Biohaven Ltd (BHVN) 2021 Q4 法說會逐字稿

Good morning, and welcome to the Biohaven Pharmaceutical's Fourth Quarter and Full Year 2021 Earnings Call. (Operator Instructions) Please be advised that today's conference will be recorded.

早安，歡迎參加 Biohaven Pharmaceutical 2021 年第四季和全年財報電話會議。 （操作員指示）請注意，今天的會議將會錄製。

I would now like to hand the conference over to Caroline Dircks from Biohaven. Thank you, Caroline. Please go ahead.

我現在想將會議交給 Biohaven 的 Caroline Dircks。謝謝你，卡洛琳。請繼續。

Thank you, and welcome to the Biohaven's Fourth Quarter and Full Year 2021 Earnings Call. Speaking on today's call are Dr. Vlad Coric, our Chief Executive Officer; Matthew Buten, Chief Financial Officer; BJ Jones, Chief Commercial Officer; and Dr. Elyse Stock, Chief Medical Officer. Also speaking on today's call are Dr. Michael Bozik; and Dr. Steven Dworetzky, who will be joining Biohaven as President, Biohaven Labs and Senior Vice President, Biohaven Labs, respectively; and Cliff Bechtold, President and General Manager, Biohaven Ireland.

謝謝，歡迎參加 Biohaven 的 2021 年第四季和全年財報電話會議。我們的執行長 Vlad Coric 博士在今天的電話會議上發言。馬修‧布滕，財務長； BJ 瓊斯，首席商務官；和首席醫療官 Elyse Stock 博士。邁克爾·博齊克 (Michael Bozik) 博士也在今天的電話會議上發言。 Steven Dworetzky 博士，他將加入 Biohaven，分別擔任 Biohaven 實驗室總裁和 Biohaven 實驗室高級副總裁；以及 Biohaven Ireland 總裁兼總經理 Cliff Bechtold。

We're also pleased to announce the addition of Jennifer Porcelli to Biohaven Pharmaceuticals as Vice President, Investor Relations.

我們也很高興地宣布 Jennifer Porcelli 加入 Biohaven Pharmaceuticals，擔任投資者關係副總裁。

Earlier this morning, we issued a press release announcing the fourth quarter 2021 highlights, and a summary of year-end results. A copy of this press release can be found on our website at biohavenpharma.com, and we will file our Form 10-K later today.

今天早上早些時候，我們發布了一份新聞稿，公佈了 2021 年第四季的亮點以及年終業績摘要。您可以在我們的網站 biohavenpharma.com 上找到本新聞稿的副本，我們將在今天稍後提交 10-K 表格。

Before we begin, let me remind everyone that today's discussion contains forward-looking statements based on the environment as we currently see it, and include risks and uncertainties. A list and description of risks and uncertainties associated with an investment in Biohaven can be found in the company's filings with the U.S. Securities and Exchange Commission. Please be aware that you should not place undue reliance on any forward-looking statements we make today.

在開始之前，讓我提醒大家，今天的討論包含基於我們目前所看到的環境的前瞻性陳述，並包括風險和不確定性。與 Biohaven 投資相關的風險和不確定性的清單和描述可以在該公司向美國證券交易委員會提交的文件中找到。請注意，您不應過度依賴我們今天所做的任何前瞻性陳述。

For this call, we will focus on non-GAAP financial measures. Detailed descriptions of these non-GAAP measures and reconciliations to the most comparable GAAP measures can be found in our SEC filings. An archive of today's call will be posted to Biohaven's website in the Investor Relations section.

在本次電話會議中，我們將重點放在非公認會計準則財務指標。這些非 GAAP 衡量標準的詳細描述以及與最具可比性 GAAP 衡量標準的調整可以在我們向 SEC 提交的文件中找到。今天電話會議的檔案將發佈到 Biohaven 網站的投資者關係部分。

With that, I will turn the call over to our CEO, Dr. Vlad Coric.

接下來，我會將電話轉給我們的執行長 Vlad Coric 博士。

Thank you, Caroline. Good morning, and thank you to our investors for joining the year-end fourth quarter earnings call.

謝謝你，卡洛琳。早安，感謝我們的投資人參加年終第四季財報電話會議。

Fourth quarter 2021 has been another standout quarter in what was simply an exceptional year for Biohaven. NURTEC ODT has become the #1 prescribed migraine treatment in its class, allowing patients and doctors the ability to customize a single therapy to treat and prevent migraine. Business performance continues to exceed all expectations with 2021 year-end day sale revenues of $463 million in net revenue and over 1.6 million prescriptions since our launch.

2021 年第四季是 Biohaven 不平凡的一年中又一個出色的季度。 NURTEC ODT 已成為同類中排名第一的偏頭痛處方治療藥物，使患者和醫生能夠定制單一療法來治療和預防偏頭痛。自我們推出以來，業務業績持續超出所有預期，2021 年底銷售收入淨收入達到 4.63 億美元，處方數量超過 160 萬張。

Our strong revenue growth highlights the value that our differentiated product brings to patients and physicians. The only simple-to-use oral migraine medication with dual indications to stop your migraine attack now and prevent your next one.

我們強勁的營收成長凸顯了我們的差異化產品為患者和醫生帶來的價值。唯一易於使用的口服偏頭痛藥物，具有雙重適應症，可立即停止偏頭痛發作並預防下一次偏頭痛發作。

Our global strategic collaboration with Pfizer for markets outside the U.S. is well underway, and our teams are working lockstep to prepare for an expanding global launch of rimegepant. This partnership will serve as a catalyst for the creation of a world-class migraine business that will open the door to delivering rimegepant to millions of patients around the globe. Imagine what our global commercialization with Pfizer will achieve for patients.

我們與輝瑞針對美國以外市場的全球策略合作正在順利進行，我們的團隊正在齊心協力，為擴大 rimegepant 的全球上市做準備。此次合作將成為創建世界級偏頭痛業務的催化劑，為全球數百萬患者提供 Rimegepant 敞開大門。想像一下我們與輝瑞的全球商業化將為患者帶來什麼。

We are extremely pleased to announce this morning the CHMP positive opinion for rimegepant in the EU, recommending the granting of a marketing authorization for the prophylaxis and acute treatment of migraine. I want to congratulate the Biohaven and Pfizer teams for this exceptional outcome and working closely with the CHMP to achieve this milestone.

今天早上，我們非常高興地宣布 CHMP 對 rimegepant 在歐盟的積極意見，建議授予用於預防和急性治療偏頭痛的營銷授權。我要祝賀 Biohaven 和輝瑞團隊取得這一非凡成果，並與 CHMP 密切合作以實現這一里程碑。

With the recent positive data for our pivotal trial of rimegepant in the acute treatment of migraine in China and South Korea, we are targeting a regulatory submission in the second half of 2022, and if approved, this will unlock a market of greater than 120 million acute migraine patients in China, who may benefit from the release provided by the #1 migraine treatment in its class.

最近，我們在中國和韓國進行的 rimegepant 急性偏頭痛治療關鍵試驗取得了積極的數據，我們的目標是在 2022 年下半年向監管機構提交申請，如果獲得批准，這將釋放超過 1.2 億的市場中國的急性偏頭痛患者可能會受益於同類排名第一的偏頭痛治療藥物的釋放。

In addition to the market growth and anticipated expansion of NURTEC ODT around the globe, our team is completing the NDA submission of zavegepant in the U.S., which we anticipate will be filed later this year. Zavegepant is the only intranasal CGRP receptor antagonist in late-stage development and has demonstrated an ultra-rapid onset of action within 15 minutes of administration. If ultimately approved, we believe that zavegepant will provide an important treatment option to enhance speed to migraine relief and a nonoral formulation for patients with prominent nausea or vomiting at the time of the migraine attack. While we are very proud of our robust CGRP franchise and the positive impact that it's having on patients, we continue to focus on advancing other novel and potentially best-in-class therapies for patients suffering from neurologic and neuropsychiatric disorders.

除了 NURTEC ODT 在全球的市場成長和預期擴張之外，我們的團隊正在美國完成 zavegepant 的 NDA 提交，我們預計將於今年稍後提交。 Zavegepant 是唯一處於後期開發階段的鼻內 CGRP 受體拮抗劑，並已證明在給藥後 15 分鐘內起效超快。如果最終獲得批准，我們相信 zavegepant 將提供一種重要的治療選擇，以加快偏頭痛緩解速度，並為偏頭痛發作時出現明顯噁心或嘔吐的患者提供非口服製劑。雖然我們對我們強大的 CGRP 專營權及其對患者的積極影響感到非常自豪，但我們將繼續專注於為患有神經系統和神經精神疾病的患者開發其他新穎且可能是一流的療法。

We are excited to announce this morning the acquisition of 2 new platforms to our pipeline. We acquired what we believe is a potentially best-in-class Kv7 ion channel activator for epilepsy and other neurologic indications that we will discuss in further detail later in this presentation.

今天早上，我們很高興地宣布收購了兩個新平台。我們獲得了一種我們認為可能是同類最佳的 Kv7 離子通道活化劑，用於治療癲癇和其他神經系統疾病，我們將在本簡報的後面進一步詳細討論。

We are also pleased to report that we have licensed a late-stage myostatin targeting asset from Bristol-Myers Squibb that is expected to enter Phase III clinical trials in spinal muscular atrophy, or SMA, later this year. The license of taldefgrobep will become the third drug candidate to enter the clinic that we have licensed from BMS. With the 2 additions to our portfolio announced this morning and the discovery engine of Biohaven Labs, our clinical pipeline is robust, and we believe will fuel the development of new innovative drugs for patients.

我們也很高興地報告，我們已從百時美施貴寶獲得了後期肌肉生長抑制素靶向資產的許可，預計該資產將於今年晚些時候進入脊髓性肌肉萎縮症（SMA）的III 期臨床試驗。 taldefgrobep的許可將成為我們獲得BMS許可的第三個進入診所的候選藥物。隨著今天早上我們宣布的產品組合中的兩項新增產品以及 Biohaven Labs 的發現引擎，我們的臨床管道非常強大，我們相信這將推動為患者開發新的創新藥物。

In the U.S., we have raced ahead of the competition, and NURTEC continues to be the #1 migraine treatment in its class. Our commitment to innovation in the treatment of migraine is strong as we continue to strive for excellence and look forward to bringing this leading therapy to patients around the world.

在美國，我們在競爭中處於領先地位，NURTEC 仍然是同類產品中排名第一的偏頭痛治療藥物。我們堅定地致力於偏頭痛治療創新，不斷追求卓越，並期待將這種領先的療法帶給世界各地的患者。

The new CGRP oral medications are just beginning to scratch the surface of the migraine market in the U.S. The oral CGRP class is showing strong growth and continues to gain momentum into 2022. To put the progress in perspective, oral CGRPs as a class recorded a remarkable net sales of approximately $1 billion in 2021, while only representing a small fraction about 5% to 6% of the overall migraine scripts. We believe that the oral CGRP class will show growth for many years and ultimately, will become first-line therapy for migraine.

新的 CGRP 口服藥物剛開始觸及美國偏頭痛市場的表面。年淨銷售額約10 億美元，但僅佔偏頭痛總量的一小部分，約5% 至6%。我們相信，口服 CGRP 類藥物將持續多年成長，並最終成為偏頭痛的第一線治療方法。

Looking specifically at fourth quarter market share versus triptans, the oral CGRPs continued to gain market share. This reflects the limitations of these older therapies and the advantages offered by the new oral CGRP class. The oral CGRPs have shown quarterly increases in both TRx and NBRx volume compared to the triptans. As you can see, there is a significant growth opportunity ahead of us, and we are already seeing the increased penetration of oral CGRPs as patients increasingly become more informed about the fast and lasting benefits of dual-acting NURTEC ODT.

