Verona Pharma PLC (VRNA) 2022 Q4 法說會逐字稿

Welcome to Verona Pharma's Fourth Quarter and Full Year 2022 Financial Results and Operating Highlights Conference Call. (Operator Instructions) Earlier this morning, Verona Pharma issued a press release announcing its financial results for the 3 months and full year ended December 31, 2022. A copy can be found in the Investor Relations tab on the corporate website, www.veronapharma.com.

歡迎來到 Verona Pharma 的第四季度和 2022 年全年財務業績和經營亮點電話會議。 （操作員說明）今天上午早些時候， Verona Pharma 發布了一份新聞稿，宣布了其截至 2022 年 12 月 31 日的三個月和全年的財務業績。可以在公司網站 www.veronapharma 的“投資者關係”選項卡中找到一份副本。 com。

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. Any such forward-looking statements represent management's estimates as of the date of this conference call.

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、計劃和前景的陳述均為前瞻性陳述。這些前瞻性陳述基於管理層當前的預期。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，這些因素可能導致我們的實際結果、業績或成就與我們在前瞻性陳述中明示或暗示的預期存在重大差異。任何此類前瞻性陳述均代表管理層截至本次電話會議之日的估計。

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 use to change. As a reminder, this call is being recorded and will remain available for 90 days.

雖然公司可能會選擇在未來的某個時候更新此類前瞻性陳述，但即使後續事件導致其用途發生變化，公司也沒有義務這樣做。提醒一下，此通話正在錄音中，並將保留 90 天。

I'd now like to turn the call over to Dr. David Zaccardelli, Chief Executive Officer.

我現在想把電話轉給首席執行官 David Zaccardelli 博士。

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。今天和我在一起的是我們的首席財務官 Mark Hahn；我們的首席醫療官 Kathy Rickard 博士；和我們的商務高級副總裁 Chris Martin。

2022 was a momentous year for Verona Pharma and first and foremost, for the millions of patients suffering from COPD. Supported by the groundbreaking results from our Phase III ENHANCE trials, we believe ensifentrine, if approved, has the potential to change the treatment paradigm for COPD. We are on track to submit a new drug application to the FDA in the second quarter of 2023. Over the past year, we announced positive top line results from our Phase III ENHANCE trials evaluating nebulized ensifentrine for the maintenance treatment of COPD in moderate to severe COPD patients. Ensifentrine successfully met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function as well as remarkable reduction in rate and risk of exacerbations. The success of these trials advances us closer to providing ensifentrine to a patient population in urgent need of new effective treatment options.

2022 年對於 Verona Pharma 來說是重要的一年，首先對於數百萬患有 COPD 的患者來說也是如此。在我們 III 期 ENHANCE 試驗的突破性結果的支持下，我們相信 ensifentrine 如果獲得批准，有可能改變 COPD 的治療模式。我們有望在 2023 年第二季度向 FDA 提交新藥申請。在過去的一年裡，我們宣布了 III 期 ENHANCE 試驗的積極頂線結果，該試驗評估霧化 ensifentrine 用於中度至重度 COPD 維持治療慢性阻塞性肺病患者。 Ensifentrine 成功地達到了 ENHANCE-1 和 ENHANCE-2 的主要終點，表明肺功能有統計學意義和臨床意義的改善，以及惡化率和風險的顯著降低。這些試驗的成功使我們更接近於為迫切需要新的有效治療方案的患者群體提供 ensifentrine。

Additionally, this strong clinical data allowed us to significantly strengthen our financial position through an upsized $150 million equity offering in August and a $150 million non-dilutive debt financing facility with Oxford Finance in October as well as through March 3, $58.6 million from ADS sales under our ATM program.

此外，這一強大的臨床數據使我們能夠通過 8 月份擴大的 1.5 億美元股權發行和 10 月份與 Oxford Finance 的 1.5 億美元非稀釋債務融資機制以及到 3 月 3 日從 ADS 銷售中獲得 5860 萬美元，從而顯著加強我們的財務狀況在我們的 ATM 計劃下。

With that said, let me take a step back and provide a brief review of our ENHANCE program. As a reminder, the ENHANCE-1 and ENHANCE-2 trials were each designed to enroll approximately 800 moderate to severe symptomatic COPD subjects for a total of approximately 1,600 subjects across sites, primarily in the United States and Europe. The trials replicated measurements of efficacy and safety over 24 weeks and ENHANCE-1 also evaluated longer-term safety in approximately 400 subjects over 48 weeks. Subjects received ensifentrine or placebo as either monotherapy or added on to a single long-acting bronchodilator with approximately 69% of subjects across ENHANCE-1 and 55% in ENHANCE-2 receiving either a LAMA, long-acting muscarinic antagonist or LABA, long-acting beta agonist. Additionally, approximately 20% of subjects in ENHANCE-1 and 15% in ENHANCE-2 received inhaled corticosteroids with concomitant LAMA or LABA.

