Zogenix, Inc. (ZGNX) 2021 Q3 法說會逐字稿

This is the conference operator. Welcome to the Zogenix, Inc. Third Quarter 2021 Financial Results Conference Call. (Operator Instructions) The conference is being recorded. (Operator Instructions)

這是會議操作員。歡迎參加 Zogenix, Inc. 2021 年第三季財務績效電話會議。 （操作員指示）會議正在錄音。 （操作員說明）

I would now like to turn the conference over to Brian Ritchie of LifeSci Advisors. Please go ahead, Mr. Ritchie.

我現在想將會議轉交給 LifeSci Advisors 的 Brian Ritchie。請繼續，里奇先生。

Thank you, operator, and thank you all for joining the Zogenix management team this afternoon. On today's call are Chief Executive Officer, Dr. Stephen Farr; Chief Operating Officer, Ashish Sagrolikar; Chief Development Officer, Dr. Gail Farfel; Chief Medical Officer, Dr. Brad Galer; and Chief Financial Officer, Michael Smith.

謝謝運營商，也感謝大家今天下午加入 Zogenix 管理團隊。出席今天電話會議的有執行長 Stephen Farr 博士；營運長 Ashish Sagrolikar；首席開發長蓋爾法菲爾博士；首席醫療官 Brad Galer 博士；和首席財務官邁克爾·史密斯。

This afternoon, Zogenix issued a news release providing a business update and announcing financial results for the 3 and 9 months ended September 30, 2021. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Zogenix management will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Zogenix's press release issued today and the company's SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, November 4, 2021. Zogenix undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.

今天下午，Zogenix 發布了一份新聞稿，提供業務更新並公佈截至2021 年9 月30 日的3 個月和9 個月的財務業績。請注意，今天電話會議中討論的某些資訊包含在私人證券訴訟的安全港條款中改革法案。我們提醒聽眾，在這次電話會議中，Zogenix 管理層將做出前瞻性聲明。由於與公司業務相關的風險和不確定性，實際結果可能與這些前瞻性陳述中明示或暗示的結果有重大差異。這些前瞻性陳述受到 Zogenix 今天發布的新聞稿和該公司向 SEC 提交的文件（包括 10-K 表格年度報告和後續文件）中包含的警示性聲明的限制。本次電話會議還包含時間敏感信息，僅截至本次直播之日（2021 年11 月4 日）準確。Zogenix 不承擔修改或更新任何前瞻性陳述以反映本次直播之後發生的事件或情況的義務。電話會議。

Now, I'll turn the call over to Dr. Stephen Farr. Dr. Farr?

現在，我將把電話轉給史蒂芬法爾博士。法爾博士？

Thank you, Brian, and good afternoon to everyone, and thank you for joining us. I'm delighted to be here with you today to provide updates on another strong productive quarter for Zogenix as we continue to execute on the commercial launch of FINTEPLA in Dravet syndrome, prepared for a potential launch Lennox-Gastaut syndrome and advance our late-stage development programs for both FINTEPLA and MT1621.

謝謝布萊恩，大家下午好，謝謝您加入我們。我很高興今天能與大家一起提供Zogenix 另一個強勁生產季度的最新情況，我們將繼續執行用於Dravet 綜合徵的FINTEPLA 的商業上市，為潛在的Lennox-Gastaut 綜合徵上市做好準備，並推進我們的後期階段FINTEPLA 和 MT1621 的開發計劃。

Positive momentum for the launches of FINTEPLA in the U.S. and Europe continue. And once again, we achieved solid quarter-over-quarter growth in the number of prescribers of, patients on and net sales of FINTEPLA in both regions. In a moment, Ashish will provide additional color and perspective on the FINTEPLA market dynamics that are leading to the success and continued growth.

FINTEPLA 在美國和歐洲推出的積極勢頭仍在繼續。我們再次在兩個地區的 FINTEPLA 處方者數量、患者數量和淨銷售額方面實現了季度環比的穩健增長。稍後，Ashish 將為 FINTEPLA 市場動態提供更多見解和觀點，這些動態將帶來成功和持續成長。

We also remain excited with upcoming opportunities to potentially expand FINTEPLA as a treatment option in other severe refractory childhood onset epilepsy syndromes. Towards this goal, in September, we submitted a supplemental NDA to the FDA, seeking to expand the label indication of FINTEPLA the treatment of seizures associated with Lennox-Gastaut syndrome or LGS. There are an estimated 30,000 to 50,000 patients suffering from LGS in the United States, and notably, the majority of patients have uncontrolled seizures despite taking existing approved anti-seizure medications.

我們也對即將到來的機會感到興奮，有可能將 FINTEPLA 擴大為其他嚴重難治性兒童癲癇症候群的治療選擇。為了實現這一目標，我們在 9 月向 FDA 提交了補充新藥申請，尋求擴大 FINTEPLA 的標籤適應症，用於治療與 Lennox-Gastaut 綜合徵或 LGS 相關的癲癇發作。據估計，美國有 30,000 至 50,000 名 LGS 患者患有 LGS，值得注意的是，儘管服用了現有經批准的抗癲癇藥物，但大多數患者的癲癇發作仍不受控制。

Also, we're now getting close to starting our global Phase 3 trial of FINTEPLA patients with CDKL5 deficiency disorder or CDD. Several sites in the United States have recently being cleared to begin screening patients, and we anticipate the first patient enrolling in the study within the next few weeks. David Farfel, our Chief Development Officer, will provide more detail on both of these programs later on the call.

此外，我們現在即將開始對患有 CDKL5 缺乏症或 CDD 的 FINTEPLA 患者進行全球 3 期試驗。美國的幾個站點最近已獲準開始篩檢患者，我們預計第一名患者將在未來幾週內加入研究。我們的首席開發長 David Farfel 將在稍後的電話會議上提供有關這兩個項目的更多詳細資訊。

Last, during the quarter, we were pleased with the progress being made through regulatory interactions and ongoing development space for the MT1621 program on investigational substrate enhancement therapy for thymidine kinase 2 deficiency or TK2d. Brad Galer, our Chief Medical Officer, will walk you through this progress in more detail on this call.

