Verona Pharma PLC (VRNA) 2024 Q3 法說會逐字稿

Good morning, everyone, and welcome to Verona Pharma's Third Quarter 2024 Financial Results and Operating Highlights Conference Call. (Operator Instructions) Earlier this morning, Verona Pharma issued a press release announcing its financial results for the three months ended September 30, 2024. A copy can be found in the Investor Relations tab on the corporate website, www.veronapharma.com.

大家早安，歡迎參加維羅納製藥 2024 年第三季財務業績和營運亮點電話會議。(操作員指示)今天早些時候，維羅納製藥發布了一份新聞稿，宣布了其截至 2024 年 9 月 30 日三個月的財務業績。您可以在公司網站 www.veronapharma.com 的「投資者關係」標籤中找到副本。

Before we begin, I'd like to remind you that during today's call, statements about the company's future expectations, plans and prospects are forward-looking statements. These forward-looking statements are based on management's current expectations.

在我們開始之前，我想提醒您，在今天的電話會議中，有關公司未來預期、計劃和前景的陳述都是前瞻性的陳述。這些前瞻性陳述是基於管理階層目前的預期。

These statements are neither promises nor guarantees and involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from our expectations expressed or implied by the forward-looking statements.

這些聲明既不是承諾也不是保證，涉及已知和未知的風險、不確定性和其他重要因素，可能導致我們的實際結果、業績或成就與前瞻性聲明表達或暗示的預期存在重大差異。

Any such forward-looking statements represent management's estimates as of the date of this conference call. While the company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change.

任何此類前瞻性陳述均代表管理階層截至本次電話會議之日的估計。儘管公司可能選擇在未來某個時間點更新此類前瞻性陳述，但它不承擔任何這樣做的義務，即使後續事件導致其觀點發生變化。

As a reminder, this conference call is being recorded and will remain available for 90 days. I'd now like to turn the floor over to Dr. David Zaccardelli, Chief Executive Officer. Sir, you may begin.

提醒一下，本次電話會議正在錄音，並將保留 90 天。現在我想把發言權交給執行長 David Zaccardelli 博士。先生，您可以開始啦。

Thank you, and welcome, everyone, to today's call. We are extremely pleased to be with you today to share our remarkable achievements in the third quarter, highlighted by the launch of Ohtuvayre. With me today are Mark Hahn, our Chief Financial Officer; Dr. Kathy Rickard, our Chief Medical Officer; Chris Martin, our Chief Commercial Officer; and Dr. Tara Rheault, our Chief Development Officer.

謝謝大家，歡迎大家參加今天的電話會議。我們非常高興今天能與大家分享我們在第三季取得的顯著成就，其中最引人注目的是 Ohtuvayre 的推出。今天和我在一起的是我們的財務長馬克‧哈恩 (Mark Hahn)；我們的首席醫療官 Kathy Rickard 博士；克里斯馬丁（Chris Martin），我們的首席商務官；以及我們的首席開發長 Tara Rheault 博士。

The third quarter was exceptional for Verona Pharma, marked by the US launch of Ohtuvayre for the maintenance treatment of COPD and continued progress on our clinical development programs.

第三季對維羅納製藥來說是非凡的，標誌著 Ohtuvayre 在美國上市，用於 COPD 的維持治療，並且我們的臨床開發項目繼續取得進展。

First, let's review the outstanding launch of Ohtuvayre, which is grounded in its broad COPD indication and the compelling benefits Ohtuvayre provides to COPD patients. After just seven weeks, net product sales were $5.6 million for the third quarter. We are excited as demand for Ohtuvayre continues to escalate, with net sales for October exceeding the third quarter.

首先，讓我們回顧一下 Ohtuvayre 的出色上市，其基礎是其廣泛的 COPD 適應症以及 Ohtuvayre 為 COPD 患者提供的令人信服的益處。光是七週後，第三季的淨產品銷售額就達到了 560 萬美元。我們非常高興，Ohtuvayre 的需求持續成長，十月的淨銷售額超過了第三季。

Now let's review some key launch metrics. Through the end of October, only 12 weeks after fully launching Ohtuvayre, more than 5,000 Ohtuvayre prescriptions have been filled, with more than 2,200 unique HCPs prescribing Ohtuvayre. Our launch efforts continue to focus on promoting Ohtuvayre to the highest prescribing 14,500 HCPs.

現在讓我們回顧一下一些關鍵的發布指標。截至 10 月底，即 Ohtuvayre 全面推出僅 12 週後，Ohtuvayre 處方量已超過 5,000 張，有超過 2,200 名獨特的 HCP 開出了 Ohtuvayre 處方。我們的推廣工作持續致力於向處方量最高的 14,500 名醫療保健專業人員推廣 Ohtuvayre。

In 12 weeks, approximately 30% of our 2,500 Tier 1 HCPs have prescribed Ohtuvayre. As a reminder, Tier 1 HCPs write on average 150 COPD maintenance treatment prescriptions per month. We also continue to see that once an HCP prescribes Ohtuvayre, they increased their prescribing to more patients in their practice.

在 12 週內，我們 2,500 名一級 HCP 中約有 30% 開了 Ohtuvayre 處方。提醒一下，一級 HCP 平均每月開立 150 張 COPD 維持治療處方。我們還發現，一旦醫療保健提供者開了 Ohtuvayre 處方，他們就會在實踐中為更多患者開出更多處方。

We are impressed by the breadth and depth of prescribers and prescriptions this early in the launch. Importantly, HCPs are prescribing Ohtuvayre across a broad range of COPD patients, including background single, dual and approximately 50% on triple therapy. This broad utilization across all patient types is consistent with our market research and continues to highlight the significant unmet need across the COPD patient population.

在推出初期，我們對處方人員和處方的廣度和深度印象深刻。重要的是，HCP 為廣泛的 COPD 患者開出 Ohtuvayre 處方，包括背景單一療法、雙重療法和大約 50％ 的三重療法患者。這種對所有患者類型的廣泛利用與我們的市場研究一致，並繼續凸顯了 COPD 患者群體中尚未滿足的巨大需求。

Initial feedback from both patients and health care providers about the potential of Ohtuvayre to deliver a meaningful impact against COPD, regardless of disease severity and background therapy, is extremely encouraging and is all supported by the early refill data.

來自患者和醫療保健提供者的初步反饋表明，無論病情嚴重程度和背景治療如何，Ohtuvayre 對 COPD 都有可能產生有意義的影響，這一反饋非常令人鼓舞，並且所有這些都得到了早期補充數據的支持。

Our commercial activities to engage HCPs continue to increase month over month. Through the first 12 weeks of launch, we have reached more than 90% of our Tier 1 and Tier 2 HCPs through in-person or digital promotion. Our speaker programs with HCPs continue to accelerate, and we expect to have approximately 120 programs completed by the end of 2024.

我們與 HCP 合作的商業活動逐月持續增加。在推出後的前 12 週內，我們已透過現場或數位推廣涵蓋了 90% 以上的一級和二級 HCP。我們與 HCP 合作的演講者計畫繼續加速推進，預計到 2024 年底將完成約 120 個項目。

We recently presented new analysis from the Phase III ENHANCE studies evaluating Ohtuvayre in COPD. Presentations at CHEST and ERS conferences highlighted subgroup and pooled efficacy and safety analysis from the ENHANCE trial as well as the impact of Ohtuvayre on COPD-related health care resource utilization in the unmet need in COPD based on real-world claims data.

