Verona Pharma PLC (VRNA) 2023 Q3 法說會逐字稿

Welcome to Verona Pharma's Third Quarter 2023 Financial Results and Operating Highlights Conference Call. (Operator Instructions)

歡迎參加 Verona Pharma 2023 年第三季財務業績和營運亮點電話會議。 （操作員說明）

Earlier this morning, Verona Pharma issued a press release announcing its financial results for the 3 months ended September 30, 2023. A copy can be found in the Investor Relations tab on the corporate website, www.veronapharma.com.

今天早上早些時候，Verona Pharma 發布了一份新聞稿，公佈了截至2023 年9 月30 日的3 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. 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.

在開始之前，我想提醒您，在今天的電話會議中，有關公司未來期望、計劃和前景的陳述均為前瞻性陳述。這些前瞻性陳述是基於管理階層目前的預期。這些陳述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、績效或成就與前瞻性陳述所表達或暗示的預期有重大差異。

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. As a reminder, this call is being recorded and will remain available for 90 days. I'd now like to turn the call over to Dr. David Zaccardelli, Chief Executive Officer. Please go ahead.

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。儘管該公司可能選擇在未來某個時候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。請注意，此通話正在錄音，並將保留 90 天。我現在想將電話轉給執行長 David Zaccardelli 博士。請繼續。

Thank you, and welcome, everyone, to today's call. With me today are Mark Hahn, our Chief Financial Officer; Dr. Kathy Rickard, our Chief Medical Officer; and Chris Martin, our Senior Vice President of Commercial.

謝謝大家，歡迎大家參加今天的電話會議。今天和我在一起的有我們的財務長馬克‧哈恩 (Mark Hahn)； Kathy Rickard 博士，我們的首席醫療官；克里斯馬丁（Chris Martin），我們的商務高級副總裁。

The third quarter continued our constant progress toward our goal of providing ensifentrine as a novel treatment for COPD patients. In August, the FDA accepted for review our new drug application seeking approval of ensifentrine for the maintenance treatment of patients with COPD. The agency assigned a PDUFA target action date of June 26, 2024, and is not currently planning to hold an advisory committee meeting to discuss the application. We look forward to continuing our work with the FDA during their review. If approved, ensifentrine is expected to be the first novel mechanism available for the treatment of COPD in more than 10 years. We believe that bronchodilator and nonsteroidal anti-inflammatory activity has the potential to change the treatment paradigm for COPD.

第三季度，我們繼續朝著為慢性阻塞性肺病患者提供恩西芬鹼作為一種新型治療方法的目標不斷取得進展。 8 月，FDA 受理了我們的新藥申請，尋求批准 ensifentrine 用於 COPD 患者的維持治療。該機構指定 PDUFA 的目標行動日期為 2024 年 6 月 26 日，目前不打算召開諮詢委員會會議來討論該申請。我們期待在 FDA 審查期間繼續與他們合作。如果獲得批准，ensifentrine 預計將成為 10 多年來第一個可用於治療 COPD 的新機制。我們相信支氣管擴張劑和非類固醇抗發炎活性有可能改變慢性阻塞性肺病的治療模式。

Recently, we hosted an in-person investor meeting in New York to provide an overview of our commercial preparations for the potential U.S. launch of ensifentrine with the company's senior management team and key opinion leader, Dr. Jamie Rutland. During the meeting, we shared detailed overview of preparations for the planned launch of ensifentrine, including a review of the current COPD market, unmet treatment needs, launch access, distribution, reimbursement strategies and plans for field deployment. For those who may have missed it, a replay of the meeting is available on our website.

最近，我們在紐約舉辦了一次現場投資者會議，與公司的高階管理團隊和關鍵意見領袖 Jamie Rutland 博士一起概述了我們為在美國推出 ensifentrine 的商業準備情況。會議期間，我們詳細介紹了恩西芬汀計劃上市的準備工作，包括對當前慢性阻塞性肺病市場的回顧、未滿足的治療需求、上市准入、分配、報銷策略和現場部署計劃。對於那些可能錯過了會議的人，我們的網站上提供了會議的重播。

Overall, we believe we are very well positioned to launch ensifentrine with many key hires already in place across our commercial team and strong relationships being built on both the physician and payer fronts. With this, we are confident we will be able to quickly capitalize on the U.S. launch of ensifentrine, pending approval next June.

總體而言，我們相信我們已經做好了推出 ensifentrine 的準備，我們的商業團隊已經聘請了許多關鍵員工，並且在醫生和付款人方面建立了牢固的關係。有了這一點，我們有信心能夠快速利用在美國推出的 ensifentrine（等待明年 6 月獲得批准）的機會。

In September, we presented additional analyses of the ENHANCE-1 24-week exacerbation data at ERS, which demonstrated treatment with ensifentrine resulted in a substantial decrease in the rate and risk of moderate and severe COPD exacerbation. In addition, it highlighted the impact of ensifentrine treatment on health care resource utilization related to COPD, including fewer physicians' office visits, emergency department visits and hospitalizations compared with placebo treatment. In October, we presented additional analyses from the ENHANCE-1 and ENHANCE-2 study at the CHEST annual meeting.

9 月，我們在 ERS ​​上對 ENHANCE-1 24 週急性加重數據進行了進一步分析，結果表明，恩西芬汀治療可顯著降低中度和重度 COPD 急性惡化的發生率和風險。此外，它還強調了恩西芬鹼治療對與慢性阻塞性肺病相關的醫療保健資源利用的影響，包括與安慰劑治療相比更少的醫生就診、急診就診和住院治療。 10 月，我們在 CHEST 年會上展示了 ENHANCE-1 和 ENHANCE-2 研究的更多分析。

The data from pooled analyses demonstrated that treatment with ensifentrine resulted in substantial reductions in the rate and risk of COPD exacerbations regardless of recent exacerbation history, and the medication was well tolerated across patient groups. Additionally, subgroup data analysis demonstrated treatment with ensifentrine resulted in improvements in lung function, symptoms, quality of life endpoints and reductions in the rate and risk of exacerbations regardless of background therapy as well as reductions in daily rescue medication use. Also at CHEST, we launched the disease awareness campaign titled unspoken COPD. The campaign highlights the severe impact COPD has on patients' daily life and encourages HCPs to engage in deeper conversations to fully understand COPD's impact on each patient in their practice.

