Achieve Life Sciences Inc (ACHV) 2025 Q3 法說會逐字稿

Greetings, and welcome to the Achieve Life Sciences third quarter 2025 earnings conference call and webcast. (Operator Instructions) As a reminder, this conference is being recorded.

各位好，歡迎參加 Achieve Life Sciences 2025 年第三季財報電話會議和網路直播。（操作說明）提醒各位，本次會議正在錄音。

I would now like to turn the call over to Nicole Jones, Achieve's Vice President, Strategic Communications and Stakeholder Relations. Thank you. You may begin.

現在，我想把電話交給 Achieve 的策略傳播和利害關係人關係副總裁 Nicole Jones。謝謝。你可以開始了。

Thank you, operator. Good morning, everyone, and thank you for joining us today. From Achieve Life Sciences, we are joined by Rick Stewart, Chief Executive Officer; Dr. Mark Rubenstein, Interim Chief Medical Officer; Jamie Xinos, Chief Commercial Officer; and Mark Oki, Chief Financial Officer. The management team will be available for Q&A following the prepared remarks. A replay will be available later today using the information in the earnings press release or by visiting the Achieve Life Sciences website.

謝謝接線生。各位早安，感謝大家今天收看我們的節目。來自 Achieve Life Sciences 的有：首席執行官 Rick Stewart；臨時首席醫療官 Mark Rubenstein 博士；首席商務官 Jamie Xinos；以及首席財務官 Mark Oki。管理團隊將在發言結束後接受提問。今天晚些時候，您可以透過財報新聞稿中的資訊或造訪 Achieve Life Sciences 網站觀看重播。

Today's conference call will contain certain forward-looking statements, including statements regarding the goals, strategies, beliefs, expectations and future potential operating results of Achieve. Although management believes these statements are reasonable based on estimates, assumptions and projections as of today, these statements are not guarantees of future performance.

今天的電話會議將包含一些前瞻性陳述，包括有關 Achieve 的目標、策略、信念、預期和未來潛在營運績效的陳述。儘管管理層認為這些聲明是基於目前的估計、假設和預測而做出的合理陳述，但這些聲明並不能保證未來的表現。

Time-sensitive information may no longer be accurate at the time of any telephonic or webcast replay. Actual results may differ materially as a result of risks, uncertainties and other factors, including, but not limited to, the factors set forth in the company's filings with the SEC. Achieve undertakes no obligation to update or revise any of these forward-looking statements. Please refer to Achieve documents available on our website and filed with the SEC concerning factors that could affect the company. I'll now turn the call over to Rick.

電話或網路直播重播時，時效性資訊可能已不再準確。由於風險、不確定性和其他因素，實際結果可能與預期有重大差異，包括但不限於公司向美國證券交易委員會提交的文件中列出的因素。Achieve不承擔更新或修改任何前瞻性聲明的義務。有關可能影響公司的因素，請參閱我們網站上提供的 Achieve 文件以及向美國證券交易委員會提交的文件。現在我將把電話交給里克。

Thank you, Nicole, and good morning, everyone. This has been another truly significant quarter for Achieve in our mission to get a new treatment for nicotine dependence into the hands of patients. Our priorities of NDA submission, NDA acceptance and ultimately NDA approval for cytisinicline as a treatment for nicotine dependence in smoking cessation have advanced significantly this quarter.

謝謝你，妮可，大家早安。對 Achieve 而言，這又是一個意義非凡的季度，我們在將治療尼古丁依賴的新療法送到患者手中的使命中取得了重大進展。本季度，我們關於向戒菸者提交 NDA、接受 NDA 以及最終批准 cytisinicline 作為尼古丁依賴治療藥物的 NDA 申請的優先事項取得了顯著進展。

These priorities have now been reinforced by the recent announcement that the FDA has awarded Achieve a Commissioner's National Priority Voucher or CNPV for the e-cigarette or vaping indication. This is a significant recognition of the importance of cytisinicline in addressing the emerging public health crisis caused by vaping.

最近，FDA宣布授予Achieve公司電子煙或霧化適應症的專員國家優先券（CNPV），這進一步強化了這些優先事項。這充分體現了對細胞毒素在應對電子煙引發的新興公共衛生危機方面的重要性的認可。

The CMPV is designed to provide enhanced FDA communications and an expedited NDA review time line, reducing the potential NDA approval to 1 to 2 months from a standard 10 to 12 months. The implications are enormous for patients and physicians and are significantly value enhancing for our stockholders.

CMPV 旨在加強與 FDA 的溝通，加快 NDA 審查時間，將 NDA 的潛在批准時間從標準的 10 至 12 個月縮短至 1 至 2 個月。這對患者和醫生來說意義重大，並且能顯著提升我們股東的價值。

A rapid approval of the vaping indication means cytisinicline could be launched eight months earlier than expected. This would allow Achieve to potentially pioneer the first and only FDA-approved treatment for the 60% of people who want to quit vaping.

電子煙適應症的快速核准意味著細胞毒素可能比預期提早八個月上市。這將使 Achieve 有可能率先推出首個也是唯一獲得 FDA 批准的治療方法，幫助 60% 想要戒除電子煙的人。

During the quarter, we hit several regulatory milestones related to our smoking cessation indication. Most notably, the FDA acceptance of our new drug application for cytisinicline for review and set a PDUFA or approval date of the June 20, 2026. Additionally, we submitted the 120-day safety review to the FDA on time. All interactions with the FDA remain normal and timely.

本季度，我們在戒菸適應症方面取得了多項監管里程碑式的進展。最值得注意的是，FDA 已接受我們關於細胞毒素的新藥申請，並設定了 PDUFA 或批准日期為 2026 年 6 月 20 日。此外，我們按時向FDA提交了120天安全審查報告。與FDA的所有互動均保持正常和及時。

To put our progress into perspective, nearly 29 million adults in the United States smoke cigarettes and more than 15 million people attempt to quit every year. Smoking remains the leading cause of preventable death in the US. Approximately 0.5 million deaths annually are attributable directly to smoking, costing over $600 billion each year in smoking-related US health care costs and lost productivity.

為了更清楚地了解我們所取得的進展，美國有近 2,900 萬成年人吸煙，每年有超過 1500 萬人嘗試戒菸。吸菸仍然是美國可預防死亡的首要原因。每年約有 50 萬人死於吸煙，每年與吸煙相關的美國醫療保健費用和生產力損失超過 6000 億美元。

Numerous comorbidities, including respiratory, cardiovascular and metabolic disease and of course, cancer result from cigarette smoking and countless lives are impaired. This is the urgent need Achieve is focused on and cytisinicline is designed to address.

吸菸會導致多種併發症，包括呼吸系統疾病、心血管疾病、代謝性疾病，當然還有癌症，無數人的生活因此受到損害。這是 Achieve 所關注的迫切需求，而 cytisinicline 正是為了解決這一需求而設計的。

Smoking cessation is an immense addressable market that has no new FDA-approved treatment options for nearly 20 years. Patients and physicians are frustrated by the lack of adequate tools to help drive success in their quit journey. The message is clear, Achieve is not quitting on you.

戒菸是一個巨大的潛在市場，但近 20 年來，FDA 尚未批准任何新的戒菸治療方案。患者和醫生都對缺乏足夠的工具來幫助他們成功戒菸感到沮喪。訊息很明確，Achieve 不會放棄你。

With cytisinicline, Achieve is on the threshold of delivering a potential game changer for the millions hoping to quit. Fundamentally, it is clear that the narrative surrounding smoking and vaping has to change. Nicotine dependence has to be acknowledged as a medical condition in much the same way as obesity is now recognized with the advent of GLP-1s.