最後，在本季度，我們對針對胸苷激酶 2 缺陷或 TK2d 的研究性底物增強療法的 MT1621 項目透過監管互動和持續開發空間所取得的進展感到高興。我們的首席醫療官 Brad Galer 將在本次電話會議上更詳細地向您介紹這項進展。

I also would like to remind you of our upcoming virtual investor event of the November 8, that will feature presentations by key opinion leaders on disease overview and natural history of TK2d and their experience with MT1621 as a treatment option for these TK2d patients.

我還想提醒您注意我們即將於 11 月 8 日舉行的虛擬投資者活動，該活動將由主要意見領袖就 TK2d 的疾病概述和自然史以及他們使用 MT1621 作為這些 TK2d 患者的治療選擇的經驗進行演講。

With that, I'll now hand the call over to Ashish. Ashish?

現在，我將把電話轉給 Ashish。阿什什？

Thank you, Steve. The continued solid growth for FINTEPLA in the third quarter, completing our first year of commercialization, all within a restricted COVID environment and in single rare indication, is reflective of the strong support we are seeing from patients, caregivers, health care providers and payers. That support paired with potential in multiple new indications and geographies provides us with confidence in FINTEPLA's commercial growth outlook in the short, medium and long term.

謝謝你，史蒂夫。 FINTEPLA 在第三季度持續穩健成長，完成了我們商業化的第一年，所有這些都是在受限制的新冠疫情環境下和單一罕見適應症中實現的，這反映了我們從患者、護理人員、醫療保健提供者和付款人那裡看到的大力支持。這種支持加上多個新適應症和地區的潛力，讓我們對 FINTEPLA 的短期、中期和長期商業成長前景充滿信心。

Starting with the U.S., during the third quarter, over 130 new patients were referred to the REMS program and 133 new patients started reimbursed therapy with FINTEPLA. This progress reflects a steady cadence of new patient adds, similar to the prior quarters from this year. By the end of the third quarter, over 990 patients in the U.S. have been prescribed FINTEPLA and referred to the REMS program.

從美國開始，第三季有超過 130 名新患者被轉介至 REMS 計劃，133 名新患者開始接受 FINTEPLA 報銷治療。這項進展反映了新患者增加的穩定節奏，與今年前幾季類似。截至第三季末，美國已有超過 990 名患者接受了 FINTEPLA 治療並轉至 REMS 計畫。

Adherence to the FINTEPLA therapy also remains strong and remarkably consistent with our experience in the long-term clinical trial and expanded access program. Since launch, the discontinuation rate is around 14% overall and 11% within Dravet syndrome patients. We believe these rates are substantially lower than typically observed with other anti-seizure medications commonly used to treat refractory epilepsies.

對 FINTEPLA 療法的依從性也仍然很強，並且與我們在長期臨床試驗和擴大使用計劃中的經驗非常一致。自推出以來，整體停藥率約為 14%，Dravet 症候群患者的停藥率為 11%。我們相信這些比率大大低於通常用於治療難治性癲癇的其他抗癲癇藥物的觀察結果。

We estimate that in the U.S., our market penetration among eligible Dravet syndrome patients is currently about 15% to 20%. Our internal research indicates that we should be able to increase the market penetration by at least threefold with time. For example, brand awareness for FINTEPLA among U.S. neurologists and epileptologists has almost doubled since late 2020 and is now higher than 80%. To take advantage of this momentum, we recently completed the expansion of our field-based sales and medical teams by adding experienced professionals with deep understanding of the epilepsy market.

我們估計，在美國，我們在符合條件的 Dravet 症候群患者中的市場滲透率目前約為 15% 至 20%。我們的內部研究表明，隨著時間的推移，我們應該能夠將市場滲透率提高至少三倍。例如，自 2020 年底以來，美國神經科醫生和癲癇科醫生對 FINTEPLA 的品牌認知度幾乎翻了一番，目前已超過 80%。為了利用這一勢頭，我們最近透過增加對癲癇市場有深入了解的經驗豐富的專業人員來完成了現場銷售和醫療團隊的擴張。

The field sales team is now configured to educate and support an expanded list of health care providers about FINTEPLA in Dravet syndrome. While it's still early, we have already seen some positive trends with respect to increased physician engagement leading to new prescribers in the fourth quarter. We continue to be very pleased with the payer coverage for FINTEPLA in both private and government sector. Typically, it takes 2 to 4 weeks for a new patient to receive FINTEPLA once they are referred to the REMS program and payer coverage continues to be strong with effectively all patients receiving positive insurance determinations.

現場銷售團隊現在已配置為向更多醫療保健提供者提供關於 Dravet 綜合徵 FINTEPLA 的教育和支援。雖然現在還為時過早，但我們已經看到了一些積極的趨勢，即醫生參與度的增加導致第四季度出現新的處方者。我們仍然對 FINTEPLA 在私營和政府部門的付款人覆蓋範圍感到非常滿意。通常，新患者在被轉介至 REMS 計劃後需要 2 至 4 週的時間才能接受 FINTEPLA，付款人承保範圍仍然很大，實際上所有患者都收到了積極的保險決定。

During the third quarter, we supported the Dravet community through various local and virtual events, including a unique FINTEPLA photo diary contest through social media. More than 700 caregivers participated in that event. As you all probably know, November is epilepsy awareness month. In this month, our team is participating in more than 30 community events, both virtually and in-person to support and educate Dravet patients and caregivers.

在第三季度，我們透過各種本地和虛擬活動支持 Dravet 社區，包括透過社群媒體舉辦的獨特的 FINTEPLA 攝影日記比賽。 700多名護理人員參加了這項活動。眾所周知，十一月是癲癇意識月。本月，我們的團隊參加了 30 多項虛擬和現場社區活動，以支援和教育 Dravet 病患和照護者。

In Europe, the launch of FINTEPLA in Dravet syndrome in Germany is continuing to progress very well, and our patient and prescriber base continues to grow steadily. We continue to add new patients to reimbursed therapy in France through the temporary authorization of use program and currently in 8 additional countries through our Zogenix Access program. We have made significant progress in our pricing and reimbursement negotiations in the major European markets with objective of reaching final determinations and executing commercial launches next year.

