MannKind Corp (MNKD) 2025 Q2 法說會逐字稿

Good morning, and welcome to the MannKind Corporation Second Quarter 2025 Financial Results Conference Call. As a reminder, this call is being recorded on August 6, 2025, and will be available for playback on the MannKind Corporation website shortly after the conclusion of this call and available for approximately 90 days.

早上好，歡迎參加 MannKind Corporation 2025 年第二季財務業績電話會議。提醒一下，本次通話將於 2025 年 8 月 6 日錄製，並將在通話結束後不久在 MannKind Corporation 網站上播放，播放期約為 90 天。

This call will contain forward-looking statements. Such forward-looking statements are subject to risks and uncertainty, which can cause actual results to differ materially from these stated expectations. For further information on the company's risk factors, please see the Form 10-Q for the quarterly period ended June 30, 2025, now on file with the SEC, the earnings release and the slides prepared for this presentation. Joining us today from MannKind are Chief Executive Officer, Michael Castagna and Chief Financial Officer, Chris Prentiss.

本次電話會議將包含前瞻性陳述。此類前瞻性陳述具有風險和不確定性，可能導致實際結果與所述預期有重大差異。有關公司風險因素的更多信息，請參閱截至 2025 年 6 月 30 日的季度 10-Q 表（現已提交給美國證券交易委員會）、收益報告和為本次演示準備的幻燈片。今天與我們一起出席的還有 MannKind 執行長 Michael Castagna 和財務長 Chris Prentiss。

I would now like to turn the conference over to Mr. Castagna. Please go ahead.

現在我想將會議交給卡斯塔尼亞先生。請繼續。

Thank you, operator, and good morning, everybody, and thank you for joining us for our second quarter earnings call. As we look out, we're focused on creating more shareholder value, minimizing dilution and enhancing our flexibility as we enter the next phase of our growth. The next six to eight quarters are going to showcase our cumulative work over the past seven years. Let me talk about the five pillars of our success. First, we're on the heels of TETON 2 readout here in September, and we'll actually await those results as that provides upside to our current business plans in the future.

謝謝接線員，大家早安，謝謝大家參加我們的第二季財報電話會議。展望未來，隨著我們進入下一個成長階段，我們將專注於創造更多的股東價值、最大限度地減少股權稀釋並增強我們的靈活性。接下來的六到八個季度將展示我們過去七年的累積工作。讓我來談談我們成功的五大支柱。首先，我們緊跟著 9 月的 TETON 2 讀數，我們實際上會等待這些結果，因為這將為我們未來的當前業務計劃帶來好處。

Second, Afrezza is positioned for continued growth. [peace] is now filed. I just want to put this in context; we target about 25% of all rapid-acting scripts. 1% of the rapid-acting market is roughly $300 million run rate in Afrezza. We have a strong balance sheet. With the announcement today of Blackstone, we now have access to additional capital to provide us flexibility over the coming years. Fourth, in our opinion, inhaled clofazimine is not getting enough credit in terms of meaningful opportunity that this has in our future.

其次，Afrezza 已做好持續成長的準備。 [和平]現已提交。我只是想把這個放在上下文中；我們的目標是所有速效藥物的 25% 左右。 1% 的速效市場相當於 Afrezza 的運作率約為 3 億美元。我們擁有強勁的資產負債表。隨著黑石集團今天宣布加入，我們現在可以獲得額外資本，為未來幾年提供靈活性。第四，我們認為，吸入式氯法齊明在我們未來所具有的有意義的機會方面沒有得到足夠的重視。

Fifth, our Nintedanib DPI, I'm proud to announce, will now move forward into Phase II, and I want to thank our team for all the hard work they've done. Chris will talk about further details on the Blackstone deal later in our discussion today. Our Q2 highlights are highlighted by record revenue of Tyvaso DPI sales, also record referrals for patients in Q2, which should set us up for Q3.

第五，我很自豪地宣布，我們的尼達尼布 DPI 現已進入第二階段，我要感謝我們的團隊所做的所有努力。克里斯將在今天晚些時候的討論中談論有關黑石交易的更多細節。我們第二季度的亮點是 Tyvaso DPI 銷售創紀錄的收入，同時也創下了第二季度患者轉診數量的記錄，這為我們第三季度的業績奠定了基礎。

Our inhaled Clofazimine for NTM, we expect to meet our interim target ahead of schedule, which is 100 valuable patients. Additionally, we've now advanced the dry powder formulation into preclinical studies and we anxiously await those results to move into earlier lines of treatment in the future. Nintedanib DPI for IPF, we plan to launch our trial called INFLO by year-end 2025.

我們的吸入式氯法齊明用於治療 NTM，我們預計將提前實現中期目標，即 100 名有價值的患者。此外，我們現在已經將乾粉配方推進到臨床前研究階段，我們焦急地等待這些結果在未來進入更早期的治療領域。尼達尼布 DPI 用於治療特發性肺纖維化 (IPF)，我們計劃在 2025 年底前啟動名為 INFLO 的試驗。

On the endocrine side, we're excited about the pediatric indications being submitted, and this now sets us up for launch prep as we look out over the next four quarters. Our endocrine business unit had strong performance in Q2 with $18.3 million in revenue or 13% growth over 2024. And for the Afrezza opportunity, the application to submit our label update is expected here in Q4 for a decision.

在內分泌方面，我們對提交的兒科適應症感到興奮，這為我們接下來四個季度的上市準備做好了準備。我們的內分泌業務部門在第二季表現強勁，營收為 1,830 萬美元，比 2024 年成長 13%。對於 Afrezza 的機會，我們預計將在第四季度提交標籤更新申請並做出決定。

On the financial side, we had Q2 revenues of $77 million or 6% over 2024 and year-to-date revenues of $155 million or 12% over 2024. Chris will dig into the details shortly on this one. We had a strong balance sheet with $201 million in cash, and we now have expansion capital of $500 million from Blackstone of for nondilutive capital to accelerate our growth and innovation as we look out.

從財務方面來看，我們第二季的營收為 7,700 萬美元，比 2024 年成長 6%，年初至今的營收為 1.55 億美元，比 2024 年成長 12%。克里斯很快就會深入探討這個問題的細節。我們的資產負債表表現強勁，擁有 2.01 億美元現金，目前我們從黑石集團獲得了 5 億美元的擴張資本，用於非稀釋性資本，以加速我們的成長和創新。

Let me start out on our orphan lung opportunity with MannKind 101. The NTM market is expected to exceed $1 billion by the end of the decade. Our focus will be in the US and Japan, which have the highest populations and highest opportunity for growth. It's also the two markets that we've seen the highest enrollment rates in our trial.

讓我先來談談我們與 MannKind 101 合作的孤兒肺機會。預計到本世紀末，NTM 市場規模將超過 10 億美元。我們的重點將放在美國和日本，這兩個國家人口最多，成長機會也最多。這也是我們在試驗中看到入學率最高的兩個市場。

This is a global health concern, but a real issue in these two countries. As we think about the inhaled clofazimine development program, these are the three pillars we look at. Number one, direct lung delivery could enhance the tolerability profile minimizing side effects. We can confidently say after 90 patients enrolled, we have not seen significant patient dropout early on in the trial. We do not know what arm patients are on, but there's just not been a lot of dropout. So the tolerability does look like it is holding up early on in the trial.

這是一個全球性的健康問題，但也是這兩個國家面臨的現實問題。當我們思考吸入式氯法齊明發展計畫時，我們會關注這三大支柱。首先，直接肺部輸送可以增強耐受性，最大限度地減少副作用。我們可以自信地說，在 90 名患者入組後，我們並未在試驗初期發現大量患者退出的情況。我們不知道患者使用哪種藥物，但退出治療的人數不多。因此，耐受性在試驗早期確實看起來是可以維持的。

Our active ingredient is a guideline endorsed antibiotic with decades-long clinical track record. This drug is already used in clinical practice around the world. But due to the limitations highlighted above, we believe this is a real opportunity to transform patients' lives. And finally, the convenient dosing cycle with one month on and two months off will provide a dose-free phase that minimizes treatment burden and potentially enhances adherence. We presented the ICoN-1 global Phase III trial.

我們的活性成分是經過指南認可的抗生素，擁有數十年的臨床記錄。該藥物目前已在世界各地的臨床應用中。但由於上述強調的局限性，我們相信這是一個改變患者生活的真正機會。最後，一個月服用藥物、兩個月停藥的便捷給藥週期將提供無劑量階段，從而最大限度地減輕治療負擔並可能提高依從性。我們展示了 ICoN-1 全球 III 期試驗。

I want to remind people that this is a co-primary endpoint in the US of sputum culture conversion and patient-reported outcomes. For the ex-US market, it is just sputum culture conversion. We have Fast Track QIDP & Orphan designation given us 12 years of exclusivity. And to date, we are now at 90 patients enrolled. We need 100 evaluable patients to hit our interim analysis in 2026. Let me remind you that some of the baseline patients will not have a positive sputum culture when they enrolled, and they will not be included in the interim analysis.