憑藉著細胞毒素，Achieve 即將為數百萬希望戒菸的人帶來潛在的變革性產品。從根本上講，圍繞吸煙和電子煙的說法必須改變。尼古丁依賴必須被承認為一種疾病，就像肥胖症隨著 GLP-1 的出現而被承認一樣。

There are clear similarities between the obesity and nicotine dependent market dynamics. Nicotine dependence is a neurobiological condition resulting from an overabundance in the number of nicotinic receptors in the brain and needs to be treated as such.

肥胖症和尼古丁依賴症的市場動態之間有明顯的相似之處。尼古丁依賴是一種神經生物學疾病，是由於大腦中尼古丁受體數量過多所造成的，需要進行相應的治療。

As I mentioned in the introduction, comorbidities are a significant life impairment as a result of smoking, anything from COPD, asthma, cardiovascular disease, cancer, type-2 diabetes. The list is long. We decided to specifically investigate the impact of cytisinicline in smokers with COPD in ACHIEVE 2 Phase III clinical trials. Our recent publication in Thorax highlighted cytisinicline's potential to help individuals with COPD who remain smokers.

正如我在引言中提到的，吸菸會導致多種併發症，嚴重損害生活質量，包括慢性阻塞性肺病、氣喘、心血管疾病、癌症、2 型糖尿病等等。名單很長。我們決定在 ACHIEVE 2 III 期臨床試驗中專門研究細胞毒素對患有 COPD 的吸菸者的影響。我們最近在 Thorax 上發表的文章強調了金雀花鹼在幫助患有 COPD 且仍然吸煙的個體方面的潛力。

As a reminder, approximately 6 million of the 16 million Americans diagnosed with COPD continue to smoke today. In our two Phase III trials, we saw the smokers with COPD had higher quit rates on cytisinicline compared to placebo. COPD smokers on placebo did not quit at all.

需要提醒的是，在被診斷出患有慢性阻塞性肺病的 1,600 萬美國人中，約有 600 萬人至今仍在吸菸。在我們的兩項 III 期試驗中，我們發現與安慰劑相比，患有 COPD 的吸菸者使用金雀花鹼的戒菸率更高。服用安慰劑的慢性阻塞性肺病吸菸者完全沒有戒菸。

We were thrilled to see this outcome within this subgroup as these patients are often amongst the most difficult to treat due to the severity of their progressive illness. We know that quitting smoking improves the effectiveness of COPD treatments and helps reduce exacerbations and hospitalizations since smoking worsens symptoms and increases disease progression. These findings underscore psytisinicline's potential impact in offering meaningful benefits to one of the most vulnerable patient populations.

我們很高興看到這個亞組取得了這樣的結果，因為這些患者由於病情進展迅速且病情嚴重，往往是最難治療的群體之一。我們知道，戒菸可以提高 COPD 治療的效果，並有助於減少病情加重和住院治療，因為吸菸會加重症狀並加速疾病進展。這些發現凸顯了吡咯烷酮在為最脆弱的患者群體之一帶來實質益處方面的潛在影響。

Dr. Mark Rubenstein will discuss the findings in more detail in a minute. Jamie will also discuss Achieve's data-driven digital commercialization strategy and provide an update. I'd like to set the stage by noting that many large and specialty pharmaceutical companies have embraced AI as a powerful tool to advance precision targeting of both physicians and patients.

馬克·魯賓斯坦博士稍後將更詳細地討論這些發現。Jamie也將討論Achieve的數據驅動型數位化商業化策略，並提供最新進展。首先我想指出，許多大型專業製藥公司已經將人工智慧視為推動精準定位醫生和患者的強大工具。

What differentiates Achieve's commercial strategy is the integrated nature of our ecosystem and platform. Achieve leverages AI and machine learning to drive next best action orchestration, omnichannel marketing and audience activation across health care professionals, patients and payers. By utilizing a unified HIPPA compliant data warehouse and generative AI, Achieve is able to optimize campaigns, enhance engagement and measure ROI across all channels.

Achieve的商業策略與眾不同之處在於我們生態系統和平台的整合性。Achieve 利用人工智慧和機器學習來推動醫療保健專業人員、患者和支付方的最佳行動方案製定、全通路行銷和受眾激活。透過利用統一的符合 HIPAA 標準的資料倉儲和生成式人工智慧，Achieve 能夠優化行銷活動、增強用戶參與度並衡量所有管道的投資回報率。

For Achieve Life Sciences, this represents a scalable model for deploying AI-powered commercialization at launch while minimizing infrastructure investment. Without getting into too much technical jargon, the benefits of an AI or data-driven approach include channel sequencing, determining the next best action, e-mail, social ad, webinar invite or rep visit for each audience, message optimization, using AI-driven models to tailor messaging to behavioral and conceptual data.

對於 Achieve Life Sciences 而言，這代表了一種可擴展的模式，可以在產品發佈時部署 AI 驅動的商業化，同時最大限度地減少基礎設施投資。無需過多技術術語，人工智慧或數據驅動方法的優勢包括管道排序、確定針對每個受眾的最佳下一步行動（電子郵件、社交廣告、網路研討會邀請或代表拜訪）、資訊優化、使用人工智慧驅動的模型根據行為和概念數據自訂資訊。

Dynamic measurement, real-time KPI or performance monitoring and tracking, allowing optimization mid-campaign. These powerful AI-driven tools allow integrated payer, HCP and patient activation through a single HIPAA-compliant environment. The integrated platform is cost efficient, ensuring resources are applied with targeted precision to providing improved revenue outcomes. I'm sure you will share Achieve's excitement with the commercial buildup prior to launch in the third or fourth quarter next year.

動態測量、即時 KPI 或績效監控和追蹤，允許在行銷活動中進行最佳化。這些強大的 AI 驅動工具允許透過一個符合 HIPAA 標準的環境實現支付方、醫療保健專業人員和患者的整合活化。此整合平台具有成本效益高，可確保資源精準應用，進而提高營收成果。我相信您也會和 Achieve 一樣，對明年第三或第四季正式發布前的商業推廣活動感到興奮。

Turning to updates on our team. We had two promotions and one new hire. Dr. Mark Rubenstein became our Interim Chief Medical Officer, and Craig Donnelly was promoted to Chief Operations Officer. Eric Atkinson joined us recently as Chief Legal Officer. Dr. Rubenstein is a seasoned physician and executive with deep experience in patient care, clinical development, scientific research and medical affairs leadership with a strong focus on nicotine cessation and preventative medicine.

接下來是團隊的最新情況。我們進行了兩次晉升，並新招了一名員工。馬克·魯賓斯坦博士成為我們的臨時首席醫療官，克雷格·唐納利晉升為營運長。Eric Atkinson 最近加入我們，擔任首席法務官。魯賓斯坦博士是一位經驗豐富的醫生和高階主管，在病患照護、臨床發展、科學研究和醫療事務領導方面擁有豐富的經驗，尤其專注於尼古丁戒斷和預防醫學。

Having served as our Head of Medical Affairs since 2024, he brings a strong understanding of our programs, pipeline and strategic objectives, along with real-world experience treating patients who are eager to quit nicotine. Dr. Rubenstein is steeped in the world of smoking cessation and nicotine dependence. In his academic career, he led a clinical and translational research program focused on nicotine addiction and smoking cessation as a professor at UCSF.