總結分析的數據表明，無論近期是否有急性加重史，恩西芬汀治療均可顯著降低 COPD 急性惡化的發生率和風險，並且該藥物在各患者組中具有良好的耐受性。此外，亞組數據分析表明，無論背景治療如何，恩西芬汀治療均可改善肺功能、症狀、生活品質終點，並降低病情加重的發生率和風險，並減少每日救援藥物的使用。同樣在 CHEST，我們發起了名為「不言而喻的慢性阻塞性肺病」的疾病意識活動。這項活動強調了慢性阻塞性肺病對患者日常生活的嚴重影響，並鼓勵醫護人員進行更深入的對話，以充分了解慢性阻塞性肺病在實踐中對每位患者的影響。

Turning to our global partnering strategy. Nuance Pharma, our development partner in Greater China, has continued their Phase III trial evaluating ensifentrine for the maintenance treatment of COPD in China. As a reminder, Nuance Pharma has exclusive rights to develop and commercialize ensifentrine in Greater China, and as such, will play a key role in addressing the global need for a novel treatment for COPD. We look forward to providing updates as the trial progresses. Looking ahead, we are expanding our pipeline, starting with a plan to initiate 2 clinical programs. We are developing a fixed-dose combination formulation with ensifentrine and glycopyrrolate, a LAMA for the maintenance treatment of COPD delivered via a nebulizer.

轉向我們的全球合作策略。我們在大中華區的開發夥伴 Nuance Pharma 持續進行 III 期試驗，評估 ensifentrine 在中國用於慢性阻塞性肺病維持治療的效果。需要提醒的是，Nuance Pharma 擁有恩西芬汀在大中華區的獨家開發和商業化權利，因此，它將在滿足全球對慢性阻塞性肺病新型治療方法的需求方面發揮關鍵作用。我們期待隨著試驗的進展提供最新資訊。展望未來，我們正在擴大我們的產品線，首先計劃啟動 2 個臨床項目。我們正在開發一種含有 ensifentrine 和格隆溴銨的固定劑量組合製劑，這是一種透過霧化器維持治療 COPD 的 LAMA。

Fixed-dose combination therapies are commonly used in the treatment of COPD. Historically, in DPI and pMDI therapies only. Based on market research, there is an unmet need for a nebulized fixed-dose combination therapy. We believe the combination of ensifentrine with a LAMA will provide COPD patients with the first nebulized fixed-dose combination that has bronchodilation through a dual mechanism and also nonsteroidal anti-inflammatory effects of PDE inhibition. With a feasible formulation is developed, we plan to submit an investigational due drug application to the FDA and if cleared, start a Phase II clinical trial assessing the safety and efficacy of a fixed dose formulation of ensifentrine and glycopyrrolate in the second half of 2024.

固定劑量合併療法通常用於治療慢性阻塞性肺病。從歷史上看，僅用於 DPI 和 pMDI 療法。根據市場研究，對霧化固定劑量聯合療法的需求尚未被滿足。我們相信，恩西芬汀與 LAMA 的組合將為 COPD 患者提供第一個霧化固定劑量組合，該組合透過雙重機制具有支氣管擴張作用，並具有抑制 PDE 的非類固醇抗發炎作用。隨著可行的製劑開發出來，我們計劃向FDA 提交研究性藥物申請，如果獲得批准，將在2024 年下半年啟動II 期臨床試驗，評估ensifentrine 和格隆溴銨固定劑量製劑的安全性和有效性。

Additionally, based on the clinical profile of ensifentrine in COPD patients, including data that supports reduction in exacerbation burden, improvement in lung function and the PDE3 and PDE4 mechanism of action supporting enhanced mucociliary clearance, we believe ensifentrine could be an effective treatment for non-cystic fibrosis bronchiectasis. This is a severe chronic condition where the airways of the lung become abnormally wide, leading to a cycle of infection, inflammation and exacerbation that cause lung tissue damage. The condition affects approximately 370,000 patients in the U.S., and there are currently no therapies approved specifically for non-CF bronchiectasis.

此外，根據ensifentrine 在COPD 患者中的臨床概況，包括支持減輕病情加重負擔、改善肺功能以及支持增強黏膜纖毛清除的PDE3 和PDE4 作用機制的數據，我們相信ensifentrine 可能是治療非慢性阻塞性肺病的有效方法。囊性纖維化支氣管擴張。這是一種嚴重的慢性疾病，肺部氣道變得異常寬大，導致感染、發炎和病情惡化的循環，從而導致肺組織損傷。在美國，這種疾病影響著大約 37 萬名患者，目前還沒有批准專門用於非 CF 支氣管擴張的治療方法。

Physicians use bronchodilators, antibiotic, steroid and surgery to treat patients. If our NDA is approved, we plan to commence a Phase II clinical trial to assess the efficacy and safety of nebulized ensifentrine in patients with non-CF bronchiectasis in the second half of 2024, subject to clearance by the FDA. We are pleased with our constant progress in all areas, including regulatory, commercial preparation and new program development. I will now turn the call over to Mark to review our financial results for the third quarter.

醫生使用支氣管擴張劑、抗生素、類固醇和手術來治療病人。如果我們的 NDA 獲得批准，我們計劃在 2024 年下半年開始一項 II 期臨床試驗，以評估霧化恩西芬汀對非 CF 支氣管擴張患者的療效和安全性，並需獲得 FDA 批准。我們對我們在所有領域不斷取得的進展感到高興，包括監管、商業準備和新專案開發。我現在將電話轉給馬克，以審查我們第三季的財務表現。

Thank you, Dave, and good morning, everyone. We ended the third quarter of 2023 with $257.4 million in cash and equivalents. We believe our balance sheet remains strong with the cash currently on hand, expected cash receipts from the U.K. tax credit program and funding anticipated to be available under the Oxford loan facility, we expect to have sufficient runway at least through the end of 2025, including the planned commercial launch of ensifentrine in the U.S. pending regulatory approval. For the quarter ended September 30, 2023, net loss after tax was $14.7 million compared to a net loss after tax of $15.6 million for the same period in 2022. This represents a loss of $0.02 per ordinary share or $0.18 per ADS for the quarter compared to a loss of $0.03 per ordinary share or $0.24 per ADS for the third quarter of 2022.