話雖如此，讓我退後一步，簡要回顧一下我們的 ENHANCE 計劃。提醒一下，ENHANCE-1 和 ENHANCE-2 試驗均旨在招募約 800 名中度至重度症狀性 COPD 受試者，跨地點總共約 1,600 名受試者，主要在美國和歐洲。這些試驗在 24 週內重複了療效和安全性測量，ENHANCE-1 還在 48 週內評估了大約 400 名受試者的長期安全性。受試者接受 ensifentrine 或安慰劑作為單一療法或加入單一長效支氣管擴張劑，ENHANCE-1 中約 69% 的受試者和 ENHANCE-2 中 55% 的受試者接受長效毒蕈鹼拮抗劑 LAMA 或長效毒蕈鹼拮抗劑 LABA作用 β 激動劑。此外，ENHANCE-1 中大約 20% 的受試者和 ENHANCE-2 中大約 15% 的受試者接受吸入皮質類固醇並同時接受 LAMA 或 LABA。

As previously announced, both the ENHANCE-1 and ENHANCE-2 trials successfully met primary and key secondary endpoints, demonstrating statistically significant improvements in lung function. In addition, ensifentrine substantially improved symptoms and quality of life, as well as reducing the rate and risk of COPD exacerbations in both trials and was well tolerated over 24 and 48 weeks. Importantly, pooled exacerbation data from ENHANCE-1 and ENHANCE-2 demonstrated that ensifentrine treatment resulted in a statistically significant 40% reduction in the rate of COPD exacerbations compared with placebo over 24 weeks.

正如之前宣布的那樣，ENHANCE-1和 ENHANCE-2試驗均成功達到了主要和關鍵的次要終點，表明肺功能在統計學上有顯著改善。此外，ensifentrine 顯著改善了症狀和生活質量，並降低了兩項試驗中 COPD 惡化的發生率和風險，並且在 24 周和 48 週內耐受性良好。重要的是，來自 ENHANCE-1 和 ENHANCE-2 的合併加重數據表明，在 24 週內，與安慰劑相比，ensifentrine 治療可使 COPD 加重率降低 40%，具有統計學意義。

Further, ensifentrine significantly decreased the risk of an exacerbation as measured by time to first exacerbation when compared with placebo by 41%. Based on the study population, we believe this magnitude of reduction in exacerbation rate and risk is unprecedented in Phase III COPD trials and further validates the importance of ensifentrine's novel mechanism, delivering nonsteroidal anti-inflammatory activity in addition to bronchodilation for the treatment of patients with COPD.

此外，與安慰劑相比，ensifentrine 顯著降低了惡化的風險（以首次惡化的時間衡量），降低了 41%。基於研究人群，我們認為這種惡化率和風險的降低幅度在 III 期 COPD 試驗中是前所未有的，並進一步驗證了 ensifentrine 的新機制的重要性，除了支氣管擴張外，還提供非甾體類抗炎活性，用於治療慢性阻塞性肺病患者慢性阻塞性肺病。

I'd also like to reiterate the consistency of the positive results between ENHANCE-1 and ENHANCE-2 trials. The totality of the data from both studies, coupled with favorable safety profile of ensifentrine, support our belief that ensifentrine will change the treatment paradigm for COPD. With this positive data in hand, we plan to submit an NDA to the FDA in the second quarter of this year. In parallel, our pre-commercialization efforts and U.S. launch activities are proceeding as planned. Following our strong ENHANCE-2 data in August, we began filling key leadership positions across commercial, HR, IT and finance. We are accelerating our efforts as we prepare for NDA submission and beyond, and we are confident that we will be well positioned for a potential U.S. launch of ensifentrine in 2024.

我還想重申 ENHANCE-1 和 ENHANCE-2 試驗之間陽性結果的一致性。兩項研究的總體數據，加上 ensifentrine 良好的安全性，支持我們的信念，即 ensifentrine 將改變 COPD 的治療模式。有了這些積極的數據，我們計劃在今年第二季度向 FDA 提交 NDA。與此同時，我們的預商業化工作和美國發射活動正在按計劃進行。根據我們 8 月份強勁的 ENHANCE-2 數據，我們開始填補商業、人力資源、IT 和財務領域的關鍵領導職位。在準備提交 NDA 及以後的工作時，我們正在加快努力，我們有信心我們將做好準備，迎接 2024 年在美國可能推出的 ensifentrine。

Turning to our global partnering strategy. In 2022, Nuance Pharma received clearance from China's Center for Drug Evaluation to begin Phase I and Phase III studies of ensifentrine for COPD in China. As a reminder, Nuance Pharma is responsible for developing and commercializing ensifentrine in Greater China. And as such, they will play a key role in addressing the global need for a novel treatment for COPD. We look forward to providing further updates as these studies progress.

轉向我們的全球合作戰略。 2022 年，Nuance Pharma 獲得中國藥品審評中心的許可，在中國開始 ensifentrine 治療 COPD 的 I 期和 III 期研究。提醒一下，Nuance Pharma 負責在大中華區開發和商業化 ensifentrine。因此，它們將在滿足全球對 COPD 新療法的需求方面發揮關鍵作用。隨著這些研究的進展，我們期待提供進一步的更新。

Currently, more than 380 million patients suffer from COPD worldwide, and it is the third leading cause of death. Despite the availability of existing COPD treatments, approximately 50% of patients experience symptoms for more than 24 days per month, and physicians require new and effective COPD therapies to provide relief to their patients. With its novel mechanism of action as a selected PDE3 and PDE4 inhibitor, we believe ensifentrine, if approved, will be groundbreaking in the field of COPD management. We expect 2023 to be another pivotal year for Verona as we advance towards our mission of delivering ensifentrine to patients with COPD.

目前，全世界有超過 3.8 億患者患有 COPD，它是第三大死亡原因。儘管現有 COPD 治療可用，但大約 50% 的患者每月出現症狀超過 24 天，醫生需要新的有效的 COPD 療法來緩解他們的患者。憑藉其作為選定的 PDE3 和 PDE4 抑製劑的新穎作用機制，我們相信 ensifentrine 如果獲得批准，將在 COPD 管理領域取得突破性進展。我們預計 2023 年將成為維羅納的又一個關鍵年，因為我們正在朝著向 COPD 患者提供恩芬特林的使命前進。

I will now turn the call over to Mark to review our financial results for 2022.

