的數據。所以我認為人們對功效感到興奮。

There's a greater level of comfort around safety, which we knew was a strong point of stage to begin with. And really sites are just -- and patients are calling us all the time on top of like the standard compassionate use request to participate in the study. So it is a very exciting time in the field. I think there's a lot going on, right? I add to it like publications in very highly claimed journals, the fact that people are talking about it in the communities and the patient communities.

安全性方面的舒適度更高了，我們知道這首先是這個階段的強項。事實上，網站只是——患者除了提出標準的同情用藥請求外，還一直在給我們打電話，要求參與研究。因此，這是該領域非常令人興奮的時刻。我認為有很多事情發生，對嗎？我補充的是，就像在備受推崇的期刊上發表的文章一樣，人們在社群和病人社群中談論它。

And that also bleeds into like strategic interest, right? You remember all our conversations kind of waiting for this inflection point to come. I think we're there, right? You never really know unless you have like historical perspective, but it does feel very different, right, both from patients, caretakers and even strategics that are now saying, wow, there's actually data out there. There's a few Phase IIs randomized placebo-controlled studies that are showing efficacy and all the kind of data sets that we wanted to see.

這也會影響戰略利益，對嗎？你還記得我們所有的談話都在等待這個轉捩點的到來。我想我們已經到了，對吧？除非你有歷史視角，否則你永遠不會真正知道，但感覺確實非常不同，對吧，無論是從病人、護理人員，甚至戰略人員的角度來看，他們現在都在說，哇，那裡真的有數據。有幾項 II 期隨機安慰劑對照研究顯示了療效以及我們希望看到的所有類型的數據集。

So I think it's not an approved drug yet, but we're definitely heading in the right direction. Let's hope that momentum just keeps on going.

所以我認為它還不是獲得批准的藥物，但我們肯定正朝著正確的方向前進。我們希望這種勢頭能夠持續下去。

No, that's great to hear and looking forward to seeing more out of the space. So with regard to 211, obviously, you still need to have further discussions with the FDA, but maybe provide a little bit of a wish list, if you will, with regard to what a registrational study might look like from your end, pending feedback as well as how are you looking to link that up with your ongoing discussions with the Defense Health Agency.

不，聽到這個消息真是太好了，期待看到更多這樣的空間。因此，關於 211，顯然，您仍然需要與 FDA 進行進一步討論，但如果您願意的話，可以提供一份願望清單，說明您這邊註冊研究的樣子，等待反饋，以及您希望如何將其與您與國防衛生局正在進行的討論聯繫起來。

So obviously, I think it's really -- the data set that we've seen is really exciting, right? It's one of those data sets that as a friend says, you just need to show one graph, right? And that is very significant. There's a 40% reduction, which is statistical significant in a very tough indication, right? I think the path forward opens up -- obviously, diabetic foot osteo is kind of a subset within diabetic foot infection. I think there's a possibility to kind of advance in both paths.

所以顯然，我認為這真的是——我們看到的數據集真的令人興奮，對吧？正如一位朋友所說，它是那些只需要顯示一個圖表的資料集之一，對嗎？這非常重要。減少了 40%，這在非常困難的指標中具有統計意義，對嗎？我認為前進的道路已經打開——顯然，糖尿病足骨病是糖尿病足感染的一個子集。我認為兩條路都有可能進步。

And that's something we're looking into and there's ongoing prepping for the discussion with the regulatory agencies. So I think that path in some ways, is pretty laid out, right? There's a specific guidance on diabetic foot infections and endpoints are around infection resolution. But of course, we want to validate and have that discussion with the agency. I think we know how the next study potentially can look like to kind of go for a registrational study.

我們正在研究這個問題，並正在為與監管機構的討論做準備。所以我認為從某種程度上來說，這條路已經規劃好了，對吧？有關於糖尿病足部感染的具體指導，終點是感染消退。但當然，我們希望與該機構進行確認和討論。我認為我們知道下一項研究可能會是什麼樣子，有點像進行註冊研究。

To your point, right, and I think the DOJ has been great in sort of understanding that they can support -- they don't want to support indications where it's solely for military use, right? They understand that the real path to success is to support programs that have a use in the private market or the standard market. So that's why they're supporting the diabetic foot. And there, they want to see a registrational study. They want to see a drug approved and then they can kind of use it in combat wound. So there's great appreciation.

正如您所說，對的，我認為司法部已經很好地理解了他們可以支持什麼——他們不想支持僅用於軍事用途的跡象，對嗎？他們明白，真正的成功之路是支持在私人市場或標準市場有用的專案。這就是他們支持糖尿病足的原因。他們希望看到一項註冊研究。他們希望看到一種藥物獲得批准，然後就可以用它來治療戰傷。因此我們非常感激。

I think there's still more data that we're getting, unfortunately, from the Ukraine war showing a lot of antibiotic resistance. And when you look at the data that we have in our study, right, we're looking at soft tissue, right? We looked at the ulcers. We saw the ulcers kind of shrink on all 3 dimensions. We're seeing a lot of other parameters kind of adding up together to a very promising picture.

