Achieve Life Sciences Inc (ACHV) 2024 Q2 法說會逐字稿

Greetings, and welcome to the Achieve Life Sciences second quarter 2024 earnings conference call and webcast. (Operator Instructions)

您好，歡迎參加 Achieve Life Sciences 2024 年第二季財報電話會議和網路廣播。（操作員說明）

I would now turn the call over to Nicole Jones, Investor Relations. Thank you, Nicole. You may begin.

我現在將把電話轉給投資者關係部的 Nicole Jones。謝謝你，妮可。你可以開始了。

Thank you, operator. Good afternoon, everyone, and thank you for joining us today.

謝謝你，接線生。大家下午好，感謝您今天加入我們。

From Achieve Life Sciences, we are joined by John Bencich, Chief Executive Officer; Dr. Cindy Jacobs, President and Chief Medical Officer; and Jerry Wan, Principal Accounting Officer. Management will be available for Q&A session following today's prepared remarks.

執行長 John Bencich 也加入了 Achieve Life Sciences 的行列；辛蒂‧雅各布斯博士，總裁兼首席醫療官；和首席會計官 Jerry Wan。在今天準備好的發言之後，管理階層將參加問答環節。

Before we begin, I'd like to remind everyone that today's conference call contains forward-looking statements based on current expectations. These statements are only predictions, and actual results may vary materially from those projected. Please refer to Achieve's documents available on our website, and filed with the SEC concerning factors that could affect the company.

在開始之前，我想提醒大家，今天的電話會議包含基於當前預期的前瞻性陳述。這些陳述僅是預測，實際結果可能與預測有重大差異。請參閱我們網站上提供的、並向 SEC 提交的有關可能影響公司的因素的文件。

I'll now turn the call over to John.

我現在將把電話轉給約翰。

Thank you, Nicole, and thanks, everyone, for joining us.

謝謝你，妮可，也謝謝大家加入我們。

We are excited to provide an update today on the tremendous progress we have made on the cytisinicline development program from both the clinical and regulatory fronts. In recent weeks, several key accomplishments have provided excellent momentum for furthering our mission of bringing cytisinicline to the millions of people who are battling nicotine dependence. Furthermore, we are pleased with the recent refinancing, which will propel us towards our first NDA submission for smoking cessation, which remains on track for filing in the first half of 2025.

我們很高興今天提供有關我們在金雀花鹼開發計劃上從臨床和監管方面取得的巨大進展的最新資訊。最近幾週，幾項關鍵成就為進一步推進我們的使命提供了良好的動力，即為數百萬正在與尼古丁依賴作鬥爭的人提供金雀花鹼。此外，我們對最近的再融資感到高興，這將推動我們提交第一份戒菸新藥申請，該申請仍有望在 2025 年上半年提交。

We'll go through each of our achievements in more detail, but briefly, in the last few months, we have received FDA breakthrough therapy designation for cytisinicline for treating e-cigarette or vaping nicotine dependence. We initiated and gained significant traction on the ORCA-OL trial evaluating the long-term safety effects of cytisinicline. We were added to the US Russell 3000 and Russell Microcap Indexes, and we refinanced our outstanding debt agreement with SVB. We are very pleased with this progress, and the support we are receiving from the scientific, regulatory and financial communities, that are setting up cytisinicline for great success.

我們將更詳細地介紹我們的每一項成就，但簡單地說，在過去的幾個月裡，我們獲得了FDA 對金雀花鹼的突破性療法指定，用於治療電子煙或電子煙尼古丁依賴。我們發起了 ORCA-OL 試驗，評估金雀花鹼的長期安全性效果，並獲得了重大關注。我們被納入美國羅素 3000 指數和羅素微型股指數，並且我們為與 SVB 的未償債務協議進行了再融資。我們對這項進展以及科學界、監管界和金融界的支持感到非常高興，金雀花鹼的研發取得了巨大成功。

I'll now turn it over to Cindy, who will give an update on recent regulatory and clinical advances. Cindy?

我現在將其交給 Cindy，她將提供最新監管和臨床進展的最新資訊。辛蒂？

Thank you, John.

謝謝你，約翰。

Recently in July, we were very pleased to have FDA grant cytisinicline Breakthrough Therapy designation for the vaping cessation indication. Breakthrough Therapy designation is important because it offers access to an FDA cross-disciplinary project management team for interactive communications with senior managers and reviewers at FDA. This will be beneficial in completing the regulatory requirements necessary for expanding cytisinicline treatment, as the first approved pharmacotherapy in treating nicotine dependence for e-cigarettes cessation, not only in adults, but also possibly for an adolescent vaping population.

最近七月，我們非常高興 FDA 授予金雀花鹼突破性療法稱號用於戒菸適應症。突破性療法認定非常重要，因為它提供了與 FDA 跨學科計畫管理團隊的接觸機會，以便與 FDA 的高階主管和審查人員進行互動溝通。這將有利於完成擴大金雀花鹼治療所需的監管要求，金雀花鹼是第一個批准的治療電子菸戒菸依賴的藥物療法，不僅適用於成人，也可能適用於青少年電子煙人群。

The public heightened issues surrounding the increasing e-cigarette use in young adults and adolescents justifies the need for urgent action towards a solution. Breakthrough Therapy designation will help to accelerate our proposed clinical program with more active FDA input.