我們最近發表了對 Ohtuvayre 治療 COPD 的 III 期 ENHANCE 研究的新分析。CHEST 和 ERS ​​會議上的報告重點介紹了 ENHANCE 試驗的亞組和匯總療效和安全性分析，以及基於真實世界索賠數據 Ohtuvayre 對 COPD 相關醫療資源利用的影響，以滿足 COPD 未滿足的需求。

At CHEST, our team interacted with approximately 1,500 HCPs at our medical and commercial booths for Ohtuvayre, highlighting the high level of interest in Ohtuvayre from HCPs. While it's still very early in the launch, we are extremely encouraged by the strong start to the US commercialization of Ohtuvayre.

在 CHEST，我們的團隊在 Ohtuvayre 的醫療和商業展位上與大約 1,500 名 HCP 進行了互動，突顯了 HCP 對 Ohtuvayre 的高度興趣。雖然該產品還處於發布初期，但 Ohtuvayre 在美國商業化的強勁開局令我們感到非常鼓舞。

Ohtuvayre is the first inhaled COPD treatment to provide both bronchodilation and nonsteroidal anti-inflammatory effects, and we are confident that it can redefine the COPD treatment paradigm. We are also pleased to report the centers for Medicare and Medicaid services recently approved a permanent product-specific J-Code for Ohtuvayre, which will be effective in January 2025.

Ohtuvayre 是第一個同時具有支氣管擴張和非類固醇抗發炎作用的吸入式 COPD 治療藥物，我們相信它可以重新定義 COPD 治療模式。我們也很高興地報告，醫療保險和醫療補助服務中心最近批准了針對 Ohtuvayre 的永久性產品特定 J-Code，該代碼將於 2025 年 1 月生效。

Alongside our successful Ohtuvayre launch, we initiated two new Phase II clinical programs during the third quarter. In September, enrolment began in a Phase II dose-ranging trial supporting a fixed-dose combination formulation with ensifentrine and glycopyrrolate, a LAMA, for the maintenance treatment of COPD delivered via a standard jet nebulizer.

隨著我們成功推出 Ohtuvayre，我們在第三季啟動了兩個新的 II 期臨床計畫。9 月，第二階段劑量範圍試驗開始招募患者，該試驗支持使用恩替芬鹼和格隆溴銨的固定劑量組合配方（LAMA）透過標準噴射霧化器進行 COPD 維持治療。

The dose-ranging trial is a randomized, double-blind, placebo-controlled, one-week crossover trial to assess lung function, ssafety,and the pharmacokinetic profile of glycopyrrolate delivered via nebulizer in approximately 40 subjects with the COPD. Following identification of an appropriate glycopyrrolate dose range, a Phase II trial assessing the fixed dose combination of ensifentrine and glycopyrrolate will be conducted.

此劑量範圍試驗是一項隨機、雙盲、安慰劑對照、為期一週的交叉試驗，旨在評估約 40 名 COPD 患者的肺功能、安全性以及透過霧化器輸送的格隆溴銨的藥物動力學特徵。在確定適當的格隆溴銨劑量範圍後，將進行 II 期試驗，評估恩替芬鹼和格隆溴銨的固定劑量組合。

Also in September, enrolment began in the Phase II trial to assess nebulized ensifentrine in patients with non-cystic fibrosis bronchiectasis. The randomized double-blind, placebo-controlled parallel group trial will enrol 180 subjects with a recent history of pulmonary exacerbations.

此外，9 月份，第二階段試驗開始招募患者，以評估霧化恩替芬鹼對非囊性纖維化支氣管擴張症患者的作用。這項隨機雙盲、安慰劑對照平行組試驗將招募 180 名近期有肺部疾病加重病史的受試者。

The trial will assess the effect of ensifentrine 3 milligram twice daily on the rate and risk of pulmonary exacerbations, ssymptoms,and quality of life. To ensure robust powering, the trial is event driven, with all subjects treated for at least 24 weeks and until the required number of exacerbation events are observed.

該試驗將評估每天兩次服用 3 毫克恩替芬鹼對肺部疾病惡化的發生率和風險、症狀以及生活品質的影響。為了確保強大的動力，該試驗採用事件驅動，所有受試者均接受至少 24 週的治療，直到觀察到所需數量的惡化事件。

Finally, turning to our global strategy. Nuance Pharma, our development partner for ensifentrine in Greater China, announced it has completed enrolment in its pivotal Phase III clinical trial evaluating ensifentrine for the maintenance treatment of COPD in China. Nuance Pharma expects to provide results from the pivotal Phase III clinical trial in 2025, and we look forward to providing an update next year.

最後，談談我們的全球策略。Nuance Pharma 是我們在大中華區的恩替芬鹼開發合作夥伴，該公司宣布已完成其關鍵的 III 期臨床試驗的招募，該試驗旨在評估恩替芬鹼在中國用於 COPD 維持治療的效果。Nuance Pharma 預計將在 2025 年提供關鍵的 III 期臨床試驗的結果，我們期待明年提供最新進展。

I will now turn the call over to Mark to review our financial results for the third quarter.

現在我將把電話轉給馬克來回顧我們第三季的財務表現。

Good morning. The third quarter was an exciting one for Verona, as we recorded our first sales of Ohtuvayre. For the partial quarter starting in August and ending on September 30, 2024, we recorded Ohtuvayre net product sales of $5.6 million. As expected, our specialty pharmacy partners are holding inventory at their contracted level of two to three weeks.

早安.第三季度對維羅納來說是令人興奮的一個季度，因為我們首次銷售了 Ohtuvayre。從 2024 年 8 月開始到 2024 年 9 月 30 日的部分季度中，我們記錄了 Ohtuvayre 淨產品銷售額為 560 萬美元。正如預期的那樣，我們的專業藥房合作夥伴的庫存量保持在合約規定的兩到三週的水平。

Cost of goods sold related to Ohtuvayre was $500,000 for the quarter ended September 30, 2024, which consisted of supply chain, post-approval production cost of inventory sold and royalties payable to Ligand.

截至 2024 年 9 月 30 日的季度，與 Ohtuvayre 相關的銷售成本為 500,000 美元，其中包括供應鏈、銷售庫存的批准後生產成本以及應付給 Ligand 的特許權使用費。

Recall that Ohtuvayre was approved in June 2024 and prior to receiving FDA approval, costs associated with the manufacturer of Ohtuvayre were expensed as R&D expense. Research and development costs were $10.6 million for the quarter ended September 30, 2024, compared to $3 million reported for the third quarter of 2023. The increase was primarily due to a $7.8 million increase in clinical trial costs as we initiated 2 Phase II trials over the course of the quarter.

回想一下，Ohtuvayre 於 2024 年 6 月獲得批准，在獲得 FDA 批准之前，與 Ohtuvayre 製造商相關的成本被計入研發費用。截至 2024 年 9 月 30 日的季度研發成本為 1,060 萬美元，而 2023 年第三季的研發成本為 300 萬美元。成長的主要原因是，由於我們在本季度啟動了兩項 II 期試驗，臨床試驗成本增加了 780 萬美元。

Selling, general and administrative expenses were $35.2 million for the quarter ended September 30, 2024, compared to $13.4 million reported for the same period in 2023. The increase was driven primarily by a $9.7 million increase in people-related costs and $2.8 million in share-based compensation, primarily related to our field sales team.

截至 2024 年 9 月 30 日的季度，銷售、一般及行政費用為 3,520 萬美元，而 2023 年同期為 1,340 萬美元。成長的主要原因是人員相關成本增加了 970 萬美元，股權激勵費用增加了 280 萬美元，主要與我們的現場銷售團隊有關。

In addition, marketing, and other commercial-related activities, including travel, increased by $7.5 million. And professional and consulting fees, information technology costs and other related support costs increased by $1.6 million as we continue to build out our organization.