我想提醒大家，這是美國痰培養轉換和病患報告結果的共同主要終點。對於美國以外的市場，這只是痰培養轉化。我們擁有快速通道 QIDP 和孤兒藥資格，享有 12 年的獨家經營權。到目前為止，我們已招募了 90 名患者。我們需要 100 名可評估的患者才能在 2026 年完成中期分析。讓我提醒您，有些基線患者在入組時不會出現陽性痰培養結果，因此他們不會被納入中期分析。

Next, I'm excited to talk about MannKind 201. As we highlighted last quarter, we've completed our Phase I study looking at three doses in single ascending and two doses in multiple ascending. We had to redesign of the trial post our FDA meeting feedback as we went into Phase II, and I'm going to share with you today that trial design.

接下來，我很高興談論 MannKind 201。正如我們在上個季度所強調的那樣，我們已經完成了第一階段的研究，研究單次遞增的三劑和多次遞增的兩劑。當我們進入第二階段時，我們必須根據 FDA 會議回饋重新設計試驗，今天我將與大家分享該試驗設計。

This trial will be named INFLO as we look forward to launching this ex-US here in 2025. This study will be looking at approximately 228 patients in a randomized placebo-controlled trial with 12 weeks of active drug, followed by six months of open-label extension where everyone can get exposure to our product. We'll be exploring two doses, which is two milligrams TID or six milligrams a day of exposure or four milligrams BID eight milligrams a day of exposure.

這項試驗將命名為 INFLO，我們期待於 2025 年在美國以外地區啟動該試驗。這項研究將對大約 228 名患者進行隨機安慰劑對照試驗，首先使用 12 週的活性藥物，然後進行為期 6 個月的開放標籤延長試驗，在此期間每個人都可以接觸到我們的產品。我們將探索兩種劑量，即每天三次 (TID) 兩毫克或每天六毫克的暴露量，或每天兩次 (BID) 四毫克或每天八毫克的暴露量。

The primary objective of the study will be looking at safety and tolerability, really specifically to make sure inhaled powders will be tolerable in this patient population. The second one will be around the FVC and efficacy signals at the early stage of 12 weeks as the primary endpoint. When we look at these doses, these are consistent and may provide equal or greater exposure than what we saw presented at [Afrezza] at ATS here in May.

研究的主要目的是考察安全性和耐受性，具體來說就是確保吸入粉末對該患者群體具有耐受性。第二個研究將圍繞12週早期的FVC和療效訊號作為主要終點。當我們查看這些劑量時，它們是一致的，並且可能提供與我們 5 月在 ATS 上看到的 [Afrezza] 相同或更大的暴露量。

Regardless of the doses, this range that we both achieved independently gives us confidence that we're in a really good spot to move this forward in the patients and hopefully see a signal here in the not-too-distant future. Now I'll close the orphan lung discussion here on Tyvaso DPI. Our Tyvaso DPI revenue continues to grow as we achieved $31 million in royalty here in Q2, which put us at about $1.2 billion DPI over the last four quarters.

無論劑量如何，我們獨立達到的這個範圍讓我們有信心，我們處於一個非常好的位置，可以在患者身上推進這一進程，並希望在不久的將來看到信號。現在我將結束關於 Tyvaso DPI 的孤兒肺討論。我們的 Tyvaso DPI 收入持續成長，因為我們在第二季度實現了 3,100 萬美元的版稅，這使得我們在過去四個季度的 DPI 收入達到約 12 億美元。

As you see, our manufacturing revenue shifted downwards from Q1 to Q2 of $22 million. And this is just due to timing of manufacturing that Chris will talk about. But as I talked about 101, 201, dry powders, these are all the things that are going on in manufacturing that we have to shift around our teams as we look forward in the future. We'll anxiously be awaiting the TETON 2 results as well as TETON 1 in 2026.

如您所見，我們的製造收入從第一季到第二季下降了 2,200 萬美元。這只是由於克里斯將要談論的製造時間問題。但正如我談到的 101、201、乾粉，這些都是製造業正在發生的事情，展望未來，我們必須在團隊中轉變這些事情。我們將焦急地等待 2026 年 TETON 2 和 TETON 1 的結果。

Now I'm going to talk about our endocrine business unit. Afrezza first half year-over-year grew 22% on new prescriptions and 17% on TRxs. We really look at this performance as we start to see how can we grow writers and how can we grow the depth of prescribing. And devil is in the details here as we think about enhancing prescribing amongst our top prescribers, but how do we more broadly adopt our prescribing base. Some of the things we're doing is really enhancing our coverage at clinical conferences.

現在我要談談我們的內分泌事業部門。Afrezza 上半年新處方量年增 22%，TRxs 成長 17%。我們真正關注的是這一表現，因為我們開始思考如何培養作家以及如何增加處方的深度。當我們考慮加強頂級處方人員的處方時，細節決定成敗，但我們如何更廣泛地採用我們的處方基礎？我們正在做的一些事情確實增強了我們在臨床會議上的報告範圍。

If you look at the building momentum we've had this year, starting at ATTD in March, all the way through ENDO, ADA, ATDC as well as children's for diabetes as well as ad boards and focus groups. We've engaged with over 3,000 health care providers and our booths have been packed with guests wanting to learn more information about Afrezza, not just in the US, but around the world.

如果你看看我們今年的發展勢頭，從三月的 ATTD 開始，一直到 ENDO、ADA、ATDC 以及兒童糖尿病以及廣告看板和焦點小組。我們與 3,000 多家醫療保健提供者進行了合作，我們的展位擠滿了想要了解更多有關 Afrezza 資訊的客人，不僅在美國，而且在世界各地。

We remain excited about the future opportunity of this product and the potential to help children as we go forward. As we look at our vision for this product, we want to enhance our messaging and field force expansion ahead of the [pediatric] launch. We need to produce a halo effect, not just for kids, but what this is going to mean for the adult Afrezza community.

我們仍然對該產品的未來機會以及未來幫助兒童的潛力感到興奮。當我們審視這款產品的願景時，我們希望在[兒科]產品推出之前加強我們的訊息傳遞和現場力量的擴展。我們需要產生一種光環效應，不僅對孩子，而且對成年 Afrezza 社區也有意義。

The new campaign you'll start to see roll out later this year will be called Insulin The Moment. And this really establishes the foundation of the product around speed and control at every moment of a patient's day. This is one of the challenges you hear when you talk to patients and providers is the stacking effect of insulin, the slow effect size of insulin and the challenges patients face whether they're using insulin through a pump or a pet. We believe launching this new campaign targeting not just health care professionals, but consumers will resonate in the challenges they face in everyday control of people using insulin.

您將在今年稍後看到這項新活動開始推出，名為「胰島素時刻」。這確實為患者一天中每個時刻的速度和控制奠定了產品的基礎。這是您在與患者和提供者交談時聽到的挑戰之一，即胰島素的累積效應、胰島素的緩慢作用大小以及患者無論是透過幫浦還是寵物使用胰島素所面臨的挑戰。我們相信，這項新活動的發起不僅針對醫療保健專業人士，而且針對消費者，也會引起他們在日常控制使用胰島素時所面臨的挑戰的共鳴。

We also will increase our share of voice. As we've talked about the expansion, we expect the full sales force to be up and running by the end of this year, and the first full quarter of their impact will start in Q1 and Q2 of next year. We are deploying medical science liaisons, key account managers, field reimbursement specialists as well as an additional 20 to 30 sales reps throughout our Afrezza footprint in adults.

我們還將增加我們的發言權。正如我們談到擴張時所說，我們預計整個銷售團隊將在今年年底前投入運營，其影響的第一個完整季度將從明年第一季和第二季開始。我們正在為 Afrezza 成人業務部署醫學科學聯絡員、大客戶經理、現場報銷專家以及其他 20 至 30 名銷售代表。

This new targeting will enhance our coverage of the market to approximately 50% in 2026. Additionally, there is future data coming that will unlock our potential in areas like gestational diabetes, inhale first being a completely naive patient newly diagnosed, getting Afrezza in the first 10 days of diagnosis as well as INHALE AIDEx, which is around an exercise study looking at Afrezza in a highly active patient population. These are the next set of generation data that we expect in 2026 and beyond.

這個新目標將使我們的市場覆蓋率在 2026 年提高到約 50%。此外，未來的數據將釋放我們在妊娠糖尿病等領域的潛力，對於新診斷的完全無症狀患者，首先吸入 Afrezza，在診斷後的前 10 天服用 Afrezza，以及 INHALE AIDEx，這是一項圍繞運動的研究，觀察高度活躍的患者群體中的 Afrezza。這些是我們預計在 2026 年及以後出現的下一組數據。

Now I'll turn it over to Chris.

現在我將把話題交給克里斯。

Thanks, Mike, and good morning, everyone. Before we get into the details of the quarterly results, I want to highlight our revenue growth over the last three years as we compare the trailing four quarters on an annual basis. This annual double-digit growth has resulted in total revenues over $300 million for the trailing four quarters, and we expect this growth to continue through both our commercial products as well as our revenues earned through our collaboration with United Therapeutics. Our overall revenues in the second quarter grew 6%, led by royalties earned on Tyvaso DPI.