公眾日益關注的圍繞年輕人和青少年電子煙使用日益增加的問題表明，有必要採取緊急行動尋求解決方案。突破性療法認定將有助於透過 FDA 更積極的投入來加速我們擬議的臨床計劃。

Although there is a general understanding that using e-cigarettes is safer, alternative to smoking, combustible cigarettes, this has led to the perception that e-cigarettes or vaping nicotine is safe, resulting in a new, younger generation becoming addicted to nicotine. The developing body of scientific and medical evidence is now showing that long-term e-cigarette use can be harmful, and may lead to more severe addiction, due to the high nicotine levels in vapes. Long-term e-cigarette use may also contribute to potential lung injury, asthma, COPD and negative cardiovascular effects.

儘管人們普遍認為使用電子煙比吸煙、可燃香煙更安全，但這導致人們認為電子煙或電子煙尼古丁是安全的，導致新一代年輕一代對尼古丁上癮。不斷發展的科學和醫學證據表明，長期使用電子煙可能有害，並且由於電子煙中的尼古丁含量較高，可能會導致更嚴重的成癮。長期使用電子煙也可能導致潛在的肺損傷、氣喘、慢性阻塞性肺病和心血管不良影響。

At the annual March meeting of the Society for Research on Nicotine and Tobacco, guidance from experts in the field was presented based on Project VECTOR, which stands for Vaping and Electronic Cigarette Toxicity Overview and Recommendation. Several recommendations were presented, which included, people who do not smoke should not use nicotine e-cigarettes, and people who use e-cigarettes should avoid long-term use of e-cigarettes. These recommendations were based on reducing long-term respiratory injury, adverse effects on the cardiovascular system and exposure to cancer-causing chemicals in vaping aerosols, as well as preventing sustained nicotine dependence.

在尼古丁和菸草研究學會三月的年度會議上，該領域的專家根據 VECTOR 計畫提出了指導，VECTOR 計畫代表電子煙和電子煙毒性概述和建議。提出了幾項建議，其中包括不吸煙的人不應使用含有尼古丁的電子煙，使用電子煙的人應避免長期使用電子煙。這些建議是基於減少長期呼吸傷害、對心血管系統的不利影響和接觸電子煙氣溶膠中的致癌化學物質，以及防止持續的尼古丁依賴。

Breakthrough Therapy was developed to expedite the clinical development of products that treat serious conditions, which there is an unmet need, and when there is preliminary evidence demonstrating potential benefit. Our justification was that long-term vaping may lead to serious conditions, that there are no approved treatments to assist people in quitting and that the positive results we observed in our ORCA-V1 trial, showed the potential benefit of cytisinicline in this setting. These criteria were all instrumental in granting us Breakthrough status. We've already submitted a request for a Type B meeting with FDA that will start interactions with their cross-disciplinary project management team and will also serve as an end of Phase II meeting for gaining agreement on the development plans for vaping cessation indication.

突破性療法的開發是為了加快治療嚴重疾病的產品的臨床開發，這些疾病的需求尚未得到滿足，並且有初步證據表明潛在的益處。我們的理由是，長期吸電子煙可能會導致嚴重的病症，沒有批准的治療方法可以幫助人們戒菸，而且我們在ORCA-V1 試驗中觀察到的積極結果表明金雀花鹼在這種情況下的潛在益處。這些標準都有助於我們獲得突破性地位。我們已經向 FDA 提交了召開 B 類會議的請求，該會議將開始與他們的跨學科專案管理團隊進行互動，並將作為第二階段會議的結束，以就戒菸指示的開發計劃達成一致。

Moving on to our lead indication smoking cessation and the status of the long-term cytisinicline exposure trial. In May, we initiated the open-label ORCA-OL trial, which is collecting long-term exposure data on cytisinicline. ORCA-OL is recruiting subjects for -- who participated in our previous Phase II and Phase III trials. We are pleased to report that all 29 clinical sites are actively enrolling subjects. Enrollment has been going very well and more than half of the proposed 650 participants have already been enrolled onto the study. Over the next few months, we will be monitoring the treatment discontinuation rate which is currently very low.

接下來討論我們主要的適應症戒菸和長期金雀花鹼暴露試驗的狀態。5 月份，我們啟動了開放標籤 ORCA-OL 試驗，該試驗正在收集金雀花鹼的長期暴露數據。ORCA-OL 正在招募參加我們先前的 II 期和 III 期試驗的受試者。我們很高興地報告，所有 29 個臨床中心都在積極招募受試者。招募工作進展順利，擬議的 650 名參與者中超過一半已經註冊參加研究。在接下來的幾個月中，我們將監測目前非常低的治療中斷率。

The enrollment objective is to ensure that we achieve the required 300 subjects exposed for 6 months at NDA submission, providing that subject retention rates continue to remain high. We anticipate possibly closing out enrollment in advance of the 650 enrollment-cap, possibly within the next 2 months.