此外，行銷和包括旅遊在內的其他商業相關活動增加了 750 萬美元。隨著我們不斷擴大組織規模，專業費用、諮詢費、資訊科技成本和其他相關支援成本增加了 160 萬美元。

For the quarter ended September 30, 2024, net loss after tax was $43 million compared to a net loss after tax of $14.7 million for the same period in 2023. This represents a loss of $0.07 per ordinary share or $0.53 per ADS for the quarter compared to a loss of $0.02 per ordinary share or $0.18 per ADS for the third quarter of 2023. Finally, our balance sheet remains strong with $336 million in cash and equivalents as of September 30, 2024.

截至 2024 年 9 月 30 日的季度，稅後淨虧損為 4,300 萬美元，而 2023 年同期的稅後淨虧損為 1,470 萬美元。這意味著本季每股普通股虧損 0.07 美元或每股 ADS 虧損 0.53 美元，而 2023 年第三季每股普通股虧損 0.02 美元或每股 ADS 虧損 0.18 美元。最後，我們的資產負債表依然強勁，截至 2024 年 9 月 30 日，現金和等價物為 3.36 億美元。

With the cash currently on hand and potential future access to the remaining $425 million under the Oaktree facilities, we expect to have sufficient runway through at least the end of 2026 as we continue the commercial ramp of Ohtuvayre in the US and execute on our two ongoing Phase II clinical trial programs.

憑藉目前手頭上的現金和未來可能獲得的 Oaktree 設施下剩餘的 4.25 億美元，我們預計至少到 2026 年底將有足夠的資金，因為我們將繼續在美國推進 Ohtuvayre 的商業化，並執行我們正在進行的兩個 II 期臨床試驗計劃。

I'll now turn the call back over to the operator for the Q&A.

我現在將電話轉回給接線員進行問答。

(Operator Instructions) Andrew Tsai, Jefferies.

(操作員指示) Andrew Tsai，傑富瑞 (Jefferies)。

Congrats on the strong launch and the strong execution. First question is your -- the data point around October net sales exceeding Q3. So does that mean we're run rating at least $17 million fourth quarter without considering any type of growth in November and December?

恭喜您的順利發布和出色執行。第一個問題是您的—10 月份淨銷售額超過第三季的數據點。那麼，這是否意味著，如果不考慮 11 月和 12 月的任何成長，我們對第四季的營業額評級至少為 1700 萬美元？

Or should we start to think about some new variables that could come into play, like holiday period or patients starting to drop out? Or do you think the sheer volume of patient adds can offset any type of headwinds like these discontinuations?

或者我們應該開始考慮一些可能發揮作用的新變量，例如假期或患者開始退出？或者您認為增加的患者數量絕對可以抵消任何類似停藥帶來的不利因素嗎？

Andrew, thanks for the question. Yes. So clearly, we're not providing any guidance for Q4. I think your math stands as it is. At this time, we don't see any reason or rationale for any slowdown in the number of patients and the interest and the acceleration that we've seen in October. And so we'll, of course, closely monitor it and continue our efforts as we have in the past several weeks.

安德魯，謝謝你的提問。是的。因此很明顯，我們不會為第四季度提供任何指導。我認為你的數學計算結果是正確的。目前，我們沒有發現任何理由或理由導致患者數量、關注度和加速度出現像 10 月那樣的放緩。因此，我們當然會密切關注，並繼續我們的努力，就像過去幾週一樣。

So we look forward to a continued acceleration of use of Ohtuvayre. Clearly, there's been a lot of interest, as has already been demonstrated. A lot of need, as we've talked about in the past, for an additional novel mechanism like Ohtuvayre in COPD, and we continue to get incredible feedback from physicians and patients, for that matter, really looking forward to Ohtuvayre in their treatment paradigm.

因此，我們期待 Ohtuvayre 的使用能持續加速。顯然，人們對此表現出了濃厚的興趣，這一點已經得到證實。正如我們過去所談到的，慢性阻塞性肺病 (COPD) 中非常需要像 Ohtuvayre 這樣的額外新機制，而且我們不斷從醫生和患者那裡得到令人難以置信的反饋，就此而言，他們真的很期待 Ohtuvayre 在他們的治療模式中的作用。

So we're very excited about what has occurred in this very early part of the launch over the initial 12 weeks, and we expect that to continue.

因此，我們對最初 12 週內發布的初期階段所取得的進展感到非常興奮，我們希望這種情況能持續下去。

Very good to hear. And then just as a follow-up. 5,000 prescriptions filled through October. By chance, are you willing to disclose how many unique patients you have as of October? And any other metrics you're planning to provide in the next earnings call?

很高興聽到這個消息。然後只是作為後續行動。截至十月已開立 5,000 張處方。您是否願意透露截至 10 月您有多少位獨立患者？您還計劃在下次財報電話會議上提供其他指標嗎？

Yes. No, thanks. I think the best way to characterize it at this point is it's very fluid, as you can imagine, that patient adds are increasing week-over-week. Of the over 5,000, of course, the majority of those are -- vast majority of those are unique patients.

是的。不，謝謝。我認為目前最好的描述方式是它非常不穩定，正如你所想像的，患者人數每週都在增加。當然，在這 5,000 多人中，大多數人——絕大多數都是獨特患者。

Refills have started as they should, although very early on in that process, and some of the first patients are starting to be refilled from earlier in the launch.

儘管補貨工作才剛開始，但已按計劃開始了，部分首批患者已開始接受早期補貨。

So I think it's best to characterize it as accelerating at this time. There's a substantial number of patients that have been referred in over the past couple of weeks as we expect. Those are continue to be processed, and we expect the patient adds to continue to grow.

因此我認為此時最好將其描述為正在加速。正如我們預期的那樣，過去幾週有大量患者被轉診。這些仍在繼續處理中，我們預計患者數量將繼續增加。

Yasmeen Rahimi, Piper Sandler.

亞斯明·拉希米，派珀·桑德勒。

Yes. And congrats on a great quarter. I want to stick with the theme of Andrew's question. I guess, it seems like things are progressing really well, but can we talk about past December into 2025? Should we be expecting that in the beginning of the year before JPMorgan, you could come out and provide some consensus or some guidance in terms of what revenue expectations are?

是的。恭喜您本季取得優異成績。我想繼續安德魯問題的主題。我想，事情似乎進展得很順利，但我們可以談談去年 12 月到 2025 年的情況嗎？我們是否應該期待，在年初摩根大通之前，您能就收入預期提供一些共識或指導？

I think it seems like you've had a great quarter, but there's just a lot of room trying to figure out how the next five quarters are going to go. So is there an opportunity to kind of help us understand like beyond fourth quarter what things are going to look like in 1Q, 2Q, 3Q? That's question one.

我認為您似乎度過了一個很棒的季度，但仍有很大空間需要了解接下來的五個季度將會如何發展。那麼是否有機會幫助我們了解第四季以後第一季、第二季、第三季的情況呢？這是第一個問題。

Question two is, do you have any insight on who are -- what are the type of patients that are being prescribed Ohtuvayre? We recently did a KOL call and shockingly found out that the doctor was noting that majority of his patients are patients who failed triple therapy. So even if you don't have quantitative numbers, what are you hearing from the doctors in terms of how they're using Ohtuvayre?

第二個問題是，您是否了解，哪些類型的患者接受了 Ohtuvayre 的治療？我們最近撥打了 KOL 電話，震驚地發現醫生指出他的大多數患者都是三重療法失敗的患者。所以，即使你沒有定量數字，你從醫生那裡聽說了他們如何使用 Ohtuvayre 嗎？

And then the third question is, where do you want to be in terms of physician outreach in the next -- by year end, by mid next year? Sorry for that sort of three-part long questions, and I'll jump back in the queue.

第三個問題是，您希望在明年年底或明年年中，醫師的推廣工作能有什麼進展？抱歉，我問了這種長達三個部分的問題，我將重新回到隊列中。

Right. Yas, thanks for those question. I'll sort of not take them in any particular order. But I first would characterize it, as I mentioned during the call, the Ohtuvayre is being prescribed broadly across all patient segments, including patients on background single, dual and triple therapy as we expected. With regard to triple therapy, nearly 50% of the prescriptions are on -- for patients that are on triple therapy.