自 2024 年以來，他一直擔任我們的醫療事務主管，對我們的計畫、研發管線和策略目標有著深刻的理解，並且擁有治療渴望戒除尼古丁患者的實際經驗。魯賓斯坦博士對戒菸和尼古丁依賴領域非常了解。在他的學術生涯中，他曾擔任加州大學舊金山分校的教授，並領導了一項以尼古丁成癮和戒菸為重點的臨床和轉化研究計畫。

Prior to joining Achieve, Dr. Rubenstein served as the Head of Medical Affairs at Blick, where he spearheaded the company's strategy to help smokers and vapors quit through FDA-approved medications and digital support tools. His deep understanding of the nicotine dependence landscape positions him to seamlessly lead our clinical and medical efforts as we move toward potential approval and commercialization. It's been great to work with Dr. Rubenstein in his new role.

在加入 Achieve 之前，魯賓斯坦博士曾擔任 Blick 的醫療事務主管，在那裡他領導了公司的策略，透過 FDA 批准的藥物和數位支援工具幫助吸菸者和電子煙使用者戒菸。他對尼古丁依賴領域的深刻理解，使他能夠順利地領導我們的臨床和醫療工作，朝著潛在的批准和商業化邁進。與魯賓斯坦博士在他新的職位上共事非常愉快。

We promoted Craig Donnelly to Chief Operations Officer. Since joining Achieve in 2022, Craig has shown outstanding leadership in manufacturing and regulatory. In his new role, he will align our supply chain and commercial strategy as we prepare to launch cytisinicline. With over 25 years in biopharma, his expertise will be key as we build the infrastructure to deliver cytisinicline to patients and move achieve into a commercial stage company.

我們提拔克雷格·唐納利為營運長。自 2022 年加入 Achieve 以來，Craig 在製造和監管方面展現了傑出的領導能力。在他的新職位上，他將負責協調我們的供應鏈和商業策略，為推出金雀花鹼做準備。憑藉超過 25 年的生物製藥經驗，他的專業知識對於我們建立向患者提供細胞毒素的基礎設施以及將 Achieve 推向商業化階段的公司至關重要。

Lastly, in October, we welcomed Eric Atkinson as our new Chief Legal Officer, who will oversee our legal strategy, corporate governance, compliance and risk management. With over 25 years' experience in the pharmaceutical and biotech industries, specifically in legal, regulatory and M&A, Eric has already been a tremendous asset as we move cytisinicline through regulatory review and get ready for a potential launch.

最後，在 10 月份，我們迎來了 Eric Atkinson 擔任新的首席法律官，他將負責監督我們的法律策略、公司治理、合規和風險管理。Eric 在製藥和生物技術行業擁有超過 25 年的經驗，尤其是在法律、監管和併購方面，在我們推進 cytisinicline 通過監管審查並為潛在的上市做準備的過程中，他已經成為了巨大的資產。

Thanks to our world-class team and relentless focus on execution, we continue to deliver on our milestones and move confidently towards bringing a much needed new treatment to market. With that, I'll now turn it over to Dr. Rubinstein.

憑藉我們世界一流的團隊和對執行的不懈努力，我們不斷實現里程碑目標，並充滿信心地朝著將急需的新療法推向市場的目標邁進。接下來，我將把麥克風交給魯賓斯坦博士。

Thank you, Rick, and good morning, everyone. As a clinician who spent much of my career helping people overcome nicotine dependence, I'm honored to serve as Interim Chief Medical Officer during this pivotal time for the company. I'm also excited to continue to build on the solid foundation we have established thus far.

謝謝你，里克，大家早安。身為畢生致力於幫助人們克服尼古丁依賴的臨床醫生，我很榮幸能夠在公司這個關鍵時期擔任臨時首席醫療官。我也很興奮能夠繼續在我們迄今為止所建立的堅實基礎上發展。

Since last quarter, we have met several important milestones and our regulatory process remains on track. Most notably, the FDA has accepted our NDA for cytisinicline, initiating the review process and setting a PDUFA action date of June 20, 2026. All interactions with FDA remain normal and on track.

自上個季度以來，我們已經實現了幾個重要的里程碑，我們的監管流程也仍在按計劃進行。最值得注意的是，FDA 已接受我們關於細胞毒素的新藥申請，啟動了審查程序，並將 PDUFA 行動日期定為 2026 年 6 月 20 日。與FDA的所有互動均保持正常，並按計劃進行。

We submitted our 120-day safety update, ensuring that the most current and comprehensive long-term safety data are available for review from the ORCA-OL trial. In this submission, we included data on 411 individuals with at least six months of cumulative cytisinicline exposure and 214 with at least one year of cumulative cytisinicline through the submission cutoff date of June 4, 2025.

我們提交了 120 天安全性更新報告，確保 ORCA-OL 試驗中最新、最全面的長期安全性數據可供審查。本次提交的數據包括截至 2025 年 6 月 4 日提交截止日期前，411 名至少有六個月累積細胞毒素暴露史的個體和 214 名至少有一年累積細胞毒素暴露史的個體的數據。

In October, our ORCA-OL long-term exposure study received its fourth and final comprehensive safety review from the Data Safety Monitoring Committee. The DSMC found that adverse events were mostly mild in severity and no serious adverse events were deemed to be treatment related. Additionally, there were no safety concerns with the drug.

10 月，我們的 ORCA-OL 長期暴露研究獲得了資料安全監測委員會的第四次也是最後一次全面安全審查。資料安全監測委員會 (DSMC) 發現，不良事件大多為輕度，沒有嚴重不良事件被認為與治療有關。此外，該藥物不存在任何安全問題。

Furthermore, we were pleased to report that our last ORCA-OL participant completed the study in October, marking 334 participants who completed one full year of the trial. The final site closeout visit took place at the end of October, representing an important milestone in our long-term development program. We are thrilled with the outcomes from ORCA-OL.

此外，我們很高興地報告，我們最後一位 ORCA-OL 參與者於 10 月完成了研究，至此，共有 334 名參與者完成了為期一年的試驗。10 月底進行了最終的現場收尾考察，這標誌著我們長期開發計畫的一個重要里程碑。我們對 ORCA-OL 的成果感到非常滿意。

Long-term studies can be challenging when it comes to retention of participants for one-year treatment requirements. So it is encouraging to see so many participants choosing to stay on treatment well in excess of what the FDA requested.

長期研究在維持參與者完成一年治療方面可能面臨挑戰。因此，看到這麼多參與者選擇繼續接受治療，而且治療時間遠遠超過 FDA 的要求，令人鼓舞。

As someone who's treated countless patients struggling with nicotine dependence, I know firsthand how difficult it is for people to remain engaged in any quit attempt. Seeing participants stay committed for a full year truly underscores the tolerability and appeal of cytisinicline. We believe their willingness to remain on cytisinicline speaks to its favorable side effect profile and possible efficacy benefit and is a strong signal of the potential impact cytisinicline could have in clinical practice.

身為一名治療過無數尼古丁依賴症患者的醫生，我親身經歷過戒菸對任何人來說有多麼困難。看到參與者堅持一整年，真正凸顯了金雀花鹼的耐受性和吸引力。我們認為，他們願意繼續服用金絲桃鹼，說明該藥物副作用較小，療效可能較好，這強烈表明金絲桃鹼在臨床實踐中可能產生影響。

In terms of patient experience in the OL trial, we collected exit survey responses from participants and are encouraged by their feedback. Over 97% of respondents believe cytisinicline helped them quit or reduce their nicotine use.