註冊目標是確保我們在提交 NDA 時達到 300 名受試者暴露 6 個月的要求，前提是受試者保留率繼續保持較高水準。我們預計可能會在未來 2 個月內，在 650 名註冊人數上限之前結束註冊。

As a reminder, the primary analysis for this study will be to evaluate the rate of serious adverse events thought to be related to cytisinicline treatment. And we have engaged the same independent Data Safety Monitoring Committee who had oversight of ORCA-2, ORCA-3 and ORCA-V1 studies to oversee and review safety events during this open-label study. We plan to provide general summary updates following the completion of this committee's safety reviews with the first meeting expected to occur in the fourth quarter, and subsequent meetings to be determined by the committee members thereafter.

提醒一下，本研究的主要分析將是評估被認為與金雀花鹼治療相關的嚴重不良事件的發生率。我們還聘請了負責監督 ORCA-2、ORCA-3 和 ORCA-V1 研究的獨立資料安全監測委員會來監督和審查這項開放標籤研究期間的安全事件。我們計劃在該委員會的安全審查完成後提供一般摘要更新，第一次會議預計將在第四季度舉行，隨後的會議將由委員會成員決定。

Based on our agreement with FDA, the necessary clinical data from ORCA-OL remains on track to support an NDA submission during the first half of 2025. As we continue our monitoring of subjects being treated in the open-label study and their exposure timing, we can further refine our guidance in the future on the NDA submission timing. Overall, I'm very pleased with the rapid progress we have made both in the clinic and with regulators since our last update.

根據我們與 FDA 的協議，ORCA-OL 的必要臨床數據仍有望在 2025 年上半年提交 NDA。隨著我們繼續監測開放標籤研究中接受治療的受試者及其暴露時間，我們可以在未來進一步完善新藥申請提交時間的指導。總體而言，自上次更新以來，我對我們在診所和監管機構方面取得的快速進展感到非常滿意。

I'll now turn it back over to John.

我現在將其轉回給約翰。

Thanks, Cindy.

謝謝，辛蒂。

Turning now to the financial updates. We recently completed a $20 million debt refinancing with Silicon Valley Bank, that refinanced our existing debt facility and extended the maturity date from August 1, 2024, to December 1, 2027. This refinancing continues our partnership with SVB, and further solidifies their confidence in Achieve and the cytisinicline program. The refinancing also lowers our cost of capital, extends our cash runway and provides access to additional capital as cytisinicline moves through the regulatory approval process with FDA.

現在轉向財務更新。我們最近與矽谷銀行完成了 2,000 萬美元的債務再融資，為我們現有的債務融資進行了再融資，並將到期日從 2024 年 8 月 1 日延長至 2027 年 12 月 1 日。這次再融資延續了我們與 SVB 的合作關係，並進一步鞏固了他們對 Achieve 和金雀花素計劃的信心。再融資也降低了我們的資本成本，擴大了我們的現金跑道，並隨著金雀花鹼透過 FDA 的監管審批流程提供了獲得額外資本的機會。

I'll now hand the call over to Jerry for additional financial updates. Jerry?

我現在將把電話轉給傑里以獲取更多財務更新。傑瑞？

Thank you, John. Good afternoon, everyone.

謝謝你，約翰。大家下午好。

As John mentioned, we successfully entered into a debt refinancing agreement with SVB that provides for up to $20 million in availability. Under the terms of this new agreement, the $20 million term loan is divided into three tranches. The first tranche of $10 million was received at closing, the second tranche of $5 million will be available upon FDA acceptance of the new drug application for cytisinicline, and the final $5 million tranche will be available subject to SVB's discretion and credit committee approval.

正如 John 所提到的，我們成功與 SVB 簽訂了債務再融資協議，提供高達 2000 萬美元的可用資金。根據這項新協議的條款，2000萬美元的定期貸款分為三個部分。交易完成時已收到第一筆 1000 萬美元，第二筆 500 萬美元將在 FDA 接受金雀花鹼新藥申請後提供，最後一筆 500 萬美元將在 SVB 酌情決定和信用委員會批准後提供。

The outstanding principal will accrue interest at a floating rate per annum equal to the greater of 7%, as the prime rate minus 1%. The loan facility includes an interest-only period through December 31, 2025, followed by 24 monthly payments of principal plus interest to the maturity date of December 1, 2027. Upon achieving certain regulatory and financial milestones, there is an option for a six-month extension to the interest-only period and maturity date.

未償還本金將以每年 7% 的浮動利率計息，即優惠利率減去 1%。該貸款安排包括截至2025年12月31日的只付息期，隨後按24個月支付本金加利息，直至2027年12月1日到期日。在實現某些監管和財務里程碑後，可以選擇將只還息期和到期日延長六個月。

Furthermore, the initial outstanding debt, including principal and accrued interest, subject to certain terms and limitations can be converted into Achieve's common stock at SVB's discretion before repayment at a conversion price of $7 per share. Subsequent tranches may be converted based on a 150% premium to Achieve's stock closing price at that time with a minimum price of $4.85 per share. Importantly, while the loan is outstanding, SVB cannot short sell or hedge Achieve stock. We can repay and retire all outstanding convertible debt at any time before conversion, by paying a premium, based on the repayment date.