我現在將電話轉給馬克審查我們 2022 年的財務業績。

Thank you, Dave. Good morning. We ended 2022 with $227.8 million in cash and equivalents. Starting in January, we ran the ATM program through last Friday, and during that time, we raised net proceeds of approximately $56.9 million. After giving effect to the proceeds from the ATM facility, our pro forma cash and equivalents at December 31, 2022, was $284.7 million. Between the cash currently on hand, the expected receipts from the U.K. tax credit program and funding expected to be available under the $150 million Oxford loan facility, we believe our cash runway will extend through at least the end of 2025, including the planned commercial launch of ensifentrine in the United States.

謝謝你，戴夫。早上好。到 2022 年底，我們擁有 2.278 億美元的現金和等價物。從 1 月開始，我們在上週五運行了 ATM 計劃，在此期間，我們籌集了大約 5690 萬美元的淨收益。在使 ATM 設施的收益生效後，我們在 2022 年 12 月 31 日的備考現金和等價物為 2.847 億美元。在目前手頭的現金、英國稅收抵免計劃的預期收入以及 1.5 億美元牛津貸款機制下預計可獲得的資金之間，我們相信我們的現金跑道將至少延續到 2025 年底，包括計劃中的商業啟動美國的 ensifentrine。

For the year ended December 31, 2022, the net loss after tax was $68.7 million compared to a net loss after tax of $55.6 million for the prior year. The loss in 2022 was higher primarily due to $40 million of nonrecurring revenue related to the Nuance agreement, which more than offset the higher R&D spend in 2021. This represents a loss of $0.13 per ordinary share or $1.04 per ADS for the year compared to a loss of $0.12 per ordinary share or $0.96 per ADS in 2021.

截至 2022 年 12 月 31 日止年度，稅後淨虧損為 6870 萬美元，上年稅後淨虧損為 5560 萬美元。 2022 年的虧損較高主要是由於與 Nuance 協議相關的 4000 萬美元非經常性收入，這足以抵消 2021 年較高的研發支出。與2021 年每股普通股虧損 0.12 美元或每股 ADS 虧損 0.96 美元。

Research and development costs were $49.3 million for the year ended December 31, 2022, compared to $79.4 million reported for the year 2021. The decrease was primarily due to lower clinical trials and other development costs of $27.9 million, resulting from the ENHANCE studies nearing completion in 2022 and a $4.2 million decrease in share-based compensation charges.

截至 2022 年 12 月 31 日止年度，研發成本為 4930 萬美元，而報告的 2021 年為 7940 萬美元。減少的主要原因是 ENHANCE 研究即將完成，導致臨床試驗和其他開發成本減少 2790 萬美元2022 年，基於股份的薪酬費用減少 420 萬美元。

Selling, general and administrative expenses were $26.6 million for the year ended December 31, 2022, compared to $33.9 million reported for the prior year. The decrease of $7.3 million was primarily due to lower share-based compensation charges.

截至 2022 年 12 月 31 日止年度，銷售、一般和管理費用為 2660 萬美元，而上年報告的費用為 3390 萬美元。減少 730 萬美元主要是由於基於股份的補償費用減少。

The U.K. R&D tax credit for 2022 was $9.6 million compared to a credit of $15.6 million for the year ended December 31, 2021. The decrease of $6 million is in line with our lower qualifying R&D expenditure incurred with the ENHANCE program in 2022.

英國 2022 年的研發稅收抵免額為 960 萬美元，而截至 2021 年 12 月 31 日止年度的抵免額為 1560 萬美元。減少 600 萬美元與我們在 2022 年通過 ENHANCE 計劃產生的合格研發支出相符。

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

我現在將把電話轉回接線員進行問答。

(Operator Instructions) Our first question will come from Andreas Argyrides with Wedbush Securities.

（操作員說明）我們的第一個問題將來自 Wedbush Securities 的 Andreas Argyrides。

Just 1 from us here. So Sunosi and Regeneron have guided to top line results from the Phase III study of DUPIXENT in moderate to severe COPD type 2 inflammation later this month. The KOLs we've spoken with have about a 20% reduction in exacerbations as being clinically meaningful, which is well below the 40% ensifentrine showed. So curious to get your thoughts on their readout and what impact positive data may have on the commercial landscape and ensifentrine's positioning in exacerbations.

我們這裡只有 1 個。因此，Sunosi 和 Regeneron 在本月晚些時候指導了 DUPIXENT 治療中度至重度 COPD 2 型炎症的 III 期研究的頂級結果。與我們交談過的 KOL 將急性加重減少了約 20%，這具有臨床意義，遠低於 ensifentrine 顯示的 40%。很想知道你對他們的讀數有什麼看法，以及積極數據可能對商業前景和 ensifentrine 在惡化中的定位產生什麼影響。

Andreas, thanks for the question. I'm going to ask Kathy to give her perspective as a pulmonologist on DUPIXENT and its impact. Overall, I think that we are intrigued by the study. But I think we need to keep in mind that patient population is much more limited than that we address with ensifentrine and so we don't really see a big impact. But Kathy, you may want to comment on it?