正確的。是的，謝謝你提出這些問題。我不會按照任何特定的順序來接受它們。但我首先要對它進行描述，正如我在電話會議中提到的那樣，Ohtuvayre 被廣泛應用於所有患者群體，包括我們預期的接受單一、雙重和三重療法治療的患者。就三聯療法而言，近 50% 的處方是針對接受三聯療法的患者。

So I think we're very encouraged by the breadth of prescribing across all patient types. And as we expected from our market research that there was keen interest in using Ohtuvayre in patients who were on triple therapy and still needing improvement, we knew that was a large unmet medical need, and that's how physicians are also utilizing it as well as in other patient types earlier on -- in the treatment paradigm.

因此，我認為我們對針對所有類型患者開立處方的廣度感到非常鼓舞。而且，正如我們從市場調查中預料的那樣，人們對接受三聯療法但仍需改善的患者使用 Ohtuvayre 有著濃厚的興趣，我們知道這是一個巨大的未滿足的醫療需求，這也是醫生們早期也在治療模式中將其用於其他類型的患者的方式。

With regard to forecasting, I think it's a little premature at the moment to review it. I think we'll need to assess the continued launch dynamics through the fourth quarter, which we will. I think you've seen, historically, we are very transparent, and we've provided the guidance the best we can, while not getting ahead of ourselves and making sure that we characterize it properly.

關於預測，我認為現在對其進行評價還為時過早。我認為我們需要評估第四季持續的發布動態，我們會這樣做。我想你已經看到，從歷史上看，我們是非常透明的，我們盡最大努力提供指導，同時又不超越自己，並確保我們正確地描述它。

But we're very encouraged, very excited. And as you can see, there is great interest in utilizing Ohtuvayre. And so we expect 2025 to be an enormous year of growth and utilization of Ohtuvayre in the treatment of COPD, and we'll look to characterize that.

但我們非常受鼓舞，也非常興奮。如您所見，人們對利用 Ohtuvayre 表現出了濃厚的興趣。因此，我們預計 2025 年將是 Ohtuvayre 在 COPD 治療領域發展和應用的巨大一年，我們將對此進行描述。

I guess, I'll turn it over to Chris on maybe where we'd want to be in outreach over the coming quarters.

我想，我將把這個任務交給克里斯，也許他想談談我們在未來幾季中想要開展哪些推廣活動。

Yas, thank you for the question. I think when we think about physician outreach, we continue to focus on our Tier 1 and Tier 2 physicians. Those, as Dave mentioned on the call, are 14,500 doctors, give or take. And on average, the Tier 1s write about 150 prescriptions and the Tier 2s around 50.

是的，謝謝你的提問。我認為，當我們考慮醫生外展時，我們繼續關注我們的一級和二級醫生。正如戴夫在電話中提到的，大約有 14,500 名醫生。平均而言，一級醫生開出約 150 張處方，二級醫生開出約 50 張處方。

We want to continue to reach them and increase our frequency against these customers as we move into Q4 and into Q1. One of the things that we've seen early in launch is that as we increase the interactions we have with these physicians, their ability and willingness to adopt Ohtuvayre accelerates.

隨著進入第四季度和第一季度，我們希望繼續與他們保持聯繫，並增加針對這些客戶的頻率。我們在發布初期就發現的一件事是，隨著我們與這些醫生的互動增加，他們採用 Ohtuvayre 的能力和意願也隨之增強。

And we believe that's an important aspect as we move into Q4 and Q1 and into 2025 is to continue to reach as many as we can, but also increase our frequency in the times that we call on them, not only with reps, but interacting with them through digital nonpersonal channels as well. We see this provides direct benefit to their increasing on their overall prescribing.

我們認為，隨著我們進入第四季度、第一季和 2025 年，這是一個重要的方面，即繼續盡可能多地接觸客戶，同時增加我們拜訪他們的頻率，不僅與銷售代表聯繫，還透過數位非個人管道與他們互動。我們看到這為他們整體處方量的增加提供了直接的益處。

Ram Selvaraju, H.C. Wainwright.

拉姆·塞爾瓦拉朱，H.C.溫賴特。

Congrats on all the progress. Really very impressive commercial metrics here. Firstly, I wanted to ask if you could comment on any emerging prescriber trends, particularly with respect to preferences in combination regimens that prescribers are expressing they have a predilection for with respect to ensifentrine.

祝賀你取得的所有進展。這裡的商業指標確實令人印象深刻。首先，我想問您是否可以對任何新出現的處方趨勢發表評論，特別是關於聯合治療方案的偏好，處方者表示他們對恩替芬鹼有偏好。

Are there specific existing modalities that they are preferring to pair ensifentrine with? Or are you really just seeing sort of no preference and the drug effectively being very broadly deployed without any underlying emerging trends at this point?

他們是否傾向於將恩替芬特林與現有的特定方式配對？或者您真的只是看到了某種偏好，而且這種藥物實際上被非常廣泛地使用，而目前還沒有任何潛在的新興趨勢？

Ram, thanks for the question. Yes, I would say it's really the latter. I think that what we're seeing is a prescribing across the spectrum of patients, as I mentioned, patients on single, dual and triple therapy with no particular stated interest in certain combinations or certain drugs or certain LAMAs or LABA, but rather the classes as they're generally utilized interchangeably in practices.

Ram，謝謝你的提問。是的，我想說確實是後者。我認為我們看到的是一種針對各類患者的處方，正如我提到的那樣，接受單藥、雙藥和三藥療法的患者對某些組合、某些藥物、某些 LAMA 或 LABA 沒有特別的興趣，而是對在實踐中通常互換使用的類別感興趣。

As I mentioned, there is a great interest, of course, using it on top of triple therapy, as nearly 50% of the patients are on triple therapy currently. And we expected that, again, feedback from physicians is very positive. And they're seeing, again, responses as they'd expect to in patients being treated early on in the launch.

正如我所提到的，人們對將其與三聯療法結合使用非常感興趣，因為目前近 50% 的患者都在接受三重療法。我們再次期望醫師的回饋非常正面。他們再次看到，在臨床試驗啟動初期接受治療的患者身上，出現了他們所預期的反應。

So again, very, very excited and really shows how much Ohtuvayre and a novel mechanism was needed in the treatment of COPD. And we're seeing it utilized again across the spectrum of patients. And again, currently, a preference on top of triple because that was, of course, the highest unmet medical need as those patients really have nowhere else to go in treatment. And if they remain symptomatic on triple Ohtuvayre, it's definitely being preferred.

所以，再次感到非常非常興奮，這確實表明了 Ohtuvayre 和一種新機制在治療 COPD 方面有多重要。我們看到它再次被各類患者所運用。再次，目前，我們優先考慮三倍以上的治療，因為這當然是未滿足的最高醫療需求，因為這些患者真的沒有其他地方可以接受治療。如果服用三重 Ohtuvayre 後症狀仍然存在，那麼這絕對是首選。

Great. And then with respect to the clinical indications that you are now starting to pursue proof-of-concept clinical evidence for, in particular, bronchiectasis. Can you talk a little bit about how the commercial experience with Ohtuvayre, increasing awareness of Ohtuvayre among prescribers is likely to frame these additional opportunities and how you go about pursuing them?

偉大的。然後就臨床指徵而言，您現在開始尋求概念驗證臨床證據，特別是針對支氣管擴張症。您能否簡單談談 Ohtuvayre 的商業經驗，提高處方人員對 Ohtuvayre 的認識可能會如何建構這些額外的機會，以及您如何去追求這些機會？

Have those prescribers who've effectively acquainted themselves with the product since it's been launched expressed an interest in the progress of those additional indications as the drug continues to move forward on front beyond COPD?