此外，初始未償債務，包括本金和應計利息，在遵守某些條款和限制的情況下，SVB 可自行決定將其轉換為Achieve 的普通股，然後以每股7 美元的轉換價格償還。隨後的部分可能會根據當時Achieve股票收盤價150%的溢價進行轉換，最低價格為每股4.85美元。重要的是，當貸款未償還時，SVB 不能賣空或對沖 Achieve 股票。我們可以在轉換前的任何時間透過根據還款日期支付溢價來償還和償還所有未償還的可轉換債務。

Let's now turn to the second quarter financials. As of June 30, 2024, the company's cash, cash equivalents, restricted cash and short-term investments were $61.3 million as compared to $66.4 million from the prior quarter. We believe our current cash balance is sufficient to provide us runway into the second half of 2025. The company incurred a net loss of $8.5 million for the quarter ended June 30, 2024, as compared to a net loss of $8.2 million for the same quarter in the prior year. Net loss for the six months ended June 30, 2024, decreased to $15 million, as compared to $17.2 million for the same period in 2023. We expect our quarterly operating expenses will increase, as we progress forward with the ORCA-OL trial.

現在讓我們來看看第二季的財務狀況。截至 2024 年 6 月 30 日，該公司的現金、現金等價物、限制性現金和短期投資為 6,130 萬美元，而上一季為 6,640 萬美元。我們相信我們目前的現金餘額足以為我們提供進入 2025 年下半年的跑道。該公司截至 2024 年 6 月 30 日的季度淨虧損 850 萬美元，而上年同期淨虧損 820 萬美元。截至 2024 年 6 月 30 日的六個月淨虧損減少至 1,500 萬美元，而 2023 年同期為 1,720 萬美元。隨著 ORCA-OL 試驗的進展，我們預計季度營運費用將會增加。

I'll now turn the call back over to John.

我現在將把電話轉回給約翰。

Thank you, Jerry.

謝謝你，傑瑞。

Smoking remains the leading cause of preventable death, killing over 8 million people globally each year, including nearly 0.5 million in the US. Smoking is recognized as a major cause of various cancers, respiratory disease, lung injury, cardiovascular disease, Type 2 diabetes and dementia. We believe that cytisinicline can help address the root cause of these disorders and have an impact through disease reduction.

吸菸仍然是可預防死亡的主要原因，每年在全球造成超過 800 萬人死亡，其中美國有近 50 萬人死亡。吸煙被認為是導致各種癌症、呼吸道疾病、肺損傷、心血管疾病、2 型糖尿病和癡呆症的主要原因。我們相信金雀花鹼可以幫助解決這些疾病的根本原因，並透過減少疾病產生影響。

Focusing on COPD as an example, according to the CDC, approximately 80% of COPD is caused by smoking and 38% of the 16 million US adults with COPD currently smoke. If we are able to help patients with COPD quit smoking, there is potential to significantly reduce the number and severity of exacerbations, and in the long term, potentially reduce the number of COPD patients.

以慢性阻塞性肺病為例，據美國疾病管制與預防中心(CDC) 稱，約80% 的慢性阻塞性肺病是由吸菸引起的，目前美國1,600 萬名患有慢性阻塞性肺病的成年人中，有38% 吸煙。如果我們能夠幫助慢性阻塞性肺病患者戒菸，就有可能顯著減少病情加重的數量和嚴重程度，從長遠來看，有可能減少慢性阻塞性肺病患者的數量。

In addition, vaping continues to be an emerging health crisis with an estimated 11 million adults and 2 million middle and high school students using e-cigarettes in the US. The long-term health effects from inhalation of vape products that are heavily unregulated is of utmost concern. These statistics highlight the urgent need for effective cessation treatments, especially since no new products have been FDA approved in nearly 20 years.

此外，電子煙仍然是一種新興的健康危機，在美國估計有 1,100 萬成年人和 200 萬中學生使用電子煙。吸入嚴重不受監管的電子煙產品對健康的長期影響是最令人擔憂的。這些統計數據凸顯了對有效戒菸治療的迫切需要，特別是因為近 20 年來沒有任何新產品獲得 FDA 批准。

There are no FDA-approved treatments for e-cigarettes cessation and concern is growing as evidence emerges on their long-term use. Cytisinicline has the potential to be a first-in-class treatment to address the unique challenges of quitting vaping. Currently, there are more nicotine products available than any time in history, which has been fueled by continued innovation in ways to deliver nicotine to consumers. This includes the increasingly popular flavored nicotine products like ZYN, which has seen triple-digit growth in recent years. Regardless of the nicotine delivery mechanism, we believe cytisinicline can play a critical role in addressing this health crisis and achieving better long-term outcomes for patients.