謝謝戴夫，大家早安。截至 2023 年第三季末，我們的現金及等價物為 2.574 億美元。我們相信，我們的資產負債表仍然強勁，目前手頭上有現金、來自英國稅收抵免計劃的預期現金收入以及牛津貸款安排下預計可用的資金，我們預計至少到 2025 年底將有足夠的跑道，包括計劃在美國商業推出ensifentrine，尚待監管部門批准。截至2023 年9 月30 日的季度，稅後淨虧損為1,470 萬美元，而2022 年同期的稅後淨虧損為1,560 萬美元。這意味著該季度每股普通股虧損0.02 美元，每股美國存托股虧損 0.18 美元。2022 年第三季每股普通股虧損 0.03 美元，每股美國存託股虧損 0.24 美元。

Research and development costs were $3 million for the quarter ended September 30, 2023, compared to cost of $9.8 million for the third quarter of 2022. The decrease was primarily due to a $7.9 million decrease in clinical trial costs as all study conduct and analysis under the Phase III ENHANCE program were complete, whereas in the same period in 2022, significant costs were incurred associated with even ongoing study conduct.

截至2023 年9 月30 日的季度，研發成本為300 萬美元，而2022 年第三季的研發成本為980 萬美元。這一下降主要是由於臨床試驗成本減少了790 萬美元，因為所有研究進行和分析都在III 期 ENHANCE 計劃已完成，而在 2022 年同期，即使正在進行的研究也會產生大量成本。

The 2023 third quarter clinical trial and other development costs also include the impact of $2.2 million of credits received related to the final financial reconciliation of a Phase III enhanced program supplier. This decrease was partially offset by an increase of $0.7 million in people-related costs. Selling, general and administrative expenses were $13.4 million for the quarter ended September 30, 2023, compared to $5.3 million reported for the same period in 2022. This increase was primarily due to a $4.7 million increase in people-related costs as well as an increase of $2.9 million for costs primarily related to the build-out of the distribution network and work related to payer disease education as well as advancing the commercial and information technology infrastructure in preparation for potential commercial launch. I'll now turn the call back over to the operator for the Q&A.

2023 年第三季臨床試驗和其他開發成本還包括與 III 期增強計畫供應商的最終財務對帳相關的 220 萬美元信貸的影響。這一減少被人事相關成本增加 70 萬美元部分抵銷。截至2023 年9 月30 日的季度，銷售、一般和管理費用為1,340 萬美元，而2022 年同期報告的銷售、一般和管理費用為530 萬美元。這一增長主要是由於人員相關成本增加470 萬美元以及290 萬美元的費用主要涉及分銷網絡的建設、付款人疾病教育相關工作以及推進商業和資訊技術基礎設施，為潛在的商業推出做好準備。我現在將把電話轉回給接線員進行問答。

(Operator Instructions) Our first question comes from Andrew Tsai with Jefferies.

（操作員說明）我們的第一個問題來自 Jefferies 的 Andrew Tsai。

Appreciate all the updates as well. So first question is only to the extent you can share. How are FDA discussions going about the NDA? What kind of questions have as the agency asked you since accepting the filing. And as it relates to the PDUFA, what exactly keeps you guys up at night, what would be the risks here really in your view? And then secondly, let's just say ensifentrine is approved. As we think about your initial launch cadence, could it be realistic to think that an initial low-hanging fruit could be patients who are taking an additional therapy after triple specifically Daliresp. So can we expect ensifentrine to immediately displace Daliresp specifically, could that be the low-hanging fruit immediately upon launch?

也感謝所有的更新。所以第一個問題只是在你可以分享的範圍內。 FDA 關於 NDA 的討論進展如何？自從接受申請以來，該機構問了您哪些問題？就 PDUFA 而言，到底是什麼讓你們徹夜難眠，你們認為這裡真正的風險是什麼？其次，我們就說 ensifentrine 已獲得批准。當我們考慮您最初的啟動節奏時，是否可以現實地認為，最初的容易實現的目標可能是在三倍特別是 Daliresp 後接受額外治療的患者。那麼，我們是否可以期望 ensifentrine 立即取代 Daliresp，這可能是上市後立即實現的目標嗎？

Great. Thanks, Andrew, for the questions. And maybe I'll start on the first one and then turn it over to Chris for his thoughts on the launch. With regard to the FDA questions, there, what I would say is typical during the review process, as you'd expect, the FDA asked for data, different questions, clarifications. And I would say it's very typical and normal in my experience, especially at this stage, of course, relatively early in the review even prior to mid-cycle. So I think it's going well from our view. With regard to what keeps us up at night and PDUFA risk, again, I think we feel we have an extremely strong package that we submitted across CMC, nonclinical, clinical and the total benefit to risk of ensifentrine, we believe, is very compelling. So at this time, I think we're comfortable where we're at in the FDA review process. So with that, I'll turn it over to Chris and talk about the launch.

偉大的。謝謝安德魯提出的問題。也許我會從第一個開始，然後將其交給克里斯，詢問他對發布的想法。關於 FDA 的問題，我想說的是審查過程中的典型問題，正如你所期望的那樣，FDA 要求提供數據、不同的問題和澄清。我想說，根據我的經驗，這是非常典型和正常的，特別是在這個階段，當然，在審查的相對早期，甚至在周期中期之前。所以我認為從我們的角度來看一切進展順利。關於讓我們徹夜難眠的原因和 PDUFA 風險，我認為我們認為我們在 CMC、非臨床、臨床方面提交了一個非常強大的一攬子計劃，我們相信，安西芬鹼風險的總效益非常引人注目。所以目前，我認為我們對 FDA 審查流程感到滿意。因此，我將把它交給克里斯並談論發布。

Thanks, Dave, and Andrew, I appreciate the question. As we think about kind of that launch cadence and who is the first patient, that a physician may prescribe ensifentrine to. I think it's important to kind of just ground everybody in what's happening with these patients today. We know today there's a 8.6 million patients treated with COPD maintenance medications. We also know today that at least half of them, either if they're in a single, a dual, a triple agent are remaining symptomatic. And when a patient has persistent symptoms, physicians are very likely to add new therapies or try to help these patients start to feel better and hopefully prevent the risk of exacerbations in the future. So if we think about that 8.6 million, really, what we hear in our market research is there are 2 groups of patients that the physicians see as low-hanging fruit or patients that they would try and defending very quickly on.