自從該產品上市以來，那些已經熟悉該產品的處方人員是否對這款藥物在治療 COPD 以外的疾病方面取得的進展表示出興趣？

Yes. No, thanks for the question, Ram. I think that our interest in using ensifentrine in non-CF bronchiectasis came from a number of avenues, one of them being an incredibly strong interest from KOLs, physicians that, as we consulted with them, it made great sense to them that ensifentrine pharmacology as a PD3, PD4 inhibitor as a bronchodilator and a nonsteroidal anti-inflammatory could have great promise in bronchiectasis.

是的。不，謝謝你的提問，拉姆。我認為我們對在非 CF 支氣管擴張中使用恩替芬鹼的興趣來自多個管道，其中之一是來自 KOL 和醫生的強烈興趣，當我們諮詢他們時，他們非常明白恩替芬鹼作為 PD3、PD4 抑製劑作為支氣管擴張劑和非類固醇抗發炎藥在治療支氣管擴張方面具有巨大前景。

And so clearly, there's interest broadly from physicians in it. With that said, of course, we're very focused on Ohtuvayre and COPD. Specifically on the commercial front, we will continue to progress ensifentrine in research and in clinical development for non-CF bronchiectasis as we are now progressing with our Phase II study.

顯然，醫生們對此有廣泛的興趣。話雖如此，我們當然非常關注 Ohtuvayre 和 COPD。具體在商業方面，我們將繼續推進恩替芬特林在非 CF 支氣管擴張症方面的研究和臨床開發，因為我們目前正在進行第二階段的研究。

I think we will all see how that looks in the future as that study, ultimately, because exacerbation is an endpoint, and it's at least a 24-week trial, you're talking about data probably well into 2026 at the moment. But let's get the trial enrolled and see where we're at.

我認為我們都會看到這項研究在未來的表現，最終，因為病情惡化是一個終點，而且這至少是一個 24 週的試驗，你現在談論的數據可能要到 2026 年。但讓我們先參加試驗，看看結果如何。

Great. And then lastly, this is just an accounting question. You mentioned earlier that certain expenses associated with manufacturing product prior to launch have now been shifted into the SG&A line or away from the R&D line as it were.

偉大的。最後，這只是一個會計問題。您之前提到，產品上市前製造相關的某些費用現已轉移到銷售、一般和行政費用（SG&A）項目，或者說轉移到研發項目之外。

So I was just wondering if you could give us a general maybe qualitative breakdown of which expenses going forward are likely to be segregated into the R&D line versus the SG&A line. For example, the speaker programs, how are you accounting for those? Are there any expenses, in other words, that are associated with effectively commercial activities that you are going to continue to book in the R&D line item?

所以我只是想知道您是否可以給我們一個大致的定性細分，說明未來哪些費用可能會被劃分到研發費用線和銷售、一般和行政費用線。例如，演講者程序，您如何解釋這些？換句話說，是否有任何與有效商業活動相關的費用您將繼續記入研發項目中？

Ram, this is Mark. Thanks for the question. The numbers that I was referring to were specifically related to inventory production costs. And so before approval, those were expensed as R&D. And you can imagine since it's a blow, filled, sealed product that the finished goods were produced after approval, so therefore, put into inventory. But the API was produced before approval, and that would have been expensed as R&D expense.

拉姆，這是馬克。謝謝你的提問。我所指的數字與庫存生產成本具體相關。因此，在獲得批准之前，這些都被當作研發費用。你可以想像，因為它是一種吹塑、填充、密封的產品，成品是在獲得批准後生產的，因此被放入庫存中。但 API 是在獲得批准之前生產的，因此應將其計入研發費用。

All the commercial costs, speaker programs, travel, et cetera, marketing programs all get expensed in the period in which they are incurred as part of SG&A expense.

所有商業成本、演講者計劃、差旅費等行銷計劃均在發生的期間作為銷售、一般和行政費用的一部分計入費用。

Tom Shrader, BTIG.

BTIG 的湯姆·施拉德 (Tom Shrader)。

Congratulations. Just looking at the physician number and the prescription number, it seems like you have a lot of people writing one or two prescriptions to try the drug.

恭喜。僅查看醫生編號和處方號，似乎有很多人開了一兩張處方來嘗試這種藥物。

Do you know what they're looking for to get more excited? And I guess, the flip side is I assume you have power users. What do they tell you to refine your marketing pitch as to why they're already committed?

您知道他們在尋找什麼才能讓他們更興奮嗎？我想，另一方面，我認為你們有高級用戶。他們告訴你什麼來改進你的行銷宣傳，以及為什麼他們已經做出承諾？

Yes. Tom, let me just make a few comments, and I'll turn it over to Chris for more detail. I think it's -- yes, of course, there are physicians who prescribe it one or two patients and want to see how it works in their hands and in their patients. Clearly, that's their typical behaviour that can be expected and that goes on.

是的。湯姆，請容許我發表幾點評論，然後我會將問題交給克里斯來詳細說明。我認為——是的，當然，有些醫生會給一兩個病人開這種藥，想看看它在他們手中和病人身上的效果。顯然，這是他們的典型行為，是可以預料的，而且這種情況還在繼續。

As you mentioned, there are also physicians which are, let's just say, heavy adopters and are prescribing it quite a bit within their practice, as they've seen responses in patients and as they've had really a need in order to use Ohtuvayre in their practice. So we're seeing the spectrum of that.

正如您所說，也有一些醫生是該藥物的重度採用者，他們在實踐中大量使用這種藥物，因為他們看到了患者的反應，而且他們確實需要在實踐中使用 Ohtuvayre。所以我們看到了它的範圍。

I think it's also challenging to look at prescriber numbers and patient prescriptions and all of that because it's very fluid, as I referred to, and that just in the past couple of weeks, there are substantial numbers of being written that are currently in process on the payer side as well as being adjudicated and make sure that they're going to be filled and going through that process.

我認為查看處方數量和患者處方等也很有挑戰性，因為正如我提到的那樣，它們非常不穩定，而且僅在過去幾週內，就有大量的處方正在付款方處理中，也正在裁決中，確保它們能夠得到填寫並經過該流程。

So any numbers are out of date literally by the end of the day. And so we're trying to characterize for you and being very transparent about where we stand at the moment. But your characterization is also correct in how physicians look at it in their practice.

因此，到一天結束時，任何數字實際上都已過時。因此，我們試圖向您描述我們目前的狀況，並且非常透明地說明我們目前的立場。但您的描述對於醫生在實踐中如何看待這個問題也是正確的。

And maybe, Chris, you can comment on it.

也許，克里斯，你可以對此發表評論。

Yes, Tom. As far as when we look at the breadth and depth of these prescribers, one of the things that's been very encouraging to us and very exciting to us is the fact that what we see is, like you discussed, there's many physicians that start writing off one or two, but we also see over the course of the launch in these early stages that once they write one or two, they're exposed to the patient feedback, they continue to accelerate their usage. I think that's something Dave mentioned in his opening comments.

是的，湯姆。就我們考察這些處方器的廣度和深度而言，讓我們感到非常鼓舞和興奮的事情之一是，正如您所討論的那樣，我們看到許多醫生開始放棄一兩種處方器，但我們也看到，在早期階段的發布過程中，一旦他們寫了一兩種處方器，他們就會接觸到患者的反饋，並繼續加快使用速度。我認為這是戴夫在開場白中提到的事情。

What we see is it's a combination of patient experience and also increased frequency and interactions with our field sales personnel. We have to keep in mind that these doctors have been doing the same thing for 10 to 15 years, and Ohtuvayre as a novel mechanism and as an add-on across all the spectrum of COPD patients that remain symptomatic in their practice is something that we have to continue to talk to them about.