特別是與曲坦類藥物相比，第四季度的市場份額來看，口服 CGRP 繼續獲得市場份額。這反映了這些舊療法的局限性和新的口服 CGRP 類別提供的優勢。與曲坦類藥物相比，口服 CGRP 的 TRx 和 NBRx 體積每季都有增加。正如您所看到的，我們面前有一個巨大的成長機會，隨著患者越來越了解雙效 NURTEC ODT 的快速和持久益處，我們已經看到口服 CGRP 的滲透率不斷提高。

We continue to update this slide regarding the oral CGRP class penetration compared to the injectable monoclonal antibodies. Oral CGRP antagonist continue to drive the growth of the overall CGRP market. Injectable mAbs are limited to prevention and many patients consider an injection less desirable compared to a single dissolving pill.

我們將繼續更新這張關於口服 CGRP 類滲透與注射單株抗體相比的幻燈片。口服 CGRP 拮抗劑持續推動整個 CGRP 市場的成長。可注射的單株抗體僅限於預防，許多患者認為與單一溶解藥丸相比，注射較不可取。

Given the projected size of the overall market, we remain focused and committed to investing in the long-term success of NURTEC ODT as the only medication that can provide acute and preventative treatment.

考慮到整個市場的預期規模，我們仍然專注並致力於投資 NURTEC ODT 作為唯一可以提供急性和預防性治療的藥物，使其長期成功。

Our world-class global commercialization partnership for rimegepant with Pfizer will allow us to bring what is the leading oral CGRP antagonist in the U.S. to patients worldwide suffering from migraine. Our mutual goal continues to be gaining approvals to deliver dual therapy NURTEC ODT rapidly to as many patients as possible around the world. There are approximately 1 billion patients who suffer from migraine across the globe.

我們與輝瑞公司在 rimegepant 方面建立了世界級的全球商業化合作夥伴關係，這將使我們能夠將美國領先的口服 CGRP 拮抗劑帶給世界各地的偏頭痛患者。我們的共同目標仍然是獲得批准，向世界各地盡可能多的患者快速提供雙重療法 NURTEC ODT。全球約有 10 億患者患有偏頭痛。

The news release this morning regarding the positive CHMP opinion for rimegepant, or VYDURA, as it will be marketed in Europe to treat acute and prevent episodic migraine is exciting. In addition to the regulatory progress in the EU, we also recently received positive Phase II data in our China, South Korea study for the treatment of migraine. We anticipate filing an NDA in China later this year.

今天早上發布的消息令人興奮，CHMP 對 rimegepant 或 VYDURA 給予積極的意見，因為它將在歐洲上市，用於治療急性和預防陣發性偏頭痛。除了歐盟的監管進展之外，我們最近還在中國和韓國的偏頭痛治療研究中收到了積極的第二期數據。我們預計今年稍晚在中國提交 NDA。

The global market opportunity for rimegepant is becoming a reality and the expansion of NURTEC ODT beyond the U.S. continues to be robust. With multiple approvals in migraine for both acute and prevention, double-digit submissions across the globe and multiple pivotal trials ongoing, we are seeing the results of our differentiated product. We are confident in the power of our collaboration with Pfizer and their long history of successfully launching and building partnered brands around the world.

rimegepant 的全球市場機會正在成為現實，NURTEC ODT 在美國以外的擴張持續強勁。隨著偏頭痛治療急性和預防性偏頭痛的多項批准、全球範圍內兩位數的提交以及正在進行的多項關鍵試驗，我們正在看到我們差異化產品的結果。我們對與輝瑞合作的力量以及他們在全球成功推出和建立合作品牌的悠久歷史充滿信心。

With the positive Phase III data of zavegepant, which is another cornerstone of our unparalleled CGRP franchise, Biohaven has the only intranasal CGRP antagonist with ultra-rapid migraine relief and the potential to usher in a new era of nonoral CGRP targeting migraine therapies. Our CMO, Elyse Stock, will update you on the progress in our regulatory efforts for zavegepant later during the presentation.

zavegepant 是我們無與倫比的CGRP 特許經營權的另一個基石，憑藉其積極的III 期數據，Biohaven 擁有唯一一種鼻內CGRP 拮抗劑，具有超快速緩解偏頭痛的作用，並有可能開創非口服CGRP標靶偏頭痛治療的新時代。我們的行銷長 Elyse Stock 將在稍後的簡報中向您介紹我們在 zavegepant 監管工作中取得的最新進展。

Now moving from one cutting-edge development platform to the next, we are excited this morning to announce the acquisition of Channel Biosciences, a subsidiary of Knopp Biosciences, and our Kv7 platform, an innovative potassium channel platform that is expected to move into the clinic by the end of this year. Later in the presentation, you will hear directly from the clinicians and scientists who developed this platform. We believe the lead molecule BHV-7000 has the potential to be a best-in-class potassium channel modulator for epilepsy and represents a validated mechanism of action with other broad therapeutic applications.

現在從一個尖端開發平台轉向下一個尖端開發平台，今天早上我們很高興地宣布收購 Knopp Biosciences 的子公司 Channel Biosciences 以及我們的 Kv7 平台，這是一個創新的鉀通道平台，預計將進入臨床到今年年底。在稍後的演示中，您將直接聽到開發該平台的臨床醫生和科學家的意見。我們相信，先導分子 BHV-7000 有潛力成為同類最佳的癲癇鉀通道調節劑，並代表了與其他廣泛治療應用相關的經過驗證的作用機制。

We are especially excited to welcome the entire Kv7 team from Channel Biosciences or Knopp Biosciences to Biohaven, and this includes their leaders, Dr. Mike Bozik and Steven Dworetzky, who will be joining our company to ensure that the lead assets are efficiently advanced to patients. Mike and Steven will be discussing the exciting program with you in more detail shortly.

我們特別高興地歡迎來自 Channel Biosciences 或 Knopp Biosciences 的整個 Kv7 團隊來到 Biohaven，其中包括他們的領導者 Mike Bozik 博士和 Steven Dworetzky，他們將加入我們公司，以確保將領先資產有效地推進給患者。麥克和史蒂文很快就會與您更詳細地討論這個令人興奮的計劃。

In what has been a morning filled with new announcements, we are pleased to announce more breaking news with the acquisition of taldefgrobep from Bristol-Myers Squibb. Taldefgrobep is an anti-myostatin adnectin and a Phase III-ready asset that already had a sizable human safety database in pediatric populations. Given the recent proof-of-concept data of other myostatin targeting agents, our intention is to initiate a Phase III study in the first half of 2022 for the treatment of spinal muscular atrophy. Importantly, this acquisition further extends the neuroscience R&D collaboration between Biohaven and BMS. This is our third late-stage asset licensed from BMS to enter the clinic and Cliff Bechtold, who previously was the development lead for this asset at BMS, will speak in more detail about this differentiated product in just a few minutes.

在充滿新公告的早晨，我們很高興宣布從百時美施貴寶收購 taldefgrobep 的更多突發新聞。 Taldefgrobep 是一種抗肌生成抑制素 Adnectin，是一種已進入 III 期臨床試驗的資產，已在兒科人群中擁有相當大的人類安全資料庫。鑑於其他肌肉生長抑制素標靶藥物的最新概念驗證數據，我們的計畫是在 2022 年上半年啟動一項治療脊髓性肌肉萎縮症的 III 期研究。重要的是，此次收購進一步擴大了 Biohaven 和 BMS 之間的神經科學研發合作。這是我們獲得 BMS 許可進入臨床的第三個後期資產，而先前擔任 BMS 該資產開發負責人的 Cliff Bechtold 將在幾分鐘內更詳細地介紹這個差異化產品。

To summarize, we have a strong portfolio of product opportunities that we believe will deliver value for patients and investors in the near term and for years to come. Our goal is to continue to deliver best-in-class therapies from our promising pipeline for patients across the globe.

總而言之，我們擁有強大的產品機會組合，我們相信這些機會將在短期和未來幾年為患者和投資者帶來價值。我們的目標是繼續透過我們有前景的產品線為全球患者提供一流的治療方法。

I'd like to now introduce Matthew Buten, our new Chief Financial Officer, who joined us in December. As a former managing director of Foresite Capital, Matt brings to Biohaven more than 20 years of experience in health care investment, investment banking and strategic structuring deals for both large and small cap companies. We are thrilled to have him. I would also like to thank Jim Engelhart for his long service and dedication to Biohaven. We wish Jim well in his much-deserved retirement.

我現在想介紹一下 Matthew Buten，我們的新任財務官，他於 12 月加入我們。作為 Foresite Capital 的前董事總經理，Matt 為 Biohaven 帶來了 20 多年在醫療保健投資、投資銀行和大型和小型公司戰略結構交易方面的經驗。我們很高興擁有他。我還要感謝 Jim Engelhart 對 Biohaven 的長期服務和奉獻。我們祝福吉姆在當之無愧的退休生活中一切順利。

Matt will now review the details and results of our financial performance in the fourth quarter and year end of 2021.

Matt 現在將審查我們 2021 年第四季和年底財務業績的詳細資訊和結果。

Thank you, Vlad. First, let me say how thrilled I am to be here for today's call. As many of you have seen, I've joined the Biohaven team in early December right off the heels of the company announcing an incredible strategic collaboration with Pfizer, enabling us to gain access to their industry-leading expertise and global footprint to turbocharge global commercialization efforts for rimegepant.

謝謝你，弗拉德。首先，我要說的是，我很高興能夠參加今天的電話會議。正如你們許多人所看到的，我於12 月初加入了Biohaven 團隊，緊接著該公司宣布與輝瑞(Pfizer) 進行令人難以置信的戰略合作，使我們能夠獲得他們行業領先的專業知識和全球足跡，從而推動全球商業化為Rimegepant而努力。

I've been following Biohaven's progress for many years while I was at Foresite, and I couldn't be more enthusiastic about the opportunity to join this incredible team, especially at a time like this as I look at the opportunities in front of us. Some of the guiding principles that I've incorporated in my role from learnings during the transition of my predecessor, Jim Engelhart, are threefold: maximizing value for shareholders is top of mind, ensuring we're adequately capitalized, limiting dilution for shareholders whenever possible. This was and will continue to be a critical focus for us. This dovetails into the next key tenet of our strategy, which is ultimately getting to a place of profitability.

在 Foresite 工作期間，我多年來一直關注 Biohaven 的進展，對於有機會加入這個令人難以置信的團隊，我感到非常興奮，尤其是在這樣的時刻，當我看到我們面前的機會時。我從前任吉姆·恩格爾哈特 (Jim Engelhart) 過渡期間學到的經驗中汲取的一些指導原則包括三個方面：首先考慮的是股東價值最大化，確保我們資本充足，盡可能限制股東的股權稀釋。這曾經並將繼續成為我們的重點關注點。這與我們策略的下一個關鍵原則相吻合，即最終實現盈利。

This is critical for us, ensuring we are well positioned to realize long-term revenue streams. We have obviously made tremendous inroads since the launch of our dual acute prevention label, and we see strong growth as we eventually pursue more of the extension opportunities for NURTEC in pediatric migraine pain adjacencies and other non-migraine indications.

這對我們來說至關重要，確保我們能夠實現長期收入流。自從我們的雙重急性預防標籤推出以來，我們顯然已經取得了巨大的進展，並且隨著我們最終在兒科偏頭痛疼痛鄰接和其他非偏頭痛適應症方面尋求更多NURTEC 的擴展機會，我們看到了強勁的增長。

And finally, maintaining that steadfast financial discipline while continuing to ensure we are driving access to new patient starts, investing wisely in a brand that is still relatively new in a market that only continues to grow rapidly. These are the critical components of our strategy, and I look forward to sharing more updates in the months ahead as we make progress.