目前還沒有 FDA 批准的戒菸治療方法，隨著長期使用電子煙的證據出現，人們的擔憂與日俱增。Cytisinicline 有潛力成為解決戒菸獨特挑戰的一流治療方法。目前，可用的尼古丁產品比歷史上任何時候都多，這得益於向消費者提供尼古丁的方式的不斷創新。其中包括日益流行的調味尼古丁產品，如 ZYN，近年來實現了三位數的成長。無論尼古丁傳遞機制如何，我們相信金雀花鹼可以在解決這個健康危機和為患者實現更好的長期結果方面發揮關鍵作用。

We've had a great first half of 2024 and expect the momentum to carry forward as we look to our objectives for the remainder of the year. We are now focused on closing out enrollment and continuing our focus on monitoring of subjects in the ORCA-OL trial, continuing preparations for the NDA submission, which remains on track for the first half of 2025, and conducting the end of Phase II meeting with FDA for the vaping cessation indication.

我們度過了 2024 年上半年的美好時光，並期望在我們實現今年剩餘時間的目標時繼續保持這一勢頭。我們現在的重點是結束招募並繼續關注 ORCA-OL 試驗中受試者的監測，繼續準備新藥申請（NDA 提交），該申請將在 2025 年上半年按計劃進行，並與FDA 的戒菸指徵。

The support that we expect to receive from FDA having a Breakthrough status, should further de-risk the program and expedite our ability to move through the regulatory approval process. We look forward to providing further updates on the vaping program after our end of Phase II meeting with the agency has been conducted.

我們期望從具有突破性地位的 FDA 獲得的支持應該會進一步降低該計劃的風險，並加快我們通過監管審批流程的能力。我們期待在與該機構的第二階段會議結束後提供有關電子煙計劃的進一步更新。

In closing, we are excited about what lies ahead for the company in the coming months. We greatly appreciate the dedication of our trial participants and health care providers and the continued support of our shareholders. We remain committed to advancing our mission and in our belief of cytisinicline's potential to help millions of people overcome nicotine dependence. In parallel, we believe strongly that we can create shareholder value by bringing to market the first, new FDA-approved nicotine dependence product in nearly 2 decades, with the potential to become the market leader and generate substantial revenues.

最後，我們對公司未來幾個月的前景感到興奮。我們非常感謝試驗參與者和醫療保健提供者的奉獻以及股東的持續支持。我們仍然致力於推進我們的使命，並相信金雀花鹼有潛力幫助數百萬人克服尼古丁依賴。同時，我們堅信，透過將近 20 年來首個經 FDA 批准的新型尼古丁依賴產品推向市場，我們可以創造股東價值，並有潛力成為市場領導者並產生可觀的收入。

Thank you for joining us today. We look forward to continuing our progress, and we will now open the line for questions.

感謝您今天加入我們。我們期待繼續取得進展，現在我們將開通提問熱線。

(Operator Instructions) Thomas Flaten, Lake Street Capital.

（操作員說明）Thomas Flaten，Lake Street Capital。

Good afternoon, everybody. Congrats on all the progress. Cindy, a couple of questions for you. You mentioned the retention rate in your prepared comments, I was wondering if you could share with us what that is? And then also, can I infer from your comments around potentially ending enrollment sooner that -- enrollment pace is accelerating?

大家下午好。祝賀所有的進步。辛迪，有幾個問題想問你。您在準備好的評論中提到了保留率，我想知道您能否與我們分享一下那是什麼？另外，我能否從您關於可能提前結束入學的評論中推斷出——入學速度正在加快？

Well, the enrollment actually started off in an accelerated manner, and we don't give exact numbers, but given that we have over half of the intended 650, kind of tells you how well that enrollment has gone over the last couple of months. Our most important thing now is looking at the discontinuation rate. And if the discontinuation rate remains low and it's like single digits, then we're looking at how many subjects we really need to enroll to get then 300 at six months and 100 at one year? We certainly don't need 500 to 600 subjects at six months and one year. So that's where we're looking at when do we then, look at closing enrollment early to basically save cost on the trial.

嗯，註冊實際上是以一種加速的方式開始的，我們沒有給出確切的數字，但考慮到我們已經完成了預定 650 名的一半以上，這可以告訴你過去幾個月註冊的進展。我們現在最重要的是專注於停藥率。如果停藥率仍然很低並且就像個位數，那麼我們就會考慮我們真正需要註冊多少科目才能在六個月內達到 300 門，在一年內達到 100 門？我們當然不需要六個月和一年的 500 到 600 個受試者。因此，這就是我們要考慮的問題，我們什麼時候考慮儘早結束註冊，以基本上節省試驗成本。

Got it. And then once you have the 300 patients with six months of data, are there any other gating items that we should be thinking about, as it relates to completing the NDA package? Or is that pretty much set and you're waiting to staple [this kind of to the] back of it?

知道了。然後，一旦您獲得了 300 名患者的六個月數據，我們是否應該考慮任何其他門控項目，因為它與完成 NDA 套件有關？或者已經準備好了，你正在等待將[這種]釘在它的背面？

That is the last piece for the [ClinRegs] for the NDA. I mean obviously, once you get to six months, you have to monitor all the data, collect it, lock the database, write it up. So, there is that period of time. But then you see, then or kind of thread the results of that long exposure into the ISS documents that will be ready and waiting for that last piece of information for the NDA.