安德烈亞斯，謝謝你的提問。我將請 Kathy 作為一名肺科醫生對 DUPIXENT 及其影響給出她的觀點。總的來說，我認為我們對這項研究很感興趣。但我認為我們需要記住，患者人數比我們使用 ensifentrine 解決的人數要有限得多，因此我們並沒有真正看到很大的影響。但是凱西，你可能想對此發表評論？

Sure. So as Dave said, the population would be different because this would be a much smaller population of COPD patients. In general, they're looking for patients who have high eosinophils and so forth and without actually having a protocol in front of you, I can't tell you all the differences. But then generally, they're looking at a niche area (inaudible) affects patients for that. And certainly 20% might be good in that population since they're usually taking a whole bunch of other medications also. But what's remarkable about ensifentrine is that we have about 40% in a total COPD population. So it doesn't matter whether you have high eosinophils or not or whether you have (inaudible) or not, whether you're on inhaled steroids or not. We see this remarkable decrease in exacerbations in a general COPD population. So I think that's what makes the difference between ensifentrine and looking at a compound like DUPIXENT.

當然。正如戴夫所說，人口會有所不同，因為這將是一個小得多的慢性阻塞性肺病患者群體。總的來說，他們正在尋找嗜酸性粒細胞高等的患者，而且在您面前沒有實際的方案，我無法告訴您所有差異。但一般來說，他們正在尋找一個利基區域（聽不清）影響患者。當然，20% 對那個人群來說可能是好的，因為他們通常還服用一大堆其他藥物。但是 ensifentrine 的非凡之處在於我們在 COPD 總人口中有大約 40%。因此，無論您是否有高嗜酸性粒細胞，或者您是否有（聽不清），無論您是否服用吸入類固醇，都無關緊要。我們看到一般 COPD 人群的急性加重顯著減少。所以我認為這就是 ensifentrine 和研究像 DUPIXENT 這樣的化合物之間的區別。

And would -- just a quick follow-up there. Would positive data, I'm assuming DUPIXENT maybe on the market, would that impact any pricing, especially given the benefit that ensifentrine has shown in exacerbations compared to DUPIXENT?

並且會 - 只是在那裡快速跟進。積極的數據，我假設 DUPIXENT 可能在市場上，會影響任何定價，特別是考慮到與 DUPIXENT 相比，ensifentrine 在惡化中顯示出的好處？

I don't know, Chris, do you want to comment in general on where we are with pricing?

我不知道，克里斯，你想對我們的定價進行一般性評論嗎？

Yes, I can do that. Andreas, I think when we think about pricing with ensifentrine, we've used the current nebulized products as kind of a baseline floor for ensifentrine, those products by the time we launch will be somewhere around $1,400 a month. One of the things that we realize and you just mentioned there, the results on exacerbations are very impactful, not only to the physician community but to the payer community. And when we've talked to payers to date within Medicare Part D, Medicare Advantage, they expect ensifentrine to be priced at a premium versus those current products. I think some of the other dynamics that we have in play as we think about pricing or the impact of the Inflation Reduction Act, and that legislation on how we might price ensifentrine going into the market.

是的，我能做到。安德烈亞斯，我認為當我們考慮使用 ensifentrine 定價時，我們使用當前的霧化產品作為 ensifentrine 的基線底線，這些產品在我們推出時將在每月 1,400 美元左右。我們意識到的一件事，你剛剛在那裡提到，惡化的結果非常有影響，不僅對醫生社區而且對付款人社區。當我們與 Medicare D 部分（即 Medicare Advantage）中的付款人交談時，他們預計 ensifentrine 的定價將高於目前的產品。我認為在我們考慮定價或《降低通脹法案》的影響時，我們還有其他一些動態在起作用，以及關於我們如何為進入市場的 ensifentrine 定價的立法。

But the important thing here is that the profile of ensifentrine, which provides bronchodilation, improvements in symptoms and the marketable market results on exacerbation, provide a lot of price flexibility for us as we think about what that value would be as we get to launch. So I think we feel very confident that ensifentrine's value is great within the marketplace. And we also feel like from a payer perspective, the receptivity to pricing ensifentrine at a premium versus the current products is a very positive reception as well.

但這裡重要的是，ensifentrine 的概況提供支氣管擴張、症狀改善和惡化的可銷售市場結果，為我們提供了很大的價格靈活性，因為我們考慮了我們開始推出時的價值。所以我認為我們對 ensifentrine 的市場價值非常有信心。我們還覺得，從付款人的角度來看，與當前產品相比，對 ensifentrine 溢價定價的接受度也是一種非常積極的接受度。

Okay. Great. Congrats with all the progress. Thanks.

好的。偉大的。祝賀所有的進步。謝謝。

Thanks, Andreas.

謝謝，安德烈亞斯。

Our next question will come from Joon Lee with Truist Securities.

我們的下一個問題將來自 Truist Securities 的 Joon Lee。

This is [Asim] on for Joon. First question is about the NDA. Just wondering how the NDA process is going. And then just also wondering what's the rate limiting step to getting a European partner on board, your strategy for your European regulatory process and sort of that nature?

這是 Joon 的 [Asim]。第一個問題是關於 NDA。只是想知道 NDA 流程進行得如何。然後還想知道讓歐洲合作夥伴加入的限速步驟是什麼，您的歐洲監管流程策略以及類似的性質？

Sure. Thanks so much for the question. The NDA is progressing very well. And as we guided, we're tracking to have a submission in the second quarter. All the components to it are coming together, not only, of course, the clinical, which is always important. And in this case, it was one of the rate-limiting steps, but also, of course, the CMC, the nonclinical and other aspects of the NDA. So we're very pleased where we're at with it and looking forward to that submission.