謝謝，麥克，大家早安。在我們了解季度業績細節之前，我想先重點介紹一下我們過去三年的收入成長情況，因為我們將過去四個季度與年度情況進行了比較。每年兩位數的成長使得過去四個季度的總收入超過 3 億美元，我們預計這種成長將透過我們的商業產品以及我們與 United Therapeutics 合作獲得的收入繼續下去。我們第二季的總營收成長了 6%，其中主要來自 Tyvaso DPI 的版稅收入。

Tyvaso DPI royalties contributed $31 million in the second quarter, an increase of 22% over the same quarter last year. Collaboration and services revenue consist primarily of manufacturing revenue based on production volumes sold through to UT and the recognition of deferred revenue. We recorded revenue of $23 million in the second quarter, a 12% decrease from the prior year as a result of the net impact of onetime items in both periods. Afrezza net revenues for the second quarter were $18 million, a 13% increase over the prior year. As Mike discussed earlier, we are encouraged by the recent performance of Afrezza in new and recurring prescriptions over the prior year and expect this trend to continue.

Tyvaso DPI 特許權使用費在第二季度貢獻了 3,100 萬美元，比去年同期成長了 22%。協作和服務收入主要包括基於透過 UT 銷售的生產量的製造收入和遞延收入的確認。我們第二季的收入為 2300 萬美元，由於兩個時期一次性項目的淨影響，比上年下降 12%。Afrezza 第二季淨收入為 1,800 萬美元，較上年成長 13%。正如 Mike 之前所討論的，我們對 Afrezza 在去年新處方和重複處方中的表現感到鼓舞，並預計這一趨勢將繼續下去。

V-Go net revenue was approximately $4 million for the second quarter, an 8% decrease from the prior year, driven by lower product demand. As V-Go is not actively promoted, we are pleased with the results of the product thus far this year. As we look ahead to the second half of the year, we anticipate continued growth in our royalty revenue driven by net sales of Tyvaso DPI.

V-Go 第二季淨收入約 400 萬美元，較前一年下降 8%，原因是產品需求下降。由於 V-Go 並未積極推廣，因此我們對今年迄今的產品效果感到滿意。展望下半年，我們預計在 Tyvaso DPI 淨銷售額的推動下，我們的特許權使用費收入將持續成長。

We expect collaboration and services revenue for the second half of 2025 to be in line with the $51 million recorded in the first half of this year. The quarterly results of CNS revenue have fluctuated this year. This is primarily driven by the timing of manufacturing, as we balance the production for the period in terms of Tyvaso DPI, Afrezza and our development programs.

我們預計 2025 年下半年的合作與服務收入將與今年上半年的 5,100 萬美元持平。今年中樞神經系統營收各季度業績波動較大。這主要是由製造時間決定的，因為我們要根據 Tyvaso DPI、Afrezza 和我們的開發計劃來平衡該期間的生產。

Lastly, we anticipate Afrezza will continue its growth trajectory based on the recent underlying performance and our expanded promotional efforts. On the expense side, R&D has increased over the prior year period as enrollment in the ICoN-1 trial of inhaled clofazimine is progressing well and preparations are underway to initiate the Phase II IPF study for our MannKind 201 program later this year.

最後，我們預計 Afrezza 將基於近期的基本業績和我們擴大的促銷力度繼續保持成長軌跡。在費用方面，由於吸入氯法齊明的 ICoN-1 試驗的招募進展順利，並且我們正在為今年稍後啟動 MannKind 201 計劃的第二階段 IPF 研究做準備，因此研發費用比去年同期有所增加。

Additionally, our team is developing a DPI formulation for our clofazimine program as well as additional potential pipeline assets. Selling, general and administrative expense has increased compared to the prior period, primarily driven by investments in expanding our commercial infrastructure. As you may recall, we had paused investment in Afrezza at the beginning of 2024, while awaiting pediatric trial data and reduced the sales force.

此外，我們的團隊正在為我們的氯法齊明專案以及其他潛在的管道資產開發 DPI 配方。銷售、一般及行政開支較上一期間增加，主要由於擴大商業基礎設施的投資。您可能還記得，我們​​在 2024 年初暫停了對 Afrezza 的投資，同時等待兒科試驗數據並減少了銷售人員。

With the potential approval of Afrezza in the pediatric indication, we're now enhancing our commercial organization, having deployed a medical science liaison team and will expand the sales force later in the year. Today, we also shared that MannKind has entered into a strategic financing arrangement with Blackstone, providing access up to $500 million in nondilutive funding.

隨著 Afrezza 在兒科適應症方面可能獲得批准，我們目前正在加強我們的商業組織，部署了一個醫學科學聯絡團隊，並將在今年稍後擴大銷售團隊。今天，我們也分享了 MannKind 與黑石集團達成戰略融資協議的消息，該協議可提供高達 5 億美元的非稀釋性融資。

This capital, secured on favorable terms and combined with our quarter end cash and investments balance, of $201 million reinforces our strong liquidity position and is available to be strategically deployed across our key growth initiatives, including supporting our commercial build-out for the potential pediatric launch of Afrezza, advancing our development pipeline and allowing us the ability to move quickly on business development opportunities. Mike and I and other members of the management team will represent the company at the Wells Fargo, Cancer, H.C. Wainwright and Morgan Stanley conferences in September. We look forward to seeing folks there and in other forums this quarter.

這筆以優惠條件獲得的資本加上我們季度末的現金和投資餘額共計 2.01 億美元增強了我們強大的流動性狀況，並可在我們的關鍵增長計劃中進行戰略部署，包括支持我們為可能在兒科推出的 Afrezza 進行商業擴張、推進我們的開發管道並使我們能夠迅速抓住業務發展機會。麥克和我以及管理團隊的其他成員將於 9 月代表公司參加富國銀行、癌症、H.C. Wainwright 和摩根士丹利會議。我們期待本季在那裡和其他論壇上見到大家。

With that, I will turn the call back over to Mike.

說完這些，我將把電話轉回給麥克。

Thank you, Chris, and thank you for the team's hard work on the Blackstone deal, which is really going to provide us the capital we need to produce these anticipated catalysts over the coming quarters. As you've seen, we've executed the first half successfully, and we have several planned opportunities here in the second half for continued execution of our plan. As we look to our stairway of building value, Tyvaso deep dive will continue to be the foundation in the near term.

謝謝你，克里斯，也感謝你的團隊在黑石交易上所做的努力，這將真正為我們提供在未來幾個季度產生這些預期催化劑所需的資金。正如您所看到的，我們已經成功執行了上半年，並且在下半年我們計劃了幾個機會來繼續執行我們的計劃。當我們展望建構價值的階梯時，Tyvaso 深度挖掘將在短期內繼續成為基礎。

As you look out into the longer term, the endocrine build with international expansion as well as pediatric expansion will continue to not only make MannKind more efficient but allow us to help more patients around the world as we go forward. Inhaled clofazimine is a meaningful opportunity and let me remind you that every 1,000 patients are approximately $100 million in revenue.

從長遠來看，隨著國際擴張以及兒科擴張的持續推進，內分泌科的建設不僅將使 MannKind 更加高效，而且使我們能夠在未來幫助世界各地的更多患者。吸入氯法齊明是一個有意義的機會，讓我提醒你，每 1,000 名患者大約有 1 億美元的收入。

We've also advanced this dry powder inhalation because we believe in order to penetrate the earlier lines of treatment, you're going to need something that's much easier for patients versus the refractory population we're currently studying. Nintedanib DPI is well underway. We've now selected the CRO, and we plan to initiate the INFLO trial here in the near future.

我們也改進了這種乾粉吸入劑，因為我們相信，為了滲透到早期的治療方法中，你需要一種對患者來說比我們目前正在研究的難治性人群更容易接受的方法。尼達尼布 DPI 正在順利進行中。我們現在已經選擇了 CRO，並計劃在不久的將來在這裡啟動 INFLO 試驗。

As you continue to see Ofev as a meaningful contributor to growth in the IPF space, we're hopefully excited to provide another option for patients as we go forward. We'll be sharing some of the new data at upcoming scientific conferences with ADCES in August here in Phoenix as well as ISPAD, which is a pediatric conference here in the fall. I want to thank everyone for all their hard work this quarter as we really can start to see the fruition of all of our work over the last seven years coming together this year and next year, and we look forward to continuing to execute our plan and share those updates in the future quarters.

當您繼續將 Ofev 視為 IPF 領域成長的重要貢獻者時，我們希望能夠在未來為患者提供另一種選擇。我們將在 8 月於鳳凰城舉行的 ADCES 科學會議以及秋季於鳳凰城舉行的兒科會議 ISPAD 上分享一些新數據。我要感謝大家本季的辛勤工作，因為我們真的可以開始看到我們過去七年的所有工作在今年和明年取得成果，我們期待繼續執行我們的計劃並在未來幾季分享這些更新。

Thank you for your time today, and we'll now open up for questions.