這是 NDA [ClinRegs] 的最後一部分。我的意思顯然是，一旦到了六個月，你就必須監視所有數據，收集數據，鎖定資料庫，然後將其寫入。所以，就有那麼一段時間。但你會看到，然後或者有點將長期暴露的結果串入國際太空站文件中，這些文件將準備好並等待 NDA 的最後一條訊息。

Justin Walsh, JonesTrading.

賈斯汀·沃爾什，瓊斯交易公司。

Can you expand on the potential advantages of having vaping cessations specifically on your label versus broader labels focused more generally on nicotine?

您能否詳細闡述專門在您的標籤上明確戒菸與更普遍關注尼古丁的更廣泛標籤相比的潛在優勢？

Yes. Thanks for the question, Justin. So, with respect to the labeling, I think the core indication will be smoking cessation for nicotine dependence, and there can certainly be some off-label usage in other forms of nicotine addiction. But I think with respect to vaping in particular, we think it would be very powerful to be able to promote directly to e-cigarette users, given the size of that market. We look at smoking overall, here in the US, there's approximately 28 million adult smokers. And the vaping indication is now 11 million and growing. So, it is a very, very large segment. And I think, to be able to promote as the first and likely only treatment there, we think, would be very powerful.

是的。謝謝你的提問，賈斯汀。因此，就標籤而言，我認為核心指示是尼古丁依賴的戒菸，並且在其他形式的尼古丁成癮中肯定可能存在一些標籤外使用。但我認為，特別是在電子煙方面，考慮到市場的規模，我們認為能夠直接向電子煙使用者推廣將是非常強大的。我們從整體來看吸菸情況，在美國，大約有 2,800 萬名成年吸菸者。目前電子煙的使用量已達 1,100 萬，而且還在持續增加中。所以，這是一個非常非常大的部分。我認為，能夠在那裡推廣作為第一種也可能是唯一的治療方法，我們認為，這將是非常強大的。

Great. And a quick follow-up. I don't know how much you can actually say, but I was wondering if there's any color you can provide on potential discussion points leading into your end of Phase II meeting with the FDA?

偉大的。並快速跟進。我不知道你實際上能說多少，但我想知道你是否可以就與 FDA 的第二階段會議結束時的潛在討論點提供任何資訊？

Do you want me to take that, John?

約翰，你想讓我接受嗎？

Yes, Cindy.

是的，辛迪。

Yes. So, for the end of Phase II meeting, we'll have a list of questions. It will all be based that, we have smoking cessation as our first indication. The biggest one will be that we only need one Phase III because of the Phase II is a supporting trial. And there'll be other discussions, as far as, what do we need and any additional safety data because we'll have all the long-term exposure from this open-label study that should be appropriate for the vaping cessation as well as the smoking cessation indication. So, we'll get some good clarity and agreement on what is required. So, there's no surprises, and we can actually then advance to that supplemental NDA faster.

是的。因此，在第二階段會議結束時，我們將列出一份問題清單。這一切都基於我們將戒菸作為我們的第一個適應症。最大的一個是我們只需要一個第三階段，因為第二階段是一個支持性試驗。就我們需要什麼和任何額外的安全數據而言，還會有其他討論，因為我們將從這項開放標籤研究中獲得所有長期暴露，這些數據應該適合戒菸以及使用電子煙。因此，我們將就所需內容達成一定的明確性並達成一致。因此，這並不奇怪，我們實際上可以更快地推進補充 NDA。

[Frank Brisebois, Oppenheimer].

[弗蘭克·布里斯博伊斯，奧本海默]。

[Dan] on for Frank. Thanks for taking questions. Just quickly one regarding the open label ORCA, we know this is a safety trial, but will you be looking at any efficacy in this trial? Is there anything from an efficacy perspective that you could get from this trial potentially for labeling purposes? Any thoughts there?

[丹] 代表弗蘭克。感謝您提出問題。關於開放標籤 ORCA，我們知道這是一項安全性試驗，但您會關注該試驗的任何功效嗎？從功效角度來看，您是否可以從該試驗中獲得任何可能用於標籤目的的資訊？有什麼想法嗎？

Yes, we will be looking at efficacy, especially for retreatment of individuals that have already been treated with cytisinicline as well as individuals that were originally on the placebo seeing it for the first time. FDA definitely views this as a primary safety study. So I'm not sure, because it's not a randomized study that we're going to get any of that in the label, but certainly, we will be publishing it and we are collecting efficacy.

是的，我們將研究療效，特別是對於已經接受過金雀花鹼治療的個體以及最初使用安慰劑的個體的再治療。FDA 明確認為這是一項主要的安全性研究。所以我不確定，因為這不是一項隨機研究，我們將在標籤中獲得任何這些內容，但當然，我們將發布它並且我們正在收集功效。

John Vandermosten, Zacks.