謝謝戴夫和安德魯，我很欣賞這個問題。當我們考慮那種啟動節奏以及誰是第一個病人時，醫生可能會給他開恩西芬汀。我認為讓每個人都了解今天這些患者所發生的事情很重要。我們知道今天有 860 萬名患者接受慢性阻塞性肺病維持藥物治療。今天我們也知道，至少有一半的人，無論是單藥、雙藥或三藥，仍然有症狀。當患者出現持續症狀時，醫生很可能會增加新的治療方法或嘗試幫助這些患者開始感覺好一些，並有望防止未來病情惡化的風險。因此，如果我們考慮到這 860 萬人，實際上，我們在市場研究中聽到的是，有兩組患者被醫生視為唾手可得的目標，或者他們會很快嘗試並捍衛的患者。

The first is the group of patients that are on single LAMA or LABA or a LABA ICS product. And when they look at our data, and they look at what the data Dave described, they think of ensifentrine as being the potential drug to add to these patients if it's approved. And they think about doing that at a very high rate. The second group of patients, which is the patients that potentially could even be on Daliresp of today, are these patients on dual and triple therapy that are looking for additional symptom relief and help. And the physicians add ensifentrine in about 20% to 45% of the time in these patients, treatment arm in meter. I think the important thing to keep in mind here is in that patient group that I'm talking about there, there's about 75,000 to 85,000 patients on Daliresp today that are still -- that could potentially be an option for physicians to add a PDE3, 4 mechanism too.

第一組是使用單一 LAMA 或 LABA 或 LABA ICS 產品的患者。當他們查看我們的數據以及戴夫描述的數據時，他們認為如果安西芬汀獲得批准，它是可以添加到這些患者身上的潛在藥物。他們考慮以非常高的速度來做這件事。第二組患者，即今天可能接受 Daliresp 治療的患者，是正在尋求額外症狀緩解和幫助的雙重和三重治療的患者。醫生在這些患者中約 20% 至 45% 的時間裡添加恩西芬鹼，治療劑量以公尺為單位。我認為這裡要記住的重要一點是，在我正在談論的患者群體中，今天大約有 75,000 至 85,000 名患者仍在使用 Daliresp，這可能是醫生添加 PDE3 的一個選擇， 4機制也。

So we believe very strongly that there are 2 distinct patient populations, either those patients on single bronchodilator or LABA/ICS and those patients that are on dual and triple that ensifentrine could be added to very easily. And I think it's all driven by the fact that these patients remain symptomatic. They remain having issues in their daily lives and the physicians are actively looking for new mechanisms to be able to layer on top of the patient's treatment path, so they can get them going back to doing some of the normal things that they want to do in their daily lives.

因此，我們堅信有 2 個不同的患者群體，要么是使用單一氣管擴張劑或 LABA/ICS 的患者，要么是使用雙聯和三聯安西芬鹼的患者，可以輕鬆添加到其中。我認為這一切都是因為這些患者仍然有症狀。他們在日常生活中仍然遇到問題，醫生正在積極尋找新的機制，以便能夠在患者的治療路徑之上進行分層，這樣他們就可以讓他們回到做一些他們想做的正常事情。他們的日常生活。

Next question comes from Yasmeen Rahimi with Piper Sandler.

下一個問題來自亞斯明·拉希米 (Yasmeen Rahimi) 和派珀·桑德勒 (Piper Sandler)。

Thank you so much for all the updates. Would love to dig a little bit more into these 2 new studies that you spoke about. I guess, where are you in the formulation process at this junction? If you could just give us some color beyond what you've said and how soon could you have it completed? And then what would a design -- what would like the study design look like for a fixed condo? What would the duration be and the size, et cetera, and the same goes for the second Phase II study in the -- that you're also planning to kick off. So I think a lot of clients would love to hear maybe beyond the initial indication around size, costs associated with them? And what's sort of the cadence of the next steps? Just a little bit more granular that would be really helpful for us.

非常感謝您的所有更新。我很樂意深入研究您提到的這兩項新研究。我想，在這個十字路口，你處於制定過程的哪個階段？如果您能給我們一些超出您所說的內容的話，您能多快完成它？那麼固定公寓的設計是什麼樣的──書房設計是什麼樣的呢？持續時間和規模等等，您也計劃啟動的第二個二期研究也是如此。因此，我認為除了最初的指示之外，很多客戶還想聽聽有關尺寸和相關成本的資訊？下一步的節奏是怎麼樣的？只要更細化一點，對我們來說確實很有幫助。

So let me just talk briefly about the formulation, and then I'll turn it over to Kathy to talk about both the trial design concepts for fixed combo as well as for bronchiectasis. Within fixed combo product formulation development, we are advancing with the typical formulation development where we're co-formulating both glycopyrrolate and ensifentrine and the nebulized formulation. Of course, there's acute chemistry that we can look at. There's also a longer-term stability data that gets generated at 3 and 6 months, typically under normal and accelerated conditions to convince us that we have a commercially acceptable on formulation. So that work is ongoing as we speak. Certain aspects can't be sped up, especially when you're looking at 6-month stability time point. We expect to be more fully informed on the co-formulation somewhere in the first quarter of 2024. And that's why we provided the guidance that we'll be looking to initiate the studies actually for both fixed dose combo and bronchiectasis in the second half of '24. So with that, I'll give -- turn it over to Kathy for her thoughts on the design.

因此，讓我簡單地談談配方，然後我將把它交給 Kathy，談談固定組合和支氣管擴張的試驗設計概念。在固定組合產品配方開發中，我們正在推進典型的配方開發，其中我們共同配製格隆溴銨和恩西芬汀以及霧化配方。當然，我們可以觀察一些尖銳的化學反應。還有 3 個月和 6 個月產生的長期穩定性數據（通常是在正常和加速條件下），以讓我們相信我們擁有商業上可接受的配方。因此，就在我們發言時，這項工作正在進行中。某些方面無法加快，尤其是當您考慮 6 個月的穩定時間點時。我們預計將在 2024 年第一季更全面地了解聯合製劑。這就是為什麼我們提供了指導，我們將尋求在 2024 年下半年啟動針對固定劑量組合和支氣管擴張的實際研究'24。因此，我會將其交給 Kathy，詢問她對設計的想法。

Sure. So let's talk about first the fixes combination. So certainly, we're in early stages of development of what a part of how will look like. We know what in general we would like to do or need to do in a Phase II type program, so the initial studies for that. So our goals will be to first establish efficacy and some initial safety and probably designs that are similar to our Phase II studies that we did for ensifentrine to begin with more likely be a shorter design maybe up to anywhere up to about 12 weeks or so. But also we need to establish dose ranging. So that would be the goal of the studies that we would do for Phase II is to look at initial efficacy and safety and dose-ranging.