我們看到的是，這是患者體驗與現場銷售人員的頻率和互動的結合。我們必須牢記，這些醫生已經做同樣的事情 10 到 15 年了，而 Ohtuvayre 作為一種新的機制以及在實踐中對所有仍有症狀的 COPD 患者的附加治療是我們必須繼續與他們討論的事情。

And they are extremely excited about what Ohtuvayre can provide and then, ultimately, what Ohtuvayre can do to help their patients. So I think what we see early on is very, very encouraging from an adoption and then moving from one or two to what we would call believers and a doctor who's much more entrenched in using Ohtuvayre.

他們對 Ohtuvayre 所能提供的服務以及 Ohtuvayre 最終能為患者提供的幫助感到非常興奮。因此我認為我們早期看到的情況非常令人鼓舞，從採用到後來從一兩個人發展成為我們所說的信徒，以及一位更堅定地使用 Ohtuvayre 的醫生。

Chris, can I ask a quick follow-up on your infrastructure? How often are you giving patients drug for a month? And what is your conversion rate looks like? How does all that stuff you set up seem to be operating?

克里斯，我可以快速詢問一下你的基礎設施嗎？您一個月給病人服藥幾次？您的轉換率是多少？你設定的所有東西運行得怎麼樣？

Yes. Good question, Tom. We're very pleased with how our infrastructure has been set up. I think one of the things that we talked about very early on was our data infrastructure and the infrastructure to understand where these patients are, and that has worked extremely well so that we're able to understand and kind of work to make sure that patients gets access to the drug.

是的。問得好，湯姆。我們對現有的基礎設施建設感到非常滿意。我認為我們很早就討論的事情之一是我們的數據基礎設施和了解這些患者所在位置的基礎設施，這些基礎設施運作得非常好，因此我們能夠了解並開展工作，確保患者能夠獲得藥物。

What I will say today is that of those 5,000 dispensed scripts, the majority -- a significant majority of those are paid TRxs. We were seeing very positive trends within the payer side. We talked about Medicare Part B and medical benefit, and all those assumptions that we had early on are playing out to be very consistent and true to what we thought going into launch. So that makes us very encouraged about the systems and the process that we put in place.

我今天要說的是，在發放的 5,000 份處方中，大多數——絕大多數都是付費 TRx。我們看到付款方呈現非常正面的趨勢。我們討論了醫療保險 B 部分和醫療福利，我們早期所做的所有假設都與我們在發佈時的想法非常一致且準確。因此，我們對所建立的系統和流程感到非常鼓舞。

Edward Thomason, VLK.

愛德華·托馬森，VLK。

And good to see the prints today. Well done. Just a question, please, on the ramp-up again. You mentioned, this is specifically to Mark, about inventory build. Can you just go -- talk through the dynamics there so we could better understand how that is playing out?

很高興今天看到這些印刷品。做得好。請問一下，關於升級，還有什麼問題嗎？您提到，這是專門針對馬克的，關於庫存建設。您能否簡單談談那裡的動態，以便我們更好地了解事情進展？

And then roughly, if you can split it out, how much of the percentage of that -- of the initial sales we saw in Q3 is actually in market sales versus inventory build?

然後粗略地講，如果您可以將其分開，我們在第三季度看到的初始銷售額中，實際上有多少百分比是市場銷售與庫存建設？

Thanks, Edward. I'm not sure I quite understood the second part of that question. Can you repeat that part?

謝謝，愛德華。我不確定我是否完全理解了該問題的第二部分。你能重複一下那部分嗎？

I just asked whether you can disclose how much of the sales that was reported in Q3 relates to inventory build versus actual in-market sales.

我只是問您是否可以透露第三季報告的銷售額中有多少與庫存建設有關，有多少與實際市場銷售有關。

Okay. Inventory build in the channel, sure. So we haven't disclosed the number. But you can imagine that in a period of rising sales, they're building their inventory and holding about two to three weeks, depending on the different specialty pharmacy partner.

好的。當然，通路中會建立庫存。因此我們沒有透露這個數字。但你可以想像，在銷售額上升的時期，他們正在建立庫存並持有大約兩到三週的庫存，這取決於不同的專業藥房合作夥伴。

It could be anywhere in that range, nobody more than three weeks on hand. And so you can imagine that we've been on the market for eight weeks at the end of September. So probably, about 1/4 or so of the inventory -- of the sales would be in inventory at that time.

它可能處於這個範圍內的任何位置，沒有人能留出超過三週的時間。所以你可以想像，九月底我們已經上市八週了。因此，大概當時銷售額的四分之一左右都是庫存。

Okay. That's good to know. And then a separate question actually relates to the IP. I noticed a slight change where you've now talked about a couple of additional patents pending, notably one that's on COPD exacerbations.

好的。很高興知道這一點。然後另一個問題實際上與 IP 有關。我注意到一個細微的變化，您現在談到了幾個額外的正在申請的專利，特別是一個關於 COPD 惡化的專利。

Can you just talk through how important that patent might be to commercial prospect? And does that patent related just to ensifentrine or specifically the use of PD3, PD4s against COPD exacerbations?

能談談專利對商業前景有多重要嗎？該專利是否僅與恩替芬鹼有關，還是具體與使用 PD3、PD4 治療 COPD 急性發作有關？

Yes. So let me talk broadly. Of course, all our IP is, I think, very important as and is -- when you look at it holistically. We did file a number of patents as you're referring to. The effect on exacerbations is one of them after the enhanced results. Those are in process.

是的。那麼讓我廣泛地講一下。當然，我認為，從整體來看，我們所有的智慧財產權都非常重要。正如您所說，我們確實提交了一些專利。對急性惡化的影響是增強結果之後的結果之一。這些正在進行中。

We expect a number of them to be listed in the Orange Book over the coming 1 to 1.5 years as they continue to be prosecuted. All of those would -- are important, again, in the totality of them, as they should be in protecting our intellectual property.

我們預計，隨著這些案件繼續受到起訴，其中許多案件將在未來一到一年半內被列入橙皮書。所有這些都非常重要，因為它們應該保護我們的智慧財產權。

So I think we were specific, of course, it's related to Ohtuvayre, and we'll see at the end of the day how the claims are read and constructed. But all our patents are important. Of course, it's grounded in our polymorph patent and our formulation patent. And the additional patents limited to the effect of Ohtuvayre are also critically important.

所以我認為我們很具體，當然，它與 Ohtuvayre 有關，我們最終會看到這些主張是如何解讀和建構的。但我們的所有專利都很重要。當然，這是基於我們的多晶型專利和配方專利。而僅限於Ohtuvayre效果的附加專利也至關重要。

Okay. And one last question, if I may. Just can you confirm how many patients from the ENHANCE clinical program have been converted into commercial prescriptions? And has there been demand amongst the existing user base for Ohtuvayre?

好的。如果可以的話，我還有最後一個問題。您能否確認有多少來自 ENHANCE 臨床計畫的患者已經轉化為商業處方？現有的用戶群對 Ohtuvayre 有需求嗎？

Yes. So we -- when we ended the ENHANCE clinical trials, patients were discontinued at the end of the trial. We did not have any long-term follow-up studies ongoing. So as you know that time gap was substantial between the write-up of the NDA, plus the year of review at the FDA. So we wouldn't know which patients that were in the trial may have come back and be on commercial Ohtuvayre.

是的。因此，當我們結束 ENHANCE 臨床試驗時，患者在試驗結束時就停止了治療。我們沒有進行任何長期的追蹤研究。所以如您所知，NDA 的撰寫和 FDA 的審查之間存在相當大的時間差距。因此，我們不知道參加試驗的哪些患者可能會回來服用商業化的 Ohtuvayre。

Joon Lee, Truist.