感謝您今天的時間，現在我們可以開始提問了。

(Operator Instructions) Olivia Brayer, Cantor Fitzgerald

（操作員指示）Olivia Brayer，Cantor Fitzgerald

Hey, good morning, guys. Thank you for the question and congrats on a great deal with Blackstone. Can you maybe walk us through what a best case might look like just in terms of timelines for a potential bridging study in IPF? I think the BREEZE study took two to three months. And I think with DPI already on the market, maybe there's a much faster timeline to approval than what we saw for PAH. And then I have a follow-up on the nintedanib program.

嘿，大家早安。感謝您的提問，並祝賀您與黑石集團達成了一項偉大的交易。您能否向我們介紹 IPF 潛在橋接研究的時間表方面的最佳情況？我認為 BREEZE 研究花了兩到三個月的時間。我認為，由於 DPI 已經上市，其核准時間可能比 PAH 快得多。然後我會跟進尼達尼布計劃。

Sorry, the first one was around what the bridge could look like for Tyvaso DPI and IPF.

抱歉，第一個問題是關於 Tyvaso DPI 和 IPF 之間的橋樑是什麼樣子的。

Yeah, exactly, and just how you're thinking about timeline for it, Mike, just given -- I know it will be a much faster timeline than what we saw with PAH, hopefully, no CRL is involved. But just how that could realistically play out, right, if TETON 2 ends up being positive and then TETON 1, when could this ultimately come to market, I guess, is what I'm thinking for DPI.

是的，確實如此，Mike，您是如何考慮時間表的，只是考慮到——我知道它將比我們在 PAH 中看到的時間表要快得多，希望不涉及 CRL。但這究竟會如何發展呢？如果 TETON 2 最終獲得正面成果，而 TETON 1 最終何時才能上市，我想，這就是我對 DPI 的思考。

Yeah, I mean it's hard for me to comment on UT's regulatory strategy and clinical strategy here. I think what you could just -- as you lay out the data readout that UT has communicated, that's to say it comes out in September and TETON 1 is next year, you got now some time to meet with the FDA and kind of work through what that could look like and potentially get as much work done, as you can before your TETON 1 readout because TETON 1 is really for the US market per se. So that's our optimism is around -- let's get the TETON 2 results and then hopefully, UT will accelerate and meet with FDA on what that could look like.

是的，我的意思是我很難在這裡評論 UT 的監管策略和臨床策略。我認為您可以做的就是 - 當您列出 UT 傳達的數據讀數時，也就是說它將於 9 月發布，而 TETON 1 將於明年發布，您現在有時間與 FDA 會面並研究它可能是什麼樣子，並在 TETON 1 讀數之前完成盡可能多的工作，因為 TETON 1 本身就是針對美國市場的。所以我們的樂觀態度是——讓我們得到 TETON 2 的結果，然後希望 UT 能夠加速並與 FDA 會面，討論結果如何。

And I think some of the effect size that you'll see in the trial will drive some of the, I'll say, ideal opportunity here with FDA. But I think it's too soon for us to speculate the clinical strategy there. I don't want to speak for UT.

我認為，您在試驗中看到的一些效果大小將推動 FDA 的一些理想機會。但我認為現在推測其臨床策略還為時過早。我不想代表 UT 發言。

Okay. Understood. And then on your nintedanib DPI program, can you maybe just talk about how you're thinking about this drug in context of some of the new updates in that space. Is this basically a replacement to current oral background therapies and then hopefully gets used in combination with newer treatments as they come to market? And then also just a question around whether you guys were able to come to an agreement with FDA around which patients to enroll in that Phase II around naive patients versus patients that are already on background therapy?

好的。明白了。然後，關於您的尼達尼布 DPI 計劃，您能否結合該領域的一些新進展，談談您對這種藥物的看法。這基本上是否可以取代目前的口服背景療法，然後希望與上市的新療法結合使用？然後還有一個問題，你們是否能夠與 FDA 達成協議，確定哪些患者可以參加 II 期臨床試驗，是初治患者還是已經接受背景治療的患者？

Yeah. I think that was one of the challenges you kind of heard me say we had to recreate the trial. When we were looking at the original design, it was really about taking nintedanib patients or patients that failed nintedanib and then enrolling them in this and showing more of a non-inferiority design. I think the FDA was adamant on a placebo-controlled on top of general background therapy design as they've given the feedback to other parties. It just doesn't work when you think about the treatment paradigm in the US, the IRB approvals you need.

是的。我想這就是你們聽到我說我們必須重新進行試驗所面臨的挑戰之一。當我們研究原始設計時，它實際上是關於招募尼達尼布患者或尼達尼布治療失敗的患者，然後讓他們參與其中，並展示更多的非劣效性設計。我認為 FDA 堅持在一般背景治療設計的基礎上進行安慰劑對照，因為他們已經向其他方提供了回饋。當你考慮美國的治療模式和所需的 IRB 批准時，它根本行不通。

You really just can't do a placebo-blinded trial for six months. And so that's what made us pivot the work over the last three months and really look at an ex-US market where it does take, call it, three months to get access to the standards of care. You could run a placebo-controlled trial and get them through the safety and clinical IRBs and protect patients at the end of the day. So we've kind of put all the things the FDA requested into the trial. It's just going to be done more ex-US than US per se. And I think that will give us the data we need to have the conviction we need to move to Phase III. And we even upsized the trial a little bit from where we were thinking just to make sure the results that we do get are a little bit more robust.

你確實無法進行為期六個月的安慰劑盲法試驗。因此，我們在過去三個月中調整了工作重點，真正關注美國以外的市場，在那裡，患者確實需要三個月的時間才能獲得標準的照護。您可以進行安慰劑對照試驗，並讓它們通過安全和臨床 IRB 審查，最終保護患者。因此，我們將 FDA 要求的所有東西都納入了試驗中。只不過，這項措施更多地在美國以外實施，而不是在美國本身實施。我認為這將為我們提供所需的數據，讓我們有信心進入第三階段。我們甚至稍微擴大了試驗規模，以確保我們得到的結果更加穩健。

The next phase will be the Phase III -- and I think if you look out in the IPF market, we would expect, hopefully, BI's product to get approved. We'd expect Tyvaso DBI to be out there. And so as we look out over the two-year window, there could be now four drugs for IPF, maybe five if Bristol-Myers gets there. And then you can see this really being on top of background therapy and designed the way that the FDA expects. As you see those other agents, about 70% of the time, those trials have background therapy on top of, right? And so that's one big area. The second big area is going to be the fact that majority of people cannot tolerate the two options that are out there today.

下一階段將是第三階段——我認為如果你關注 IPF 市場，我們希望 BI 的產品能夠獲得批准。我們預計 Tyvaso DBI 會出現在那裡。因此，當我們展望未來兩年時，我們可能會發現目前有四種治療特發性肺纖維化的藥物，如果百時美施貴寶能夠做到這一點，那麼可能會有五種。然後你可以看到這確實是在背景治療的基礎上，按照 FDA 期望的方式設計的。如您所見，其他藥物大約有 70% 的試驗都是在基礎治療的基礎上進行的，對嗎？這是一個很大的領域。第二個重要領域是，大多數人無法容忍目前存在的兩個選擇。

And we think there's a lot of patients who either choose to not take current treatment and die because the side effects are so severe. And there's a large population there that we believe an inhaled nintedanib could really help and hopefully by them the time they need for life. And so that's really where we look at the two populations, those that are intolerable for the current agents, -- and as the market expands with combination treatment, we think there's a huge opportunity there.

我們認為，有許多患者要不是選擇不接受目前的治療，就是因為副作用太嚴重而死亡。我們相信吸​​入式尼達尼布確實可以幫助那裡的大量人群，並希望能夠延長他們所需的生命時間。因此，我們真正關注的是兩類人群，即那些無法忍受現有藥物的人群——隨著聯合治療市場的擴大，我們認為那裡存在著巨大的機會。

And as we go to Phase III, that we think those other drugs being on the market will help us execute a better Phase III trial.

當我們進入第三階段時，我們認為市場上的其他藥物將幫助我們進行更好的第三階段試驗。

Faisal Khurshid, Leerink Partners.

Faisal Khurshid，Leerink Partners。

Hey guys, thanks for taking the question. I wanted to ask also on 201. Can you discuss your sort of level of confidence in using nintedanib DPI on top of background pirfenidone, both from a safety perspective and also the ability to clear a difference versus a placebo arm that includes background therapy on an efficacy basis as well?

嘿夥計們，謝謝你們回答這個問題。我也想問 201。您能否從安全性角度，以及在療效方面與包括背景療法的安慰劑組相比，明確差異的能力，談談您對在背景吡非尼酮基礎上使用尼達尼布 DPI 的信心程度？

I have Wasim here. Wasim why don't you comment on pirfenidone?