最後，保持堅定的財務紀律，同時繼續確保我們推動新患者的啟動，明智地投資於一個在持續快速成長的市場中仍相對較新的品牌。這些是我們策略的關鍵組成部分，隨著我們取得進展，我期待在未來幾個月分享更多更新。

So with that in mind, let me take you through some of the financial highlights from the past year. The press release we issued this morning contains details of our financial results for the fourth quarter of 2021 with further details in our 10-K, which should be filed shortly. And rather than read through all these details, my comments will focus on some key financial results.

因此，考慮到這一點，讓我帶您回顧過去一年的一些財務亮點。我們今天早上發布的新聞稿包含 2021 年第四季度財務業績的詳細信息，以及我們應很快提交的 10-K 中的更多詳細信息。我的評論將重點放在一些關鍵的財務業績，而不是通讀所有這些細節。

NURTEC ODT achieved net sales of $190 million in Q4, demonstrating another quarter of strong performance, increasing 40% versus Q3 and increasing 440% year-over-year, driven largely by increased sales volume in NURTEC ODT and expanded and improved managed care reimbursement.

NURTEC ODT 在第四季度實現了1.9 億美元的淨銷售額，展現了又一個季度的強勁業績，與第三季度相比增長了40%，同比增長了440%，這主要是由於NURTEC ODT 銷量的增加以及管理式醫療報銷的擴大和改進。

The oral CGRP market continues to grow at an exceptional pace, carving out a small but expanding market share for migraine drugs while generating almost -- while generating over $1 billion in revenues last year. In total, oral CGRP market revenues grew greater than 400% for the full 2021 year, while Biohaven grew revenues over 600%. As the market continues to grow, we expect to see higher-than-market rates of growth for the oral class of CGRPs as well as for Biohaven.

口服 CGRP 市場繼續以驚人的速度成長，為偏頭痛藥物佔據了一小部分但不斷擴大的市場份額，同時去年創造了超過 10 億美元的收入。總體而言，2021 年全年口服 CGRP 市場收入成長超過 400%，而 Biohaven 收入成長超過 600%。隨著市場持續成長，我們預計口服類 CGRP 以及 Biohaven 的成長率將高於市場。

In the fourth quarter, we benefited from a large and growing market, which supported higher volume. And in addition, we had some favorable seasonality, which impacted us in a few ways. Higher volume and net price as payer constraints on patients such as deductibles and coinsurance were largely satisfied, resulting in reduced co-pay assistance for Biohaven. This is in addition to direct efforts we made to encourage refills.

第四季度，我們受益於龐大且不斷成長的市場，這支持了更高的銷售量。此外，我們還遇到了一些有利的季節性因素，這在幾個方面對我們產生了影響。由於支付者對患者的免賠額和共同保險等限制基本上得到滿足，因此數量和淨價較高，導致 Biohaven 的共付援助減少。這是我們為鼓勵補充所做的直接努力的補充。

We also experienced favorable payer mix with lower rebate payers. And as we discussed, the influence of positive seasonal factors as well as market growth in our Q4 results during webcast presentations and investor meetings as well as last year on our year-end earnings call. Many of these favorable contributors we experienced in Q4 are typical and expected with patient supportive pharma programs, and they pull back along with the typical seasonal changes anticipated in Q1, and it could have an impact on volume as well as sequential revenues.

我們也經歷了有利的付款人組合和較低的回扣付款人。正如我們在網路廣播演示和投資者會議以及去年年終收益電話會議上討論的，積極的季節性因素以及市場成長對我們第四季業績的影響。我們在第四季度經歷的許多有利貢獻者都是患者支持性製藥計劃的典型和預期貢獻者，它們隨著第一季預期的典型季節性變化而回落，這可能會對銷售和連續收入產生影響。

Now as we go down the P&L, R&D investment in the quarter on a non-GAAP basis was $76.4 million compared to $57.8 million in the prior quarter, an increase of $18.6 million or 32%. The increase is primarily due to continued funding of post-approval international pipeline expansion spending for rimegepant as well as our late-stage product candidates, including zavegepant, troriluzole and verdiperstat, which combined with the vast majority of our spend.

現在，當我們向下看損益表時，以非公認會計準則計算，本季的研發投資為 7,640 萬美元，而上一季的研發投資為 5,780 萬美元，增加了 1,860 萬美元，即 32%。這一增長主要是由於 rimegepant 以及我們的後期候選產品（包括 zavegepant、troriluzole 和 verdiperstat）的批准後國際管道擴張支出的持續資助，這與我們的絕大多數支出相結合。

SG&A expense in the quarter on non-GAAP basis was $189.3 million compared to $114 million in the prior quarter, an increase of the prior year quarter -- an increase of $75.3 million or 66%. Most of our SG&A costs continue to support commercial sales of NURTEC ODT as we invest behind our novel dual indication therapy with less than 50% of our spend on personnel costs and the rest supporting our promotional spend.

以非公認會計準則計算，本季的 SG&A 費用為 1.893 億美元，上一季為 1.14 億美元，較去年同期增加 7,530 萬美元，即 66%。我們的大部分 SG&A 成本繼續支持 NURTEC ODT 的商業銷售，因為我們投資於我們的新型雙適應症療法，其中不到 50% 的支出用於人員成本，其餘的用於支持我們的促銷支出。

Now moving on to the full year 2021 results. NURTEC ODT achieved net sales of $462.5 million for 2021, growing $399 million or 627%, demonstrating very strong performance. This is driven by increased volume in NURTEC ODT, which benefited from a partial year of sales associated with the expanded label to include prevention compared to a partial year of sales in 2020 with only at the acute label. Net revenues were also benefited by improvements in net price realization.

現在我們來看 2021 年全年業績。 NURTEC ODT 2021 年淨銷售額為 4.625 億美元，成長 3.99 億美元，即 627%，表現非常強勁。這是由 NURTEC ODT 銷售增加推動的，與 2020 年僅包含急性標籤的部分銷售年度相比，NURTEC ODT 的銷售量受益於與擴展標籤相關的部分年度銷售，包括預防。淨收入也受益於淨價格實現的改善。

R&D investment for the year ended 2021 on a non-GAAP basis was $287.1 million compared to $195.4 million in the prior year period, an increase of $91.7 million or 47%. Again, the increase was primarily due to our continued investment in our post-approval international [product expansion] opportunities from rimegepant as well as other late-stage product candidates and preclinical research. The late-stage products, I mentioned earlier, also comprised the vast majority of our spend for the year.

2021 年終了年度的研發投資（以非公認會計原則計算）為 2.871 億美元，較上年同期的 1.954 億美元增加了 9,170 萬美元，增幅為 47%。同樣，這一增長主要是由於我們對 rimegepant 以及其他後期候選產品和臨床前研究的批准後國際[產品擴展]機會的持續投資。我之前提到的後期產品也佔了我們今年支出的絕大多數。

SG&A expense for 2021 on a non-GAAP basis was $623.6 million compared to $428.6 million in the prior year, an increase of $195 million or 45%. The increase was primarily due to increased promotional activities supporting NURTEC ODT commercial sales in 2021 for the treatment and prevention of migraine which got its dual indication approval in May '21, and compare that to the same period in 2020, which reflects precommercial and promotional NURTEC ODT spend, which was launched in March of '20.

以非公認會計準則計算，2021 年的 SG&A 費用為 6.236 億美元，而前一年為 4.286 億美元，增加了 1.95 億美元，即 45%。這一增長主要是由於支持2021 年用於治療和預防偏頭痛的NURTEC ODT 商業銷售的促銷活動增加，該產品於21 年5 月獲得雙重適應症批准，並將其與2020 年同期相比，這反映了NURTEC 的預先商業和促銷ODT 支出，於 20 年 3 月啟動。

Now turning to our balance sheet. Pro forma for the closing of our collaboration and subscription agreements with Pfizer in early January, we have access to approximately $1 billion of liquidity. As of December 2021, we have $367 million in cash and cash equivalents and marketable securities, immediate access to $125 million from our debt facility with Sixth Street and an additional $500 million of cash we received on January 4 from Pfizer.

現在轉向我們的資產負債表。預計一月初我們與輝瑞公司達成合作和認購協議後，我們可以獲得約 10 億美元的流動資金。截至2021 年12 月，我們擁有3.67 億美元的現金和現金等價物以及有價證券，可以立即從我們與第六街的債務融資中獲得1.25 億美元，以及我們於1 月4 日從輝瑞公司收到的另外5 億美元現金。

Let me echo what Vlad said about our excitement over our recently announced acquisition of Channel Biosciences, adding a valuable Kv7 program for epilepsy and potentially other indications to our pipeline. The terms of the deal are as follows: upfront consideration comprised of $65 million of Biohaven stock and $35 million in cash. Successful -- success-based milestone payments broken down as follows: BHV-7000 regulatory milestones of up to $325 million for U.S., EMA and Japan approvals for epilepsy and $250 million for additional geographies and additional indications for Kv7. BHV-7000 sales-based commercial milestones of up to $562.5 million with the full amount achievable upon reaching $3 billion in annual sales. And we'll pay scale royalties for BHV-7000 of high single digits to low teens. And for additional programs, we'll pay starting royalties in the mid-single digits.

讓我重複 Vlad 所說的，我們對最近宣布收購 Channel Biosciences 感到興奮，為我們的產品線增加了一個有價值的 Kv7 治療癲癇和潛在其他適應症的項目。交易條款如下：預付款包括 6,500 萬美元的 Biohaven 股票和 3,500 萬美元的現金。成功——基於成功的里程碑付款細分如下：BHV-7000 監管里程碑為美國、EMA 和日本批准用於癲癇治療的最高 3.25 億美元，以及用於 Kv7 的其他地區和其他適應症的 2.5 億美元。 BHV-7000 基於銷售的商業里程碑高達 5.625 億美元，年銷售額達到 30 億美元後即可全額實現。我們將為 BHV-7000 支付高個位數到低十位數的特許權使用費。對於其他項目，我們將支付中等個位數的起始版稅。

And with that, let me turn it over to BJ Jones, our Chief Commercial Officer. BJ?

接下來，讓我將其交給我們的首席商務官 BJ Jones。北京？

Thank you, Matt, and good morning all. 2021 has been a transformational year for Biohaven and NURTEC ODT. We remain enthusiastic about the brand's success to date and significant impact we've had in the lives of so many patients with migraine and their loved ones.

謝謝你，馬特，大家早安。 2021 年對 Biohaven 和 NURTEC ODT 來說是轉型的一年。我們對該品牌迄今為止的成功以及我們對眾多偏頭痛患者及其親人的生活產生的重大影響仍然充滿熱情。

Looking back at the year, NURTEC ODT experienced strong and steady growth in market as health care professionals and patients became more familiar with the brand's unique and what we believe to be best-in-class profile. We began the year singularly focused on promotion in acute therapy, which produced a healthy growth curve through the spring. And once NURTEC received agency approval for preventive therapy, we witnessed dramatic acceleration in our growth rate, with early trial among established subscribers as well as those new to brand. We remain confident that NURTEC ODT's unique profile as the first and only medication proven to treat and prevent migraines is well positioned to shift the paradigm in migraine treatment to dual therapy.