約翰范德莫斯坦，扎克斯。

Wanted to ask what your screening success rate is for the OL trial. And then also on that same theme, have you been able to enroll out of the 12-week cytisinicline exposure patients and enroll a bunch of those? Or has it been pretty even between, I guess, the patients that were in the placebo, the 6-week?

想問一下你們的 OL 試驗篩選成功率是多少。然後，同樣的主題，您是否能夠從 12 週金雀花鹼暴露患者中招募並招募一批這樣的患者？或者我猜，服用安慰劑（六週）的患者之間的情況是否相當均勻？

Sure. I mean, the one nice thing is the screen fail rate. We look at screen fail. The screen fail rate has been half or even lower than what we normally see, which we kind of hopefully expected, because most of these individuals had already screened through, and were on the previous ORCA studies. So, we had hoped the screen fail rate would be low, which it is.

當然。我的意思是，一件好事是螢幕故障率。我們看看螢幕故障。篩檢失敗率比我們通常看到的低一半甚至更低，這也是我們所希望的，因為這些人中的大多數已經通過篩檢，並且參加了先前的 ORCA 研究。所以，我們本來希望螢幕故障率會很低，事實也確實如此。

Interesting, all of the Phase III and even the Phase II vaping study, two-thirds of the individuals had already been treated with cytisinicline. So it's the same sort of two-thirds of the individuals on the open label have already been treated with cytisinicline coming in. So we are getting some placebos, which is great, because then that means we have more subjects overall treated with cytisinicline. And then we also have those coming in that helps us get to the six months and one year sooner.

有趣的是，在所有的 III 期甚至 II 期電子煙研究中，三分之二的人已經接受過金雀花鹼治療。因此，開放標籤上的三分之二的個體已經接受過金雀花鹼治療。所以我們得到了一些安慰劑，這很好，因為這意味著我們有更多的受試者總體上接受金雀花鹼治療。然後我們也有一些進來，幫助我們提前六個月和一年。

Okay. Great. And when we look at the Breakthrough Therapy designation that was granted, and you kind of look the way that could help you. I mean, I guess, I could put it three ways where, it might accelerate the trial pace, reduce the cost or increase the likelihood of ultimate approval there. In those three areas, what do you see as the biggest help from this FDA program?

好的。偉大的。當我們看到所授予的突破性療法稱號時，您會想到可以幫助您的方法。我的意思是，我想，我可以用三種方式來表達，它可能會加快試驗速度，降低成本或增加最終批准的可能性。在這三個領域，您認為 FDA 計劃的最大幫助是什麼？

I think both right now, quicker agreement to what the Phase III clinical trial will look like. And then once that we're getting through that trial, then negotiating a rolling submission, and then obviously, upon having it being submitted to priority review. So, it's kind of taking time off through all aspects of the development.

我認為現在雙方都可以更快地就 III 期臨床試驗的情況達成一致。然後，一旦我們通過了該試驗，然後就滾動提交進行談判，然後顯然，將其提交給優先審查。因此，在開發的各個方面都需要花費一些時間。

Great. And last question, it's still on the vaping theme. You had some money coming in from the grants. Have we received that all yet? Or are there still funds that are going to be offsetting some of your expenses in the future? How does it look on that side of things?

偉大的。最後一個問題，仍然是電子煙主題。你從補助金中得到了一些錢。我們已經收到全部了嗎？或者還有資金可以抵銷你未來的一些開銷嗎？事情的這一面看起來怎麼樣？

Yes. On the grant side of things, the vaping Phase II trial, which is where the grant was directed previously. We have received all the funding related to that. So that's now complete, but we'll continue to look for future opportunities, in particular, given the strong support we've received from NIH and NIDA historically.

是的。在資助方面，電子煙第二階段試驗，這是先前資助的方向。我們已收到與此相關的所有資金。現在已經完成了，但我們將繼續尋找未來的機會，特別是考慮到我們歷來獲得 NIH 和 NIDA 的大力支持。

[Michael Higgins, Ladenburg Thalmann].

[邁克爾希金斯，拉登堡塔爾曼]。

This is [Farhana] on behalf of Michael. Congratulations from us on our progress this quarter. So, one question from us. Last week, JAMA published a series of papers on vaping and following the recent Breakthrough Therapy designation. Are you hearing any activities from the FDA, the NIH or any other government agencies that may support your development in the vaping indication?

我是代表麥可的[Farhana]。我們對本季取得的進展表示祝賀。那麼，我們有一個問題。上週，《美國醫學會雜誌》發表了一系列關於電子煙和最近突破性療法稱號的論文。您是否聽說 FDA、NIH 或任何其他政府機構可能支持您在電子煙適應症方面的發展？

Yes. Thanks for the question, [Farhana]. We're continuing to track all the activities going on across the spectrum in particular with respective vaping in particular. So, we do expect more support on that front. I think the biggest piece that we're looking to here in the near term would be through the Breakthrough designation, now that we have that in place with FDA, and then as i just mentioned previously, continuing to look to see if there's additional support we might be able to garner from NIH and NIDA. I think those are the two most critical areas.