不幸的是，我認為我們從烏克蘭戰爭中得到的更多數據顯示了大量抗生素抗藥性。當您查看我們研究中的數據時，我們正在查看軟組織，對嗎？我們觀察了潰瘍。我們看到潰瘍在三個維度上都有所縮小。我們看到許多其他參數加在一起形成了一個非常有希望的圖像。

And obviously, there's excitement, and we'll know formally where we are towards the end of the year. But the data looks very good. And I think there's -- we're excited to kind of have the discussion with them and potentially have them to complete and so forth. I mean, to date, they've put in almost $40 million non-dilutive in the program. So quite dramatic support, and we'd never gotten to this point without them.

顯然，我們很興奮，我們將在今年年底正式知道我們的進展。但數據看起來非常好。我認為——我們很高興能與他們進行討論，並有可能讓他們完成等等。我的意思是，到目前為止，他們已經在該計劃中投入了近 4000 萬美元的非稀釋性資金。他們的支持非常巨大，如果沒有他們的支持，我們永遠不會達到今天的水準。

No, that's great. Great feedback. And then my last question is around 004. And I guess I wanted to maybe get a little more color from you as well as those on the call with regard to the utility and what the FDA should be able to garner from the real-world evidence that you're looking to provide them? Like what is the general use for that and the benefits for the program?

不，那太好了。很好的反饋。我的最後一個問題是關於 004 的。我想也許我想從您以及電話中的其他人那裡得到更多關於實用性的信息，以及 FDA 應該能夠從您希望向他們提供的真實世界證據中獲得什麼？例如它的一般用途是什麼以及對程序有什麼好處？

Right. So that's a great question. I think we have seen in the past drugs that were either approved or conditionally approved or accelerated approval based on microbiology, right? Again, it's not a trivial path to pursue. I think in CF, there is data historically that some of the antibiotics were approved either based on FEV1, so kind of improvement in clinical and breathing capacity of these patients as well as patient-reported outcome, right? So that's been kind of the historical approvals in antibiotics.

正確的。這是一個很好的問題。我想我們過去看到過一些藥物是根據微生物學獲得批准、有條件批准或加速批准的，對嗎？再說一遍，這不是一條容易走的路。我認為在 CF 中，歷史數據顯示一些抗生素是根據 FEV1 獲得批准的，因此這些患者的臨床和呼吸能力以及患者報告的結果都有所改善，對嗎？這就是抗生素的歷史性批准。

We have seen cases of approval on microbiology, which obviously kind of potentially can help accelerate the path going forward. There is quite a lot of data out there that supports the notion that patients that harbor bacterial infections have a worst outcome, worst prognosis, worst survival. I -- actually, there was just a recent paper that just came out. I was reading this morning exactly on even patients that are taking the modulators. We're still seeing persistent infection of pseudomonas and this is a nasty bug, right? It's not a good thing to have this thing in the lung.

我們已經看到了微生物學領域獲得批准的案例，這顯然可能有助於加速前進的道路。有大量數據支持這樣的觀點：患有細菌感染的患者的結果最差，預後最差，存活率最差。我——實際上，最近剛發表了一篇論文。我今天早上讀到的正是有關正在服用調節劑的患者的文章。我們仍然看到假單胞菌的持續感染，這是一種令人討厭的細菌，對嗎？肺裡有這個東西可不是什麼好事。

So I think we're trying to sort of get alignment, get as much information as we can on historically, what do patients do look at registries in the US and Europe and kind of gather all the information, trying to build the case and see whether there's a path to somehow hasten and sort of get a shorter [full path].

所以我認為我們正在嘗試協調一致，盡可能多地獲取歷史信息，看看患者在美國和歐洲的登記處做了什麼，並收集所有信息，試圖建立案例，看看是否有辦法以某種方式加快並縮短治療時間[完整路徑​​]。

Again, everything depends on discussion with the regulatory agency. It's still early in the process, but we're looking for some alignment in our thinking, whether it makes sense and whether we pursue that path going forward.

再次強調，一切都取決於與監管機構的討論。這個過程還處於早期階段，但我們正在尋求思想上的一致，看看這是否有意義，以及我們是否會繼續沿著這條道路前進。

(Operator Instructions) Yale Jen, Laidlaw & Company.

（操作員指示）Yale Jen，Laidlaw＆Company。

Congrats to get the 004 program to start and, hopefully, finish in first quarter next year. Just a follow-up on the 004. I understand that the study just started in July, but any updates or preliminary look in terms of the enrollment status? And then I have some follow-ups as well.