在歐洲，用於治療 Dravet 症候群的 FINTEPLA 在德國的上市進展順利，我們的患者和處方者基礎繼續穩定成長。我們繼續透過臨時授權使用計畫在法國增加新病患接受報銷治療，目前在另外 8 個國家透過我們的 Zogenix Access 計畫增加新病患接受報銷治療。我們在歐洲主要市場的定價和報銷談判取得了重大進展，目標是明年達成最終決定並執行商業發布。

Following the submission of our sNDA for LGS, we are now ramping our launch preparations for this new and potentially significant indication for FINTEPLA. We are conducting market research, advisory boards and one-on-one discussions with health care providers, caregivers and payers to best understand the need of the LGS community. These preparations are already helping us to refine our go-to-market strategies. And along with our expanded commercial team, will position us to launch FINTEPLA immediately upon potential approval in 2022.

在提交 LGS 的 sNDA 後，我們現在正在加緊為 FINTEPLA 的這一新的、潛在的重要適應症進行上市準備。我們正在進行市場研究、諮詢委員會以及與醫療保健提供者、護理人員和付款人的一對一討論，以更好地了解 LGS 社區的需求。這些準備工作已經幫助我們完善了進入市場的策略。與我們擴大的商業團隊一起，我們將在 2022 年獲得批准後立即推出 FINTEPLA。

In summary, we are pleased with our sales -- strong sales growth in the United States, continued positive momentum in Europe and preparations for the potential commercial expansion of FINTEPLA into LGS. We anticipate continued growth in all key geographies and look forward to updating you in the coming months.

總而言之，我們對我們的銷售感到滿意——美國的銷售成長強勁，歐洲的持續積極勢頭，以及為 FINTEPLA 向 LGS 的潛在商業擴張做好準備。我們預計所有主要地區都會持續成長，並期待在未來幾個月內向您通報最新情況。

Now, I will turn the call over to Gail to share exciting new data on FINTEPLA. Gail?

現在，我將把電話轉給 Gail，分享有關 FINTEPLA 的令人興奮的新數據。蓋爾？

Thank you, Ashish. I'll echo the enthusiasm expressed by Steve and Ashish around our submission of the sNDA for LGS, which was submitted on September 27 with a request for priority review, which if granted, will set an FDA goal to take action on the submission in 6 months. A standard review would establish a 10-month review time line.

謝謝你，阿什什。我同意 Steve 和 Ashish 對我們提交 LGS 的 sNDA 所表達的熱情，該 sNDA 於 9 月 27 日提交，並提出優先審查請求，如果獲得批准，FDA 的目標將是在 6 年內對該提交採取行動幾個月。標準審查將確定 10 個月的審查期限。

The submission consisted of safety and efficacy data from 263 LGS patients who participated in our positive Phase 3 trial, which met the primary and key secondary endpoint. The sNDA submission also contained non-clinical chronic toxicology and carcinogenicity studies and no new safety concerns were observed. Furthermore, prospective assessment of cardiac valvulopathy studies did not reveal any microscopic changes at any dose level.

提交的資料包括參加我們積極的 3 期試驗的 263 名 LGS 患者的安全性和有效性數據，該試驗達到了主要和關鍵的次要終點。提交的 sNDA 還包含非臨床慢性毒理學和致癌性研究，沒有觀察到新的安全性問題。此外，心臟瓣膜疾病研究的前瞻性評估並未揭示任何劑量水平下的任何微觀變化。

Next, we recently presented results from the interim analysis of our ongoing 12-month Phase 3 open-label extension study of FINTEPLA in LGS patients at the 2021 Annual Meeting of the Child Neurology Society. The results demonstrated that FINTEPLA produced highly statistically significant improvements in the frequency of drop seizures in 247 patients enrolled in all the new extension.

接下來，我們最近在兒童神經病學協會 2021 年年會上展示了對 LGS 患者進行的 FINTEPLA 為期 12 個月的 3 期開放標籤擴展研究的中期分析結果。結果表明，FINTPLA 對所有新擴展項目中登記的 247 名患者的癲癇發作頻率產生了高度統計顯著的改善。

The median reduction in drop seizure frequency was 39.4% at 3 months and at 51.8% for patients who were assessed over months 10 to 12, and the reductions at both time points at p-values less than 0.001 compared with baseline. Of the 170 patients evaluated in the interim analysis at months 10 to 12, 51.2% reached a 50% improvement threshold and 25.3% reached the 75% improvement threshold, which is considered a profound level of improvement.

在第 10 至 12 個月進行評估的患者中，癲癇發作頻率中位數下降在 3 個月時為 39.4%，為 51.8%，與基線相比，兩個時間點的下降幅度均小於 0.001。在第 10 至 12 個月的中期分析中評估的 170 名患者中，51.2% 達到 50% 改善閾值，25.3% 達到 75% 改善閾值，這被認為是深刻的改善水平。

These results highlight the durable and positive effect of long-term FINTEPLA treatment in LGS patients. To date, the safety profile in the LGS studies is comparable with results seen in the Dravet syndrome trials and our experience in the post-marketing setting. This profile in conjunction with FINTEPLA's unique mechanism of action, highlights the potential for FINTEPLA to become a meaningful treatment option for LGS patients and their families, particularly considering the highly refractory nature of this condition.

這些結果凸顯了長期 FINTEPLA 治療對 LGS 患者的持久和積極作用。迄今為止，LGS 研究的安全性與 Dravet 症候群試驗的結果以及我們在上市後環境中的經驗相當。這項概況與 FINTEPLA 獨特的作用機制相結合，凸顯了 FINTEPLA 成為 LGS 患者及其家人有意義的治療選擇的潛力，特別是考慮到這種疾病的高度難治性。

I'd also add that we remain on track to submit a J-NDA in Japan to Japan's Pharmaceutical and Medical Devices Agency by the end of 2021.

我還想補充一點，我們仍有望在 2021 年底前向日本藥品醫療器材管理局提交日本 J-NDA。

Now, let's move on to our newest FINTEPLA program in CDKL5 deficiency disorder or CDD. CDD is a rare, severe and highly refractory childhood onset epilepsy in which patients experience multiple symptoms, such as gastrointestinal, visual and sleep disturbances in addition to treatment-resistant seizures. Zogenix has joined the (inaudible) Foundation, the University of Pennsylvania and other industry collaborators to support a 3-year non-interventional study of patients with CDD to characterize developmental trajectories and clinical features of this disorder.