回顧這一年，隨著醫療保健專業人士和患者越來越熟悉品牌的獨特性以及我們認為是一流的形象，NURTEC ODT 經歷了強勁而穩定的市場成長。今年伊始，我們特別關注急性療法的推廣，該療法在整個春季產生了健康的成長曲線。一旦 NURTEC 獲得機構批准用於預防性治療，我們就見證了我們的成長率急劇加速，在老用戶和新品牌用戶中進行了早期試驗。我們仍然相信，NURTEC ODT 作為第一種也是唯一一種被證明可以治療和預防偏頭痛的藥物，其獨特的特性能夠很好地將偏頭痛治療模式轉變為雙重療法。

We're very pleased with fourth quarter sales of $190 million, an increase of 40% over prior quarter, which totaled $463 million in our first full year of commercialization. With NURTEC ODT only now approaching its second anniversary in market, we've achieved $526 million in revenue since launch. We're certainly proud of our commercial team and what it's accomplished with passionate support from every member of the Biohaven family because we realize that every prescription filled is a potential life-changing moment for patients and those they love.

我們對第四季銷售額達到 1.9 億美元感到非常滿意，比上一季成長了 40%，在我們商業化的第一個全年銷售額中總計達到 4.63 億美元。 NURTEC ODT 剛上市兩週年，自推出以來我們已經實現了 5.26 億美元的收入。我們當然為我們的商業團隊以及在Biohaven 家族每一位成員的熱情支持下所取得的成就感到自豪，因為我們意識到每一張處方對於患者及其所愛的人來說都是潛在改變生活的時刻。

The new year brings with a tremendous opportunity as the oral CGRP class continues to penetrate what is a highly dissatisfied market. As Vlad mentioned earlier, we're witnessing significant penetration of the generic triptan market as well as significant growth from patients who haven't filled the prescription in years and have made do with over-the-counter meds and other means to address their migraine attacks. With a tremendous clinical advance of oral CGRPs, we see old habits changing.

新的一年帶來了巨大的機遇，因為口服 CGRP 課程繼續滲透到這個高度不滿意的市場。正如弗拉德之前提到的，我們正在見證曲坦類仿製藥市場的顯著滲透，以及多年來未按處方配藥、僅靠非處方藥和其他方法來解決偏頭痛的患者的顯著增長攻擊。隨著口服 CGRP 臨床的巨大進步，我們看到舊習慣正在改變。

In the most recent Spherix stats, evidence suggests physicians are optimistic about [rimegepant] and expect their adoption to accelerate in the months ahead. Not surprisingly, we see a similar dynamic among preventive therapies. Physicians predict strong uptick of oral CGRPs, specifically NURTEC, while generic therapies continued to erode over time. Although changing physician prescribing behavior doesn't happen overnight, these data are a leading indicator of the evolution taking place across the migraine market that will come to fruition in the months and years to come.

在最新的 Spherix 統計數據中，有證據表明醫生對 [rimegepant] 持樂觀態度，並預計在未來幾個月內其採用將加速。毫不奇怪，我們在預防性療法中看到了類似的動態。醫生預測口服 CGRP（尤其是 NURTEC）的劑量將強勁上升，而仿製藥療法將隨著時間的推移而持續減弱。儘管醫生處方行為的改變不會在一夜之間發生，但這些數據是整個偏頭痛市場正在發生的演變的領先指標，並將在未來的幾個月和幾年內取得成果。

Another leading indicator is physician satisfaction with migraine therapies, and as you can see by this graph, oral CGRPs dominate. Even among these impressive class data, a consistent theme shows NURTEC is the brand of choice among physicians, and highlighted here, we see NURTEC chosen as the brand with the highest level of satisfaction.

另一個領先指標是醫生對偏頭痛治療的滿意度，正如您從該圖中看到的，口服 CGRP 占主導地位。即使在這些令人印象深刻的班級數據中，一致的主題也表明 NURTEC 是醫生的首選品牌，並且在此強調，我們看到 NURTEC 被選為滿意度最高的品牌。

As the market leader, NURTEC is poised to benefit differentially by the growth dynamics among the oral CGRPs. We're also encouraged by the class volume growth within the last few weeks. In early Q1, we anticipated slower uptake for all the seasonal factors that are endemic to our industry, i.e. new year insurance plan changes, deductible annual resets, prescription acceleration in year-end refills in Q4, et cetera, but we are seeing earlier return to growth trends than in years past.

作為市場領導者，NURTEC 有望從口服 CGRP 的成長動態中獲益。過去幾週班級人數的成長也讓我們感到鼓舞。在第一季初期，我們預計我們行業特有的所有季節性因素的吸收速度會較慢，例如新年保險計劃變化、年度免賠額重置、第四季度年終補充處方加速等，但我們看到了更早的回報與過去幾年相比的成長趨勢。

In closing, 2021 has been an amazing year. We're pleased with our position as market leader in a rapidly growing market with high unmet needs. We continue to perform well across all launch measures as prescriber and patient trial in advocacy steadily growing. In addition, I'm pleased to report we've maintained NURTEC's extremely strong formulary access for both acute and preventive indications.

最後，2021 年是令人驚奇的一年。我們對自己在快速成長且需求未滿足的市場中作為市場領導者的地位感到滿意。隨著處方者和患者試驗的倡導穩步增長，我們在所有啟動措施中繼續表現良好。此外，我很高興地報告，我們一直保持 NURTEC 針對急性和預防性適應症的極其強大的處方准入。

With that, I'd like to introduce you to another NURTEC patient, Greg, with a great testimony to share.

至此，我想向您介紹另一位 NURTEC 患者 Greg，並分享一個精彩的見證。

I'm a retired Green Beret from the Army, 21 years, 7 combat tours. I have a TBI and bad migraine headaches. I started to take NURTEC ODT, and I think it has changed my life. I used to live in my closet between migraine headaches and all my other problems after 7 combat tours, I had lost hope. NURTEC has made my life so much better. I've now started Blue Ridge Safehouse. It's a nonprofit to help active duty guys like me.

我是一名退休的綠色貝雷帽軍人，服役 21 年，參加過 7 次戰鬥。我患有創傷性腦損傷和嚴重的偏頭痛。我開始服用 NURTEC ODT，我認為它改變了我的生活。在 7 次戰鬥旅行之後，我曾經因偏頭痛和所有其他問題而住在衣櫃裡，我失去了希望。 NURTEC 讓我的生活變得更美好。我現在開始了藍嶺安全屋。這是一個幫助像我這樣的現役軍人的非營利組織。

Patients like Greg and so many others make what we do every day so incredibly worthwhile.

像格雷格和其他許多人這樣的患者讓我們每天所做的事情變得非常有價值。

And at this point, I'd like to hand it over to my partner, Elyse Stock, our Chief Medical Officer.

現在，我想將其交給我的合作夥伴、我們的首席醫療官 Elyse Stock。

Thank you, BJ. Oh my goodness, so much has happened in this last quarter, and I'm really delighted to share it with you.

謝謝你，BJ。天哪，上個季度發生了很多事情，我真的很高興與您分享。

Before I start, I really wanted to thank the fantastic people that I work with at Biohaven because they are really the ones who are delivering the milestones that I'll be sharing with you this morning. With these talented individuals, we will be able to unleash the potential of our multiple assets and bring multiple therapies to patients here in the U.S. as well as with our Pfizer colleagues across the globe.

在開始之前，我真的想感謝在 Biohaven 與我一起工作的出色人員，因為他們確實實現了我今天早上將與大家分享的里程碑。有了這些才華橫溢的個人，我們將能夠釋放我們多種資產的潛力，並與美國輝瑞全球各地的同事一起為美國患者提供多種治療方法。

So far this year, and I'll remind you, we're only in February, we're delivering on important milestones. Just yesterday, we received news of a positive opinion from the CHMP on our filing with NURTEC for both acute and preventive treatment of migraine. This quarter, we also had positive top line results from our NURTEC acute treatment of migraine study in Asia. At the end of last year, we delivered positive results on our second registrational intranasal zavegepant trial. We're expecting further milestones to be achieved over the course of the year, but I'll delve into each of our most recent achievements just a bit more.

今年到目前為止，我要提醒您，我們才進入二月，我們正在實現重要的里程碑。就在昨天，我們收到 CHMP 對我們向 NURTEC 提交的偏頭痛急性和預防性治療申請的積極意見的消息。本季度，我們在亞洲進行的 NURTEC 偏頭痛急性治療研究也取得了正面的頂線結果。去年年底，我們的第二次鼻內 zavegepant 註冊試驗取得了積極的結果。我們預計在這一年中將實現更多的里程碑，但我將進一步深入研究我們最近的每項成就。

Our impressive CGRP franchise at Biohaven is just unparalleled in our industry. NURTEC ODT remains our cornerstone marketed product and the only oral migraine product indicated for the acute treatment of migraine as well as for prevention. Yesterday, we got news from the CHMP that we've been given a positive opinion on our oral -- on our NURTEC submission for this dual treatment.

我們在 Biohaven 令人印象深刻的 CGRP 特許經營權在我們行業中是無與倫比的。 NURTEC ODT 仍然是我們的基石行銷產品，也是唯一適用於偏頭痛急性治療和預防的口服偏頭痛產品。昨天，我們從 CHMP 得到消息，我們對我們的 NURTEC 提交的這種雙重治療的口頭意見給予了積極的意見。

For those of you following closely, we were not required to attend an oral explanation. We were quickly able to address all of the issues raised and really appreciate the speed and collaborative nature of the European regulator. The ability to treat a large number of patients across the migraine continuum is a truly innovative approach to the treatment of migraine, and we look forward to an approval over the coming weeks.

對於那些密切關注的人來說，我們不需要參加口頭解釋。我們很快就能夠解決提出的所有問題，並非常欣賞歐洲監管機構的速度和協作性質。能夠治療偏頭痛連續體中的大量患者是一種真正創新的偏頭痛治療方法，我們期待在未來幾週內獲得批准。

Earlier this month, we also announced positive results from our fourth positive Phase III study of rimegepant for the acute treatment of migraine, which was conducted in China and Korea. This study met its co-primary endpoints of freedom from pain and freedom from the most bothersome migraine-associated symptom, also known as MBS, which includes nausea, phonophobia and photophobia at 2 hours, following a single oral dose of rimegepant.

本月早些時候，我們還宣布了在中國和韓國進行的用於急性偏頭痛治療的 rimegepant 的第四項 III 期研究的積極結果。這項研究達到了其共同主要終點，即在單次口服劑量rimegepant 後2 小時內無疼痛和無最令人煩惱的偏頭痛相關症狀（也稱為MBS），包括噁心、恐聲症和畏光症。

As seen in the graph, a single oral dose of rimegepant 75 milligram provides statistically significant relief of migraine symptoms and return to normal function at 2 hours and delivered sustained efficacy that lasted up to 48 hours for many patients. Rimegepant showed broad efficacy across multiple clinically meaningful endpoints and a favorable safety and tolerability profile that was consistent with prior clinical trial results in the United States.

如圖所示，單次口服 75 毫克 Rimegepant 可顯著緩解偏頭痛症狀，並在 2 小時內恢復正常功能，並為許多患者提供持續長達 48 小時的持續療效。 Rimegepant 在多個具有臨床意義的終點中顯示出廣泛的療效，並且具有良好的安全性和耐受性，與美國先前的臨床試驗結果一致。

Our work with Pfizer has brought us great collaborative colleagues, and I'm confident that they will be able to take these tremendous accomplishments and expand our global footprint bringing relief to patients suffering with migraine across the globe.

我們與輝瑞的合作為我們帶來了出色的合作同事，我相信他們將能夠利用這些巨大的成就並擴大我們的全球足跡，為全球偏頭痛患者帶來緩解。

As I said before, we will continue to expand our program with life cycle studies of NURTEC ODT, both within neuroscience, as well as explore a wide variety of scientifically relevant indications outside of migraine as we follow the science of the CGRP antagonist.