當然。非常感謝你的問題。 NDA 進展順利。正如我們所指導的那樣，我們正在跟踪在第二季度提交一份報告。它的所有組成部分都聚集在一起，當然，不僅僅是臨床，這總是很重要。在這種情況下，它是限速步驟之一，當然還有 CMC、NDA 的非臨床和其他方面。因此，我們對目前的進展感到非常高興，並期待著提交。

As far as partnering goes, our strategy remains the same in that we are looking to partner ensifentrine outside the United States. As you know, we have done that already in Greater China with Nuance Pharma. These conversations are all different, as partners are different. Their needs are different, their size, their scope, et cetera. And so some of these timing, we can't control other than sticking with our strategy, which we're very confident in. And so I expect partnering to be a focus of 2023, as I've mentioned before. And we look forward to updating everyone as we have more to report on our partnering but it is definitely our articulated strategy.

就合作而言，我們的戰略保持不變，因為我們希望在美國以外的地區與 ensifentrine 合作。如您所知，我們已經通過 Nuance Pharma 在大中華區做到了這一點。這些對話都是不同的，因為合作夥伴是不同的。他們的需求不同，大小、範圍等等。因此，除了堅持我們非常有信心的戰略之外，我們無法控制其中一些時間。因此，正如我之前提到的，我預計合作將成為 2023 年的重點。我們期待更新每個人，因為我們有更多關於我們合作的報告，但這絕對是我們明確的戰略。

Our next question will come from Tom Shrader with BTIG.

我們的下一個問題將來自 BTIG 的 Tom Shrader。

Some general questions. Do you expect to launch on approval? Do you expect that will be your level of preparedness? And then for Chris, can you give us a sense of what a good payer acceptance ramp would look like in this area? We're a little less experienced. What should you have in terms of, I would say, at a year or something like that? And then also, what do you expect for the co-pay to be for this drug?

一些一般性問題。您希望在獲得批准後啟動嗎？您預計這將是您的準備水平嗎？然後對於克里斯，你能告訴我們在這個領域一個好的付款人接受斜坡是什麼樣子的嗎？我們經驗少了點。我想說，在一年或類似的時間裡，你應該擁有什麼？然後，您期望這種藥物的共付額是多少？

Chris, do you want to go ahead and take those?

克里斯，你想繼續拿走那些嗎？

Yes. Tom, I'll start on launch on approval. Across the organization, we've been working a very comprehensive launch readiness plan that involves not only the commercial department but as Dave mentioned in his talk, other departments to support commercial as we get ready for launch, including CMC, finance, and that plan is progressing very well.

是的。湯姆，我會在批准後開始發布。在整個組織中，我們一直在製定一個非常全面的啟動準備計劃，不僅涉及商業部門，而且正如 Dave 在他的演講中提到的那樣，其他部門在我們準備啟動時支持商業，包括 CMC、財務和該計劃進展順利。

We -- our plan is to launch as soon as possible after approval. It is a important point that once we get approval, we will have to get product into the channel, that does take a couple of weeks. And then we also will be hiring reps at the time of approval. We're not going to bring reps on before approval. So there will be training. But our plan is to launch as quickly after approval as possible. And the organization is working toward those plans, and we're in a very good shape to launch as quickly as possible after approval.

我們——我們的計劃是在獲得批准後儘快啟動。重要的一點是，一旦我們獲得批准，我們就必須將產品引入渠道，這確實需要幾週的時間。然後我們也將在批准時招聘代表。在獲得批准之前，我們不會聘請代表。所以會有培訓。但我們的計劃是在獲得批准後儘快啟動。該組織正在朝著這些計劃努力，我們的狀態非常好，可以在獲得批准後儘快啟動。

As far as your second question on payer acceptance, I think it's really important to think about ensifentrine differently than what you typically see with launches today because launches today typically launch within Medicare Part D, as in dog or commercial. And those payer channels tend to have very tight restrictions for new products at launch. Ensifentrine's primary reimbursement channel is Medicare Part B, as in boy. And we know within Medicare Part B that our access will be available at launch for physicians.

至於你關於付款人接受的第二個問題，我認為以不同於你今天通常看到的發射方式來考慮 ensifentrine 真的很重要，因為今天的發射通常在 Medicare D 部分內發射，就像在狗或商業中一樣。而這些付費渠道往往在新產品發佈時有非常嚴格的限制。 Ensifentrine 的主要報銷渠道是 Medicare B 部分，就像男孩一樣。我們知道在 Medicare B 部分中，我們的訪問權限將在啟動時提供給醫生。

And we can see that with what will happen with YUPELRI. YUPELRI had very high access and acceptance rates at launch, with YUPELRI in that channel, and that caused the product to be able to be used by the physicians. There are some important steps that we have to go through within the Medicare Part B channel. But those are things that we're working on today. Those include ensuring that we're covered under existing coverage policies, which we believe that will be the case with ensifentrine.

我們可以看到 YUPELRI 會發生什麼。 YUPELRI 在發佈時具有非常高的訪問率和接受率，YUPELRI 在該渠道中，這使得該產品能夠被醫生使用。我們必須在 Medicare B 部分渠道中完成一些重要步驟。但這些是我們今天正在努力的事情。其中包括確保我們受到現有保險政策的保護，我們相信 ensifentrine 就是這種情況。

We also are establishing and getting our paperwork ready for a product-specific J-code. That J-code submission will go in immediately upon approval. And then we should expect to get that product-specific J-code within 3 to 6 months. In the meantime, you use the existing nonspecific J-code to get coverage and get payment to the pharmacies. So we feel very, very confident that ensifentrine coverage and overall ability to be used by the physicians is going to be high at launch and high throughout the first year.