現在，讓我們繼續討論針對 CDKL5 缺乏症或 CDD 的最新 FINTEPLA 項目。 CDD 是一種罕見、嚴重且高度難治性的兒童期起病性癲癇，患者除了難治性癲癇發作外，還會出現多種症狀，例如胃腸道、視覺和睡眠障礙。 Zogenix 已加入（聽不清楚）基金會、賓州大學和其他產業合作者，支持一項針對 CDD 患者的為期 3 年的非干預性研究，以描述這種疾病的發展軌跡和臨床特徵。

In a small open-label study conducted by Dr. Orrin Devinsky, NYU Langone Medical Center and presented at the American Epilepsy Society Annual Meeting in 2020. Treatment with fenfluramine produced closely meaningful reductions in future frequency with a 90% reduction in generalized atonic seizures and a 55% reduction in tonic seizures in a case series of 6 patients with CDD with a median treatment duration of 5.3 months. These initial compelling results form the basis of our decision to launch a study of FINTEPLA in CDD patients, and we anticipate the first patient will enroll shortly.

紐約大學蘭格尼醫學中心的Orrin Devinsky 博士進行了一項小型開放標籤研究，該研究在2020 年美國癲癇協會年會上發表。芬氟拉明治療使未來的發作頻率顯著降低，全身性失張力發作減少了90%，並且在 6 名 CDD 患者的病例係列中，中位治療持續時間為 5.3 個月，強直性癲癇發作減少 55%。這些令人信服的初步結果構成了我們決定在 CDD 患者中進行 FINTEPLA 研究的基礎，我們預計第一位患者很快就會入組。

The placebo-controlled fixed-dose 2-arm trial will enroll 80 patients randomized to either 0.7 milligrams per kilogram per day FINTEPLA or placebo. FDA confirmed earlier this year in a Pre-IND meeting at a single positive randomized controlled trial could form the basis of a supplemental NDA in this indication.

這項安慰劑對照固定劑量 2 臂試驗將招募 80 名患者，隨機接受每天每公斤 0.7 毫克的 FINTEPLA 或安慰劑。 FDA 在今年稍早的 IND 前會議上確認，一項陽性隨機對照試驗可以構成該適應症補充 NDA 的基礎。

With that, I'll turn it over to Brad for an overview of our MT1621 program.

接下來，我會將其交給 Brad，以概述我們的 MT1621 計劃。

Thank you, Gail. We made meaningful progress on our MT1621 program throughout the quarter, expanding and enhancing our planned data set that will be included in our NDA submission in 2022. Among these additional data was an updated analysis of our primary efficacy trial, Study 101, formerly termed a retro study for the final CSR that will be included in the NDA.

謝謝你，蓋爾。我們整個季度在MT1621 專案上取得了有意義的進展，擴大和增強了我們計劃的資料集，這些資料集將包含在2022 年提交的NDA 中。這些額外資料包括對我們的主要療效試驗「研究101 」的更新分析，該試驗以前稱為「研究101」。最終 CSR 的回顧研究將包含在 NDA 中。

The study data continued to be highly compelling and consistent with previously reported results. The primary efficacy endpoint for Study 101, an updated survival analysis using a time-dependent cost regression model shows that the difference in probability of survival between treated patients and untreated natural history control patients was consistent with previously reported results, highly statistically significant at p=0.0007. In addition to this compelling survival benefit, the majority of MT1621 treated patients also demonstrated clinically meaningful improvements in motor, respiratory and/or feeding abilities with some patients reacquiring previously lost motor milestones.

研究數據仍然非常引人注目，並且與先前報告的結果一致。研究101 的主要療效終點是使用時間依賴性成本回歸模型進行的更新生存分析，顯示接受治療的患者和未經治療的自然史對照患者之間的生存機率差異與先前報告的結果一致，在p=時具有高度統計顯著性0.0007。除了這引人注目的生存益處之外，大多數接受 MT1621 治療的患者還表現出運動、呼吸和/或進食能力方面具有臨床意義的改善，其中一些患者重新獲得了先前失去的運動里程碑。

As the literature described, and our clinical data is confirming, TK2d is a progressive disease in all patients regardless of age of onset and the spontaneous improvements in motor milestones are rarely seen in this patient population. We are continuing to make good progress on the clinical and non-clinical studies for the NDA submission. The timing for completing Study 107, which is a retrospective chart review study to collect a vital status of any untreated and treated patients in the U.S. and Europe, not involved in our sponsored studies has been impacted by the pandemic and has moved into the first quarter of 2022 from the end of this year. We are now planning for a pre-NDA meeting in the second quarter of next year and an NDA submission in the second half of 2022. In addition to our regulatory progress in the U.S., we are preparing for a scientific advice meeting with EMA first quarter of 2022.

如文獻所述，而我們的臨床數據證實，TK2d 在所有患者中都是一種進行性疾病，無論發病年齡如何，且運動里程碑的自發性改善在該患者群體中很少見。我們正在繼續在 NDA 提交的臨床和非臨床研究方面取得良好進展。研究107 是一項回顧性圖表審查研究，旨在收集美國和歐洲任何未經治療和已治療患者的生命狀況，未參與我們贊助的研究，完成研究107 的時間已受到大流行的影響，已移至第一季從今年底開始，到2022年。我們現在計劃在明年第二季度召開 NDA 前會議，並在 2022 年下半年提交 NDA。除了美國的監管進展之外，我們還在準備第一季度與 EMA 舉行的科學建議會議2022 年。

With that, let me hand it over to Mike. Mike?

那麼，讓我把它交給麥克。麥克風？

Thanks, Brad, and good afternoon, everyone. Today, we issued a press release announcing our business and financial results for the third quarter ended September 30, 2021. In the third quarter of '21, we achieved $21.4 million in FINTEPLA net product sales globally, representing 20% growth over the second quarter of 2021.