當然。那我們先來談談修復組合。當然，我們正處於開發的早期階段，部分內容會是什麼樣子。我們知道一般來說我們想在第二階段類型計劃中做什麼或需要做什麼，因此進行了初步研究。因此，我們的目標將是先確定療效和一些初步安全性，可能的設計類似於我們為 ensifentrine 所做的 II 期研究，一開始更可能是較短的設計，可能長達約 12 週左右。但我們還需要建立劑量範圍。因此，我們第二階段研究的目標是檢視初始療效、安全性和劑量範圍。

If you look at the second study, the study for non-CF bronchiectasis, the slot difference disease, slightly different type of design. We certainly would need to establish in the Phase II, again, efficacy and safety. These studies may be need to be a little longer because some of the primary endpoints for non-CF access relate to exacerbations. So they may be up to a 6-month type of design. But again, keep in mind that we are in the early phase of developing these designs, and we're starting to make more definite ideas about the designs as we get further along into our development program.

如果你看第二個研究，研究針對非 CF 支氣管擴張、槽差疾病，類型設計略有不同。我們當然需要在第二階段再次確定有效性和安全性。這些研究可能需要更長的時間，因為非 CF 路徑的一些主要終點與病情惡化有關。所以它們可能是長達 6 個月的設計類型。但再次請記住，我們正處於開發這些設計的早期階段，隨著我們進一步推進我們的開發計劃，我們將開始對這些設計做出更明確的想法。

Our next question comes from Andreas Argyrides with Wedbush Securities.

我們的下一個問題來自 Wedbush Securities 的 Andreas Argyrides。

A couple here. So and expectations of approval for ensifentrine, can you remind us what the label is likely to look like from an efficacy and safety standpoint? And then while you don't expect an AdCom, the FDA has a curious history of changing its mind on a whim. Is there a threshold at which point and AdCom would definitely not be held? And if there is an AdCom, would it necessarily be a bad thing?

這裡有一對夫婦。那麼，以及對安西芬鹼獲得批准的期望，您能否提醒我們，從功效和安全性的角度來看，標籤可能會是什麼樣子？儘管你不期待 AdCom，但 FDA 卻有著一時興起改變主意的奇怪歷史。是否有一個門檻，達到什麼程度AdCom就絕對不會舉行？如果有AdCom，一定是壞事嗎？

Great. With regard to the label for ensifentrine, again, just to remind everybody that we expect and have provided data to support an indication of the maintenance treatment of COPD, which is a fairly broad indication and consistent with recent approvals, and we believe the data provided supports that indication. We'd, of course, expect the rest of the clinical data results to be in the clinical section in the label as appropriate. Clearly, the FDA needs to continue the review, and we're quite some time away from specific labeling conversations. And so I think we'll see how that comes out. I'm sure in 2024. So -- but otherwise, we think the indication is fairly broad.

偉大的。關於恩西芬鹼的標籤，再次提醒大家，我們期望並已經提供了數據來支持慢性阻塞性肺病維持治療的適應症，這是一個相當廣泛的適應症，與最近的批准一致，我們相信所提供的數據支持該指示。當然，我們希望其餘的臨床數據結果能適當地出現在標籤的臨床部分。顯然，FDA 需要繼續審查，距離具體的標籤對話還有很長一段時間。所以我想我們會看看結果如何。我確定是在 2024 年。所以，但除此之外，我們認為這一跡象相當廣泛。

With regard to an AdCom. Yes, they've guided that they do not plan to have AdCom. And yes, you're correct. I think the FDA can decide on how they want to address that during the review. We don't expect one as time passes by, especially after mid-cycle review, for example, and even as we get into 2024, that timing gets shorter and shorter. So there's certain practicalities about it. But nonetheless, I wouldn't comment any further on the AdCom. And of course, it's in the FDA's hands.

關於 AdCom。是的，他們表示不打算擁有 AdCom。是的，你是對的。我認為 FDA 可以在審查期間決定如何解決這個問題。隨著時間的推移，我們預計不會出現這種情況，尤其是在周期中期審查之後，甚至當我們進入 2024 年時，這個時間也會變得越來越短。所以它有一定的實用性。但儘管如此，我不會對 AdCom 發表任何進一步評論。當然，它掌握在 FDA 的手中。

And just one last follow-up from us. With regard to the 2 new potential indications, maybe just some thoughts on how this potentially unlocks strategic value for the company and incident.

這只是我們最後一個的後續行動。關於這兩個新的潛在跡象，也許只是關於這如何可能為公司和事件釋放戰略價值的一些想法。

Yes. Well, sure. I mean I think it speaks loudly to what we believe ensifentrine can do in -- broadly in the treatment of COPD, either by itself or as a combination therapy. We have cleaned an excellent data from the ENHANCE trials that combining ensifentrine with a LAMA is quite advantageous as well. And so I think it speaks loudly to the power of ensifentrine, the PDE3, PDE4 mechanism and its application. And then, of course, broader than that and as we've reviewed today in non-CF bronchiectasis because of the underlying pharmacology, which has been demonstrated. So clearly, in COPD, we think it's highly applicable in other diseases like bronchiectasis. I think ultimately, any partner can see that ensifentrine's underlying pharmacology can be applied quite widely to various respiratory diseases, which we've really stated from the beginning as the full potential of ensifentrine.

是的。嗯，當然。我的意思是，我認為它充分說明了我們相信恩西芬汀可以廣泛用於治療慢性阻塞性肺病，無論是單獨治療還是作為聯合治療。我們從 ENHANCE 試驗中收集了非常好的數據，這表明將 ensifentrine 與 LAMA 聯合使用也非常有利。所以我認為它充分說明了 ensifentrine、PDE3、PDE4 機制及其應用的力量。當然，範圍比這更廣泛，正如我們今天在非 CF 支氣管擴張中所回顧的那樣，因為其潛在的藥理學已經得到證實。顯然，對於慢性阻塞性肺病，我們認為它非常適合支氣管擴張等其他疾病。我認為最終，任何合作夥伴都可以看到，恩西芬鹼的基礎藥理學可以廣泛應用於各種呼吸系統疾病，我們從一開始就真正聲明了恩西芬鹼的全部潛力。

The next question comes from Joon Lee with Truist Securities.

下一個問題來自 Truist Securities 的 Joon Lee。

This is Asim on for Joon. My first question is, what are you looking for in a European partner? And can you guide to any updates on that front? And then also just wondering if you could talk about the ramp in SG&A in preparation for launch and one could expect hiring for the around 100-person sales force.