正如我之前所說，我們將繼續在神經科學領域擴大 NURTEC ODT 生命週期研究的項目，並在我們遵循 CGRP 拮抗劑的科學原理的同時，探索偏頭痛之外的各種科學相關適應症。

Earlier this month, we enrolled our first patient in a NURTEC study of rhinosinusitis. This is just one of the NURTEC studies we intend to begin this year. Investigator-initiated trials, Phase IV clinical trials and studies in health economics will add to the wealth of information that will ultimately be available for NURTEC and will help define the scope of important information for patients, providers and payers, both within the U.S. as well as globally.

本月早些時候，我們招募了第一位患者參加 NURTEC 鼻竇炎研究。這只是我們打算今年開始的 NURTEC 研究之一。研究者發起的試驗、第四階段臨床試驗和健康經濟學研究將增加 NURTEC 最終可用的資訊財富，並將有助於為美國境內的患者、提供者和付款人確定重要資訊的範圍與全球一樣。

We recently announced positive results from our intranasal zavegepant Phase III study. Its co-primary endpoints of pain freedom and freedom from MBS at 2 hours were statistically significant and replicated the results seen in our positive Phase II study. As we hoped, it confirmed an ultra-rapid speed of onset with pain relief differentiating from placebo as early as 15 minutes with a single dose. After zavegepant treatment, patients who previously experienced moderate-to-severe pain, achieved reductions to mild or no pain. And we anticipate a filing of intranasal zavegepant for the acute treatment of migraine in the first half of this year 2022. Our oral formulation of zavegepant is being evaluated now in a Phase III study in chronic migraine.

我們最近宣布了鼻內 zavegepant III 期研究的正面結果。其共同主要終點為 2 小時內無疼痛和無 MBS，具有統計意義，重複了我們在 II 期研究中看到的結果。正如我們所希望的那樣，它證實了與安慰劑相比，單劑量起效速度超快，疼痛緩解最早可在 15 分鐘內緩解。經過扎維格泮治療後，先前經歷過中度至重度疼痛的患者，疼痛減輕至輕度或無痛。我們預計將於 2022 年上半年提交用於急性偏頭痛治療的鼻內 zavegepant 申請。

We continue to just make great progress across all of our late-stage assets, including our glutamate-modulating agents and our myeloperoxidase inhibitor platform. And over the coming months, we will see top line readouts and are excited about all of the opportunities that we have got across both common and rare diseases.

我們繼續在所有後期資產方面取得巨大進展，包括谷氨酸調節劑和髓過氧化物酶抑制劑平台。在接下來的幾個月裡，我們將看到頂線讀數，並對我們在常見和罕見疾病方面獲得的所有機會感到興奮。

Our Biohaven Laboratories also remain busy with its early discovery work, and it continues just to grow. We have more than 10 preclinical programs that include both novel small and large molecule approaches. These currently target over 12 indications with high unmet medical need.

我們的 Biohaven 實驗室也仍然忙於其早期發現工作，並且仍在不斷發展。我們有 10 多個臨床前項目，其中包括新穎的小分子和大分子方法。這些目前針對超過 12 種醫療需求未被滿足的適應症。

Our pipeline is not only advancing, but it's growing. We're delighted to have just announced the acquisition of Channel Biosciences, and we are really delighted to welcome their team into the Biohaven family. Their innovative potassium channel modulation platform is exciting, and we believe that the unique and differentiated pharmacology of their lead compound, will allow us to effectively study pediatric and adult seizure disorders. But I'll let Mike and Steven tell you about it in just a moment.

我們的管道不僅在推進，而且還在不斷增長。我們很高興剛剛宣布收購 Channel Biosciences，我們非常高興地歡迎他們的團隊加入 Biohaven 大家庭。他們的創新鉀通道調製平台令人興奮，我們相信其先導化合物獨特且差異化的藥理學將使我們能夠有效地研究兒童和成人癲癇。但我稍後會讓麥克和史蒂文告訴你這件事。

Additionally, we've added taldefgrobep, an anti-myostatin asset to our portfolio, and you will hear more about that as well. We will continue to make strategic decisions across the portfolio as our data matures with both external partnerships and internal programs. Our pipeline is large and growing, and I'm really excited about Biohaven's future.

此外，我們還在我們的產品組合中添加了 taldefgrobep（一種抗肌生長抑制素資產），您也會聽到更多相關資訊。隨著外部合作夥伴和內部計劃的數據不斷成熟，我們將繼續在整個產品組合中做出策略決策。我們的產品線規模龐大且不斷成長，我對 Biohaven 的未來感到非常興奮。

It's a real pleasure to be able to turn the call over to Mike Bozik and Steven Dworetzky to speak about Biohaven's newest innovative platform technology, Kv7.

很高興能夠將電話轉給 Mike Bozik 和 Steven Dworetzky 來談論 Biohaven 最新的創新平台技術 Kv7。

Thank you, Elyse. We couldn't be more delighted to be joining Biohaven Labs at such an exciting time for the business, and we're pleased to be delivering our Kv7 platform to the capable and efficient hands of Biohaven Pharmaceuticals. We founded the Kv7 platform at Channel Biosciences to address an ancient disease and also one of the most prevalent. In the United States alone, 3.5 million people suffer from epilepsy, a disease that can take over and disrupt your life because of seizures that can strike at any moment and comorbidities like depression and migraine headaches.

謝謝你，愛麗絲。我們非常高興能夠在如此令人興奮的業務時刻加入 Biohaven Labs，並且我們很高興將我們的 Kv7 平台交付給 Biohaven Pharmaceuticals 有能力且高效的人員。我們在 Channel Biosciences 創建了 Kv7 平台，以解決一種古老的疾病，也是最受歡迎的疾病之一。光是在美國，就有 350 萬人患有癲癇症，這種疾病可能會接管並擾亂您的生活，因為隨時可能發作的癲癇發作以及憂鬱症和偏頭痛等併發症。

Focal epilepsy is the most common form of the disease, affecting both children and adults, and for many patients, it's not easily treated. In fact, focal epilepsy is refractory in 1 in 3 adults and 1 in 4 children, often requiring 2 or more medications in highly individualized treatment regimens. Epilepsy is not only difficult to treat, but tragically, it can also be lethal. Each year, more than 1 in 1,000 people with epilepsy die from SUDEP, or sudden, unexpected death in epilepsy, in a person who was otherwise healthy.

局部性癲癇是這種疾病最常見的形式，影響兒童和成人，對許多患者來說，它並不容易治療。事實上，局部癲癇在三分之一的成人和四分之一的兒童中是難治性的，通常需要在高度個人化的治療方案中使用兩種或多種藥物。癲癇不僅難以治療，而且可悲的是，它還可能致命。 每年，超過千分之一的癲癇患者死於 SUDEP，即其他方面健康的人因癲癇突然、意外死亡。

Clearly, there's a missing piece in epilepsy treatment, and from the start, we targeted a critical regulator of neuronal excitability called Kv7, a voltage-gated potassium channel present in the brain. The field discovered Kv7 about 3 decades ago, but unlocking the pharmacology is proven difficult. Although targeting Kv7 has been clinically validated as a mechanism for seizure treatment, existing Kv7 activators carry tolerability risks. We believe our in-house team of biologists and medicinal chemists have cracked the Kv7 code. We have a library of small molecules in the platform with different pharmacology profiles and that have the potential for development in adjacent indications beyond epilepsy. We believe our lead molecule, BHV-7000, shows potential to be a best-in-class Kv7 activator.

顯然，癲癇治療中存在缺失的部分，從一開始，我們就瞄準了神經元興奮性的關鍵調節因子 Kv7，它是大腦中存在的電壓門控鉀通道。該領域大約 3 年前就發現了 Kv7，但事實證明，解開其藥理學是很困難的。儘管標靶 Kv7 已被臨床驗證為癲癇治療的機制，但現有的 Kv7 活化劑存在耐受性風險。我們相信我們內部的生物學家和藥物化學家團隊已經破解了 Kv7 密碼。我們在平台上擁有一個具有不同藥理學特徵的小分子庫，並且具有在癲癇以外的鄰近適應症中進行開發的潛力。我們相信我們的先導分子 BHV-7000 有潛力成為一流的 Kv7 活化劑。

BHV-7000, the lead candidate to emerge from our platform, was rationally designed to target Kv7. Importantly, it's structurally distinct from 2 other Kv7 activators, ezogabine and XEN1101, with patent life to at least 2039. Its profile is also highly differentiated because we dialed out the GABAergic activity intrinsic to these competing molecules. We expect BHV-7000 to be in the clinic this year an important next step in delivering what we hope will be a key missing piece for the treatment of epilepsy. The molecule also benefits from rare pediatric disease designation from the FDA.

BHV-7000 是我們平台上出現的主要候選產品，它是針對 Kv7 進行合理設計的。重要的是，它在結構上與其他 2 種 Kv7 活化劑 ezogabine 和 XEN1101 不同，專利壽命至少為 2039 年。我們預計 BHV-7000 今年將進入臨床，這是我們希望彌補癲癇治療關鍵缺失部分的重要的下一步。該分子還受益於 FDA 的罕見兒科疾病指定。

All in all, we're coming to Biohaven with a potential best-in-class treatment for epilepsy and with follow-on compounds from our Kv7 platform with a potential to treat other types of epilepsy as well as pain disorders and affective disorders.

總而言之，我們來到 Biohaven 時將帶來一種潛在的同類最佳癲癇治療方法，以及來自我們 Kv7 平台的後續化合物，這些化合物有可能治療其他類型的癲癇以及疼痛障礙和情緒障礙。

With that, I'll turn it over to my friend and colleague of 30 years, Dr. Steven Dworetzky.

接下來，我將把它交給我 30 年的朋友兼同事 Steven Dworetzky 博士。

Thanks, Mike. Let me reinforce being excited about the opportunity to be joining Biohaven Labs and working with the team to deliver BHV-7000 for rapid and efficient development by this organization.

謝謝，麥克。讓我再次對有機會加入 Biohaven Labs 並與團隊合作交付 BHV-7000 以實現該組織快速高效的開發感到興奮。

As Mike mentioned, we see BHV-7000 as highly differentiated from the existing Kv7 modulators, ezogabine and XEN1101. Those first and second generation drugs clinically validated Kv7 as a compelling target in epilepsy, but with attributes we have worked hard to overcome. For example, on the left panel, ezogabine is chemically unstable to light, and its label cites the risk of blue skin discoloration as well as a boxed warning for potential retinal effects and vision loss. In contrast, BHV-7000 is stable to photooxidation.

正如 Mike 所提到的，我們認為 BHV-7000 與現有的 Kv7 調變器、ezogabine 和 XEN1101 高度不同。這些第一代和第二代藥物在臨床上驗證了 Kv7 是治療癲癇的一個引人注目的靶點，但我們一直在努力克服其屬性。例如，在左側面板中，埃佐加賓對光化學不穩定，其標籤提到了皮膚變色的風險以及潛在視網膜影響和視力喪失的黑框警告。相比之下，BHV-7000 對光氧化穩定。

Shown in the middle panel, XEN1101, like ezogabine, has significant activity at the GABAA receptor, which may account for the off-target activities responsible for somnolence, dizziness, fatigue and other tolerability issues that have been recorded.