我這裡有 Wasim。Wasim，為什麼不評論吡非尼酮？

Hey everyone, Good Morning. This is good to hear from you. So the combination currently between oral nintedanib and oral pirfenidone, as you know, it's not happening, the combination of the side effects there. So from our perspective, we're going, as you well know, with inhaled nintedanib, the systemic exposure would be very low. So from a safety perspective, tolerability perspective, I mean, obviously, we need to do the trial. But the drug-drug interaction there, we expect it to be minimal.

大家好，早安。很高興收到您的來信。因此，如您所知，目前口服尼達尼布和口服吡非尼酮的組合不會產生副作用。因此，從我們的角度來看，如您所知，使用吸入式尼達尼布，全身暴露量會非常低。因此，從安全性和耐受性的角度來看，顯然我們需要進行試驗。但我們預期藥物之間的相互作用會很小。

As far as efficacy, I mean, we do have enough reason to believe that the efficacy of both pirfenidone and nintedanib combined, if they are tolerated, that it will be there. This is our hypothesis. And I would argue the same for the upcoming potential approval of [nerandomilast]. I mean the combination there, same thing. And the future of IPF treatment in our opinion, is really a combination therapy, which as of now with the two currently available therapies, it's not there.

就療效而言，我的意思是，我們確實有足夠的理由相信，如果吡非尼酮和尼達尼布聯合使用，其療效是可以的，只要它們能夠耐受。這是我們的假設。我也認為，對於即將批准的[nerandomilast]。我的意思是那裡的組合，同樣的事情。我們認為，特發性肺纖維化 (IPF) 治療的未來實際上是聯合療法，而目前現有的兩種療法還未實現這一點。

And we will be allowing both of those agents in the background treatment in this upcoming Phase II trial.

在即將進行的第二階段試驗中，我們將允許這兩種藥物用於背景治療。

Yeah, got it. And then what do you need to show to bring that development program into the US? And would that be something that could occur during the course of the Phase II? Or would that be just for the Phase III downstream?

是的，明白了。那麼你需要展示什麼才能將該發展計畫引入美國？這會發生在第二階段期間嗎？還是這僅適用於第三階段下游？

I think definitely, the Phase III, we feel confident if we get the results here that we need that this is a US global trial at that point. I think it's a matter of timing. So the trial enrollment could go very quickly ex US from currently what we have lined up.

我認為，在第三階段，如果我們能得到我們需要的結果，我們就有信心，這將是美國的全球試驗。我認為這是一個時間問題。因此，根據我們目前的安排，美國以外的試驗招生可能很快就會進行。

And it'll just be a timing issue by the time we get X amount of patients in and go back to the FDA and show them what they want to see, will they allow it. But I think even in the US, [Afrezza] is not when you think about, we can't go on top of Nintedanib and you're not switching them, they got to have a washout period. It's just a very difficult trial to execute in the US

這只是一個時間問題，當我們接收 X 數量的患者並回到 FDA 並向他們展示他們想要看到的東西時，他們是否會允許。但我認為，即使在美國，[Afrezza] 也不是你想的那樣，我們不能在 Nintedanib 的基礎上繼續使用，也不能更換它們，它們必須有一個洗脫期。這只是在美國執行的一項非常困難的審判

But I don't think it's an FDA issue as much as it's an IRB placebo study. will investigators even enroll 12 weeks on placebo. And we just think it's going to be a very hard trial to enroll by the time you get it through IRBs and approval, you're going to talk minimal patients relative to the expense and time. (inaudible) if you have anything else to add Okay. So that's -- so we won't roll out the US, but I think our focus is on getting this done as quickly as possible to move the program into Phase III.

但我不認為這是 FDA 的問題，而是一項 IRB 安慰劑研究。研究人員是否會招募 12 週的安慰劑受試者。我們只是認為，當您通過 IRB 和批准時，這將是一次非常困難的試驗，您將談論相對於費用和時間最少的患者。 （聽不清楚）如果您還有其他要補充的，好的。所以，我們不會在美國推出，但我認為我們的重點是盡快完成這項工作，以使該計劃進入第三階段。

And by the time you get there, you actually might be done the enrolment period.

當你到達那裡時，你可能已經完成了入學階段。

Andreas Argyrides, Oppenheimer.

安德烈亞斯·阿吉里德斯，奧本海默。

Yeah, good morning and thanks for taking our questions. Congrats on the progress in the quarter. Also on 201, can you talk about what you expect or what you're looking for in terms of a treatment effect from the Phase II, given also that it's kind of a small -- on the [Afrezza] side? And then also maybe rationale for -- Mike, you already kind of alluded to some of the rationale for going ex US, but anything also about the patient profiles abroad that makes sense as well. Trying to get a little readthrough into the TETON 2 study here.

是的，早上好，感謝您回答我們的問題。恭喜本季取得的進展。另外，在 201 上，您能否談談您對第二階段治療效果的期望或期望，因為 [Afrezza] 方面的治療效果還很小？然後也許還有理由——麥克，你已經提到了離開美國的一些理由，但任何有關國外病患資料的理由也都是合理的。嘗試在這裡對 TETON 2 研究進行一些了解。

And then, Chris, for you, maybe just again, thinking around the Blackstone deal, the rationale to do a kind of a revolving credit deal versus other traditional financing. Thank you

然後，克里斯，對你來說，也許只是再次思考黑石交易，與其他傳統融資相比，進行一種循環信貸交易的理由。謝謝

Yeah, I'll start off and I'll ask question to add. I think on the effect size, the main thing we'll be looking at is tolerability and safety because that's really the Achilles heel of nintedanib. I think when you look at the pivotal trials of that product, you can start to see a response in 12 weeks. And so that's why we made the primary endpoint. We thought what's a long enough period with placebo that you can safely go and not compromise somebody's journey and ethically enroll the trial.

是的，我先開始，然後問一些要補充的問題。我認為，就效果大小而言，我們主要關注的是耐受性和安全性，因為這確實是尼達尼布的致命弱點。我認為，當您查看該產品的關鍵試驗時，您可以在 12 週內開始看到反應。這就是我們設定主要終點的原因。我們認為，安慰劑的療程要夠長，才能保證安全，不影響病人旅程，並且符合倫理道德地參與試驗。

And we felt 12 weeks is appropriate. After 12 weeks, it's an open-label extension. So we will have hopefully a good group of patients going on for six to nine months, but it will be at their option. So I think we'll start to see that effect size, hopefully, over time, not just at the 12-week mark, but over the patients who continue. And then remember, anyone that's on placebo, we'll have the option of active drug at week 12. And so I think that's really going to give us a nice data set to power a Phase III trial appropriately.

我們認為 12 週是合適的。12 週後，這是一個開放標籤擴展。因此，我們希望有一群優秀的患者能夠堅持治療六到九個月，但這將由他們自己選擇。因此我認為，隨著時間的推移，我們將開始看到這種效果，不僅僅是在 12 週時，而是在繼續治療的患者中。然後請記住，對於任何服用安慰劑的人來說，我們都會在第 12 週選擇活性藥物。所以我認為這確實會為我們提供一個很好的數據集，以適當地支持第三階段試驗。

And I think when you look at those effect sizes, obviously, they have to be meaningful enough in FVC. So I think when the secondary endpoint will be efficacy, it will not be powered for efficacy per se. The other key aspect of the trial is really the BID and TID. So as the market does not really know and experts don't know how nintedanib actually has the effect that it does, we don't know if it's a signaling issue, a switch issue, a duration of effect of a binding receptor.

我認為，當你觀察這些效應大小時，顯然它們在 FVC 中必須足夠有意義。因此我認為，當次要終點是療效時，它本身不會以療效為動力。試驗的另一個關鍵方面實際上是 BID 和 TID。因此，由於市場並不真正了解並且專家不知道尼達尼布實際上是如何產生這種效果的，我們不知道這是一個信號問題、一個開關問題還是一個結合受體的作用持續時間問題。

And so we're actually experimenting with that in this trial design in terms of TID versus BID. Obviously, when you look at the (inaudible) data, it could even be QD, but we want to wind up with a wonky result and try to stretch [PK PD] it may not be that parameter in terms of what you're looking at from a QD versus BID. So these are insights we'll look, and you might see a difference between those two dosing regimens, and that will be important for a Phase III design. But otherwise, we think this will give us enough information to properly design and power a Phase III trial globally. (inaudible) I don't know if you have anything.

因此，我們實際上正在此試驗設計中就 TID 與 BID 進行實驗。顯然，當您查看（聽不清楚）資料時，它甚至可能是 QD，但我們希望得到一個不穩定的結果並嘗試擴展 [PK PD] 就您從 QD 與 BID 的角度來看，它可能不是那個參數。這些是我們將要研究的見解，您可能會看到這兩種給藥方案之間的差異，這對於 III 期設計非常重要。但除此之外，我們認為這將為我們提供足夠的資訊來在全球範圍內正確設計和推動第三階段試驗。（聽不清楚）我不知道您是否有任何東西。

Yeah. To add to that. So that study, as Mike mentioned, I mean, 12-week is a double-blind period. However, it's really it's a nine month study in the sense that when you include the open-label extension. So we will have -- and we have two active doses versus placebo. So we'll have data on both safety and tolerability and efficacy for nine months for most of the patients for those who are randomized to active and even the placebo will have about six months data after the transition.