謝謝布拉德，大家下午好。今天，我們發布新聞稿，公佈截至 2021 年 9 月 30 日的第三季度業務和財務業績。21 年第三季度，我們的 FINTEPLA 全球產品淨銷售額達到 2140 萬美元，比第二季度增長 20% 2021 年。

This includes FINTEPLA net sales of $18.4 million in the U.S. and $3 million in Europe. The sustained sales growth reflects the significant interest to initiate FINTEPLA therapy, we continue to observe across the Dravet communities. We recognized $22.6 million in total revenue during the third quarter of '21, which was an increase of 22% compared to $18.8 million recorded in the second quarter of 2021. Of the $22.6 million in total revenue, again, $21.4 million was in the form of product sales of FINTEPLA and $1.2 million was related to our collaboration with Nippon Shinyaku's FINTEPLA in Dravet syndrome and LGS in Japan. Our total revenue for the corresponding prior year period was $2.9 million.

其中 FINTEPLA 在美國的淨銷售額為 1,840 萬美元，在歐洲的淨銷售額為 300 萬美元。我們繼續在 Dravet 社區中觀察，持續的銷售成長反映了人們對啟動 FINTEPLA 療法的濃厚興趣。我們在 2021 年第三季確認了 2,260 萬美元的總收入，與 2021 年第二季的 1,880 萬美元相比成長了 22%。在 2,260 萬美元的總收入中，有 2,140 萬美元的形式為FINTEPLA的產品銷售額和120 萬美元與我們與日本新藥的FINTEPLA 在日本Dravet 綜合徵和LGS 方面的合作有關。我們去年同期的總收入為 290 萬美元。

R&D expenses for the third quarter were $33.3 million, a decrease as compared to the $54.4 million recorded in the corresponding period of 2020. The decrease was a result of overall R&D operating costs decreasing 24% to $26.3 million as some operating costs and activities related to FINTEPLA, Dravet and LGS late-stage development programs that concluded. This decrease was offset by a one-time $7 million charge associated with an agreement to amend our original FINTEPLA license and collaboration meeting with regards to revenue sharing on our past and future collaboration with Japan -- in Japan, sorry, with Nippon Shinyaku as well as an increased investment in MT1621 development.

第三季研發費用為 3,330 萬美元，較 2020 年同期的 5,440 萬美元有所下降。這一下降是由於整體研發營運成本下降 24% 至 2,630 萬美元，因為一些營運成本和活動與FINTEPLA、Dravet 和LGS 後期開發計劃已結束。這筆減少額被一次性700 萬美元費用所抵消，該費用與修改我們最初的FINTEPLA 許可協議和合作會議有關，涉及我們過去和未來與日本合作的收入分享——在日本，對不起，還有Nippon Shinyaku作為對 MT1621 開發的增加投資。

SG&A expenses for the third quarter ended September 30, 2021, totaled $39.5 million, and this compares to $24.6 million for the third quarter of the prior year. The increase of approximately $15 million is primarily driven by the continued investment related to the launches of FINTEPLA in the U.S. and Europe.

截至 2021 年 9 月 30 日的第三季銷售管理及行政費用總計 3,950 萬美元，而去年第三季為 2,460 萬美元。約 1500 萬美元的成長主要是由於與在美國和歐洲推出 FINTEPLA 相關的持續投資所致。

Net loss for the third quarter ended September 30, 2021, was $58 million or $1.04 per share. This compares to a net loss of $60 million or $1.08 per share in the third quarter ended September 30, 2020. We ended the third quarter with a strong balance sheet with cash and cash equivalents and marketable securities totaling $343 million.

截至 2021 年 9 月 30 日的第三季淨虧損為 5,800 萬美元，即每股 1.04 美元。相較之下，截至2020 年9 月30 日的第三季淨虧損為6,000 萬美元，即每股1.08 美元。第三季結束時，我們的資產負債表強勁，現金及現金等價物以及有價證券總計3.43 億美元。

And with that, I'll turn the call over to the operator to start our Q&A session. Operator, can you please open up the line for questions.

然後，我會將電話轉給接線員以開始我們的問答環節。接線員，您可以開通提問線路嗎？

(Operator Instructions) Our first question is from Paul Matteis with Stifel.

（操作員說明）我們的第一個問題來自 Stifel 的 Paul Matteis。

Good to see that new patient adds were relatively stable. I guess the one question I have is just -- it looks like patient adds to the REMS program were sequentially a little bit lower. Is there anything behind that? And maybe could you comment on just what you saw for demand throughout the quarter on a monthly basis and how you feel so far in October, if you're comfortable? And then, just second, I would be curious if you wouldn't mind breaking out U.S. and rest of world.

很高興看到新增患者數量相對穩定。我想我有一個問題只是——看起來患者添加到 REMS 程序的數量依次降低了一點。這背後有什麼嗎？如果您願意的話，也許您可以評論整個季度的每月需求情況以及 10 月份到目前為止您的感受嗎？然後，第二，我很好奇你是否介意突破美國和世界其他地區。

Paul, I'm going to hand that over to Ashish to address it for you. Ashish, are you on mute?

保羅，我將把這個問題交給阿什許來為你解決。阿什，你靜音了嗎？

I'm sorry. So Paul, for the Q3, despite the resurgence of COVID, the new patients add were consistent with the prior quarter. And when you look at month by month, we have seen the consistent growth. We haven't broken that out, but what we have seen is, especially when you say towards the July and August, when we had a lot of closures because of the resurgence of Delta variant, we did see a little dip there. And I think that contributed to where we are. But when you look at the overall numbers of 133 starts, which is a growth over last quarter, has been steady. In terms of U.S. and rest of the world, we haven't broken down the patient numbers because, as you know, in Europe, number of finding that -- finding number of patients actually is very difficult because of the regulations. So every patient number that we are reporting is purely from the U.S. perspective. Hope that answers your question.