恭喜 004 專案啟動，並希望在明年第一季完成。這只是 004 的後續。我知道這項研究在 7 月才剛開始，但入學情況方面有任何更新或初步進展嗎？然後我還有一些後續事宜。

Sure. So Yale, a pleasure as always. Usually, we don't give guidance specifically, but I will say, as kind of Joe kind of brought up, there is excitement on the sites, right? So it is looking very good with a lot of patients waiting to be enrolled and excitement both from patients and their caretakers. So I think we are still in line with the time line and think that the data is going to be ready in the first quarter.

當然。所以耶魯，一如既往的快樂。通常，我們不會給出具體的指導，但我想說，正如喬提到的那樣，網站上充滿了興奮，對吧？因此，情況看起來非常好，許多患者正在等待入組，患者和他們的照護人員都很興奮。所以我認為我們仍然符合時間表，並認為數據將在第一季準備好。

Okay. Great. Maybe a little follow-up on Joe's question as well. In terms of the real-world data you want to talk to FDA about, have you guys already done some work, maybe generate some documents that once -- if the FDA would like to have a chance of chatting with you and you already have that sort of material ready and also with some sort of -- whether there's any dates or time has been set up for that discussion?

好的。偉大的。也許還需要對喬的問題做一些跟進。就您想要與 FDA 討論的真實世界數據而言，您是否已經做了一些工作，也許生成了一些文件，如果 FDA 願意有機會與您交談並且您已經準備好了這類材料，並且還有某種——是否已經為該討論設定了日期或時間？

Great question. So it is an area of a lot of interest. As I mentioned, right, you see papers coming out, I'm just reading this morning a paper on this. On the company end, what we're doing is kind of threefold, right? We had a panel of KOLs convened on this and had a discussion sort of provided the recommendation, which is part of our discussion with the regulatory agencies.

好問題。因此這是一個備受關注的領域。正如我所提到的，對的，你會看到論文發表，我今天早上剛讀了一篇關於這個的論文。從公司角度來說，我們做的事情大概有三方面，對嗎？我們就此召集了一個 KOL 小組並進行了討論並提出了建議，這是我們與監管機構討論的一部分。

There is work that we're doing on real-world evidence, meaning that we are actively tapping into registries and gathering all the information, right, sort of tracking over a long period of time.

我們正在進行現實世界證據方面的工作，這意味著我們正在積極利用登記冊並收集所有信息，進行長期跟踪。

Thirdly, a literature analysis, which obviously, there's a lot of support that we've discussed in the past around this indication. So I think that's really kind of interesting to see the presence of it here through the years. And again, right, not surprising. We know it's a very nasty bug. We also did a questionnaire of our care territories along -- across the country.

第三，文獻分析，顯然，我們過去已經討論過很多關於這一指徵的支持。所以我認為看到它這麼多年來一直存在在這裡真的很有趣。再說一次，沒錯，這並不奇怪。我們知道這是一個非常討厭的病毒。我們也對全國各地的護理區域進行了調查。

And again, it's very clear, right? There is a reason why all these patients are being treated with antibiotics and they're trying to kind of get rid of infections altogether. So I think all of that data kind of feeds into that discussion. Again, this is an ongoing process, and we're getting alignment on this. I will also say, I think it's really interesting as we're having the discussion today, right, yesterday, for the first time, a drug was approved in NCFB in bronchiectasis.

再說一遍，這很清楚，對吧？所有這些病人都接受抗生素治療，並試圖徹底擺脫感染，這是有原因的。所以我認為所有這些數據都對這一討論有幫助。再次強調，這是一個持續的過程，我們正在就此進行協調。我還要說，我認為這真的很有趣，因為我們今天的討論，對吧，昨天，NCFB 首次批准了一種用於治療支氣管擴張的藥物。

And there, again, you see all the analogy, right? All the articles that kind of say, hey, the presence of bacteria is going to lead to worse clinical outcomes, reduced survival, increased mortality. And all that data is out there, right?

再一次，你看到了所有的類比，對嗎？所有文章都說，細菌的存在會導致更糟糕的臨床結果、降低存活率、增加死亡率。所有這些數據都在那裡，對嗎？

So there's a lot of analogy and I think a lot of excitement as we think about all these indications. And again, there is a lot of rationale why we don't want these patients to have these bacteria and how detrimental it is. And what we've seen in the Phase IIa was that 14% of the patients got rid of infection altogether. That's really exciting. So I think if we can replicate this kind of data, right, hopefully improve it because that was only in 10 days and this study is 2 months.