Joon Lee，Truist。

Congrats on the strong quarter. Can you talk about reimbursement rate across government and commercial channels and the rate of prescription abandonment due to co-pay or any reason? And then congrats on getting the permanent J-Code.

恭喜本季業績強勁。您能談談政府和商業管道的報銷率以及由於共同支付或其他原因而放棄處方的比例嗎？然後恭喜您獲得永久的 J-Code。

Is there any COPD treatment guideline or algorithm that is currently in the works that could be introduced soon, given the newly approved agents in COPD?

鑑於新批准的 COPD 藥物，是否有任何正在製定的 COPD 治療指南或演算法可以很快推出？

So maybe I'll have Chris just sort of comment on our general payer dynamics.

因此，也許我會讓克里斯對我們的整體付款人動態發表一些評論。

Yes. So Joon, when we think about reimbursement right now, the majority, I'd say, 80-plus percent, we thought are going through a medical benefit, either through Medicare -- traditional Medicare Part B or Medicare Advantage. And like we assumed at launch, these processes do not require significant hurdles for these patients to get. We're seeing movement within that medical benefit channel very, very, very well.

是的。所以 Joon，當我們現在考慮報銷時，我想說大多數人，超過 80%，都會享受醫療福利，無論是透過 Medicare（傳統的 Medicare B 部分）還是 Medicare Advantage。正如我們在發佈時所假設的那樣，這些流程不會給患者帶來重大障礙。我們非常非常清楚地看到了醫療福利管道內的動態。

What's also encouraging for us is across the pharmacy benefit side, which is commercial or Medicaid. We see patients having access to Ohtuvayre as well. It does require a prior auth within that process. Each plan is a little bit independent, but we're able to work through that with our SP partners in that process to get patients access to Ohtuvayre.

對我們來說，同樣令人鼓舞的是藥房福利方面，無論是商業還是醫療補助。我們看到患者也可以使用 Ohtuvayre。過程中確實需要事先授權。每個計劃都有點獨立，但我們可以與 SP 合作夥伴一起努力，讓患者能夠使用 Ohtuvayre。

The other thing that we think is very encouraging is -- and again, like what we talked about early on in launch during the setup was of the patients that have been dispensed scripts about, let's just say, well over 80% of them have a co-pay of less than $10. So they have access to Ohtuvayre, and they have access, so there's very low out-of-pocket cost as well. And I think this bodes very well for the brand long term as we think about how the launch accelerates.

我們認為非常令人鼓舞的另一件事是——再說一次，就像我們在啟動初期談到的那樣，在已經配好處方的患者中，可以說，超過 80％ 的患者自付費用低於 10 美元。所以他們可以使用 Ohtuvayre，而且他們也可以訪問，所以自付費用也很低。而且我認為，當我們考慮如何加速發佈時，這對品牌的長期發展來說是一個非常好的兆頭。

As far as your second question, which was regarding upcoming guidelines or conferences, we do know that the GOLD guidelines have a meeting in November, in a couple of days. At that guideline meeting, we believe that Ohtuvayre has an opportunity to be placed in there.

至於您的第二個問題，即有關即將出台的指南或會議，我們確實知道 GOLD 指南將於 11 月幾天后召開一次會議。在那次指導會議上，我們相信 Ohtuvayre 有機會被安排在那裡。

As we've talked about in the past, there is a dyspnea pathway and an exacerbation pathway within the guidelines, and Ohtuvayre's unique novel mechanism of action with bronchodilation, nonsteroidal anti-inflammatory allows the consensus guideline committee to be able to put Ohtuvayre in a variety of different spots there.

正如我們過去所討論過的，指南中包含呼吸困難途徑和惡化途徑，而 Ohtuvayre 獨特的支氣管擴張、非類固醇抗發炎作用機制使得共識指南委員會能夠將 Ohtuvayre 置於各種不同的位置。

Again, we think this is only an upside for Ohtuvayre. When we talk to physicians today, the big thing that we hear from our reps and the feedback back from HCPs is that we have patients that have persistent symptoms, regardless of what therapy they are on, single, dual, or triple background therapy. These persistently symptomatic patients need add-on therapy, and Ohtuvayre can be a very good choice for all these patients to provide additional bronchodilation and potential non-steroidal anti-inflammatory effects as well.

再次，我們認為這對 Ohtuvayre 來說只是一件好事。今天，當我們與醫生交談時，從我們的代表和 HCP 那裡聽到的最大問題是，我們的患者有持續的症狀，無論他們接受的是單一、雙重還是三重背景療法。這些持續有症狀的患者需要輔助治療，而 Ohtuvayre 對所有這些患者來說是一個非常好的選擇，它可以提供額外的支氣管擴張和潛在的非類固醇抗發炎作用。

Great. Well, if I could add one more. Chris, you mentioned previously that 50% of the use is as an add-on to triple therapy, which is really interesting. Has that shifted at all in the first few months of launch?

偉大的。好吧，如果我可以再添加一個的話。克里斯，您之前提到 50% 的使用是作為三重療法的附加療法，這真的很有趣。在推出後的頭幾個月裡，情況有改變嗎？

No. Joon, it's still very early to kind of say if there's been any shift. I think the thing that's very encouraging for us is we have add-on use on top of triple. But what you also see is about 50% of these other patients aren't on triple.

不。俊，現在判斷是否有任何轉變還為時過早。我認為對我們來說非常令人鼓舞的事情是我們在三倍的基礎上還有附加用途。但您也會看到，大約 50% 的其他患者並未接受三倍治療。

So remember, our market research early on said that Ohtuvayre could be used alone or as an add-on across all lines of therapy. And in these first -- through October, we're seeing that. While we're seeing about 50% of patients on triple, we're also seeing patients on a single bronchodilator. We're seeing patients on LABA ICS being added Ohtuvayre. And that is all consistent with what we said in our early market research.

所以請記住，我們早期的市場調查表明，Ohtuvayre 可以單獨使用，也可以作為所有療法的附加使用。從第一季到第十季度，我們都能看到這一點。我們發現大約有 50% 的患者使用三重藥物，但也有一些患者使用單一氣管擴張劑。我們看到接受 LABA ICS 治療的患者被添加了 Ohtuvayre。這與我們早期的市場調查所說的一致。

And when I think about the health of the launch and the health of what is the ongoing 2025 look like, being able to say that some of that real work that we did early on about unmet need and patient utilization, we're seeing that play out in these first few months of launch. And that gives us a lot of encouragement for Q4 and 2025.

當我思考此次發布的健康狀況以及 2025 年的健康狀況時，我可以說，我們早期針對未滿足需求和患者利用率所做的一些實際工作，我們看到了在發布的頭幾個月裡發揮作用。這給了我們對第四季和 2025 年很大的鼓勵。

(Operator Instructions) Boobalan Pachaiyappan, ROTH Capital Partners.

(操作員指示) Boobalan Pachaiyappan，ROTH Capital Partners。

Can you hear me?

你聽得到我嗎？

Yes, of course.

是的當然。

Congrats on the progress. So we have two. Firstly, there's been some developments in the COPD landscape, most notably the recent approval of Dupixent. So we are wondering, do you expect potential headwinds from Dupi as you think about penetrating the subsection of the COPD market comprising patients who are on triple therapy?

祝賀你取得進展。因此我們有兩個。首先，COPD 領域取得了一些進展，最引人注目的是最近批准了 Dupixent。所以我們想知道，當您考慮打入接受三聯療法的 COPD 患者這個細分市場時，您是否預計 Dupi 會給您帶來潛在的阻力？

And is there a motivation for prescribers to prioritize ensifentrine for Dupi, excluding the cost benefits offered by ensifentrine?