如中間圖所示，XEN1101 與 ezogabine 一樣，對 GABAA 受體具有顯著活性，這可能是導致嗜睡、頭暈、疲勞和其他已記錄的耐受性問題的脫靶活性的原因。

In comparison, as you can see, BHV-7000 has negligible activity for GABAA receptors. Our aim from the start was to avoid these liabilities while also maintaining potent antiseizure efficacy in vivo. Put another way, we want to maximize the therapeutic index by putting as much distance as possible between efficacy and intolerability.

相較之下，如您所見，BHV-7000 對 GABAA 受體的活性可以忽略不計。我們從一開始的目標就是避免這些責任，同時保持體內有效的抗癲癇功效。換句話說，我們希望透過在療效和不耐受之間保持盡可能大的距離來最大化治療指數。

As shown on the right panel, BHV-7000 attains that goal as both a potent activator of the Kv7 channel and was effective in preclinical seizure assays and was well tolerated.

如右圖所示，BHV-7000 作為 Kv7 通道的有效活化劑實現了這一目標，在臨床前癲癇試驗中有效，並且耐受性良好。

Allow me to share more detailed evidence in the following slide. Epilepsy happens to be a disease where the preclinical assays have excellent predictive validity in humans. What we're showing here on the left graph in the green circles is the number of animals protected from seizures with increasing dose. We demonstrate excellent potency with an ED50 of 0.5 mg per kg. Now take a look at the open red circles along the bottom of the graph. That is the measure of tolerability according to a neurological deficit with 0 reflecting normal [animal] behavior. As you can see, these animals are normal. The shaded area between the green and red results calculate a therapeutic index greater than 40 fold. On the right, you can see the similar experiment for ezogabine. The green triangles represent the antiseizure efficacy, which you see has an ED50 of about 20 mg per kg, so the potency is much lower than for BHV-7000.

請允許我在下面的幻燈片中分享更詳細的證據。癲癇恰好是一種臨床前檢測對人類具有優異預測有效性的疾病。我們在左圖的綠色圓圈中顯示的是隨著劑量的增加而免受癲癇發作的動物數量。我們展示了出色的效力，ED50 為 0.5 毫克/公斤。現在看一下圖表底部的空心紅色圓圈。這是根據神經缺陷來衡量耐受性的指標，0 反映了正常的[動物]行為。正如你所看到的，這些動物都是正常的。綠色和紅色結果之間的陰影區域計算出大於 40 倍的治療指數。在右側，您可以看到 ezogabine 的類似實驗。綠色三角形代表抗癲癇功效，您可以看到其 ED50 約為 20 毫克每公斤，因此其效力遠低於 BHV-7000。

Let me turn your attention to the red triangles, which you can see shows the neurological deficit increasing with increasing dose and is close to the efficacy dose. Thus, the therapeutic index is approximately threefold compared to more than 40 fold for BHV-7000. This approximates the clinical experience with ezogabine as the drug was poorly tolerated. We do not have the same experiment results for XEN1101, but based on Xenon reported data, we estimate its therapeutic index at approximately sixfold, somewhat better than ezogabine, but dramatically different than the greater than 40-fold therapeutic index of BHV-7000.

讓我把你的注意力轉向紅色三角形，你可以看到它顯示神經功能缺損隨著劑量的增加而增加，並且接近有效劑量。因此，與 BHV-7000 的 40 倍以上相比，治療指數約為三倍。這近似於依佐加濱的臨床經驗，因為該藥物的耐受性很差。我們沒有獲得與 XEN1101 相同的實驗結果，但根據 Xenon 報告的數據，我們估計其治療指數約為 6 倍，略好於 ezogabine，但與 BHV-7000 超過 40 倍的治療指數顯著不同。

Our aim is to develop and deliver the third-generation, best-in-class Kv7 modulator, and we hope this will give people with refractory epilepsy better control of their diseases and their lives.

我們的目標是開發和提供第三代一流的 Kv7 調製器，我們希望這將使難治性癲癇患者更好地控制他們的疾病和生活。

In closing, we believe BHV-7000 significantly differentiates from other molecules in this class of Kv7 activation. The graphic shows where we believe the superiority of our lead asset will provide the potential best-in-class for the treatment of refractory epilepsy and other neurological hyperexcitability disorders.

最後，我們認為 BHV-7000 與此類 Kv7 活化中的其他分子顯著不同。這張圖顯示了我們相信我們的主要資產的優越性將為難治性癲癇和其他神經性過度興奮性疾病的治療提供潛在的同類最佳產品。

Thanks for the chance to share a bit of the 7000 story, and now back to you, Elyse.

感謝您有機會分享 7000 故事的一些內容，現在回到您身上，Elyse。

Thanks so much. I would also like to introduce Cliff Bechtold, who will provide a brief update on the recently in-licensed anti-myostatin inhibitor.

非常感謝。我還想介紹一下 Cliff Bechtold，他將簡要介紹最近獲得許可的抗肌生長抑制素抑制劑的最新情況。

Thanks, Elyse. We're very excited to add taldefgrobep to the Biohaven portfolio. Myostatin is a well-characterized negative regulator of muscle growth. Based on a number of disease models and clinical studies, we believe a molecule that can target the signaling pathway of myostatin has potential in many different disease areas that could lead to improved strength and function in patients with muscular dystrophies and other neuromuscular diseases as an adjuvant to the current therapies.

謝謝，愛麗絲。我們非常高興將 taldefgrobep 添加到 Biohaven 產品組合中。肌肉生長抑制素是一種眾所周知的肌肉生長負調節劑。基於大量的疾病模型和臨床研究，我們相信一種能夠針對肌肉生長抑制素訊號路徑的分子在許多不同的疾病領域具有潛力，可以作為佐劑改善肌肉營養不良症和其他神經肌肉疾病患者的力量和功能到目前的治療方法。

Taldefgrobep alfa is an advanced development program that has extensive human data, especially in the pediatric population. With this robust package, we will be able to rapidly enter Phase III in neuromuscular diseases, including SMA. I know this asset very well. I led the program while I was at BMS and oversaw its development into -- from the lab into Phase III. This program will synergize with Biohaven's experience in ataxia and other rare diseases, and we are looking forward to partnering with SMA community of patients, physicians and advocacy organizations to find novel combination therapies.

Taldefgrobep alfa 是一項先進的開發計劃，擁有廣泛的人類數據，尤其是兒科人群的數據。憑藉這項強大的一攬子計劃，我們將能夠迅速進入包括 SMA 在內的神經肌肉疾病的 III 期臨床。我非常了解這項資產。我在 BMS 期間領導了該項目，並監督其從實驗室到第三階段的發展。該計劃將與 Biohaven 在共濟失調和其他罕見疾病方面的經驗產生協同作用，我們期待與 SMA 患者社區、醫生和倡導組織合作，尋找新的聯合療法。

With that background, I'm going to hand it back to Vlad.

有了這個背景，我要把它交還給弗拉德。

Thank you, Matt, BJ, Elyse, Mike, Steven and Cliff. And once again, welcome to the entire Channel Biosciences team. We're so excited to have you part of Biohaven and also on behalf of the whole team at Biohaven, we just want to say how excited we are to be working with Mike and Steven again. Many might not know this, but they were both important leaders at the BMS Neuroscience Group that many of us were all part of years back, so it's somewhat of a homecoming to have them in the company and working with us again.

謝謝馬特、BJ、愛麗絲、麥克、史蒂文和克里夫。再次歡迎整個 Channel Biosciences 團隊。我們很高興您成為 Biohaven 的一員，並代表 Biohaven 的整個團隊，我們只想說我們非常高興再次與 Mike 和 Steven 合作。許多人可能不知道這一點，但他們都是BMS 神經科學小組的重要領導者，我們中的許多人多年前都曾是該小組的成員，因此讓他們加入公司並再次與我們合作有點像回家一樣。

In closing, Biohaven has demonstrated robust growth in our commercialization of NURTEC ODT, an important maturation of our late-stage innovative pipeline. We continue to expand our clinical pipeline as well as our early-stage portfolio with a goal of increasing value and growth year-over-year.

最後，Biohaven 在 NURTEC ODT 商業化方面表現出了強勁的成長，這是我們後期創新管道的重要成熟。我們繼續擴大我們的臨床管道以及早期產品組合，目標是逐年增加價值和成長。

Our commitment to people with migraine around the globe has never been stronger, and our global expansion with Pfizer will open the door to the 1 billion people worldwide who suffer from this debilitating disease.

我們對全球偏頭痛患者的承諾從未如此堅定，我們與輝瑞的全球擴張將為全世界 10 億患有這種衰弱疾病的人打開大門。

Before opening up to Q&A, I would like to thank the entire Biohaven team for their relentless commitment, drive and value creation for patients and investors. I also want to take the opportunity to thank all the patients who have enrolled in our clinical trials, their family members and investigators who participated in advancing our pipeline. We will continue to work hard to bring novel treatments to patients living with the burden of devastating neurologic and neuropsychiatric diseases.

在開始問答之前，我要感謝整個 Biohaven 團隊為患者和投資者所做的不懈承諾、動力和價值創造。我也想藉此機會感謝所有參加我們臨床試驗的患者、他們的家人以及參與推進我們的產品線的研究人員。我們將繼續努力為患有毀滅性神經系統和神經精神疾病的患者提供新的治療方法。

Finally, thank you again to our visionary investors who have helped fund our studies and bring NURTEC ODT to patients.

最後，再次感謝我們富有遠見的投資者，他們幫助資助我們的研究並將 NURTEC ODT 帶給患者。

Operator, we'd now like to open up the call and take some questions.

接線員，我們現在要接通電話並回答一些問題。

(Operator Instructions) Our first question today is coming from Ken Cacciatore from Cowen and Company.

（操作員說明）今天我們的第一個問題來自 Cowen and Company 的 Ken Cacciatore。

Congratulations on all the progress. I was wondering with no formal guidance, could you give us a sense of comfort maybe around The Street's NURTEC-specific revenues for this year around $850 million?

祝賀所有的進展。我想知道，在沒有正式指導的情況下，您能為我們帶來安慰嗎？

And then maybe, Matt, could you speak a little bit to the thoughts on spending this year? Is that Q4 run rate good? And then a general question for you, Vlad. Obviously, really exciting new pipeline additions, but some investors do worry that increasing the pipeline investment, which you further enhanced today, could detract from NURTEC value. It's just hard to value the pipeline versus easier to value NURTEC. So can you talk about the balance of really huge spending to support NURTEC need to invest in pipeline versus potentially an exit or maybe even a split of the business or all options still on the table? Can you talk us through that?

然後，馬特，你能談談今年支出的想法嗎？第四季的運作率好嗎？然後是一個一般性問題要問你，弗拉德。顯然，新管道的增加確實令人興奮，但一些投資者確實擔心，今天進一步加強的管道投資的增加可能會降低 NURTEC 的價值。只是評估管道的價值比較困難，而評估 NURTEC 的價值則比較容易。那麼，您能否談談支持 NURTEC 需要投資管道的巨額支出與潛在退出、甚至業務分割或仍在考慮中的所有選項之間的平衡？你能跟我們談談嗎？

All right. I'll have Matt start off, and then I'll jump in.

好的。我會讓馬特開始，然後我會加入。

Yes, Ken, as you know, we don't provide guidance. So I can't really comment on the $850 million. And as it relates to sort of the Q4 run rate for expenses, we do expect modest increases on the expense side, and we just have added a few really promising assets which would be part of that calculation.

是的，肯，如你所知，我們不提供指導。所以我無法對這 8.5 億美元做出真正的評論。由於它與第四季度的費用運行率有關，我們確實預計費用方面會適度增長，而且我們剛剛添加了一些真正有前途的資產，這些資產將成為計算的一部分。

So Ken, we're excited about NURTEC. And as you know from prior discussions, when you look at where we are in our net revenue generation and where we and others believe will be in future years, there's very few drugs that have this type of potential both for patients and net revenue generation for companies. So I don't think we have a large spend to support that. I think it's an appropriate infrastructure size and spend to what we believe ultimately will be a multibillion-dollar net revenues at the peak sales.