就 OL 試驗中的患者體驗而言，我們收集了參與者的退出調查回复，並對他們反饋表示鼓舞。超過 97% 的受訪者認為，金雀花鹼幫助他們戒掉了尼古丁或減少了尼古丁的使用。

In addition to reduced cravings, our respondents reported that they believe the lack of side effects and withdrawal symptoms help them quit. Many described the treatment as the added push they needed and something that gave them the confidence to quit. Nearly all respondents indicated they would recommend cytisinicline to a friend or family member trying to quit.

除了減少菸癮之外，我們的受訪者表示，他們認為沒有副作用和戒斷症狀有助於他們戒菸。許多人表示，這種治療給了他們所需的額外動力，也讓他們有了戒菸的信心。幾乎所有受訪者都表示，他們會向想要戒菸的朋友或家人推薦金雀花鹼。

We remain on track to lock the ORCA-OL database by year-end and are preparing for presentations and further publications in 2026. Our entire team is energized by the progress and the real-world impact we are poised to deliver.

我們仍按計劃在年底前鎖定 ORCA-OL 資料庫，並準備在 2026 年進行演示和發表更多文章。我們整個團隊都因取得的進展以及即將帶來的實際影響而充滿活力。

As Rick mentioned, new post-hoc data from an analysis of the ORCA-2 and ORCA-3 trials were published in PHLX, demonstrating that cytisinicline significantly improved quit rates compared to placebo in adults with COPD. Despite having more severe tobacco use histories and greater prior prescription treatment exposure, participants with COPD achieved quit rates with cytisinicline comparable to those without COPD. These findings support cytisinicline as a potential new pharmacologic option for people with COPD who continue to smoke despite their progressive disease.

正如 Rick 所提到的，對 ORCA-2 和 ORCA-3 試驗進行分析後得出的新事後數據已發表在 PHLX 上，結果表明，與安慰劑相比，金雀花鹼顯著提高了 COPD 成年患者的戒菸率。儘管患有 COPD 的參與者有更嚴重的吸菸史和更嚴重的先前處方治療接觸史，但他們使用細胞毒素戒菸的成功率與未患 COPD 的參與者相當。這些研究結果表明，對於患有慢性阻塞性肺病但仍繼續吸煙的人來說，細胞毒素可能是一種新的藥物選擇。

Lastly, we are thrilled to have received the Commissioner's National Priority Voucher for cytisinicline and vaping cessation. This is a significant recognition of the public health importance of our work and positions us well to advance cytisinicline as the potential first FDA-approved treatment for nicotine vaping dependence.

最後，我們非常高興地獲得了專員頒發的國家優先券，用於購買細胞毒素和戒除電子煙藥物。這是對我們工作在公共衛生方面重要性的重大認可，也使我們有信心將細胞毒素作為第一個獲得 FDA 批准的尼古丁電子煙依賴治療藥物推向市場。

We are now preparing to initiate our ORCA-V2 Phase III trial for vaping cessation, including finalizing the study protocol, selecting trial sites and identifying the principal investigator. The CNPV allows us to have enhanced engagement with FDA to shorten the time frame for NDA submission and approval. That concludes my remarks, and I'll now turn the call over to Jamie to provide updates on our commercial strategy.

我們現在正準備啟動 ORCA-V2 III 期戒菸試驗，包括最終確定研究方案、選擇試驗地點和確定主要研究者。CNPV 使我們能夠加強與 FDA 的合作，從而縮短 NDA 提交和批准的時間。我的演講到此結束，現在我將把電話交給傑米，讓他介紹我們的商業策略的最新進展。

Thank you, Dr. Mark. This quarter, our team continued to make great progress in preparation for the US commercial launch of cytisinicline. Our mission is to deliver this transformative therapy to the millions of Americans who want to overcome their nicotine dependence using the most advanced tools and strategies available. Our team remains focused on three strategic imperatives, availability, access and awareness, each underpinned by a rigorous data-driven approach and a commitment to maximizing efficiency and measurable impact.

謝謝你，馬克醫生。本季度，我們的團隊在為金雀花鹼在美國的商業上市做準備方面繼續取得了巨大進展。我們的使命是利用最先進的工具和策略，為數百萬想要克服尼古丁依賴的美國人提供這種變革性的療法。我們的團隊始終專注於三個策略要務：可用性、可近性和認知度，每個要務都以嚴格的數據驅動方法為基礎，並致力於最大限度地提高效率和可衡量的影響。

Starting with availability. Our first priority is ensuring cytisinicline will be available to patients nationwide. To this end, we have made progress on several key fronts. We've selected our third-party logistics provider and will begin the implementation process in Q4, well ahead of potential approval.

首先考慮可用性。我們的首要任務是確保全國各地的患者都能獲得金雀花鹼。為此，我們在幾個關鍵領域取得了進展。我們已經選定了第三方物流供應商，並將於第四季度開始實施流程，遠早於可能的審批時間。

I'm pleased to report that our home state licensing application was accepted in Washington State. We are now in the process of working on licenses for states that will allow us to submit prior to product approval. Additionally, we have further evaluated specialty distribution options and have selected our specialty light hub partner. Administrative and logistical initiatives will begin this quarter and continue through launch. We believe these foundational steps will be critical to ensure patients can access cytisinicline and that prescriptions written are prescriptions filled.

我很高興地報告，我們向華盛頓州提交的州級執照申請已被接受。我們目前正在辦理各州的許可證，以便我們能夠在產品獲得批准之前提交申請。此外，我們也進一步評估了專業經銷方案，並選定了我們的專業照明樞紐合作夥伴。行政和後勤方面的各項工作將於本季開始，並持續到產品發布。我們相信這些基礎性步驟對於確保患者能夠獲得細胞毒素以及確保處方得到滿足至關重要。

On the access front, our focus remains on securing rapid, broad and affordable coverage for cytisinicline. Our pricing and payer research accelerated significantly in Q3, culminating in a comprehensive segmentation of payer organizations.

在獲取途徑方面，我們的重點仍然是確保快速、廣泛且負擔得起的細胞毒素覆蓋。第三季度，我們的定價和支付方研究顯著加快，最終對支付方組織進行了全面的細分。

The work identified distinct payer profiles, which will guide the alignment of our target list and inform tailored engagement strategies. We have also completed both the quantitative and qualitative phases of our pricing and contracting research. This effort provides critical insights into market access dynamics, optimal price positioning and payer expectations, laying out the foundation for a strategy designed to maximize reimbursement potential at launch.

這項工作確定了不同的付款方特徵，這將指導我們調整目標客戶名單，並為制定有針對性的合作策略提供基礎。我們也完成了定價和合約研究的定量和定性階段。這項工作為市場准入動態、最佳價格定位和支付方期望提供了重要的見解，為旨在最大限度提高上市報銷潛力的策略奠定了基礎。

Importantly, payers continue to recognize cytisinicline's differentiated profile and the importance of having a new treatment to help people overcome nicotine dependence. Beginning in Q1, we will start proactive engagement with prioritized payers to deliver pre-approval information exchange communications. Feedback from these interactions will be critical in finalizing our access and contracting strategy as we move closer to launch.

重要的是，支付者繼續認可金雀花鹼的獨特特性，以及擁有新的治療方法來幫助人們克服尼古丁依賴的重要性。從第一季開始，我們將主動與優先支付方進行溝通，以提供審批前資訊交流。隨著我們越來越接近產品發布，這些互動帶來的回饋對於最終確定我們的存取和合約策略至關重要。

Turning to awareness. Building product-specific awareness and establishing Achieve's reputation as a trusted science-driven partner continues to be a cornerstone of our strategy. In Q3, we significantly advanced our patient and HCP targeting initiatives. We have finalized patient journey mapping, communication frameworks and decile segmentation to prioritize HCPs on a series of key treatment, prescribing and engagement behaviors, allowing us to deeply understand and motivate our key targets.