並且，排除恩替芬鹼提供的成本效益，處方人員是否有動機優先為 Dupi 選擇恩替芬鹼？

Yes. Thanks for the question. I think, again, it was -- it's good for patients with COPD to have choices. It was good to see the approval of Dupixent for the treatment of COPD. I think it highlights the need that exists for additional treatments.

是的。謝謝你的提問。我認為，對於 COPD 患者來說，擁有選擇是件好事。很高興看到 Dupixent 獲得批准用於治療 COPD。我認為這凸顯了額外治療的必要性。

With that said, as you well know, Dupixent addresses the relatively narrow patient population or a narrow part of the market. Those patients who are on triple therapy, have a history of exacerbations, have an elevated eosinophil count. And by Sanofi, Regeneron's own estimation, it's in the US about 300,000 patients, so relatively modest number considering there are about 8.5 million patients who are on maintenance treatment.

話雖如此，如您所知，Dupixent 針對的是相對狹窄的患者群體或狹窄的市場部分。接受三聯療法、有病情加重病史的患者嗜酸性粒細胞數升高。根據賽諾菲和再生元自己的估計，美國約有 30 萬名患者，考慮到約有 850 萬名患者正在接受維持治療，這個數字相對較少。

Because of the large patient population and unmet medical need across the board, we don't see it impacting the commercialization of Ohtuvayre at all and, if anything, again, bring the spotlight on to the need for treatments and helping patients who are currently symptomatic and needing additional therapy.

由於患者人數龐大且未滿足的醫療需求普遍存在，我們認為它不會對 Ohtuvayre 的商業化產生任何影響，如果有的話，它再次將焦點集中在治療需求上，並幫助那些目前有症狀並需要額外治療的患者。

And even with that said, there is no specific rationale that we know of why Ohtuvayre could not be used with Dupixent if the physician thought that was the right combination for that patient as well, completely different pharmacology, the mechanism of action, of course, addressing inflammation for multiple modes could be beneficial.

即便如此，我們仍然不知道為什麼不能將 Ohtuvayre 與 Dupixent 一起使用的具體理由，如果醫生認為這對患者來說也是正確的組合，完全不同的藥理學、作用機制，當然，解決多種模式的炎症可能會有益。

And of course, Ohtuvayre's bronchodilation and impact on improving lung function acutely and helping with dyspnea on a day-in and day-out basis is key to its use as well, which some of the other types of approaches don't have that acute bronchodilation.

當然，Ohtuvayre 的支氣管擴張作用以及對急性改善肺功能和日常緩解呼吸困難的影響也是其使用的關鍵，而其他一些方法則不具備這種急性支氣管擴張作用。

So again, I think it's very good across the board and doesn't change our view because, again, of the large patient population and unmet need.

因此，我再次認為，這在各方面都是非常好的，並且不會改變我們的觀點，因為患者人數眾多且需求尚未得到滿足。

Yes. And then maybe a second one and also the final one. So you mentioned about 2 Phase II clinical programs. I was looking at the clinical trials website this morning, and this website also included a trial actually that you're currently recruiting for. It's a Phase II study to study the effect of ensifentrine on sputum markers of inflammation in COPD patients.

是的。然後也許是第二個，也是最後一個。您提到了兩個 II 期臨床項目。今天早上我在瀏覽臨床試驗網站，該網站實際上還包括一項你們目前正在招募的試驗。這是一項 II 期研究，旨在研究恩替芬特林對 COPD 患者痰液發炎標記物的影響。

So I understand the mechanistic implications of the study, especially you wanted to see or know if ensifentrine interferes with the acPGP and the PGP pathway. So that aside, but I'm curious how you plan to integrate the study outcomes into your clinical and commercial strategy.

因此，我理解這項研究的機制意義，尤其是您想了解或知道恩替芬鹼是否會幹擾 acPGP 和 PGP 路徑。除此之外，我很好奇您計劃如何將研究成果整合到您的臨床和商業策略中。

Is this specifically to collect more data, potentially focusing on exacerbation and then maybe develop an add-on clinical program or this could potentially trickle down to your cystic fibrosis program in some other way? How are you thinking about it?

這是專門為了收集更多數據，可能集中在病情惡化，然後可能開發附加臨床計劃，還是可能以其他方式滲透到您的囊性纖維化計劃中？您覺得怎樣？

Yes. Maybe I'll make a couple of comments. And Tara, you can comment as well on the study itself. But I think, again, this study is relatively small, but very mechanistic in nature, looking at the effects on sputum markers in sputum and continuing to understand the deeper pharmacology of ensifentrine and specifically its PD3, PD4 inhibition.

是的。也許我會發表一些評論。塔拉，你也可以對這項研究本身發表評論。但我認為，這項研究規模相對較小，但本質上是非常機械化的，觀察對痰中痰標記物的影響，並繼續了解恩替芬鹼的更深層次藥理學，特別是其 PD3、PD4 抑製作用。

And I think as we see the outcome of the study, we will then look at that carefully and then utilize that data in the best way we can to help patients moving forward, whether in COPD or in other indications.

我認為，當我們看到研究結果時，我們會仔細研究，然後以最佳方式利用這些數據來幫助患者取得進展，無論是慢性阻塞性肺病還是其他疾病。

And so with that, I don't know, if, Tara, do you want to add anything to that question.

因此，我不知道塔拉，您是否想對這個問題進行補充。

Yes. I think it's an 8-week crossover trial looking at inflammation through the acPGP pathway and also looking at inflammatory cell migration into the lung.

是的。我認為這是一項為期 8 週的交叉試驗，透過 acPGP 路徑觀察炎症，並觀察發炎細胞向肺部的遷移。

So as Dave mentioned, we do expect that to be helpful to better characterize the pharmacology events of ensifentrine in patients with COPD. Of course, we have already conducted a sputum study and healthy volunteers challenged with LPS and saw a nice effect across neutrophils, macrophages, eosinophils, or lymphocytes, though we do expect to see similar data in COPD patients, particularly given the strong exacerbation results from the ENHANCE program.

因此，正如戴夫所提到的，我們確實希望這有助於更好地描述恩替芬鹼在 COPD 患者中的藥理學事件。當然，我們已經進行了痰液研究，並對健康志願者進行了 LPS 攻擊，並看到中性粒細胞、巨噬細胞、嗜酸性粒細胞或淋巴細胞的良好效果，但我們確實希望在 COPD 患者中看到類似的數據，特別是考慮到 ENHANCE 計劃的強烈惡化結果。

And ladies and gentlemen, at this time, we'll be ending today's question-and-answer session. I'd like to turn the floor back over to Dr. Zaccardelli for any closing comments.

女士們、先生們，今天的問答環節到此結束。我想將發言權交還給 Zaccardelli 博士，請他發表最後評論。

Great. Thank you, everyone, for joining us on today's call and for your questions. In addition, I want to thank our shareholders for their support and especially the dedicated and talented team at Verona Pharma for their work and commitment.

偉大的。感謝大家參加今天的電話會議並提出問題。此外，我還要感謝我們股東的支持，特別是感謝維羅納製藥公司敬業且才華橫溢的團隊的工作和承諾。

We are extremely excited about the launch of Ohtuvayre and the advancement of our 2 Phase II trials as well. And we look forward to updating you on future calls and look forward to seeing you at conferences as well. Thanks very much, and have a great day.

我們對 Ohtuvayre 的推出以及我們第二階段試驗的進展感到非常興奮。我們期待在未來的電話會議上向您通報最新情況，也期待在會議上見到您。非常感謝，祝您有愉快的一天。

Ladies and gentlemen, with that, we'll conclude today's conference call and presentation. We do thank you for joining. You may now disconnect your lines.

女士們、先生們，今天的電話會議和演講就到此結束。我們非常感謝您的加入。現在您可以斷開線路了。