對不起。所以保羅，對於第三季來說，儘管新冠疫情捲土重來，但新增病患數量與上一季保持一致。當你逐月觀察時，我們看到了持續的成長。我們還沒有透露這一點，但我們所看到的是，特別是當你說到七月和八月時，由於達美變種的死灰復燃，我們有很多工廠關閉，我們確實看到了一些下降。我認為這有助於我們取得今天的成就。但如果你看看 133 起啟動的總數（比上季有所成長），就可以看出一直穩定。就美國和世界其他地區而言，我們沒有細分患者數量，因為如您所知，在歐洲，由於法規的原因，發現患者數量實際上非常困難。因此，我們報告的每位患者人數純粹是從美國的角度來看的。希望這能回答你的問題。

Yes. Can you break out U.S. and Europe in terms of FINTEPLA revenues?

是的。您能在 FINTEPLA 收入方面區分美國和歐洲嗎？

Yes, Paul. This is Mike. In the quarter, I think, $4 million was in the U.S. and $3 million was in Europe.

是的，保羅。這是麥克。我認為，本季美國有 400 萬美元，歐洲有 300 萬美元。

And Paul, I think you had a question about what are we seeing during this quarter as much as we can say. I just want to remind you that we did move forward with an expanded sales team, which became effective in the field at the beginning of the quarter. Obviously, it'll take them a few weeks to get activated and to start to have conversations with physicians. But we've been, I think, very pleased so far this quarter, with our expanding team to increase physician engagement. So that's a very positive sign for us, and we know that has led to new prescriptions. So obviously, it's early days still. I'm sure Ashish would say that. But we feel encouraged with what our expanded team is doing right now.

保羅，我想你對我們在本季看到的情況有一個盡可能多的疑問。我只是想提醒您，我們確實擴大了銷售團隊，並在本季初在該領域發揮了作用。顯然，他們需要幾週的時間才能激活並開始與醫生交談。但我認為，本季到目前為止，我們對我們不斷擴大的團隊以提高醫生參與度感到非常滿意。所以這對我們來說是一個非常積極的信號，我們知道這導致了新的處方。顯然，現在還為時過早。我確信阿什什會這麼說。但我們對我們擴大的團隊目前所做的事情感到鼓舞。

The next question is from Jason Butler with JMP Securities.

下一個問題來自 JMP 證券的 Jason Butler。

Just first one, as you're preparing for the LGS launch, can you just speak to any work that you've done with payers or plan to do with payers to get them ready for the label expansion? And then, on MT1621, can you just give us some context of any prior dialogue that you've had with regulatory consultants or KOLs in Europe that give insights on how the -- what the approval path could look like there and what you're looking to get out of a scientific advice meeting?

第一個，當您準備推出 LGS 時，您能否談談您與付款人所做的或計劃與付款人一起做的任何工作，以使他們為標籤擴張做好準備？然後，在 MT1621 上，您能否向我們提供一些您之前與歐洲監管顧問或 KOL 進行的對話的背景信息，這些對話提供了關於那裡的審批路徑如何以及您正在做什麼的見解。想要擺脫科學建議會議嗎？

Thanks, Jason. I'm going to ask Ashish to take your first question, and Brad will get ready to respond to your second one. Ashish?

謝謝，傑森。我將請阿什什回答你的第一個問題，布拉德將準備回答你的第二個問題。阿什什？

Yes. Yes, Jason, from the LGS launch, as I said in the prepared remarks, we are doing one-on-one as well as advisory boards with payers as well as every other stakeholder. What we are hearing consistently is that LGS is a challenging and unpredictable disorder. And payers do think that the data is meaningful, and they are excited. And they also are aware and appreciate that. LGS is a pretty refractory condition. We are going to be doing these conversations. We started them during last week at AMCP, and we will be continuing that in this quarter as well as next quarter. And as soon as the indication is approved, our plan is to reengage them with the label and ensure that the product gets covered.

是的。是的，Jason，從 LGS 啟動以來，正如我在準備好的發言中所說，我們正在與付款人以及所有其他利益相關者進行一對一以及顧問委員會。我們一直聽到的是 LGS 是一種具有挑戰性且不可預測的疾病。付款人確實認為這些數據有意義，他們很興奮。他們也意識到並欣賞這一點。 LGS 是一種相當難治的病症。我們將進行這些對話。我們上週在 AMCP 上開始了這些工作，我們將在本季和下個季度繼續這樣做。一旦適應症獲得批准，我們的計劃就是讓他們重新與標籤接觸並確保產品得到覆蓋。

Great. Steve?

偉大的。史蒂夫？

Brad, over to you.

布拉德，交給你了。

Jason, with regards to MT1621 in Europe, we definitely are engaging with multiple regulatory consultant experts and KOLs to help us with our path there. The KOLs are very excited, especially the ones that have utilized MT1621. As a matter of fact, one of which will be on the call on Monday, and she'll be discussing her experience as well. And they're very excited about treating with this medication as they are seeing tremendous benefit, as I mentioned, in survival, but also other non-survival benefit. The regulatory path, as I will outline on Monday, may be a bit different with a different indication, whereas in U.S., we're looking for an indication for all patients in Europe. The EMA has been a little more difficult in requesting a little bit more data, especially in the adult onset patients. So it may be a different indication with the younger age of onset patients, but I'll be providing more information on Monday.

Jason，關於歐洲的 MT1621，我們肯定正在與多名監管顧問專家和 KOL 合作，以幫助我們實現這一目標。 KOL們非常興奮，尤其是那些使用過MT1621的KOL們。事實上，其中一個將在周一進行電話會議，她也將討論她的經歷。他們對使用這種藥物進行治療感到非常興奮，因為正如我所提到的，他們看到了生存的巨大好處，而且還看到了其他非生存方面的好處。正如我將在周一概述的那樣，監管路徑可能會因適應症的不同而有所不同，而在美國，我們正在為歐洲的所有患者尋找適應症。 EMA 在要求提供更多數據方面有點困難，特別是在成年發病患者中。因此，對於發病年齡較小的患者來說，這可能是一個不同的適應症，但我將在周一提供更多資訊。

And just to add to that, the majority of the patients that suffer from TK2D are, in fact, early onset. So children as opposed to late onset. It just reflects the fact, Jason, that we have more data on adult onset or early offset we do for later on so. And that's really, I think, the issue that the EMA is addressing right now.