我們還正在為特定於產品的 J 代碼建立並準備好我們的文書工作。該 J 代碼提交將在獲得批准後立即進行。然後我們應該期望在 3 到 6 個月內獲得特定於產品的 J 代碼。同時，您可以使用現有的非特定 J 代碼來獲得保險並向藥房付款。因此，我們感到非常、非常有信心，醫生使用 ensifentrine 的覆蓋率和整體能力將在發佈時和整個第一年都很高。

The other side of that story is what you discussed there, is what are copays for patients. And when we look at the Medicare Part B channel and Medicare in general, what we see for the nebulized products over the last year is that 80% of these patients are paying less than $10 for their prescriptions of branded nebulized products. This is a extremely attractive proposition for physicians. So not only do they get access, but they have low out-of-pocket costs. So I think those dynamics allow us to be very excited about how we anticipate the uptake for ensifentrine to be when we launch in 2024.

這個故事的另一面就是您在那裡討論的內容，即患者的共付額。當我們查看 Medicare B 部分渠道和一般 Medicare 時，我們看到去年霧化產品的情況是，這些患者中有 80% 為品牌霧化產品的處方支付的費用不到 10 美元。這對醫生來說是一個極具吸引力的提議。因此，他們不僅可以獲得訪問權限，而且自付費用也很低。因此，我認為這些動態讓我們對 ensifentrine 在 2024 年推出時的預期吸收情況感到非常興奮。

And maybe just 1 quick clarification. You can talk to payers before approval? Or does everything start at approval?

也許只是 1 快速澄清。您可以在批准前與付款人交談嗎？還是一切都從批准開始？

We can have early discussions with payers before approval. Some of that is about the disease state and their needs, but we can have early discussions with payers as we move through the process.

我們可以在批准之前與付款人進行早期討論。其中一些是關於疾病狀態和他們的需求，但我們可以在整個過程中與付款人進行早期討論。

Our next question will come from Boobalan Pachaiyappan with H.C. Wainwright.

我們的下一個問題將來自 Boobalan Pachaiyappan 和 H.C.溫賴特。

This is Boobalan. Can you hear me okay?

這是布巴蘭。你能聽到我說話嗎？

Yes, perfectly.

是的，完美。

All right, right. So 3 from us. So firstly, can you speak to how efficiently ensifentrine can be manufactured and expected COGS related to traditional LAMA and LABA therapeutics?

好的，好的。所以我們有 3 個。那麼首先，您能否談談與傳統 LAMA 和 LABA 療法相關的 ensifentrine 的生產效率和預期的 COGS？

Sure, I'll make a general statement and Mark can comment on COGS, ensifentrine is a small molecule and its manufacturing has been very well sorted over the years. We believe we have an extremely efficient manufacturing process for the drug substance or API. The drug product is manufactured in the (inaudible) seal into plastic ampoules. Again, a process that's very well described, and we're very comfortable with the scale that has occurred. And I think the cost is, again, in line with other products that are manufactured in the same way.

當然，我會做一個一般性的陳述，Mark 可以評論 COGS，ensifentrine 是一種小分子，多年來它的製造已經很好地分類了。我們相信我們擁有極其高效的原料藥或 API 製造工藝。該藥物產品在（聽不清）密封中製成塑料安瓿瓶。同樣，一個描述得很好的過程，我們對已經發生的規模感到非常滿意。而且我認為成本再次與以相同方式製造的其他產品一致。

I don't know, Mark, do you want to comment?

我不知道，馬克，你想發表評論嗎？

Yes. I'll just echo your comments, Dave, that it is a small molecule. So the cost of manufacturing, those are generally fairly consistent across compounds. And I think the way you should expect or think about COGS is low single-digit percentage of sales, at least for manufacturing COGS.

是的。我只是回應你的評論，戴夫，它是一個小分子。因此，製造成本在化合物之間通常相當一致。而且我認為您應該期望或考慮 COGS 的方式是銷售額的低個位數百分比，至少對於製造 COGS 而言。

All right. Great. What will be the role of combination versus monotherapy for ensifentrine in your estimation?

好的。偉大的。在您的估計中，聯合療法與單一療法對 ensifentrine 的作用是什麼？

Well, I think, to make sure I understand the question. Are you asking how often we would see it in combination? Or maybe you can clarify your question specifically?

好吧，我想，以確保我理解這個問題。你是在問我們多久會看到它的組合？或者也許你可以具體澄清你的問題？

Yes. With respect to combination.

是的。關於組合。

Yes. Well, I think that -- as we saw in the trial, ensifentrine has been used and can be used as monotherapy, as well as we studied in combination with LAMA and LABA. I think it works in all these settings and even in addition to ICS. So we're very comfortable with ensifentrine's use along the complete treatment paradigm in COPD. And that's why I mentioned in my remarks that because of its effect both in efficacy and safety and overall benefit to risk, we think ensifentrine is going to change exactly how COPD is treated, where you're going to see ensifentrine utilized earlier in the treatment paradigm.