是的。除此之外。正如麥克提到的那樣，這項研究為期 12 週，這是一個雙盲期。然而，如果包括開放標籤擴展，這實際上是一項為期九個月的研究。因此，我們將有兩種有效劑量與安慰劑相對照。因此，對於大多數隨機接受活性藥物治療甚至接受安慰劑治療的患者，我們將獲得九個月的安全性、耐受性和療效數據，在轉變後也將獲得大約六個月的數據。

As far as treatment effect assumptions, I mean, obviously, we have our thoughts about the treatment effect. But again, this is first in patient study. So this will be the basis for our assumptions moving forward. You know we did the healthy volunteers first in humans last year. So we have those data. And the molecule is not new, right, nintedanib.

至於治療效果假設，我的意思是，顯然我們對治療效果有自己的想法。但再次強調，這在患者研究中尚屬首次。因此這將成為我們未來假設的基礎。你知道，去年我們先對健康志願者進行了人體試驗。所以我們有這些數據。而這種分子並不是什麼新分子，就是尼達尼布。

So we understand its pharmacokinetics. The Inhaler is not new. It's already into approved products, as you know. And the powder that we're using is also not new. It's already approved products. So we are very comfortable with the delivery, how we're giving it and the pharmacokinetics and pharmacodynamics are already well understood this model.

因此我們了解它的藥物動力學。吸入器並不是什麼新鮮事。正如您所知，它已經成為批准的產品。而且我們使用的粉末也不是新的。它已經是批准的產品。因此，我們對給藥方式、給藥方式以及藥物動力學和藥效動力學都已經非常了解，因此非常滿意。

And then Andreas, on the financing front, as we look out the next 18 to 24 months, we just see a number of key catalysts for us. We have our two late-stage development programs. We have starting to focus on commercial prep for one of those programs in clofazimine. And obviously, we have the pediatric launch that we hope to have in 2026, if approved. So as we look at all of those, having access to flexible capital at this point in time, just makes a lot of sense to have this instrument in place.

然後，安德烈亞斯，在融資方面，展望未來 18 到 24 個月，我們看到了一些關鍵的催化劑。我們有兩個後期開發項目。我們已經開始關注氯法齊明其中一個專案的商業化準備。顯然，如果獲得批准，我們希望在 2026 年推出兒科藥物。因此，當我們審視所有這些因素時，就會發現，在此時此刻能夠獲得靈活的資本，而實施這項工具是非常有意義的。

And then, of course, one of the key tenets here is have the ability to be reactive if business development opportunities present themselves. And so speed in those situations, I think, is really important. And so for us to be able to be in a position of strength on that side, again, just made this instrument the right choice for us and really happy to be working with a partner like Blackstone.

當然，這裡的一個關鍵原則是，當業務發展機會出現時，要有能力做出反應。所以我認為在這種情況下速度非常重要。因此，對於我們來說，能夠在這方面佔據優勢地位，再次，這一工具對我們來說是正確的選擇，並且很高興能與黑石這樣的合作夥伴合作。

Brandon Folkes, H.C. Wainwright.

布蘭登福克斯、H.C. 溫賴特。

Hi, thanks for taking my questions and congrats on the update. Maybe just changing gears a little bit to Afrezza. Can you perhaps just talk about the typical Afrezza patient today, sort of where you're gaining the most traction as we continue to see this double-digit growth? And if you've seen any evolution yet maybe over the last 12 months since the sort of inhaled -- the two data sets were published. Just unaided awareness of these data sets currently?

你好，感謝您回答我的問題，並祝賀您更新。也許只是稍微改變一下方向，轉向 Afrezza。您能否談談當今典型的 Afrezza 患者，隨著我們繼續看到這種兩位數的增長，您在哪些方面獲得了最大的關注？如果您已經看到了任何變化，也許是自吸入以來的過去 12 個月內——這兩組數據已經發布。目前對這些資料集的認識還不夠嗎？

Are they seeping into the prescribing community? As yet, just given the outreach you've done, obviously, not promoting to it, but just -- and then sort of when we think about depth and breadth of prescribing, where are you seeing the traction today on Afrezza?

他們是否已經滲透到處方社區？到目前為止，鑑於您所做的推廣工作，顯然不是對其進行推廣，而只是——然後當我們考慮處方的深度和廣度時，您今天在哪裡看到了 Afrezza 的吸引力？

Yeah, I think the first comment I'll make and Nick is with us is the -- we just got a database breakdown, and I think you can kind of indirectly see it in the earnings is that the breakdown of patients is roughly 45% type 1 and 55% type 2. Over the last year or so, we've been pivoting a little bit more to type 1, and we can see four- and eight-unit strength is growing a little bit faster than the 12 unit over the last year. So I think that would signal our execution against type 1 is growing and the uptake there is getting a little bit higher.

是的，我想我要做的第一條評論（尼克也和我們在一起）是——我們剛剛得到了數據庫細分，我想你可以在收益中間接地看到，患者的細分大約是 45％ 為 1 型，55％ 為 2 型。在過去一年左右的時間裡，我們更多地轉向了類型 1，我們可以看到，在過去的一年裡，4 個和 8 個單位的強度增長速度比 12 個單位的強度增長速度要快一些。所以我認為這表明我們針對 1 型病毒的執行力度正在加大，而且接受度也在提高。

I'll let Nick talk about -- a little bit more about the depth and breadth and some of the work you're doing.

我會讓尼克多談論你正在做的一些工作的深度和廣度。

Yeah, Thanks, Mike, and I would agree with that. I think what we're seeing overall is increased awareness -- we've changed our strategy a bit by adding targets across the field sales force where we're going after unique prescribers. We've had much more activity at congresses where we've had less of a presence in the past.

是的，謝謝，麥克，我同意這一點。我認為，我們總體上看到的是意識的提高——我們稍微改變了我們的策略，在現場銷售隊伍中增加了目標，我們追求的是獨特的處方者。我們在一些大會上開展了更多活動，而過去我們很少參加這些大會。

We're engaging more in scientific and clinical education to create awareness around the science, and the benefits of Afrezza within its competitive landscape. So overall, I would say focusing on the adult community, looking to increase unique prescribers, increasing awareness around science and clinical data, I think, is where we're starting to see ourselves making good progress, and we'll continue to do so, focus in that area for at least the next two to three quarters.

我們正在更多地參與科學和臨床教育，以提高人們對科學的認識，以及 Afrezza 在競爭環境中的優勢。所以總的來說，我想說，專注於成人社區，尋求增加獨特的處方者，提高對科學和臨床數據的認識，我認為，這是我們開始看到自己取得良好進展的地方，我們將繼續這樣做，至少在接下來的兩到三個季度專注於這個領域。

Thank you so much. Sorry, I was struggling with the mute but I apologize. Yes, maybe -- sorry, as we just think about the sales footprint and the growth, as we get the pediatric label and sort of in light of the additional capital you now have access to, are you going to think about sort of going with a full footprint for pediatrics on day one on the launch?

太感謝了。抱歉，我有點難以靜音，但我深感抱歉。是的，也許——抱歉，我們只考慮銷售足跡和增長，當我們獲得兒科標籤時，考慮到您現在可以獲得的額外資本，您是否會考慮在發布的第一天就全面開展兒科業務？

Are you thinking about sort of incremental investment, assessing the traction and sort of then perhaps layering in additional expansion, additional reps to target the pediatric indication over time? Just how should we think about sort of Afrezza investment beyond 2025?

您是否考慮過某種增量投資，評估吸引力，然後或許分層進行額外擴展、增加代表以隨著時間的推移針對兒科適應症？我們該如何看待 2025 年以後的 Afrezza 投資？

Yeah, I think we're building up the peds plan. I think our initial thoughts are number one, we decreased our sales force footprint coming into 2024. And we're running Afrezza for profitability in 2025 and really late '24 all the way into early '25. As we came out and got the pediatric data, right, our confidence level in the peds launch went up, right, in terms of lung safety and believability and the opportunity that exists there. And so as you see this year, we are -- with the hiring of Nick and the expansion of the team.

是的，我認為我們正在製定兒科計劃。我認為我們最初的想法是，到 2024 年，我們將減少銷售人員的足跡。我們經營 Afrezza 的目的是為了在 2025 年，也就是 2024 年底到 2025 年初實現獲利。當我們獲得兒科數據時，就肺部安全性和可信度以及其中存在的機會而言，我們對兒科發布的信心水平上升了。正如您今年所看到的，我們聘請了尼克並擴大了團隊。

Number one is when we decrease the footprint, we're only targeting about 25% of all rapid-acting scripts, which is mainly our target to maintain our business. In order to grow, we need to target a larger percentage of the market. The number one thing we hear is doctors do not remember, Afrezza, it's not top of mind, and it's true. Our reps are not there every week, hitting them like they're getting hit with insulin pumps from one company or another every week.