Ken，我們對 NURTEC 感到很興奮。正如您從先前的討論中知道的那樣，當您查看我們的淨收入產生情況以及我們和其他人認為未來幾年的情況時，很少有藥物對患者和淨收入產生都具有這種潛力。 。所以我認為我們沒有大量支出來支持這一點。我認為這是一個合適的基礎設施規模和支出，我們相信最終將在銷售高峰時實現數十億美元的淨收入。

And I'll give you a little bit of a glimpse as to how early we are and how much growth is ahead of us, and so in addition to the revenue from NURTEC, we do want to make sure we have other assets that can mature into the commercialization infrastructure that we have. And I think what you saw today is an addition of what I would view as to derisk mechanisms of actions that are very much fast-follower approaches. And when you look at some of the external data that's been generated in Kv7 and epilepsy and the predictability of assays to how those assets will perform in the clinic, we think these are high probability or higher probability wins in neuroscience. And that's why we're so excited to be incorporating them into the pipeline.

我將讓您大致了解我們現在的發展有多早，以及我們還有多少成長空間，因此，除了 NURTEC 的收入之外，我們確實希望確保我們擁有其他可以成熟的資產進入我們擁有的商業化基礎設施。我認為你們今天看到的內容是我所認為的消除風險行動機制的補充，這些行動機制在很大程度上是快速追隨者的方法。當您查看 Kv7 和癲癇症中產生的一些外部數據以及這些資產在臨床中表現的分析的可預測性時，我們認為這些是神經科學領域的高機率或更高機率的勝利。這就是為什麼我們如此興奮地將它們納入管道中。

Your question about M&A and other activity, as you know, we can't comment too much on that, other than to say that look, acquisitions like today in broadening the pipeline just strengthens our company, and strengthens, I think, our ability to organically generate increased revenue in future years or for something that would be of interest to other parties, right, to put together a pipeline like this. So we're going to continue to run our business, maximize investor returns and grow value, and we're going to continue to do that until there's a reason not to do.

你關於併購和其他活動的問題，如你所知，我們不能對此發表太多評論，除了說看起來，像今天這樣擴大管道的收購只會增強我們的公司，並且增強我認為我們的能力在未來幾年有機地產生增加的收入，或者為了其他各方感興趣的東西，對吧，組建這樣的管道。因此，我們將繼續經營我們的業務，最大限度地提高投資者回報並增加價值，我們將繼續這樣做，直到有理由不這樣做為止。

So thanks for the question, Ken, and I appreciate it.

謝謝你的提問，肯，我很感激。

Next question is from Charles Duncan from Cantor Fitzgerald.

下一個問題來自康托·菲茨杰拉德的查爾斯·鄧肯。

Congrats, Vlad and team, on continued good commercial execution as well as the news flow this morning. I wanted to ask a commercial question for BJ, and that is that, BJ, you mentioned in your prepared remarks that you've seen earlier returns to growth in the first quarter than perhaps you would have expected given your experience in previous years. And I'm just wondering if you could provide some more color on that. And then relative to the current, I'll call it, adoption rate of the oral CGRPs and specifically, NURTEC ODT, what message would you like prescribers to hear that could drive further adoption of the class and the drug specifically?

恭喜弗拉德和團隊繼續保持良好的商業執行力以及今天早上的新聞報導。我想向BJ 問一個商業問題，那就是，BJ，您在準備好的發言中提到，根據您前幾年的經驗，您在第一季度看到的增長恢復速度可能比您預期的要早。我只是想知道你是否可以提供更多的顏色。然後，相對於目前（我將其稱為口服 CGRP，特別是 NURTEC ODT）的採用率，您希望處方者聽到什麼資訊來推動該類別和藥物的進一步採用？

Charles, thank you for the question. I appreciate that. And I would say, just to provide a little context around the comment around the earlier growth is that it is a little bit slow in regards to what the uptake is in Q1 normally. Again, that's not just a -- either a NURTEC or a migraine issue in some sense, right? It's just more broad across the industry.

查爾斯，謝謝你的提問。我很欣賞這一點。我想說，只是為了提供一些有關早期增長的評論的背景信息，即與第一季度通常的增長相比，增長有點慢。再說一次，從某種意義上說，這不僅僅是一個 NURTEC 或偏頭痛問題，對吧？它只是在整個行業中更加廣泛。

But I will say that, again, in recent weeks, basically starting in February, we started to see what is kind of that return to growth again and I'd say, across the class, which is a positive news for us. Again, there are good reasons for that. I think a lot of it is the incremental promotion that's happening because of different products actually entering the market as well, which actually benefits everyone, especially patients. So that's a good news story overall. So that points to greater growth, and we're pleased about what that means for coming weeks.

但我要再說一遍，最近幾週，基本上從二月開始，我們開始看到再次恢復成長的情況，我想說，整個班級，這對我們來說是一個積極的消息。同樣，這是有充分理由的。我認為這很大程度上是由於不同的產品實際上進入市場而發生的增量促銷，這實際上使每個人，尤其是患者受益。總的來說，這是一個好消息。因此，這意味著更大的成長，我們對這對未來幾週意味著什麼感到高興。

As it relates to the adoption rate that's happening and what I'd like to say to prescribers, and this is essentially what we communicate on a day-to-day basis, right, with all of our customers out there is that essentially, now they have an opportunity to utilize a product for patients who have been suffering in this space for so long, with clearly very, very little risk, but tremendous upside for those individuals. And they can use it in this convenience platform, which, again, is one product.

因為它與正在發生的採用率以及我想對處方者說的話有關，這本質上是我們每天與所有客戶溝通的內容，本質上，現在他們有機會為那些在這個領域長期受苦的患者使用一種產品，顯然風險非常非常小，但對這些人來說卻有巨大的好處。他們可以在這個便利平台中使用它，這又是一個產品。

Obviously, you're right. That can treat and prevent, and it's one dose. And again, does not have the same kind of baggage, if you will, that the older medications have had in the past. And so I would say, again, I think it's part of what is the fire that's lit kind of under this marketplace is that clinicians perceive that. They see it. They actually get trial and get tremendous feedback from patients, and that is what we believe really will fuel this market going forward.

顯然，你是對的。既可治療又可預防，而且只需一劑。再說一次，如果你願意的話，它沒有與過去的舊藥物相同的包袱。所以我想再說一遍，我認為臨床醫生意識到了這一點，這也是這個市場點燃的火焰的一部分。他們看到了。他們實際上得到了試驗並從患者那裡得到了大量回饋，我們相信這將真正推動這個市場的發展。

Your next question is coming from Chris Raymond from Piper Sandler.

您的下一個問題來自 Piper Sandler 的 Chris Raymond。

Just a couple of questions on some of these new assets, if you don't mind. So I guess the anti-myostatin, just did some digging on this molecule. It looks like it's been studied already in DMD and failed to show impact on ambulatory measures. I know DMD and SMA are different in a lot of ways, but just kind of what you guys are seeing -- are you seeing in the data that sort of gives confidence in this indication? And then just thinking about Phase III design, is it contemplated this to be looked at in combo with a disease modifier like Spinraza? Any details on that sort of plan would be great.

如果您不介意的話，我想問幾個關於其中一些新資產的問題。所以我猜抗肌生長抑制素只是對這個分子進行了一些挖掘。看起來它已經在 DMD 中進行了研究，但未能顯示出對動態測量的影響。我知道 DMD 和 SMA 在很多方面都有所不同，但這就是你們所看到的——你們在數據中看到的數據是否對這一跡象充滿信心？然後想想第三階段的設計，是否考慮將其與像 Spinraza 這樣的疾病調節劑結合？有關此類計劃的任何細節都很棒。

And then I guess on the Kv7 asset, it looks like this is -- has on the Knopp website anyway, is in development for epileptic encephalopathy. Can you maybe -- is that still on the table as an indication that you're targeting? Is maybe sort of a quick path to market? Just maybe talk about that a little bit.

然後我猜想在 Kv7 資產上，它看起來是——無論如何，在 Knopp 網站上都有，正在針對癲癇性腦病進行開發。你能——這仍然在桌面上作為你的目標的指示嗎？也許這是一種快速進入市場的途徑？也許只是稍微談談這一點。

And then maybe if I can put one more question to you guys, maybe more strategic, just on how you're thinking about guidance. Are there some elements around the business that you're looking for before guiding? Or is there maybe sort of some philosophical reason to not guide?

然後也許我可以再向你們提出一個問題，也許更具策略性，只是關於你們如何考慮指導。在指導之前，您是否需要尋找一些圍繞業務的元素？或是否有某種哲學原因不予指導？

Great. Chris, just I'll turn it over to Mike in a minute to talk about Kv7 response to that comment. On myostatin, I'll also have Cliff chime in here, but the mechanism of action has not been demonstrated in DMD to establish efficacy. However, we have a very large safety database from that experience. And as you know, the Scholar Rock data in SMA with a similar myostatin targeting did suggest efficacy, and that's really the clinical proof-of-concept that is advancing our interest in this area. We also note that there's other competitors, Roche, who have a myostatin targeting agent as well. So Roche and Scholar Rock are both heading into SMA, given the recent clinical POC there. We believe that this has the potential to be a best-in-class myostatin targeting agent and excited to quickly advance into SMA given the emerging data.

偉大的。克里斯，我稍後會將其轉給麥克，討論 Kv7 對此評論的回應。關於肌肉生長抑制素，我也會在這裡請 Cliff 指出，但其作用機制尚未在 DMD 中證實，無法確定療效。然而，我們從這些經驗中獲得了一個非常大的安全資料庫。如您所知，具有類似肌肉生長抑制素靶向的 SMA 的 Scholar Rock 數據確實表明了療效，這確實是臨床概念驗證，正在推動我們對該領域的興趣。我們也注意到其他競爭對手羅氏也有肌肉生長抑制素標靶劑。鑑於最近的臨床 POC，羅氏和 Scholar Rock 都將進入 SMA 領域。我們相信，這有潛力成為同類最佳的肌肉生長抑制素標靶劑，鑑於新出現的數據，我們很高興能迅速進入 SMA 領域。

Cliff, do you want to add anything to that?

克里夫，你想補充什麼嗎？

Yes, just really quickly. I think what we learned at the Duchenne area is that this molecule is very safe. It's well tolerated in pediatric population. But we also learned that it's -- as a monotherapy, it's -- it didn't hit the significance to see a clinical benefit. What's different in SMA is the presence of the SMN upregulating therapies that are approved in the market, which we think and demonstrated by preclinical models, will show a synergistic effect. And so that's why we're targeting SMA to begin with.

是的，只是非常快。我認為我們在杜興地區了解到這種分子非常安全。它在兒童群體中具有良好的耐受性。但我們也了解到，作為單一療法，它並沒有達到臨床效益的意義。 SMA 的不同之處在於市場上批准的 SMN 上調療法的存在，我們認為並透過臨床前模型證明，將顯示出協同效應。這就是我們首先瞄準 SMA 的原因。

Great. And yes, the study would be in combination with standard of care gene therapy and others. Great. And then, Mike, do you want to comment on Kv7?