除此之外，大多數 TK2D 患者其實都是早發的。所以小兒相對來說發病較晚。這只是反映了這樣一個事實，傑森，我們有更多關於成人發病或早期抵消的數據，我們稍後會做。我認為這確實是 EMA 目前正在解決的問題。

Okay. That's helpful. And I look forward to the call on Monday.

好的。這很有幫助。我期待著週一的電話。

The next question is from Yatin Suneja with Guggenheim Securities.

下一個問題來自古根漢證券公司的 Yatin Suneja。

This is Eddie on for Yatin. Just a couple for me. Can you talk about what the potential risks are to the LGS filing? Why is there even a debate around potential acceptance? Is there anything in the non-clinical work that could create a risk? And then, assuming approval in LGS, can you talk about the cadence of patient adds next year? And do you think that will be affected by the level of off-label use you're seeing? And can you remind us what the off-label use you're seeing for FINTEPLA in 3Q?

這是亞汀的艾迪。對我來說只是一對。您能談談 LGS 備案有哪些潛在風險嗎？為什麼會存在關於潛在接受程度的爭論？非臨床工作中是否存在可能產生風險的因素？然後，假設 LGS 獲得批准，您能談談明年患者增加的節奏嗎？您認為這會受到您所看到的標籤外使用程度的影響嗎？您能否提醒我們，您在第三季看到 FINTEPLA 的超適應症用途是什麼？

Thank you. Gail, would you like to take the first question?

謝謝。蓋爾，你願意回答第一個問題嗎？

Sure. Happy to. Thanks for the question. Well, we are unaware of anything in the filing that would pose such a risk, certainly the non-clinical data are straightforward and those studies are complete. In terms of the clinical data, the same has happened, we had comprehensive and fruitful discussions with the agency in the pre-sNDA meeting as well as the end of Phase 3 meeting, and we're able to come to a good agreement about what should be included in the filing. And of course, we've done due diligence and checked our data sets for the submission. So we believe that the submission will be accepted on time.

當然。高興。謝謝你的提問。嗯，我們不知道文件中的任何內容會帶來這樣的風險，當然非臨床數據很簡單，而且這些研究是完整的。在臨床數據方面，同樣的情況也發生了，我們在sNDA前的會議以及3期會議結束時與FDA進行了全面而富有成效的討論，並且我們能夠就哪些方面達成了良好的協議應包含在備案中。當然，我們已經進行了盡職調查並檢查了我們提交的資料集。所以我們相信提交的內容會準時被接受。

And Ashish, could you address the second question?

Ashish，你能回答第二個問題嗎？

Sure. Eddie, in terms of cadence of patient adds after the LGS, I think I'll give you a perspective in terms of number of patients. As you know, in LGS, it's at least 5x or 6x larger than Dravet. So you will consequently see the number of patients coming in, it's going to be higher than what we have for Dravet syndrome. As for your second question, will that have any impact in terms of how it is being used right now. One thing I would just like to remind you and everyone is that we have only indication for Dravet syndrome, and we promote only in Dravet. However, the data tells us that, as we said previously, it's around 20% of our patients who are being prescribed FINTEPLA are for indications other than Dravet and LGS is the majority of that particular cohort. And that stayed true in Q3. Given the significant number of LGS patients and the feedback that we are hearing from the recipients, in the sense that the data is meaningful for them, they are excited to have a novel treatment options. And they are looking forward to have FINTEPLA in their toolbox because of these reasons as -- and also the current treatments are somewhat inadequate to have a control -- to have seizure control. We expect that, that will not be a huge factor.

當然。 Eddie，就 LGS 後患者增加的節奏而言，我想我會給您一個關於患者數量的看法。如您所知，在 LGS 中，它至少比 Dravet 大 5 倍或 6 倍。因此，你會看到進來的病人數量，它會比我們針對 Dravet 症候群的病人數量還要多。至於你的第二個問題，這會對它現在的使用方式產生任何影響嗎？我想提醒大家的一件事是，我們只有 Dravet 症候群的適應症，我們只在 Dravet 中進行推廣。然而，數據告訴我們，正如我們之前所說，大約 20% 的 FINTEPLA 患者用於 Dravet 以外的適應症，而 LGS 是該特定隊列中的大多數。第三季也是如此。鑑於 LGS 患者數量眾多，並且我們從接受者那裡聽到了反饋，從某種意義上說，這些數據對他們來說很有意義，他們很高興能有一種新穎的治療選擇。他們期待將 FINTEPLA 納入他們的工具箱，因為這些原因以及目前的治療方法在某種程度上不足以控制癲癇發作。我們預計，這不會成為一個重要因素。

Our next question is from Rohit Bhasin with Needham & Company.

我們的下一個問題來自 Needham & Company 的 Rohit Bhasin。

This is Rohit on for Serge. Are you noticing any particular prescriber trends for FINTEPLA thus far? And then, in terms of payer coverage, should we expect any changes for 2022?

這是羅希特（Rohit）替塞爾吉（Serge）發言。到目前為止，您是否注意到 FINTEPLA 有任何特定的處方者趨勢？那麼，就付款人覆蓋範圍而言，我們是否應該預期 2022 年會發生任何變化？

Ashish, I'll hand back to you again.

Ashish，我會再交給你。

Sounds good. So in terms of prescriber trend, Rohit, we see consistent increase month after month. And as we said previously, what we are seeing is that physicians, as we are connecting with them, they are -- as we educate them on the FINTEPLA and the transformational efficacy in Dravet syndrome. As they get comfortable with the process of the REMS as well as the entire Zogenix Central, they start using the product. And once they start using the product, it kind of snowballs from there. So we are getting good response from them. And we are not only getting prescriptions from the epileptologist, but also from the community neurologist and the neurologists at large. So that's something that has been very promising and very reassuring. In terms of payer coverage, as I said in my prepared remarks, almost every patient who is prescribed FINTEPLA is able to get it, and they have been able to get positive determination. And based on the feedback that we have from the payers, not only for Dravet but also what we are doing on LGS, the conversations we are having, we do not see any roadblocks there and any concerns there.