轉向覺察。建立產品特定認知度，並將 Achieve 打造成值得信賴的、以科學為導向的合作夥伴，這仍然是我們策略的基石。第三季度，我們大幅推動了針對病患和醫護人員的各項措施。我們已經完成了患者就醫歷程圖、溝通框架和十分位細分，以便優先考慮醫療保健專業人員的一系列關鍵治療、處方和參與行為，從而使我們能夠深入了解和激勵我們的關鍵目標群體。

Our partnership with Omnicom remains highly productive. The martech and data work streams have now an established foundation infrastructure, and we are progressing towards a unified data ecosystem to power our AI-enabled commercial platform. This will allow us to continuously optimize targeting, messaging and performance across all channels.

我們與宏盟集團的合作關係依然卓有成效。行銷技術和資料工作流程現在已經建立了完善的基礎架構，我們正在朝著統一的資料生態系統邁進，以支援我們的人工智慧商業平台。這將使我們能夠持續優化所有管道的目標定位、訊息傳遞和效果。

Turning to our team. We have continued to build out our internal commercial organization, which includes new talent leading commercial development, market access, supply chain and communications. While we have added key new hires, we are maintaining a lean, efficient internal team. Our collaborative approach with partners ensures we benefit from their deep expertise and scalable resources across every critical function.

轉向我們的團隊。我們不斷擴充內部商業組織，其中包括領導商業開發、市場准入、供應鏈和溝通的新人才。雖然我們增加了重要的新員工，但我們仍然保持著精簡且有效率的內部團隊。我們與合作夥伴採取協作方式，確保我們能夠受益於他們在各個關鍵職能方面的深厚專業知識和可擴展資源。

In summary, I want to emphasize that our progress is guided by a clear and focused commercial strategy centered on precisely targeting the highest impact audiences, both patients and providers, ensuring our efforts are concentrated where they will make the greatest difference, reaching the right audiences at the right time with the right message to deliver adoption and successful quitting and leveraging our partnership with Omnicom and deploying advanced AI-powered tools that will enable us to optimize segmentation, personalized messaging and measure engagement in real time.

總而言之，我想強調的是，我們的進展是由清晰明確的商業策略指導的，該策略的核心是精準定位最具影響力的受眾群體，包括患者和醫療服務提供者，確保我們的努力集中在能夠產生最大影響的地方，在合適的時間以合適的信息觸達合適的受眾，從而使產品採納和成功戒菸，並利用我們與盟約的合作關係

As we look ahead to our potential launch in 2026, our path is clear. We are committed to delivering cytisinicline to the millions of Americans seeking a better path to quit nicotine. We remain confident in our ability to execute efficiently, scale effectively and deliver long-term value for patients, providers and shareholders. I look forward to updating you on our continued progress as we move closer to launch. And I will now turn the call over to Mark.

展望我們可能在 2026 年推出的產品，我們的道路已經很清晰了。我們致力於為數百萬尋求更好戒菸途徑的美國人提供金雀花鹼。我們仍有信心高效執行、有效擴展規模，並為病患、醫療服務提供者和股東創造長期價值。隨著我們離發布越來越近，我期待著向您報告我們的最新進展。現在我將把通話交給馬克。

Thank you, Jamie, and good morning, everyone. We ended the third quarter with a strong balance sheet, supported by our recent capital raise and continued financial discipline.

謝謝你，傑米，大家早安。由於近期籌集的資金和持續的財務紀律，我們第三季末的資產負債表狀況良好。

As of September 30, 2025, cash, cash equivalents and marketable securities totaled $48.1 million. As we noted last quarter, our current cash runway is expected to fund operations into the second half of 2026. Total operating expenses for the three and nine months ended September 30, 2025, were $14.7 million and $40.1 million, respectively, reflecting our ongoing investment in regulatory, clinical and pre-commercial activities.

截至 2025 年 9 月 30 日，現金、現金等價物及有價證券總額為 4,810 萬美元。正如我們上個季度所指出的，我們目前的現金儲備預計可以維持營運到 2026 年下半年。截至 2025 年 9 月 30 日止的三個月和九個月的總營運支出分別為 1,470 萬美元和 4,010 萬美元，反映了我們對監管、臨床和商業前活動的持續投資。

With respect to net loss for the three and nine months ended September 30, 2025, it was $14.4 million and $40 million, respectively. We remain focused on disciplined capital allocation as we advance toward key regulatory and commercial milestones. With that, I'll turn the call back to Rick for closing remarks.

截至 2025 年 9 月 30 日止的三個月和九個月期間，淨虧損分別為 1,440 萬美元和 4,000 萬美元。我們將繼續專注於穩健的資本配置，朝著關鍵的監管和商業里程碑邁進。接下來，我將把電話轉回給里克，請他作總結發言。

Thanks, Mark. The progress discussed today underscores the momentum behind Achieve and our unwavering commitment to addressing the critical unmet needs of nicotine dependence. Our recent receipt of the FDA Commissioner's National Priority voucher for cytisinicline for vaping cessation is truly a landmark event. Being selected as one of only nine therapies in the programs in inaugural year demonstrates the urgent national need for effective treatments and the FDA's recognition for nicotine dependence in the public health crisis.

謝謝你，馬克。今天討論的進展凸顯了 Achieve 計畫的強勁勢頭，以及我們致力於解決尼古丁依賴症患者亟待滿足的關鍵需求的堅定承諾。我們最近收到了美國食品藥物管理局局長頒發的用於戒除電子煙的細胞毒素國家優先券，這確實是一件具有里程碑意義的事件。在計畫啟動的第一年，該療法被選為僅有的九種療法之一，這表明國家迫切需要有效的治療方法，也表明美國食品藥物管理局 (FDA) 認識到尼古丁依賴在公共衛生危機中的重要性。

Cytisinicline is uniquely positioned to address both of these significant public health challenges. For smokers who want to quit, it represents a potential new standard in smoking cessation at a time when it's been nearly two decades since the new treat trials have shown compelling results with cytisinicline's potential efficacy and safety profile continuing to generate excitement among both patients and clinicians.

細胞毒素在應對這兩項重大的公共衛生挑戰方面具有獨特的優勢。對於想要戒菸的吸菸者來說，這代表著戒菸領域一個潛在的新標準。近二十年來，新的治療方法試驗都取得了令人信服的結果，而細胞毒素的潛在療效和安全性也持續引起患者和臨床醫生的興奮。

For those who vape and want to quit, cytisinicline could become the first ever FDA-approved treatment, opening a nicotine-free path to quitting for the 17 million adult e-cigarette users in the US, about 60% of whom want to quit but currently have no approved options. The CMPD design means we can accelerate our efforts to bring this life-changing therapy to those who vape.

對於使用電子煙並想戒菸的人來說，細胞毒素可能成為首個獲得 FDA 批准的治療方法，為美國 1700 萬成年電子煙用戶開闢一條無尼古丁的戒菸之路，其中約 60% 的人想戒菸，但目前沒有獲批的選擇。CMPD 設計意味著我們可以加快努力，將這種改變生命的療法帶給那些使用電子煙的人。

As we look at the three key value drivers for the company, we're focused on: firstly, executing on the NDA approval and product launch with a PDUFA date set for the June 20, 2026 and a launch in the third or fourth quarter of 2026.