是的。好吧，我認為——正如我們在試驗中看到的那樣，ensifentrine 已經被使用並且可以用作單一療法，我們還結合 LAMA 和 LABA 進行了研究。我認為它適用於所有這些設置，甚至適用於 ICS。因此，我們對 ensifentrine 在 COPD 完整治療範例中的使用感到非常滿意。這就是為什麼我在我的評論中提到，由於它在有效性和安全性以及整體風險收益方面的影響，我們認為 ensifentrine 將完全改變 COPD 的治療方式，您將在治療早期看到 ensifentrine範例。

And we think avoiding ICS is always a positive attribute especially in those patients who don't require ICS. And in addition, those that are on triple therapy who have really limited to no other choices, ensifentrine, again, with its benefit to risk can play a role in helping those patients. And so we see it used a little everywhere, again in some of the -- in the treatment paradigm.

我們認為避免 ICS 始終是一個積極的屬性，尤其是對於那些不需要 ICS 的患者。此外，那些接受三聯療法的人實際上別無選擇，ensifentrine 再次以其對風險的好處可以在幫助這些患者方面發揮作用。所以我們看到它在任何地方都有一點使用，再次在一些 - 在治療範例中。

One final question from me. So given your substantial cash balance and recent success of the ensifentrine program, can you talk about the strategic vision for the company over the next 3 to 5 years?

我的最後一個問題。因此，鑑於您的大量現金餘額和最近 ensifentrine 計劃的成功，您能談談公司未來 3 到 5 年的戰略願景嗎？

Yes, sure. Very good question. Clearly, as we've been focused over the past 2, 3 years, execution on ensifentrine for COPD has been critical and will continue to be so. So in the short term, of course, we have an NDA in the medium term. We're looking for approval and launch in the COPD space. As I mentioned, that's going to be groundbreaking in the field of COPD, and we look forward to helping millions of patients with ensifentrine in that space, specifically in the U.S. but also throughout the world.

是的，當然。很好的問題。顯然，正如我們在過去 2、3 年中一直關注的那樣，執行 ensifentrine 治療 COPD 至關重要，並將繼續如此。所以在短期內，當然，我們在中期有一個保密協議。我們正在尋求批准並在 COPD 領域推出。正如我所提到的，這將是 COPD 領域的突破性進展，我們期待著在該領域幫助數百萬使用 ensifentrine 的患者，特別是在美國乃至全世界。

And I think that's an incredible opportunity over the coming years. In addition to that, we have mentioned previously, we are moving forward and in the early stages of a combination product development of a LAMA plus ensifentrine, which we think makes incredible amount of sense. We know the field is set up for combination therapy as well, and we look forward to updating everybody on the progress of that.

我認為這是未來幾年難得的機會。除此之外，我們之前提到過，我們正在推進 LAMA 加 ensifentrine 的組合產品開發的早期階段，我們認為這具有不可思議的意義。我們知道該領域也為聯合治療而設立，我們期待著向大家介紹這方面的最新進展。

In addition, of course, ensifentrine has a lot of opportunity in other respiratory diseases, asthma, for example, cystic fibrosis, possibly IPF and so there are a lot of opportunities for us to explore. We are looking to our partnership strategy with regard to these other indications because they will probably include other delivery devices, MDI or DPI. We think leveraging a partner's experience or own proprietary devices makes a lot of sense. And so we look forward to expanding into these other indications via a partnership primarily while we continue to create the value for Verona Pharma through ensifentrine and COPD in the nebulized route, and as I mentioned, through the combination product development.

另外，當然ensifentrine在其他呼吸系統疾病方面還有很多機會，比如哮喘，比如說囊腫性纖維化，可能還有IPF等等，有很多機會可以讓我們去探索。我們正在尋找關於這些其他適應症的合作夥伴戰略，因為它們可能包括其他輸送設備、MDI 或 DPI。我們認為利用合作夥伴的經驗或自己的專有設備非常有意義。因此，我們期待主要通過合作夥伴關係擴展到這些其他適應症，同時我們繼續通過霧化途徑中的 ensifentrine 和 COPD 為 Verona Pharma 創造價值，正如我提到的，通過組合產品開發。

All right. Congrats.

好的。恭喜。

Thanks so much.

非常感謝。

Our next question will come from Yasmeen Rahimi with Piper Sandler.

我們的下一個問題將來自 Yasmeen Rahimi 和 Piper Sandler。

This is Lauren on for Yas. Just a few questions. The first, based on physician feedback at the moment, which patients would they want to put on ensifentrine? And then second, have payers commented at all about the potential of ensifentrine to reduce overall COPD health care utilization? Or is the focus more narrow in short term?

這是亞斯的勞倫。只是幾個問題。首先，根據目前醫生的反饋，他們希望哪些患者使用 ensifentrine？其次，付款人是否對 ensifentrine 降低整體 COPD 醫療保健利用率的潛力發表了評論？還是短期關注面更窄？

Chris, do you want to take down those 2?

克里斯，你想幹掉那兩個嗎？

Yes, I can do that. Lauren, thanks for the question. I think when we think about physician feedback and the market research, which we've done, which is very extensive, I think in the past year, we've talked to well over 200 physicians, both pulmonologists, primary care physicians, but also nurse practitioners and PAs. And the thing that they continue to reiterate to us is this idea that ensifentrine, as Dave talked about, can be used very broadly across the treatment paradigm.