首先，當我們減少佔地面積時，我們只針對所有速效腳本的 25% 左右，這主要是我們維持業務的目標。為了實現成長，我們需要瞄準更大的市場份額。我們聽到最多的是醫生不記得了，Afrezza 並不是最受關注的藥物，這是事實。我們的銷售代表並不是每週都在那裡，而是每週都對他們進行來自不同公司的胰島素幫浦打擊。

So that's important as we close out this year, and we have a label change coming up in October that we want to get the sales force expansion so that, that label change can be communicated more widely. The second thing with peds is it's a different selling target than our traditional Afrezza use. Most of our Afrezza use comes from private practice doctors who know our data, who have open access and they listen to the scientific exchange. A lot of the future is in academic centers and children's hospitals where our reps have not traditionally been as strong nor our selling model.

因此，這一點對於我們今年年底來說非常重要，我們將在十月進行標籤變更，我們希望擴大銷售隊伍，以便更廣泛地傳播標籤變更。對兒科來說，第二個問題是它的銷售目標與我們傳統的 Afrezza 用途不同。我們大多數使用 Afrezza 的都是私人執業醫生，他們了解我們的數據，擁有開放的訪問權限，並且會傾聽科學交流。未來很大一部分是在學術中心和兒童醫院，而我們的代表傳統上在這些領域並不那麼強大，我們的銷售模式也不那麼強大。

And so we think it's really important to build a dedicated key account manager team with experience selling in institutions. It's a different skill set, and that's where the majority of peds being almost 80% are treated. When you look at our [piece] trial, we had 39 of the 50 academic target centers in the US in the trial. So we had a large percentage of them do the trial, and we think there's a really important opportunity to continue that education and expansion in kids.

因此，我們認為建立一支具有機構銷售經驗的專門大客戶經理團隊非常重要。這是一套不同的技能，大多數兒科患者（幾乎 80%）都接受過這種治療。當您查看我們的試驗時，您會發現美國 50 個學術目標中心中有 39 個參與了試驗。因此，我們讓很大一部分孩子參與了試驗，我們認為這是一個在孩子中繼續進行教育和推廣的重要機會。

The other thing we're going through to your question on the uptake will be why we believe, and we'll start to communicate this information, why do we believe the uptake in kids will be more accelerated than we've seen in adults. And anecdotally, our feedback from advisers and conferences and engagements has been very, very positive. Parents have been very excited. People are shocked. They didn't know and [ICoN] has been on the market this long. And so we just think there's a whole new opportunity to relaunch the brand and pivot the entire franchise.

關於您關於吸收率的問題，我們要討論的另一件事是，為什麼我們相信，並且我們將開始傳達這一訊息，為什麼我們相信兒童的吸收率會比成年人更快。據傳聞，我們從顧問、會議和活動中得到的回饋都非常非常正面。父母都非常興奮。人們都很震驚。他們不知道 [ICoN] 已經上市這麼久了。因此，我們認為這是一個重新推出該品牌並調整整個特許經營的全新機會。

And so we need to keep expanding in adults as we can grow there. But more importantly, going into the pediatric community early and often will be important. And I'll remind you guys, we do co-promote BAQSIMI with Amphastar. So that does allow us to go into the pediatric community and promote that product today, and that is something we're weighing as we go forward.

因此，我們需要繼續擴大成人市場，以便我們能夠在那裡成長。但更重要的是，儘早並經常進入兒科社區非常重要。我要提醒你們，我們確實與 Amphastar 共同推廣 BAQSIMI。因此，這確實使我們能夠進入兒科社區並推廣該產品，這也是我們今後正在權衡的事情。

Anthony Petrone, Mizuho Americas.

瑞穗美洲公司的安東尼‧佩特羅內 (Anthony Petrone)。

Great thanks and the Blackstone agreement. Maybe a couple on clofazimine and a follow-up on Afrezza. When we think about clofazimine ICoN ahead on the interim getting to 100 patients, if you get the desired sputum conversion outcome at interim, how does that change just the time line? Can it actually be fast tracked for clearance if you get that sputum conversion? And then when you think about building a sales force, a pulmonology-facing sales force, like what is the size of that team if you look ahead to a positive outcome?

非常感謝 Blackstone 協議。也許服用幾次氯法齊明，然後再服用 Afrezza。當我們考慮暫時讓氯法齊明 ICoN 惠及 100 名患者時，如果您暫時獲得了所需的痰液轉化結果，那麼這會如何改變時間線？如果痰液樣本轉換成功，真的可以快速通關嗎？然後，當您考慮建立一支銷售隊伍，一支面向肺病學的銷售隊伍時，如果您展望積極的結果，那麼該團隊的規模是多少？

And then I'll have a follow-up on Afrezza.

然後我會跟進 Afrezza 的情況。

I think on the sputum, obviously, that's where we're weighing the trial statistically. And if we get that interim result next year, we're going to let the trial enrollment keep happening even if we were to hit the 180 mark. So I think if it says it's good at 180, some of the debate we'll have at that time will be, do we lock the database at 180 or do you wait for the remaining 20, 30 people to hit the six month endpoint. And that will drive the timeline there with FDA. It does have QIDP designation as well as fast track.

我認為，顯然，透過痰液檢查，我們可以對試驗結果進行統計衡量。如果我們明年獲得中期結果，即使達到 180 人，我們也會繼續進行試驗招生。因此我認為如果它說 180 是好的，那麼我們當時會進行的一些爭論是，我們是否將資料庫鎖定在 180 還是等待剩下的 20、30 個人達到六個月的終點。這將推動 FDA 的時間表。它確實有 QIDP 指定以及快速通道。

So there is an opportunity for a faster review and a rolling submission, I believe, with FDA. And I think the FDA has been nothing but collaborative with this NTM asset and clofazimine. There is nothing else in development that's meaningful. We're the last option for patients at this point. And I do think the FDA wants to see this product succeed and get there if we have the data to support it. That's on that. On the pulmonary sales side, I wouldn't speculate yet the size or investment there. That's one of the reasons we put the capital up as we get closer, we'll make the right assessment opportunity. But it's not a huge footprint, right?

因此，我相信 FDA 有機會進行更快的審查和滾動提交。我認為 FDA 一直在與 NTM 資產和氯法齊明合作。開發中沒有其他有意義的事情。目前我們是患者的最後選擇。我確實認為，如果我們有數據支持，FDA 希望看到產品成功並實現這一目標。就這樣。在肺部銷售方面，我還沒有推測其規模或投資。這就是我們投入資金的原因之一，隨著我們越來越接近，我們將做出正確的評估機會。但這不是一個巨大的足跡，對吧？

This is a very specialized disease. I think the biggest thing is weighing as we continue to watch ARIKAYCE in Japan, what do you do in the Japanese market? And how do you either partner that or build it yourself. And I think those will be the key strategic questions we face over the next 12 months. As we look in those markets, there is opportunity -- significant opportunity in Japan as we look at trial enrollment, KOL support, has been in Asia for the last few weeks.

這是一種非常特殊的疾病。我認為最大的問題是，當我們繼續關注日本的 ARIKAYCE 時，您在日本市場上做什麼？您如何與他人合作或自行建立它？我認為這些將是我們在未來 12 個月面臨的關鍵策略問題。當我們觀察這些市場時，我們發現日本存在著巨大的機會，就試驗報名和 KOL 支援而言，過去幾週，這些機會一直在亞洲出現。

There's a large opportunity there and a lot of support for clofazimine. So we're really excited about it. I think it's going to be a meaningful opportunity for trajectory inflection on MannKind. And it's coming before we blink, I mean, really next year, close to this time, we'll be hopefully seeing what the interim says and going where we are.

這裡面存在著巨大的機遇，對氯法齊明的支持也很多。所以我們對此感到非常興奮。我認為這將是人類軌跡拐點的一個有意義的機會。而它就在我們眨眼之間到來，我的意思是，實際上，明年，接近這個時候，我們將滿懷希望地看到中期所說的內容以及我們所處的階段。

No, that's great. And then on Afrezza, maybe just that patient profile in pediatric from a utilization intensity standpoint. Do you imagine this is going to be kind of more meal time? Or will it be even some aspect of basal plus bolus? So just trying to get an understanding of the intensity of a pediatric patient on Afrezza versus an adult patient. Thanks.

不，那太好了。然後對於 Afrezza，從利用強度的角度來看，可能只是兒科患者的情況。您是否認為這會是更多的用餐時間？或者它甚至是基礎劑量加餐劑量的某種方面？因此，只是想了解使用 Afrezza 的兒科患者與成人患者的治療強度。謝謝。

I mean, Nick just came from the conference here in July. I'll give you my thoughts and then Nick, you can add any anecdotal feedback you have from the sessions. But I think parents stress a lot around hypoglycemia and insulin pumps and chasing their child down with injections. And I do believe parents will want to use Afrezza full time versus sometimes we hear sporadic use on top of an insulin pump, (technical difficulty) highs, holidays, things like that. So Nick, I don't know where you came back, if you want to add anything from the conference and the parent engagement you had.