當我們審視公司的三個關鍵價值驅動因素時，我們關注的是：首先，執行 NDA 批准和產品上市，PDUFA 日期定於 2026 年 6 月 20 日，並在 2026 年第三或第四季度上市。

Secondly, driving the progress on our innovative data-driven commercial platform to enable a successful launch, allowing us to precisely target both patients and physicians. And finally, the growing recognition of value in our second indication, vaping, where we recently were awarded the CNBV by the FDA. This highlights the urgency of the public health crisis in the US and enables a shortened review process of just one to two months.

其次，推動我們創新的數據驅動商業平台取得進展，以實現成功上市，使我們能夠精準地瞄準患者和醫生。最後，我們的第二項適應症——電子煙——的價值也日益得到認可，我們最近獲得了 FDA 頒發的 CNBV 認證。這凸顯了美國公共衛生危機的迫切性，並使得審查過程能夠縮短至僅一到兩個月。

At Achieve, our message is simple. We are not quitting on you. We remain committed to providing evidence-based solutions to help you succeed. I'm grateful to our patients, partners, investors and the entire Achieve team for their ongoing support and dedication.

在 Achieve，我們的訊息很簡單。我們不會放棄你們。我們始終致力於提供基於實證的解決方案，幫助您取得成功。我衷心感謝我們的患者、合作夥伴、投資者以及整個 Achieve 團隊的持續支持和奉獻。

We are energized and excited about the opportunities ahead and confident that our efforts will deliver meaningful benefits for patients and long-term value for our stockholders. I also want to thank Cindy Jacobs again for her many contributions and are pleased to have her as an ongoing consultant. Thank you for joining us today, and we look forward to sharing more updates in the quarters ahead. With that, operator, we're now ready for Q&A.

我們對未來的機會充滿熱情和興奮，並相信我們的努力將為患者帶來實際的好處，並為我們的股東創造長期價值。我還要再次感謝 Cindy Jacobs 的諸多貢獻，我們很高興能繼續聘請她擔任顧問。感謝您今天參加我們的節目，我們期待在接下來的幾季與大家分享更多最新消息。好了，操作員，我們現在可以進入問答環節了。

(Operator Instructions)

（操作說明）

Thomas Flaten, Lake Street.

Thomas Flaten，湖街。

A couple of quick follow-ups from the call itself. Jamie, I know you mentioned a specialty distributor. Does that -- should I presume that you're going to go specialty only? Or is there a retail strategy in place as well?

通話結束後，還有幾個後續問題需要快速解答。傑米，我知道你有提到一家專業經銷商。那是不是代表你們只做特色菜？或者，公司也制定了零售策略？

Thomas, this is Rick here. Jamie has actually had to step away to address an urgent matter, and she's not going to be available for the Q&A. But the rest of our executive team are here, and we're happy to take your questions. I'll turn to Jerry for any questions you might have on the commercial front.

湯瑪斯，我是里克。傑米因緊急事務不得不暫時離開，她將無法參加問答環節。但我們其他高階主管團隊成員都在這裡，我們很樂意回答您的問題。關於商業方面的任何問題，我都會向傑瑞諮詢。

Okay. So could you just repeat your question, Thomas?

好的。湯瑪斯，你能再重複一次你的問題嗎？

Yes. So in the prepared remarks, there was a comment made that you selected a specialty distributor. I was wondering if there was also a complementary retail strategy in place or are you going specialty?

是的。所以在事先準備好的演講稿中，有人提到您選擇了專業經銷商。我想知道你們是否也制定了配套的零售策略，還是打算走專營路線？

No, no, there's going to be a complementary retail strategy in place as well. But the specialty route is one of the quickest and I think the optimal route at least in the initial stages, and then we'll build out from there.

不，不，我們還會制定配套的零售策略。但專業路線是最快捷的路線之一，我認為至少在初期階段也是最佳路線，然後我們將以此為基礎逐步擴展。

Got it. And then a follow-up for Mark. The cash runway into the second half of next year, just to confirm, that does not contemplate funding the vaping study. Is that correct that we need separate funding?

知道了。然後是給馬克的後續提問。需要確認的是，這筆資金足以支撐到明年下半年，但不包括資助電子煙研究。我們需要單獨的資金，是這樣嗎？

Yes, to complete the vaping study, we'll need to raise additional capital. That's correct.

是的，為了完成電子煙研究，我們需要籌集額外的資金。沒錯。

Got it. And then, Rick, anything that you can share with respect to the protocol you anticipate having for the vaping study? I don't know what conversations you've had with FDA or how far along that is, but any insight there would be great.

知道了。瑞克，關於你預計在電子煙研究中採用的方案，你有什麼可以分享的嗎？我不知道你和FDA談過什麼，也不知道進展如何，但任何相關資訊都將不勝感激。

Yes. Thomas, it's a very similar protocol to the ones that we used for the smoking cessation trials. So it is a two-arm study, placebo for 3 milligram, 3 times daily for 12 weeks. And then it is active. It cytisinicline 3 milligrams 3 times daily for 12 weeks, roughly 400 patients in each arm.

是的。Thomas，這和我們用於戒菸試驗的方案非常相似。這是一項雙臂研究，安慰劑組每天服用 3 毫克，持續 12 週。然後它就激活了。細胞毒素 3 毫克，每日 3 次，持續 12 週，每組約 400 名患者。

There is a difference between the smoking cessation trials and the vaping trials. And we believe that the vapors are actually more nicotine dependent than necessarily the smoking population was. So they are only treated for 12 weeks, whereas in the smoking cessation trial, we had the flexibility of 6 or 12 weeks. But other than that, they're very similar.

戒菸試驗和電子煙試驗之間存在差異。我們認為，電子煙使用者實際上比吸菸者對尼古丁的依賴程度更高。因此，他們只接受了 12 週的治療，而在戒菸試驗中，我們可以靈活選擇 6 週或 12 週。除此之外，它們非常相似。

And the endpoint will be what because you can't do any kind of objective breath analysis, right?

那麼最終結果會是什麼呢？因為你無法進行任何客觀的呼吸分析，對吧？

Correct. So it's simple. It's going to be overall quit rates at end of 12 weeks of treatment and then with a 24-week follow-up.

正確的。很簡單。這將是 12 週治療結束時的整體戒菸率，然後進行 24 週的追蹤。

Gary Nachman, Raymond James.

Gary Nachman，Raymond James。

Congrats on all the progress. So first, with the priority voucher for vaping, you said you're preparing to initiate that Phase III. How are you looking for ways to accelerate it and maybe started on the earlier side of the first half of next year? Could you clarify that? And you mentioned the Phase III design. That's just going to be the same as what you've talked about previously. Just wanted to confirm that.

祝賀你們取得的所有進展。首先，關於電子煙優先券，您說您正準備啟動第三階段。你們是如何尋找加速進度的方法，或許可以在明年上半年稍早開始實施？您能解釋一下嗎？您也提到了第三階段的設計。那跟你之前談到的內容是一樣的。我只是想確認一下。

I'll take the first part of it, Gary, and then I'll hand over for a bit more detail to Dr. Mark Rubinstein. Yes, I mean, the CMPV allows us a once two months of approval. So the NPV or ROI on that eight months that we're potentially benefiting from accelerating the product launch, that's substantial. And whereas the CNPV doesn't allow the transfer of the actual voucher itself. We strongly believe that the acceleration, both in the launch period, but you also got to launch -- look at the acceleration of peak revenues by eight or nine months.