因此，當我們思考所有這些跡象時，就會發現有很多類比，而且我認為會有很多興奮。再次強調，我們有許多理由不希望這些病人感染這些細菌，以及這些細菌有多有害。我們在 IIa 期研究中看到，14% 的患者完全擺脫了感染。這真是令人興奮。所以我認為如果我們可以複製這種數據，那麼希望能夠改進它，因為那隻是在 10 天內完成的，而這項研究花了 2 個月的時間。

Then we're looking at quite an exciting value proposition, right, knock on wood that everything replicates and the interactions go the right way, but we're very excited about the combination of the real-world evidence, hopefully, the clinical outcome and the data that we've seen. And as we've tried it many times, right, the possibility to take to see a product and even extend it even further to a market, which is even greater.

然後，我們看到了一個非常令人興奮的價值主張，對吧，敲木頭，一切都複製，相互作用以正確的方式進行，但我們對現實世界的證據、希望是臨床結果和我們所看到的數據的結合感到非常興奮。正如我們多次嘗試過的那樣，對吧，看到產品甚至將其進一步擴展到市場的可能性更大。

Okay. Great. And maybe I'll just squeeze in one more. In terms of 211, you were preparing for the registration study. Just curious, what a general framework of that study might look like? And was there any time line that you will prepare for have a discussion with the FDA?

好的。偉大的。也許我還會再擠進一個。就 211 而言，您正在準備註冊學習。只是好奇，這項研究的整體架構是什麼樣的？您是否準備了與 FDA 進行討論的時間表？

Yes. So we are interested in having that discussion in the second half, so by the end of this year. I think we're gearing up to it. You do know, for example, when you're looking at -- again, right, you could kind of split and look at the DFI, in general, where there's guidance and there's a predefined endpoint, which is the infection resolution, which is supported by some of the data that we've seen, right? We're seeing the ulcer shrink, but we see all the other parameters kind of improving.

是的。因此，我們有興趣在下半年，也就是今年年底之前進行該討論。我想我們正在為此做好準備。例如，您確實知道，當您查看時 - 再次，對，您可以拆分並查看 DFI，一般來說，其中有指導和預定義的端點，即感染解決方案，這得到了我們看到的一些數據的支持，對嗎？我們看到潰瘍縮小了，但其他所有參數都有所改善。

So that's exciting, and I think that gives us like a broad framework of how to pursue. In diabetic foot osteo, you kind of look at a bit of a longer time frame and then you want to look at the whole infection resolution, which also includes like look at the bone with MRI and X-ray. So there is a broad outline of what we need to do. And again, I think there is a guidance and thinking, we'll talk to the FDA and sort of try to solidify, but there's a very clear guidance document on this, right?

這很令人興奮，我認為這為我們提供了一個如何追求的廣泛框架。對於糖尿病足骨病變，您需要觀察較長的時間範圍，然後查看整個感染解決方案，其中還包括使用 MRI 和 X 光檢查骨骼。因此，我們需要做的事情有一個大致的輪廓。再說一次，我認為有一個指導和想法，我們會與 FDA 交談並嘗試鞏固，但對此有一個非常明確的指導文件，對嗎？

So that's very helpful, and we're basically looking to kind of ratify our understanding. And again, some of the advisers that, including Benjamin Lipsky that was on our KOL call is one of the people that actually was involved in writing the guidance, right? So we feel we're in good hands, but I got to verify and have the interaction and then sort of lay out a proper design.

這非常有幫助，我們基本上希望批准我們的理解。再說一次，包括參加我們 KOL 電話會議的 Benjamin Lipsky 在內的一些顧問實際上是參與編寫指南的人之一，對嗎？所以我們覺得我們處於良好的狀態，但我必須驗證並進行互動，然後制定適當的設計。

Okay. Great. That's very helpful. And again, congrats on kick off the critical study and look forward to talking to you as well as seeing the data later on.

好的。偉大的。這非常有幫助。再次恭喜您啟動這項關鍵研究，並期待與您交談以及稍後查看數據。

Thank you, Yale. We appreciate it.

謝謝你，耶魯。我們對此表示感謝。

I'm showing no further questions. I'd like to turn the call back over to Jonathan Solomon for any concluding remarks.

我沒有其他問題。我想將電話轉回給喬納森·所羅門，請他做最後總結發言。

So I wanted to thank you all for joining us today. I look forward to keeping you posted about ongoing developments. Very exciting times in the field as the question sort of hopefully highlighted, and I hope you enjoy the rest of the summer. Thank you again.

所以我想感謝大家今天的參加。我期待向您通報最新進展。正如問題所強調的那樣，這個領域非常令人興奮的時刻，我希望你能享受剩下的夏天。再次感謝您。

Thank you for your participation. You may now disconnect. Everyone, have a great day.

感謝您的參與。您現在可以斷開連線。祝大家有個愉快的一天。