偉大的。是的，這項研究將與標準護理基因療法和其他療法結合。偉大的。然後，Mike，你想對 Kv7 發表評論嗎？

Sure. We're really excited to be joining the Biohaven team and their commitment to advancing BHV-7000 in -- for the treatment of epilepsy. And answering to your question, the drug has great sort of clinical proof-of-concept as a treatment for adult refractory focal epilepsy. So we'll clearly be advancing the drug along that path. It's an established clinical development pathway. We're following footprints in the snow. So that is a strong commitment.

當然。我們非常高興能夠加入 Biohaven 團隊以及他們致力於推進 BHV-7000 治療癲癇的承諾。回答你的問題，該藥物作為治療成人難治性局部癲癇的藥物已經得到了很好的臨床概念驗證。因此，我們顯然將沿著這條道路推進該藥物。這是一個既定的臨床開發途徑。我們追隨雪地裡的腳印。所以這是一個堅定的承諾。

We're equally committed to exploring the potential of the drug as a pediatric epilepsy treatment, including the opportunity to treat patients with KCNQ2 epileptic encephalopathy. So we'll be advancing the molecule in clinical development. As you know, there are steps that you need to take before you can treat children and certainly young children. And so we'll be doing -- taking the steps that we need to be able to walk down that path.

我們同樣致力於探索該藥物作為小兒癲癇治療的潛力，包括治療 KCNQ2 癲癇性腦病患者的機會。因此，我們將在臨床開發中推進該分子。如您所知，在治療兒童，尤其是幼兒之前，您需要採取一些步驟。因此，我們將採取我們需要的步驟來走上這條道路。

Great. And Matt, do you want to guide anything?

偉大的。馬特，你想指導什麼嗎？

Yes. I mean from a guidance perspective, I think we're going to be more comfortable getting to a place where we're guiding next year. At this point, we have a lot of variables, a lot of moving parts, including Pfizer and sort of how they're looking at this in EU from a contribution. We have prevention, which is still kind of early-ish in the launch phase. We have a highly competitive environment. So there are variables there as well. So as we get more comfortable with all those, we'll start to provide guidance.

是的。我的意思是，從指導的角度來看，我認為我們明年會更輕鬆地達到我們指導的目標。在這一點上，我們有很多變量，很多變化的部分，包括輝瑞以及他們在歐盟如何看待這個問題。我們有預防措施，但仍處於啟動階段的早期階段。我們擁有一個競爭激烈的環境。所以這裡面也存在變數。因此，當我們對所有這些感到更加滿意時，我們將開始提供指導。

Our next question is coming from Paul Choi from Goldman Sachs.

我們的下一個問題來自高盛的 Paul Choi。

Let me add my congrats on all the progress as well. My first question is for Vlad and BJ as well maybe. As you're thinking about the commercial execution strategy here in '22, you launched in the pandemic environment, which involves a lot of virtual selling. How are you thinking maybe about pivoting to more feet on the street to grow the NURTEC franchise over the course of this year and next year as we exit the pandemic?

讓我也對所有進展表示祝賀。我的第一個問題也許也是問 Vlad 和 BJ 的。當您在考慮 22 年的商業執行策略時，您是在大流行環境下推出的，其中涉及大量虛擬銷售。您如何考慮在今年和明年我們擺脫疫情後，更多地涉足街頭以發展 NURTEC 特許經營權？

And then second, on the pipeline, maybe for Elyse. As you think about the clinical strategy for SMA, is there going to be a particular focus on a subpopulation, whether it's type 1 that where you see the highest probability or type 2 and so forth? And just maybe any specifics you can provide on just sort of your high-level thoughts on clinical trial design here would be great.

其次，正在籌備中，可能是為 Elyse 設計的。當您考慮 SMA 的臨床策略時，是否會特別關注某個亞群，無論是您認為機率最高的 1 型還是 2 型等等？也許您能在這裡提供有關臨床試驗設計的高級想法的任何具體細節都會很棒。

Thanks, Paul. And with regard to this year, the pandemic -- we demonstrated the success of NURTEC despite the pandemic. And I think it reflects how debilitating this illness is and that people will go out and get a novel treatment because they're so disabled by migraine when it strikes. So we've demonstrated the ability to do this well in a very harsh environment. And what we see from the data is that as patient traffic and volume at physicians office increases, we do better. And so we believe as the pandemic gets behind us, there will be a greater opportunity to increase volume, and we are not planning anything other than modest changes to our sales force. There will be some -- like always, some optimization to ensure we're remaining highly competitive at maximizing share, but you're going to see a continued emphasis on digital and virtual in addition to the in-person, of course. But the things that made us successful during the pandemic, we're going to continue to optimize as that alleviates.

謝謝，保羅。至於今年的大流行——儘管有大流行，我們還是展示了 NURTEC 的成功。我認為這反映了這種疾病是多麼令人衰弱，人們會出去接受新的治療，因為偏頭痛發作時他們會變得非常殘疾。因此，我們已經展示了在非常惡劣的環境中做好這件事的能力。我們從數據中看到，隨著醫生辦公室的患者流量和數量增加，我們做得更好。因此，我們相信，隨著大流行的結束，我們將有更大的機會增加銷量，除了對我們的銷售團隊進行適度的改變之外，我們沒有其他計劃。像往常一樣，將會有一些優化，以確保我們在最大化份額方面保持高度競爭力，但當然，除了面對面之外，您還會看到對數位和虛擬的持續重視。但在疫情期間讓我們取得成功的事情，隨著疫情的緩解，我們將繼續優化。

BJ, you want to add anything to that?

BJ，你想補充什麼嗎？

The only thing I'll add is, very well said, Vlad, thank you, I'd say is that we are absolutely committed to what is kind of our digital-first approach. And again, that is in the full light of day, hopefully, as this pandemic passes. And the beauty is, what we can and (inaudible) build this capability so that we can actually integrate that with our feet on the street. And as Vlad mentioned, it will be what is kind of a modest incremental investment in feet on the street. But we are focused on increasing impact, right, of each one of our folks out there, and we look forward to the full year.

我唯一要補充的是，說得很好，弗拉德，謝謝你，我想說的是，我們絕對致力於我們的數位優先方法。再說一次，希望隨著這場大流行的過去，這一切都在光明之中。美妙之處在於，我們可以（聽不清楚）建立這種能力，以便我們能夠將其與我們在街上的腳步結合起來。正如弗拉德所提到的，這將是對街上人流量的適度增量投資。但我們專注於增加我們每個人的影響力，對吧，我們期待全年。

And I'd like Cliff and Elyse to maybe make a comment.

我希望 Cliff 和 Elyse 發表評論。

Yes. On the design of the SMA, I mean one thing that the field has changed significantly, and we've been partnering with thought leaders and experts in the area to understand that with the advances in the marketed products that are operating on the SMA, and we're seeing it move away from the classification of SMA 2 and 3 because they are performing differently. So partnering with the experts in the field with patient advocacy, we're still coming up with the right design to move forward.

是的。關於 SMA 的設計，我的意思是該領域發生了重大變化，我們一直在與該領域的思想領袖和專家合作，以了解隨著在 SMA 上運行的上市產品的進步，以及我們看到它脫離了SMA 2 和3 的分類，因為它們的性能不同。因此，透過與患者倡導領域的專家合作，我們仍在提出正確的設計來推進。

Our final question today is coming from Laura Chico from Wedbush.

我們今天的最後一個問題來自韋德布希的勞拉·奇科。

Just 2 on the pipeline. So first, BHV-7000. Could you talk a little bit more on how you see clinical points of differentiation manifesting? It sounds like you're highlighting GABAA activation. And I'm just curious if this -- how this plays out? Is this more on the adverse event side? And I guess, how would you elaborate or could you elaborate on how you would tease that out from a trial design perspective?

管道上只有 2 個。首先是 BHV-7000。能多談談您如何看待臨床分化點的表現嗎？聽起來你在強調 GABAA 活化。我只是好奇這會如何進行？這更多是在不良事件方面嗎？我想，你會如何詳細說明，或者你能詳細說明如何從試驗設計的角度梳理出這一點嗎？

And then just with respect to verdiperstat, I know we're getting results in around the middle of the year, but could you talk a little bit more about the communication strategy around those top line results? This is obviously a unique design evaluating a couple of different therapies in the study. So I just want to make sure I understand perhaps how the degree of disclosure might work or who will be leading that effort?

然後就 verdiperstat 而言，我知道我們將在今年年中左右獲得結果，但您能否更多地談論圍繞這些頂線結果的溝通策略？這顯然是一個獨特的設計，評估了研究中的幾種不同療法。所以我只是想確保我了解披露程度如何發揮作用，或者誰將領導這項工作？

Sure. So we'll invite Mike and Steven to comment and reply on the Kv7. Mike, do you want to start?

當然。因此，我們將邀請 Mike 和 Steven 對 Kv7 進行評論和回應。麥克，你想開始嗎？

Sure. So as you probably know, the first and second generation Kv7 activators are not specific for Kv7. They have a GABAA activation component to their pharmacology. And we specifically dialed out the GABAA activity because we're very confident, and we have the preclinical data to show that Kv7 activation alone is sufficient for efficacy and potent efficacy of that.

當然。您可能知道，第一代和第二代 Kv7 啟動器並非專門針對 Kv7。它們的藥理學具有 GABAA 活化成分。我們特別指出了 GABAA 活性，因為我們非常有信心，我們有臨床前數據表明，僅 Kv7 活化就足以實現其功效和有效功效。

And then what has really limited Kv7 activators to date is the fact that as you become effective, you bump up against side effects, somnolence, vertigo, diplopia. And when you hit those side effects, you can't go further, and so you have efficacy limitations and you also have compliance limitations. And we have preclinical evidence that we don't see this. So we will be looking for differentiation in terms of side effect profiles. And there are other liabilities that the first and second generation activators have had, including events of urinary retention. So we think we'll be differentiated both as a more potent activator of the target, which we hope will translate into very good efficacy as well as a compound that will be very well tolerated and patients will stay on the drug.

到目前為止，真正限制 Kv7 活化劑的是這樣一個事實：當你變得有效時，你會遇到副作用，嗜睡、眩暈、複視。當您遇到這些副作用時，您將無法再進一步，因此您會受到功效限制，並且也會受到合規性限制。我們有臨床前證據表明我們沒有看到這一點。因此，我們將尋找副作用方面的差異化。第一代和第二代活化劑還有其他缺點，包括尿滯留事件。因此，我們認為我們將成為一種更有效的標靶活化劑，我們希望這將轉化為非常好的療效，同時也是一種具有良好耐受性且患者將繼續用藥的化合物。

Great. And just to wrap up on the question about the HEALEY and the ALS trial. So although that's a platform trial with multiple different assets, they share a placebo arm, as an asset reads out, we will get the top line on that asset. So we're not waiting for other assets to read out. So once we get to that top line data, it will be revealed, and we're thinking somewhere around midyear.

偉大的。最後總結一下有關希利和 ALS 試驗的問題。因此，儘管這是一個使用多種不同資產的平台試驗，但它們共享一個安慰劑臂，當資產讀出時，我們將獲得該資產的頂線。所以我們不會等待其他資產讀出。因此，一旦我們獲得了最重要的數據，它就會被披露，我們正在考慮在年中左右進行。

So I know we have to wrap up now as we're out of time. So thank you, everyone, for joining us today. We deeply appreciate the support of our employees and investors as we move forward to delivering life-changing therapies to patients and talk to everyone very soon. Thank you.

所以我知道我們現在必須結束了，因為時間已經不多了。謝謝大家今天加入我們。我們非常感謝員工和投資者的支持，因為我們正在努力為患者提供改變生活的療法，並很快與每個人交談。謝謝。

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

謝謝。今天的電話會議和網路廣播到此結束。此時您可以斷開線路，度過美好的一天。我們感謝您今天的參與。