我的意思是，尼克剛參加完七月的會議。我會告訴你我的想法，然後尼克，你可以添加你在會議中得到的任何軼事回饋。但我認為父母對低血糖和胰島素幫浦以及催促孩子注射感到壓力很大。我確實相信父母會希望全天使用 Afrezza，而不是有時我們聽到在胰島素幫浦上偶爾使用，（技術困難）高峰期、假期等情況。所以尼克，我不知道你回來了，如果你想補充一些關於會議和家長參與的內容。

Yeah. I think there's -- what we hear largely from the caregivers, which tends to be the parents or the patients themselves is post diagnosis, the patients go through a series of steps, which is initiation of therapy, which tends to be MDI, perhaps looking to switch therapies or eventually going on an AID. And so I think that it's an opportunity for Afrezza to be plugged in at many different steps along the diagnosis pathway and the treatment pathway.

是的。我認為——我們主要從護理人員（往往是父母或患者本人）那裡聽到的是診斷後的情況，患者要經歷一系列步驟，即開始治療，往往是 MDI，也許希望轉換療法或最終接受 AID。因此，我認為這對 Afrezza 來說是一個機會，可以將其應用於診斷途徑和治療途徑的許多不同步驟。

I also think, as Michael had mentioned, -- there's the opportunity for meal time and multiple controls throughout the day. These are younger kids that tend to be active playing sports, grabbing meals as they go. And so I think the opportunity for pediatrics and adolescents will be slightly different from what we've seen in the adult community. And I think we're making adjustments as to how we fit into that community now.

我還認為，正如邁克爾所提到的那樣——有機會在用餐時間和全天進行多次控制。這些孩子年紀較小，喜歡積極運動，邊走邊吃飯。因此，我認為兒科和青少年的機會與我們在成人社區中看到的機會略有不同。我認為我們正在做出調整以適應該社區。

Thank you.

謝謝。

Thank you, Anthony. Yeah, we just see kids being so much more active and that's where inhaling insulin plays a much better role for patients, so.

謝謝你，安東尼。是的，我們看到孩子變得更加活躍，而吸入胰島素對患者來說發揮著更好的作用。

Yun Zhong, Wedbush.

雲中，韋德布希。

Hi, good morning. Thank you very much for taking the questions. And the first question on 201 study. I just wanted to confirm that I heard it correct that you said the placebo-controlled 12-week treatment period is not powered for efficacy. And is the goal to select one dosing regimen between the TID and BID and move it forward to Phase III? Or is it possible that both dosing regimens can move into Phase III? And also, what's the possibility of including active control arm in the Phase III or any requirement regarding inclusion of an active control arm, please?

嗨，早安。非常感謝您回答這些問題。這是 201 研究中的第一個問題。我只是想確認我聽到的是否正確，您說的安慰劑對照的 12 週治療期無法證明療效。目標是否是在 TID 和 BID 之間選擇一種給藥方案並將其推進到第三階段？或是兩種給藥方案都可以進入第三階段嗎？另外，請問在第三階段納入主動控制臂的可能性有多大，或是對納入主動控制臂有什麼要求？

I think it's a little too soon to speculate the exact Phase III design. But I think from the interactions we have with the FDA you can see adding -- we have to assume more drugs get approved. And I mean, one of the challenges is nintedanib is the majority of scripts in the US. So it's hard to add on top of nintedanib and inhaled nintedanib. So you really look at -- you're limited to pirfenidone.

我認為現在推測第三階段的具體設計還為時過早。但我認為，從我們與 FDA 的互動中，您可以看到，我們必須假設更多的藥物獲得批准。我的意思是，其中一個挑戰是尼達尼佈在美國佔了大多數處方。因此很難在尼達尼布和吸入性尼達尼布的基礎上添加。所以你真的看——你僅限於吡非尼酮。

So we really do hope that there's more drugs approved over the next one and half years so that when you run this trial, you have background therapy that you can add on top of in a placebo arm as the FDA seems insistent on the placebo control here.

因此，我們確實希望在未來一年半內能有更多的藥物獲得批准，這樣當你進行這項試驗時，你就可以在安慰劑組的基礎上添加背景療法，因為 FDA 似乎堅持在這裡進行安慰劑對照。

So it's not an active comparator as much as this placebo compared on top of background therapy. That's our running assumption today. In terms of effect size and powering the trial, should it be one or two dosing regimens, I think we're just -- we have some flexibility here in terms of -- is it 2 milligrams or 4 milligrams twice a day or 3 times a day. I think that's our focus is getting one dose regimen into Phase III. We don't expect to see a significant difference between these two narms.

因此，它並不是一種有效的比較劑，而是一種在背景療法基礎上進行對比的安慰劑。這就是我們今天的假設。就效果大小和試驗動力而言，應該採用一種還是兩種給藥方案，我認為我們只是 - 我們在這裡有一些靈活性 - 是每天兩次還是每天三次，每次 2 毫克或 4 毫克。我認為我們的重點是將單劑量方案納入第三階段。我們並不期望看到這兩個名稱之間有顯著的差異。

But let's say there is a -- as you look at the subpopulations and patient characteristics, maybe we start to see signals in one or the other, and that would drive a potential dose regimen selection.

但是假設存在 - 當您查看亞群和患者特徵時，也許我們開始在其中一個或另一個中看到信號，這將推動潛在的劑量方案選擇。

But we don't expect to go at this point with two different doses in Phase III. We expect to pick one, and we'll look for group analysis and sub analysis on patient characteristics is that does the BID versus TID show anything different. But our overall assumption is it's probably a BID exposure, and that's our working assumption, but we didn't want to get there and find out maybe TID had a better effect size or a better receptor binding that we can't see.

但我們目前並不期望在第三階段採用兩種不同的劑量。我們希望選擇一個，然後我們將對患者特徵進行組分析和子分​​析，看看 BID 與 TID 是否顯示出任何不同。但我們的總體假設是它可能是 BID 暴露，這是我們的工作假設，但我們不想到達那裡並發現 TID 可能具有我們看不到的更好的效果大小或更好的受體結合。

So part of this is you're going into a nature that no one else has ventured into in terms of inhaled nintedanib and receptor binding and directly impacting the lung. So we feel very good about that exposure, but now we just have to understand the signaling that happens in that tissue.

因此，部分原因是，你正在進入一個其他人尚未涉足的領域，即吸入尼達尼布和受體結合併直接影響肺部。因此，我們對這種暴露感到非常滿意，但現在我們只需要了解組織中發生的訊號傳導。

I see. And then a question on the $500 million loan agreement with Blackstone. Are you able to share under what conditions will you be able -- we need to draw additional capital? And would that be based on commercial or clinical milestones, please? Thank you very much

我懂了。然後是關於與黑石集團達成的 5 億美元貸款協議的問題。您能否分享一下在什麼條件下我們需要籌集額外資金？這是基於商業還是臨床里程碑？非常感謝

No. So it's up to $500 million. We draw $75 million now. We have $125 million that is committed. We, for the most part, have the ability to draw that at our discretion. So there are no specific sales milestones or development-related milestones that would be contingent upon. I think Blackstone just wants to make sure that this is growth capital, and we're putting this forward in a way that makes sense.

不。所以高達 5 億美元。我們現在提取了 7500 萬美元。我們已承諾投入 1.25 億美元。在大多數情況下，我們有能力根據自己的判斷來繪製它。因此，不存在特定的銷售里程碑或與開發相關的里程碑。我認為黑石只是想確保這是成長資本，並且我們正在以合理的方式提出這一點。

Thank you. I would now like to turn the conference back to management for closing remarks.

謝謝。現在，我想請管理階層代表作閉幕發言。

I just want to say thank you to everyone today for listening. We are very excited about where we're going in terms of the late-stage development pipeline is really starting to mature. We've spent a lot of energy and a lot of money over the years to get to this point. We now have the flexible funding that we need to make sure we can grow these assets, invest in these assets as funding a late-stage Phase III and a late-stage Phase II is important to us and being able to kind of get to the data readouts will only create more value inflection for shareholders and patients.

我只想對今天聆聽的各位表示感謝。我們對後期開發流程的進展感到非常興奮，它已經真正開始成熟。多年來，我們花費了大量的精力和金錢才達到這一點。我們現在擁有所需的靈活資金，以確保我們能夠增加這些資產，投資這些資產，因為為 III 期後期和 II 期後期提供資金對我們來說很重要，並且能夠獲得數據讀數只會為股東和患者創造更多的價值拐點。

And so we're very excited about those late-stage assets and the opportunity coming at us with peds. That's now on file. That clock is ticking, and we'll continue to update you guys on those opportunities. And thank you again for your time and look forward to follow-up questions and investor meetings in September.

因此，我們對這些後期資產以及兒科為我們帶來的機會感到非常興奮。現在已經記錄在案了。時鐘正在滴答作響，我們將繼續向你們通報這些機會。再次感謝您的時間，並期待九月份的後續提問和投資者會議。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。