是的，我能做到。勞倫，謝謝你的提問。我想當我們考慮醫生的反饋和我們所做的非常廣泛的市場研究時，我想在過去的一年裡，我們已經與 200 多名醫生進行了交談，包括肺科醫生、初級保健醫生，還有執業護士和 PA。他們繼續向我們重申的是，正如 Dave 所說，ensifentrine 可以非常廣泛地用於治療範式。

They reiterate to us that if we look at patients that are -- they have today in their practice, many of them remain symptomatic and at risk for exacerbations. And the addition of a new mechanism to these patients is something they haven't been able to do in 14 plus -- 14 to 20 years. So this gives them ability to do something very different. So if we think about how many patients are treated today, we know there's about 8.5 million treated patients. We also know that there's about 6 million of those patients on what you would consider the ENHANCE trial population, which is either LAMA or LABA or LABA/ICS patients.

他們向我們重申，如果我們看看那些——他們今天在實踐中的患者，他們中的許多人仍然有症狀並且有惡化的風險。為這些患者增加一種新機制是他們在 14 年多——14 到 20 年裡無法做到的事情。所以這讓他們有能力做一些非常不同的事情。因此，如果我們考慮一下今天有多少患者接受治療，我們就會知道大約有 850 萬接受治療的患者。我們還知道，在您認為的 ENHANCE 試驗人群中，大約有 600 萬患者是 LAMA 或 LABA 或 LABA / ICS 患者。

And in those patients, you see physicians adding ensifentrine on at a very high rate. The other group of patients are what Dave described earlier, which are these patients on dual bronchodilator or triple therapy, where the physicians have no options, and we know these patients are still symptomatic.

在這些患者中，您會看到醫生以非常高的速度添加 ensifentrine。另一組患者是 Dave 之前描述的，這些患者接受雙重支氣管擴張劑或三聯療法，醫生別無選擇，我們知道這些患者仍有症狀。

And in those patients, the physicians look at ensifentrine as an add-on as well at a very high rate in those patients because it gives them the ability to layer on an additional mechanism to the patient that could provide them this early and sustained response on bronchodilation symptoms and then the risk and rate of exacerbation. So we feel very confidently based on the market research and our interactions with KOLs that ensifentrine will be used broadly across the patient population and really change the treatment paradigm that is occurring within COPD today.

在這些患者中，醫生們將 ensifentrine 視為一種附加藥物，並且在這些患者中的比例非常高，因為它使他們能夠為患者提供一種額外的機制，從而為他們提供這種早期和持續的反應支氣管擴張症狀，然後是惡化的風險和速度。因此，根據市場研究和我們與 KOL 的互動，我們非常有信心地認為 ensifentrine 將在患者群體中廣泛使用，並真正改變當今 COPD 中發生的治療模式。

I think your second question was around payers and health care utilization. I think that's -- when we go back to a question earlier, which is around pricing, one of the reasons why the payers are believing ensifentrine would be priced at a premium versus the current products is because of that benefit that ensifentrine has on exacerbations and potentially overall health care utilization within their plans.

我認為你的第二個問題是關於付款人和醫療保健利用的。我認為那是——當我們回到之前關於定價的問題時，付款人認為 ensifentrine 的定價會比當前產品高的原因之一是因為 ensifentrine 對惡化和惡化有好處在他們的計劃中潛在的整體醫療保健利用。

We know that COPD is a high burden to the payer in the system. I think there's -- at the last data check, over $50 billion worth of indirect or direct costs are associated with COPD and complications of COPD. So the ability for ensifentrine to reduce the rate and risk of exacerbations and help improve patient symptoms and lung function is a very attractive benefit. So they're not looking at it just as a short term, but they're also looking at those implications long term, as they think about how to cover it and what they would accept as a price for ensifentrine as well.

我們知道 COPD 在系統中對付款人來說是一個沉重的負擔。我認為——在最後一次數據檢查中，超過 500 億美元的間接或直接成本與 COPD 和 COPD 並發症有關。因此，ensifentrine 能夠降低惡化的速度和風險並幫助改善患者症狀和肺功能，這是一個非常有吸引力的好處。因此，他們不僅在短期內看待它，而且還在長期看待這些影響，因為他們考慮如何覆蓋它以及他們接受的 ensifentrine 價格。

It appears there are no further questions. This concludes our question-and-answer session. I'd like to turn the conference back over to David Zaccardelli for any closing remarks.

看來沒有進一步的問題了。我們的問答環節到此結束。我想將會議轉回給 David Zaccardelli 作任何閉幕詞。

Great. Thank you, everyone, for your questions, and thank you to the patients and health care professionals who participated in ENHANCE program. We are attending several upcoming conferences, including Jefferies Biotech on the Bay Summit and ATS and look forward to speaking to many of you then. As a reminder, our near-term milestones include submitting our NDA to the FDA in the second quarter and continuing preparations for our planned U.S. commercial launch of ensifentrine.

偉大的。感謝大家提出問題，也感謝參與 ENHANCE 計劃的患者和醫護人員。我們將參加幾個即將舉行的會議，包括 Jefferies Biotech on the Bay Summit 和 ATS，期待屆時與你們中的許多人交談。提醒一下，我們近期的里程碑包括在第二季度向 FDA 提交我們的 NDA 以及繼續準備我們計劃在美國商業推出的 ensifentrine。

Finally, I'd like to thank our shareholders for their continued support and the dedicated and talented team at Verona for their commitment. Operator, that concludes today's call.

最後，我要感謝我們的股東一直以來的支持，以及維羅納敬業且才華橫溢的團隊的承諾。接線員，今天的電話會議到此結束。

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

會議現已結束。感謝您參加今天的演講。您現在可以斷開連接。