這是阿西姆為瓊代言的。我的第一個問題是，您在歐洲合作夥伴中尋找什麼？您能指導一下這方面的任何更新嗎？然後我想知道您是否可以談談為發布做準備而增加的 SG&A 費用，以及預計招募約 100 人的銷售團隊。

Great. I'll speak to the partnering and then turn it over to Mark to talk about SG&A and Chris, for the reps. But I think that with regard to European partner or, in general, our partnering strategy, it continues to be the same, that is we look to partner outside the U.S., much as we've done in Greater China with Nuance Pharma. So the strategy has not changed. I think that ideally in a partner, European or otherwise, besides, of course, elements around expertise in regulatory, clinical and commercial in the respiratory space, as you'd expect.

偉大的。我將與合作夥伴交談，然後將其交給馬克，讓其為銷售代表談論 SG&A 和克里斯。但我認為，就歐洲合作夥伴而言，或者總的來說，我們的合作策略仍然是一樣的，那就是我們希望在美國以外的地區進行合作，就像我們在大中華區與Nuance Pharma 所做的那樣。所以策略沒有改變。我認為理想的情況是在歐洲或其他地方的合作夥伴中，當然，正如您所期望的那樣，除了呼吸領域監管、臨床和商業方面的專業知識之外。

We also are looking for opportunities in partners that have expertise in device PMD or DPI device development, manufacturing and/or IP, which I think could be quite advantageous as we look for the full life cycle management and other indications for ensifentrine as well as ability to manufacture specifically drug product, but also potentially drug substance or API. And I think that this would serve us well having, of course, a second source potentially a source with a lower cost point. Keep in mind that we're looking to supply the world with ensifentrine in different markets. And so looking for somebody with that manufacturing capability is another feature of our partnering strategy. So with that, I'll turn it over to Mark for a ramp on SG&A.

我們也正在尋找在設備 PMD 或 DPI 設備開發、製造和/或 IP 方面擁有專業知識的合作夥伴的機會，我認為這可能非常有利，因為我們正在尋找 ensifentrine 的全生命週期管理和其他適應症以及能力專門生產藥品，也可生產潛在的原料藥或API。我認為，當然，擁有第二個來源（可能是成本較低的來源）對我們很有幫助。請記住，我們希望在不同的市場向世界各地提供 ensifentrine。因此，尋找具有製造能力的公司是我們合作策略的另一個特徵。因此，我會將其交給 Mark，以獲取 SG&A 的斜坡。

Sure. So if you look at SG&A over the last couple of years, you'll see that it has been ramping a year ago, it was $5-ish million in Q3, and this year, it's $13-ish million. And I think what you should expect is that, that ramp will continue for the next several quarters. Through Q2, I think that our total expense through Q2 of next year, I think that our total expense should be in the $20 million to $25 million range on a quarterly basis. That includes both SG&A and R&D. And then once we get to Q3, assuming approval at the end of June, you would see that the SG&A ramps again as we bring on the sales reps that Chris will talk about.

當然。因此，如果您查看過去幾年的 SG&A，您會發現一年前一直在增長，第三季度為 500 萬美元左右，今年為 1300 萬美元左右。我認為你應該預料到的是，這種成長將在接下來的幾季持續下去。透過第二季度，我認為我們明年第二季度的總支出，我認為我們的季度總支出應該在 2000 萬美元到 2500 萬美元之間。這包括銷售、行政管理和研發。然後，一旦我們進入第三季度，假設在 6 月底獲得批准，隨著我們引入克里斯將要談論的銷售代表，您會看到 SG&A 再次增加。

Thanks, Mark, on that. As we think about Joon, the reps and how we would potentially hire these people, we first have to think about how a structure looks like for that type of an organization. And typically, when we have a field force of about 100, you're going to look at 2 area executive directors or executive sales directors that cover the east and the west. We've brought those 2 individuals on. And then we are actively looking at the next level under that, which is the RSDs, our regional sales directors, which cover are directly rep managers. And you would expect those people to be hired maybe 3 to 4 months before PDUFA. And our plan for reps is to hire them around at PDUFA contingent on PDUFA. We've done this in the past as a team where we create a pool of candidates that we're able to hire and kind of hold until the drug is approved around the PDUFA date and quickly convert those offers into active employees with an organization.

謝謝，馬克，就此而言。當我們考慮 Joon、代表以及我們如何僱用這些人時，我們首先必須考慮該類型組織的結構是什麼樣的。通常，當我們的現場人員數量約為 100 人時，您將需要 2 名負責東部和西部的區域執行總監或執行銷售總監。我們已經把這兩個人帶上了。然後我們正在積極尋找下一個級別，即 RSD，我們的區域銷售總監，其中包括直接代表經理。您預計這些人可能會在 PDUFA 之前 3 到 4 個月被聘用。我們對代表的計劃是在 PDUFA 特遣隊僱用他們。我們過去曾作為一個團隊這樣做過，我們創建了一個候選人庫，我們可以僱用並保留這些候選人，直到藥物在 PDUFA 日期前後獲得批准，並迅速將這些候選人轉化為組織的活躍員工。

So our plan would be to have those reps come on right after PDUFA and then have them trained and ready to go sell ensifentrine if it's approved. I think the other important aspect here is we believe that a proper field force covering ensifentrine not only includes field-based reps, but also ways that we can interact with doctors virtually and also support the reimbursement pathway with field reimbursement managers. So I think as you think about the totality of the commercial organization, we want to make sure that we cover the physicians and the patients in a way that they can -- they see how the utility of the product but then can also get the product to the patients that are most in need. And again, all those -- that large number of representatives and people to support that would be coming around PDUFA right after PDUFA.

因此，我們的計劃是讓這些代表在 PDUFA 後立即上崗，然後對他們進行培訓，並準備好在獲得批准後出售 ensifentrine。我認為這裡的另一個重要方面是，我們相信覆蓋恩西芬汀的適當現場力量不僅包括現場代表，還包括我們可以與醫生進行虛擬互動的方式，並支持與現場報銷經理的報銷途徑。所以我認為，當你考慮商業組織的整體時，我們希望確保我們以一種他們能夠做到的方式覆蓋醫生和患者——他們看到產品的效用，然後也可以獲得產品給最需要幫助的患者。再說一遍，所有這些——大量的代表和人民將在 PDUFA 推出後立即支持 PDUFA。

Next question comes from Tom Shrader with BTIG.

下一個問題來自 BTIG 的 Tom Shrader。

I've all combination questions. So the specific LAMA you used, how derisking is that for the class? The molecules ever not play together? Or is it really the mechanisms you're working out? And then there's some old data for ensifentrine. It was really quite striking that it made LAMA's work faster. Maybe for Kathy, does that data hold up in your mind? And is that something that you would be very eager to try to see if you can repeat? And I have a follow-up on bronchiectasis.