是的。謝謝你的提問，[法爾哈納]。我們將繼續追蹤整個範圍內發生的所有活動，特別是各自的電子煙活動。因此，我們確實期望在這方面獲得更多支持。我認為我們近期最重要的目標是透過突破性指定，現在我們已經與 FDA 合作，然後正如我之前提到的，繼續尋找是否有額外的支持我們也許可以從 NIH 和 NIDA 獲得。我認為這是兩個最關鍵的領域。

And I think when you look across the overall landscape of what's being done in terms of other existing smoking cessation products being studied across the vaping indication. There really isn't too much happening in that space. So, we think driving this program forward quickly can really move the needle in a category that has no approved products currently.

我認為，當你縱觀整個電子煙適應症研究的其他現有戒菸產品的整體情況時。那個空間裡確實沒有發生太多事情。因此，我們認為快速推進該計劃確實可以在目前尚無批准產品的類別中取得進展。

Ilya Zubkov, Freedom Broker.

伊利亞·祖布科夫，自由掮客。

My first question is on the ORCA-OL trial. So, given the swift recruitment of trial participants, do you plan to publish any interim results from the trial this year?

我的第一個問題是關於 ORCA-OL 試驗的。那麼，考慮到試驗參與者的迅速招募，您今年是否計劃公佈試驗的中期結果？

Published? No. When we go and have and complete our Data Safety Monitoring Committee, we will at least give an update, as far as where we are with the safety monitoring in general. But right now, not publishing it.

已發表？不。當我們成立並完成資料安全監控委員會時，我們至少會提供最新的信息，以了解我們在安全監控方面的整體情況。但現在，還沒有發布。

Okay, thank you. And I have another one on the anticipated e-cigarettes trial. I know that it is difficult to discuss the details before meeting with the FDA. But as the higher [risk of vaping] for adolescents was mentioned, are you considering targeting this population in e-cigarettes study as well?

好的，謝謝。我還有另一篇關於預期的電子煙試驗的文章。我知道在與 FDA 會面之前很難討論細節。但正如所提到的，青少年[吸電子煙的風險]較高，您是否也考慮在電子煙研究中針對這一人群？

Yes, but more in a post-marketing kind of arena. So, the most important thing for us is to complete a Phase III for vaping cessation in young adults. But like our other studies, young adults we define as 18 years and older. So, we will have younger adults and looking at that as well for a future potential adolescent program.

是的，但更多的是在售後領域。因此，對我們來說最重要的是完成年輕人戒菸的第三階段。但與我們的其他研究一樣，我們將年輕人定義為 18 歲及以上。因此，我們將吸引年輕人，並為未來潛在的青少年計劃考慮這一點。

Thomas Flaten, Lake Street Capital.

托馬斯‧弗拉頓（Thomas Flaten），湖街資本公司。

John or Cindy, I just wanted to confirm. So, assuming you have a good end of Phase II meeting with FDA around the end of the year, what would be your intentions be with respect to actually starting a study? Would that be done under your own account? Or would you anticipate working with a partner on that? And what would the timing be? I'm just thinking from a modeling perspective more than anything right now.

約翰還是辛迪，我只是想確認一下。那麼，假設您在今年年底左右與 FDA 的 II 期會議圓滿結束，那麼您對於實際開始一項研究的意圖是什麼？會在您自己的帳戶下完成嗎？或者您預計會與合作夥伴就此展開合作嗎？時機是什麼？我現在只是從建模的角度思考。

Yeah. Thanks for the question, Thomas. I think on -- next steps on the vaping program, I think the most important piece is getting through the end of Phase II meeting, really understanding what's required going forward and seeing what sort of support we might be able to garner from FDA to accelerate that. I think with respect to starting a new trial, it's really probably more middle of next year at the earliest. The focus is going to continue to be getting that NDA on file first half of 2025 and driving the core indication forward to approval.

是的。謝謝你的提問，托馬斯。我認為，關於電子煙計劃的下一步，我認為最重要的是完成第二階段會議的結束，真正了解未來需要什麼，並看看我們能夠從 FDA 獲得什麼樣的支持來加速。我認為就開始新的試驗而言，最早可能要等到明年中旬。重點將繼續是在 2025 年上半年提交 NDA，並推動核心適應症獲得批准。

Thank you. At this time, we have reached the end of the question-and-answer session.

謝謝。此時，我們的問答環節已經結束了。

Now, I'd like to turn the call back over to the management team for any closing comments.

現在，我想將電話轉回管理團隊以徵求結束意見。

Thanks again, everyone, for joining us today. We look forward to providing additional updates as we progress through the balance of this year and drive the program forward towards NDA submission in the first half of 2025.

再次感謝大家今天加入我們。我們期待在今年剩餘的時間內提供更多更新，並推動該計劃在 2025 年上半年提交 NDA。

So again, appreciate the continued support, and have a great afternoon.

再次感謝您的持續支持，並祝您有個愉快的下午。

And ladies and gentlemen, that does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

女士們、先生們，今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與。