蓋瑞，我先講第一部分，然後我會把更多細節交給馬克魯賓斯坦博士。是的，我的意思是，CMPV允許我們每兩個月獲得一次批准。因此，加快產品上市帶來的八個月淨現值或投資報酬率是可觀的。然而，CNPV 並不允許轉讓實際的代金券本身。我們堅信，無論是在發布初期還是發布初期，加速成長——看看高峰收入在八、九個月內達到高峰——都是如此。

So yes, it's extremely valuable. And yes, we are going to go back to the agency because I think we need to take advantage of the benefits under the CNBV to see where we could streamline the agreed clinical trial design. You remember that we got breakthrough designation originally. Now that is reinforced by the CNBV. So we do see that there's potential for some kind of streamlining of it. I'll hand over to Dr. Mark.

所以，是的，它非常有價值。是的，我們將再次與該機構聯繫，因為我認為我們需要利用 CNBV 的優惠政策，看看我們能否簡化已商定的臨床試驗設計。你還記得我們最初獲得的是突破性發現認定嗎？現在，CNBV 也強化了這一點。因此，我們看到這方面存在某種簡化的潛力。接下來交給馬克醫生。

Yes. So just to clarify, you wanted to hear a little bit more about the study design. And so as Rick has said, it will be a 12-week trial of cytisinicline with behavior versus placebo with behavioral treatment with follow-up at 12 weeks and 24 weeks. We will be biochemically confirming I understand the prior caller's question about confirmation with J B CO and he is correct that is only to detect cigarette smoke.

是的。所以，為了確認一下，您想了解更多關於研究設計的資訊。正如里克所說，這將是一項為期 12 週的試驗，比較金雀花鹼聯合行為療法與安慰劑聯合行為療法的效果，並在 12 週和 24 週進行追蹤。我們將透過生化方法進行確認。我理解之前來電者關於使用 J B CO 進行確認的問題，他是對的，那隻能偵測香菸煙霧。

However, we will also be employing blood analysis and saliva. We're looking to see which we can do more rapidly to look for coin, which is a biomarker of nicotine exposure so that we can confirm self-report. Does that answer your question?

但是，我們也會採用血液分析和唾液分析。我們正在研究哪種方法可以更快地找到coin，coin是尼古丁暴露的生物標記物，以便我們能夠確認自我報告。這樣回答了你的問題嗎？

Yes. And I guess just in terms of size, it sounds like you're going to try and streamline that the way that Rick described and will it be the same dosing as what you currently have for smoking.

是的。我猜就尺寸而言，聽起來你打算按照 Rick 描述的方式進行簡化，劑量會和你目前吸食的劑量一樣嗎？

Exactly. Same dosing.

確切地。劑量相同。

Okay. And then I guess since I have you, Mark, maybe just regarding the benefits for cytisinicline in COPD patients that you just published. And this is also for Rick, but maybe just talk about a little bit more just about what you saw in those patients, like how much of a benefit there was? And then, Rick, are you still having conversations with potential partners to do a study in that patient group? So what's the status there?

好的。那麼，既然有你，馬克，我想就你剛剛發表的關於細胞毒素對 COPD 患者益處的文章談談吧。這也是問里克的，或許你可以再多談談你在那些病人身上觀察到的情況，例如他們從中獲得了多大的益處？里克，你還在和潛在的合作夥伴洽談，準備對該患者群體進行研究嗎？那麼，那邊的現況如何？

Again, I'll kind of flip that one as well as Dr. Mark can answer part of it. Look, I think the key is that the effect that we saw, the benefit that we saw in COPD smokers was quite remarkable. We'd always suspected that those were potentially the highest beneficiaries because to be a COPD smoker, you have to be highly nicotine dependent when you have a progressive disease like COPD. And our belief was that they could well be the real beneficiaries.

我再換個角度來回答這個問題，因為馬克博士可以回答其中的一部分。我認為關鍵在於，我們看到的效果，我們在 COPD 吸煙者身上看到的益處是相當顯著的。我們一直懷疑這些人可能是最大的受益者，因為對於患有 COPD 等進行性疾病的 COPD 患者來說，吸菸者必然對尼古丁高度依賴。我們當時就認為，他們很可能才是真正的受益者。

By being COPD smokers, they are impairing the efficacy of the standard corticosteroid treatment. and the anti-IL-33 simply don't work in the smoking population. So we see that there are 6 million COPD smokers in the US today. And we believe strongly that cytisinicline can have a significant impact on making sure that their current treatment actually works more effectively.

由於慢性阻塞性肺病患者吸煙，他們會降低標準皮質類固醇治療的療效，而且抗IL-33藥物對吸煙人群根本無效。所以我們看到，目前美國有600萬名慢性阻塞性肺病吸菸者。我們堅信，金雀花鹼可以對他們目前的治療產生重大影響，確保其療效更佳。

So there's a kind of unique characteristic to this in terms of a 6 million population of patients with COPD who actually have the ability to benefit from cytisinicline. And that can parallel with other respiratory companies because we believe there should be an interest in ensuring that they can target that 6 million population. So over to you, Dr. Mark.

因此，就 600 萬 COPD 患者而言，這具有一種獨特的特點，他們實際上能夠從細胞毒素中受益。這一點與其他呼吸系統公司的情況類似，因為我們認為應該確保他們能夠瞄準那 600 萬人口。那麼，接下來就交給馬克博士了。

Sure. Thank you, Rick. So one of the things that we saw were that these patients with COPD were older, they were heavier smokers. They had higher levels of dependence and higher levels of depression, all of which we know are associated with poor outcomes.

當然。謝謝你，里克。我們發現的一個現像是，這些患有慢性阻塞性肺病的患者年齡較大，而且吸菸量也較大。他們的依賴程度和憂鬱程度都較高，而我們都知道，這些都與不良後果有關。

However, despite that, with cytisinicline, their quit rates were roughly the same as what we saw in smokers without COPD. For example, the odds ratio without COPD was 5.2 and with COPD was 5.3. So basically the same. And interestingly, and I think Rick had mentioned this earlier, patients on placebo were -- had a tremendously difficult time quitting. Really, when you have COPD, given those -- probably those other factors that you are heavier smoker and older, you couldn't really quit unless you use cytisinicline.

然而，儘管如此，使用細胞毒素後，他們的戒菸率與我們在沒有 COPD 的吸菸者中看到的戒菸率大致相同。例如，未患 COPD 的患者的優勢比為 5.2，患有 COPD 的患者的優勢比為 5.3。所以基本上是一樣的。有趣的是，我想里克之前也提到過這一點，服用安慰劑的患者戒菸非常困難。確實，如果你患有 COPD，考慮到那些因素——可能還有其他因素，例如你吸菸量更大、年齡更大——除非你使用細胞毒素，否則你真的無法戒菸。

Okay. That's really helpful. And then just last one, Rick. Pfizer, I think, is bringing CHANTIX back to the market. So what are your thoughts on how that impacts the overall smoking cessation market? Will that potentially help it grow again? And I'm not sure if you've seen how Pfizer is pricing CHANTIX with generics available. So if you have any color on that.

好的。這真的很有幫助。最後一位是里克。我認為，輝瑞公司正在將 CHANTIX 重新推向市場。那麼，您認為這會對整個戒菸市場產生什麼影響？這是否有可能幫助它再次生長？我不知道你是否了解輝瑞公司在仿製藥上市的情況下是如何為 CHANTIX 定價的。所以如果你在上面塗了顏色的話。

Well I mean, I can take a kind of strategic view on it. Why reintroduce CHANTIX when the generics have basically taken over the market. There's no value in the promotional activity because it really drives them towards the generic rather than the brand.