我所有的問題都是組合題。那麼你使用的特定 LAMA，對於該類別來說有多大的風險？分子從來沒有一起玩過嗎？或者這真的是你正在研究的機制嗎？還有一些關於 ensifentrine 的舊數據。令人驚訝的是，它使 LAMA 的工作速度更快。也許對凱西來說，這些數據在你的腦海中成立嗎？您是否會非常渴望嘗試看看是否可以重複這一點？我對支氣管擴張進行了追蹤。

Great. Thanks, Tom. Yes, I'll turn it over to Kathy to talk about her glycopyrrolate, in general and then potentially how ensifentrine and glycopyrrolate work together.

偉大的。謝謝，湯姆。是的，我將把它交給 Kathy，談談她的格隆溴銨的一般情況，然後可能介紹 ensifentrine 和格隆溴銨如何一起發揮作用。

Yes. So glycopyrrolate is like other LAMAs. Works very similar. They've been in use for a long time. So we know a lot about them from that perspective, and they all work fairly similar. So I don't expect to have any surprises from their FSC or whatever that we look at in studies from that perspective. As far as acting faster, we do have some older data that shows that it's not just LAMAs, but also for beta agonist that when you combine the 2 together, you do get a shortening of the response time to peak efficacy. Again, those were done in shorter studies, but I wouldn't expect that that would go away. I would expect to still see that in the combination type of when we use them together from that perspective. I don't -- was there another question I'm forgetting?

是的。所以格隆溴銨和其他 LAMA 一樣。工作原理非常相似。它們已經使用了很長時間。因此，從這個角度來看，我們對它們了解很多，而且它們的工作原理都非常相似。因此，我預計他們的 FSC 或我們從這個角度研究的任何內容都不會令人感到意外。就行動速度而言，我們確實有一些較舊的數據表明，不僅是 LAMA，而且對於 β 激動劑來說，當將兩者結合在一起時，達到峰值療效的反應時間確實會縮短。同樣，這些都是在較短的研究中完成的，但我不認為這種情況會消失。我希望當我們從這個角度一起使用它們時，仍然會在組合類型中看到這一點。我不知道──我還忘了另一個問題嗎？

I haven't asked it yet. Just historically on bronchiectasis, have bronchodilators been tried and failed? Are you mostly betting or focused on the anti-inflammatory properties to show this as an effective drug?

我還沒問。就歷史上的支氣管擴張而言，是否嘗試過支氣管擴張劑但失敗了？您是否主要押注或關注其抗發炎特性以證明其是一種有效的藥物？

Bronchodilators have not failed per se. As was mentioned, there are no approved drugs for non-CF bronchiectasis. Bronchiectasis had some similar things that we see that are similar to COPD, for example, infections, they have widening of the airways and they have destruction in the airways and increased mucus. So many of the things that they -- we see in bronchiectasis, we see effects from ensifentrine and COPD. So for example, bronchodilation may help clear out the mucus better. It doesn't necessarily work like you would see in somebody with asthma where you're actually looking to actually bronchodilate the airway, but you're looking for increasing, getting rid of the mucus and all those sitting in the airways because that's what's causing all the underlying infections when you have stuff sitting there if it gets infected and then you lead to exacerbations.

支氣管擴張劑本身並沒有失敗。如前所述，目前還沒有批准用於治療非 CF 支氣管擴張的藥物。支氣管擴張症有一些與慢性阻塞性肺病相似的症狀，例如感染、氣道擴張、氣道破壞和黏液增多。我們在支氣管擴張中看到了很多東西，我們看到了恩西芬汀和慢性阻塞性肺病的影響。例如，支氣管擴張可能有助於更好地清除黏液。它不一定像您在氣喘患者中看到的那樣起作用，您實際上是在尋求真正擴張氣道的支氣管，但您正在尋求增加、清除黏液和所有滯留在氣道中的東西，因為這就是導致氣道阻塞的原因。所有潛在的感染，當你有東西放在那裡時，如果它被感染，然後會導致病情惡化。

So do we use them? Yes, we use them. We use everything we have because we don't have anything else to use. So we're going to use bronchodilators, or you can use steroids for you, whatever we have available because that's what we have to use to treat bronchiectasis. I think we also think from ensifentrine perspective, both on the non-steroidal anti-inflammatory effect and its ability to increase mucociliary clearance will help clear mucus out of the airways and help prevent and decrease exacerbations that we may see with patients with bronchiectasis.

那我們使用它們嗎？是的，我們使用它們。我們使用我們擁有的一切，因為我們沒有其他東西可以使用。因此，我們將使用支氣管擴張劑，或者您可以使用類固醇，無論我們有什麼可用的，因為這是我們必須用來治療支氣管擴張的藥物。我認為我們也從恩西芬鹼的角度來看，無論是非類固醇類抗發炎作用還是其增加粘液纖毛清除的能力都將有助於清除氣道中的粘液，並有助於預防和減少支氣管擴張患者可能出現的病情加重。

(Operator Instructions) Our next question comes from Dipesh Patel with H.C. Wainwright.

（操作員說明）我們的下一個問題來自 Dipesh Patel 和 H.C.溫賴特。

This is Dipesh, covering for Boobalan, H.C. Wainwright. In one of the HCP-focused market research slides that you presented last month, we see that ensifentrine's twice-a-day dosing schedule was the least preferred attribute among 7 others. So the score was not that bad. Thinking long term, how do you expect the twice-a-day regimen to potentially impact ensifentrine's market adoption?

我是 Dipesh，為 H.C. Boobalan 報道。溫賴特。在您上個月展示的一張以 HCP 為重點的市場研究幻燈片中，我們發現 ensifentrine 每天兩次的給藥方案是其他 7 個特性中最不受歡迎的特性。所以成績沒有那麼差。從長遠來看，您預計每天兩次的治療方案會對安西芬汀的市場採用產生怎樣的潛在影響？

Great. Chris, do you want to speak to it?

偉大的。克里斯，你想和它談談嗎？

Yes. Thanks, Dave, and I appreciate the question, Dipesh. I think you're referring to the slide on the attributes of drugs. Attribute to ensifentrine and how physicians rated that. I think it's really important to just ground ourselves on how impressive the response was from physicians on the profile of ensifentrine. As you mentioned, that was the lowest score, but it's still well above the median. But for every attribute that's listed from least important, the most important, ensifentrine score is extraordinarily high within a physician's mindset. And I think that plays based on what we've heard in qualitative and KOL interactions to the unmet need that still exists in the marketplace.

是的。謝謝，戴夫，我很欣賞這個問題，迪佩什。我想你指的是關於藥物屬性的幻燈片。歸因於 ensifentrine 以及醫師的評價。我認為，讓我們了解醫生對安西芬汀的反應是多麼令人印象深刻，這一點非常重要。正如您所提到的，這是最低分數，但仍遠高於中位數。但對於從最不重要到最重要排列的每一個屬性，在醫生的觀念中，安西芬汀的得分都非常高。我認為，這一點是基於我們在定性和 KOL 互動中所聽到的，以滿足市場上仍然存在的未滿足的需求。

As we discussed earlier, 50% of these patients are having persistent symptoms. So the physicians are looking for drugs that have the potential to have an effect on their patient lives that potentially ensifentrine could have. We talk specifically to doctors about BID dosing, one of the things that's interesting is what we hear from them is that many patients struggle, and Kathy can talk about this, but many patients struggle when they wake up in the morning because single or once-a-day drugs tend to lose their effect over time. So in their mind, sometimes the BID dosing is very beneficial for the patient because they get that evening dose that allows them to wake up in a better place than maybe they would have with a single once-a-day type product.

正如我們之前討論的，50% 的患者有持續的症狀。因此，醫生們正在尋找可能像安西芬汀那樣對病人生活產生影響的藥物。我們專門與醫生談論BID 劑量，有趣的事情之一是我們從他們那裡聽到的是，許多患者都在掙扎，凱西可以談論這一點，但許多患者在早上醒來時會感到掙扎，因為單身或曾經-每日服用的藥物往往會隨著時間的推移而失去作用。因此，在他們看來，有時 BID 給藥對患者非常有益，因為他們晚上服用的劑量可以讓他們在比服用單一一天一次的產品更好的地方醒來。

So when we look at overall adoption and how physicians look at the profile, we don't believe that a BID dose is a hindrance at all. And you can see that on the second part of that slide, which basically says that 90% of the HCPs believe that they'll be adopting ensifentrine within the first year of launch. And that's a remarkably high adoption rate. And it, again, speaks to the unmet need and the overall differentiated profile that ensifentrine has.

因此，當我們考慮整體採用情況以及醫生如何看待該情況時，我們認為 BID 劑量根本不會成為障礙。您可以在該幻燈片的第二部分看到這一點，該部分基本上表明 90% 的 HCP 相信他們將在推出的第一年內採用 ensifentrine。這是一個非常高的採用率。它再次說明了安西芬鹼尚未滿足的需求和整體差異化特徵。

Great. I have a couple of more questions. You may have touched on this in some of the prior questions, but can you discuss the challenges you anticipate solving as you work on testing the combinability of ensifentrine plus LAMA in a single nebulizer formulation. And I think you had noted earlier on, just to confirm that you're going to be expecting the clinical trial to begin second half of '24 on that?

偉大的。我還有幾個問題。您可能在之前的一些問題中已經提到過這一點，但是您能否討論一下您在測試單霧化器配方中的 ensifentrine 和 LAMA 的組合性時預計要解決的挑戰。我想您之前已經注意到，只是為了確認您預計臨床試驗將於 24 年下半年開始？

Yes. Our general cadence for that development would be getting through the formulation development activities, which takes some time because you want to see the durability of the formulation. That's nothing new in drug development. And we're -- that work is ongoing. With regard to challenges, I think it's nothing that we know other than getting the work done and having the data to support the plan forward, we believe the formulation can work, but we need the data to support that. We need to make sure that the dose delivered for both ensifentrine and glycopyrrolate, when co-formulated is where we want it to be. So there's a lot of technical aspects in a formulation, the chemistry, the dose deliver, the particle size generation, all of that work, which, of course, we've done previously with ensifentrine, we need to do with the combination. So that work will be ongoing. And that's why it puts us in looking at a clinical trial in the second half of 2024.

是的。我們發展的一般節奏是完成配方開發活動，這需要一些時間，因為你想看到配方的耐久性。這在藥物開發中並不是什麼新鮮事。我們——這項工作正在進行中。關於挑戰，我認為除了完成工作並有數據來支持計劃前進之外，我們不知道什麼，我們相信制定的方案是可行的，但我們需要數據來支持。我們需要確保恩西芬汀和格隆溴銨共同配製時的劑量達到我們想要的劑量。因此，在配方、化學、劑量輸送、粒徑產生等所有這些工作中存在著許多技術方面，當然，我們之前已經對安西芬汀做過這些工作，我們需要對組合進行處理。因此這項工作將持續進行。這就是為什麼我們考慮在 2024 年下半年進行臨床試驗。

Got it. And final question. How should we think about R&D expenses moving forward? Specifically, what will the remaining R&D expense relate to?

知道了。最後一個問題。我們該如何看待未來的研發費用？具體來說，剩餘的研發費用與什麼有關？

Go ahead, Mark.

繼續吧，馬克。

Yes. Thanks for the question. So I think in the very near term, you should expect R&D expenses to be fairly limited because we're not running any clinical trials. As we get into the back half of next year, they should go up marginally. These Phase II programs that we're talking about are not in the same scope that you used to seeing ensifentrine during our Phase III program. They're much smaller. So the expense levels will be back more like Verona had in the 2019 time frame. I think single-digit, low to mid-single-digit quarterly R&D expense for the foreseeable future until we get to a Phase III program.

是的。謝謝你的提問。因此，我認為在短期內，您應該預期研發費用將相當有限，因為我們沒有進行任何臨床試驗。當我們進入明年下半年時，它們應該會小幅上漲。我們正在討論的這些二期項目與您在我們三期項目中看到的 ensifentrine 的範圍並不相同。它們要小得多。因此，費用水準將恢復到 2019 年維羅納的水準。我認為在可預見的未來，在我們進入第三階段計畫之前，季度研發費用將為個位數、中低個位數。

This concludes our question-and-answer session. I would like to turn the conference back over to Dr. David Zaccardelli for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給 David Zaccardelli 博士發表閉幕詞。

Great. Thank you, everybody, for attending today's call. We appreciate your support, and we look forward to updating you in the future at conferences. Have a great day.

偉大的。謝謝大家參加今天的電話會議。我們感謝您的支持，並期待在未來的會議上向您通報最新情況。祝你有美好的一天。

The conference has now concluded. Thank you for attending today's presentation. You may all now disconnect.

會議現已結束。感謝您參加今天的演講。你們現在可以斷開連結了。