嗯，我的意思是，我可以從戰略角度來看這個問題。既然仿製藥已經基本佔據了市場，為什麼還要重新推出 CHANTIX 呢？這種促銷活動毫無價值，因為它實際上會引導消費者選擇通用產品而不是品牌產品。

So it's going to take -- if they're going to promote it, then it's going to be an interesting kind of ROI on that investment. And regardless of whether CHANTIX varenicline is in the market, I think the differentiation between cytisinicline in terms of not just its efficacy, but also the superior overall side effect profile and particularly focusing on that nausea and vomiting experience in the first few days of taking varenicline or CHANTIX, -- we clearly believe we've got a much superior product.

所以，如果他們要推廣它，那麼這項投資的回報率將會非常有趣。無論 CHANTIX 伐尼克蘭是否上市，我認為，就其療效而言，以及就其整體副作用而言，尤其是就服用伐尼克蘭或 CHANTIX 的最初幾天的噁心和嘔吐體驗而言，細胞毒素與 CHANTIX 的區別在於——我們顯然相信我們擁有更優越的產品。

I mean cytisinicline has 5 times less incidence of nausea and vomiting than varenicline does and less than half of the other side effects, be sleep disturbances, abnormal dams and nightmares, headache, et cetera. So it's a huge market. There are about 8 million scripts for smoking cessation annually.

我的意思是，與伐尼克蘭相比，金絲桃素引起噁心和嘔吐的發生率低 5 倍，其他副作用（如睡眠障礙、異常睡眠和噩夢、頭痛等）的發生率也低不到一半。所以這是一個巨大的市場。每年約有800萬份戒菸處方。

At peak, CHANTIX had about 2.8 million scripts written, 75% of those were in the US So regardless, I think that we have the benefits and the advantage over generic varenicline, and we see that as not being a necessary stumbling block.

CHANTIX 的處方量在高峰期達到了約 280 萬張，其中 75% 在美國。因此，無論如何，我認為我們比通用伐尼克蘭具有優勢和益處，我們認為這不應該是必要的絆腳石。

Brandon Folkes, H.C. Wainwright.

布蘭登·福克斯，H.C. 溫賴特。

Congratulations on all the progress. Maybe for me, can you just elaborate on the commercial infrastructure overlap you expect between smoking cessation and vaping? And then given that vaping now comes to the market earlier in the launch of the smoking cessation, which is probably not going to be at peak.

祝賀你們取得的所有進展。也許我想請您詳細說明您認為戒菸和電子煙在商業基礎設施方面有哪些重疊之處？而且，考慮到電子煙現在上市的時間比戒菸產品上市的時間更早，而戒菸產品上市的時間可能還沒達到高峰。

Does that change your commercial infrastructure outlook or how you're looking at sort of launching these two products in tandem or I guess, not launching them in tandem, but I guess maximizing their potential in tandem. Just any changes to the go-to-market strategy? And then along the same lines, just with the priority voucher, how are you doing manufacturing just that vaping maybe earlier in the process than perhaps you had planned?

這是否會改變您對商業基礎設施的看法，或者您是否考慮同時推出這兩款產品，或者，我猜，不是同時推出它們，而是最大限度地發揮它們協同作用的潛力？市場推廣策略有任何變化嗎？同樣地，憑藉優先券，你們是如何比原計劃更早開始生產電子煙的呢？

Brandon, thanks for the question. We are anticipating or estimating that the vaping indication will be launched around about 12 to 14 months after the smoking cessation indication. And I think that is really a really beneficial time because it allows us to effectively knock out any of the wrinkles that might be as a result, and we've got some learning to be done from the launch of the smoking cessation.

布蘭登，謝謝你的提問。我們預計或估計，電子煙適應症將在戒菸適應症推出後約 12 至 14 個月推出。我認為這確實是一個非常有利的時期，因為它使我們能夠有效地消除可能由此產生的任何皺紋，而且我們還需要從戒菸計劃的啟動中吸取一些經驗教訓。

Are we targeting different markets or different patients? The answer is yes. We're targeting a much younger patient population. The typical age of smokers in our clinical trials is around about 55 years old. They've been smoking for somewhere up to 30 years. And our key strategy here is a highly motivated quitters.

我們的目標市場不同還是目標患者群不同？答案是肯定的。我們的目標患者群更加年輕化。我們臨床試驗中吸菸者的典型年齡約為 55 歲。他們吸煙的時間可能長達30年。我們的關鍵策略是招募那些有很強離職意願的人。

So of that -- of the 29 million smokers currently in the US, we're estimating that approximately 7 million are highly motivated quitters. On the vaping target population, it's different. So they are a much younger population. Again, average age in our Phase II trial was 33 to 35. On average, they've been vaping between eight -- or five and eight years, and we're already starting to experience some of the comorbidities associated with vaping.

因此，據我們估計，在美國目前 2,900 萬名吸菸者中，約有 700 萬人是戒菸動機很高的人。對於電子煙目標族群來說，情況則有所不同。所以他們的人口結構就年輕得多。同樣，我們在 II 期試驗中受試者的平均年齡為 33 至 35 歲。平均而言，他們使用電子煙的時間在八年到五到八年之間，我們已經開始經歷一些與電子煙相關的併發症。

So I think that the fundamental approach to targeting the patients will remain the same. But I think that the younger population of vapors are more digitally inclined than the perhaps slightly older population for smoking cessation.

所以我認為，針對患者的根本方法將保持不變。但我認為，年輕的電子煙使用者群體比年紀稍長的戒菸使用者群體更傾向於使用數位化方式。

Again, we think that gives us a kind of an advantage because the ability to communicate directly to the patients digitally is a fundamental part of our overall strategy. From a physician standpoint, it won't make any difference. The physicians all we've got to do is make them aware of the benefits of cytisinicline in vapors because they will already be aware of the benefits in the smoking population.

我們認為這給我們帶來了一種優勢，因為能夠以數位化方式直接與患者溝通是我們整體策略的重要組成部分。從醫生的角度來看，這不會有任何區別。我們只需要讓醫生們了解霧化器中含有金雀花鹼的好處，因為他們已經了解了吸菸人群中金雀花鹼的好處。

So I think that's the slight nuance between the two populations. In terms of manufacturing, it will be the same. It's 3 milligrams 3 times daily. But as far as is concerned, it's 3 milligrams 3 times daily over 12 weeks only. It won't have the flexibility that we've seen in the smoking cessation at 6 or 12 weeks.

所以我認為這就是這兩個群體之間的細微差別。從製造工藝上看，情況將是一樣的。每次3毫克，每日3次。但就目前而言，劑量為每天 3 次，每次 3 毫克，療程僅 12 週。它不會像我們在 6 週或 12 週戒菸療程中看到的那樣具有靈活性。

(Operator Instructions) There are no further questions at this time. I will now turn the call back to Mr. Rick Stewart. Please continue.

（操作說明）目前沒有其他問題。現在我將把電話轉回給里克·斯圖爾特先生。請繼續。

I'd just like to thank you for your time and attention. We are progressing rapidly with both the smoking cessation indication. We're excited about the prospect of a PDUFA date in June and actually launching the product for smokers who have few treatment options at the current time. From a vaping standpoint, obviously, the CNBV is a real recognition of the value of cytisinicline in treating vapers who want to quit, and we look forward to updating you on our next quarterly call. Thank you very much.

我只想感謝您抽出時間關注此事。我們在戒菸適應症方面取得了快速進展。我們對 6 月份的 PDUFA 日期充滿期待，並希望能夠真正為目前治療選擇有限的吸煙者推出該產品。從電子煙的角度來看，顯然，CNBV 真正認可了細胞毒素在治療想要戒菸的電子煙使用者方面的價值，我們期待在下次季度電話會議上向您匯報最新情況。非常感謝。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線了。