聽起來不錯。因此，就處方者趨勢而言，羅希特，我們看到逐月持續成長。正如我們之前所說，我們所看到的是，當我們與醫生聯繫時，他們是——當我們對他們進行 FINTEPLA 和 Dravet 綜合徵的轉化功效教育時。當他們熟悉 REMS 以及整個 Zogenix Central 的流程後，他們開始使用該產品。一旦他們開始使用該產品，它就會像滾雪球一樣滾雪球。所以我們得到了他們的良好回應。我們不僅從癲癇專家那裡得到處方，還從社區神經科醫生和廣大神經科醫生那裡得到處方。所以這是非常有希望和令人放心的事。在付款人保險方面，正如我在準備好的發言中所說，幾乎每個接受 FINTEPLA 處方的患者都能夠得到它，並且他們已經能夠得到積極的決定。根據我們從付款人那裡得到的回饋，不僅是 Dravet 的回饋，還有我們在 LGS 上所做的事情以及我們正在進行的對話，我們沒有看到任何障礙和任何擔憂。

Our next question is from Esther Rajavelu with UBS.

我們的下一個問題來自瑞銀集團的 Esther Rajavelu。

I guess a couple for me, two on Zogenix and one on TK2d. The first one, you referred to increasing prescriptions from new docs. So can you give us a sense for whether these are community epileptologists or part of larger comprehensive treatment centers? And then, on the drop-off rate, at what point in the therapy are patients dropping off? And if you can share the average duration of therapy, that would be helpful. And then, lastly, on TK2d, if you can talk about what steps you may have to take next year as you're going through the regulatory process to identify patients? Or do you expect the majority of these patients to be readily available for treatment if the therapy is approved?

我猜對我來說有兩個，兩個在 Zogenix 上，一個在 TK2d 上。第一個，您提到了新醫生增加處方。那麼您能否讓我們了解這些人是社區癲癇專家還是大型綜合治療中心的一部分？然後，關於退出率，患者在治療的哪個階段退出？如果您可以分享治療的平均持續時間，那將會有所幫助。最後，關於 TK2d，您能否談談明年在透過監管流程來識別患者時可能需要採取哪些步驟？或者，如果該療法獲得批准，您是否預計這些患者中的大多數都可以隨時接受治療？

Yes. Thanks for your questions. I'm going to ask Ashish again to take the first 2 for you.

是的。感謝您的提問。我要再次請 Ashish 為您拿走前 2 個。

Yes. So Esther, I think, in terms of the prescriptions from new docs, as we add more physicians, majority of them are community neurologists, as you can imagine, the all epileptologists who were part of our clinical trials and at the large centers are already prescribing the product and are signed up for the REMS program. So every new prescriptions that or every new physician that we are bringing in there coming from this community neurologist group. They are and also from centers because, quite frankly, there are many centers where we did not have access to physicians for a long period of time because of COVID, I think slowly, they are opening up. And as we make inroads at them, we have seen prescriptions from that. As far as your second question on the drop off, usually, it takes around 5 months on an average. It ranges between 4 and 6 and then, they try and reach the maximum dose that they can tolerate and see the impact. One great thing about FINTEPLA is that as you escalate the dose, it will start working for you. But if it doesn't, you will know that pretty quickly. And I think that has been the range that we have seen. And usually, they stay on the therapy for that long, and then they decide to drop off. And majority of these drop-offs are because the product did not work for them. And when you take that out, the patients who have started the therapy, they are still on the therapy. So we have patients who started last August when we launched the product. They are still on therapy. And we also have majority of the patients who are part of our open-label extension and the expanded access program still on the therapy. So the average duration is much, much longer at this point in time. For TK2, I'll hand it over to Brad.

是的。所以埃絲特，我認為，就新醫生的處方而言，隨著我們增加更多的醫生，其中大多數是社區神經科醫生，正如你可以想像的那樣，參與我們臨床試驗和大型中心的所有癲癇科醫生都已經是開出產品處方並註冊參加 REMS 計劃。因此，我們帶來的每一個新處方或每位新醫生都來自這個社區神經病學家小組。他們來自中心，因為坦白說，由於新冠疫情，許多中心我們在很長一段時間內無法接觸到醫生，我認為它們正在慢慢開放。當我們在這些領域取得進展時，我們已經看到了其中的處方。至於你的第二個問題，通常平均需要5個月左右。它的範圍在 4 到 6 之間，然後，他們嘗試達到他們可以忍受的最大劑量並觀察影響。 FINTEPLA 的一大優點是，當您增加劑量時，它就會開始為您發揮作用。但如果沒有，您很快就會知道。我認為這就是我們所看到的範圍。通常，他們會堅持治療很長時間，然後決定停止治療。大多數流失是因為該產品不適合他們。當你把它去掉時，那些已經開始治療的患者，他們仍然在接受治療。因此，我們有去年八月推出該產品時開始使用的患者。他們仍在接受治療。我們的開放標籤擴展和擴展准入計劃中的大多數患者仍在接受治療。所以此時的平均持續時間要長得多。對於 TK2，我將把它交給 Brad。

I'll take that for Brad. Referring to the question about trying to increase the number of identified patients. Obviously, 1 year into a lease base, this becomes a very critical activity in conjunction with work you're doing in development to get the product approved. So we're working in a number of areas right now. I want to give another advertisement for our Investor Day that's coming up next Monday, where we'll talk a lot more about this. But we clearly have ongoing activities right now relating to increasing disease awareness also to increase a diagnosis. So helping physicians to be able to identify TK2d earlier. And a key component of that is no surprise, is genetic testing. And we have a number of activities associated with improving the availability of genetic testing for TK2d. So we'll be thrilled to tell you all about that on Monday.

我會為布拉德接受這個。關於試圖增加確診患者數量的問題。顯然，在租賃基礎一年後，這將成為一項非常關鍵的活動，與您為獲得產品批准而進行的開發工作相結合。所以我們現在正在多個領域開展工作。我想為下週一即將舉行的投資者日做另一則廣告，我們將在會議上詳細討論這一點。但我們現在顯然正在進行與提高疾病意識以及增加診斷相關的活動。從而幫助醫生能夠更早辨識 TK2d。毫不奇怪，其中一個關鍵的組成部分是基因檢測。我們進行了許多與提高 TK2d 基因檢測可用性相關的活動。因此，我們將很高興在周一告訴您這一切。

Our next question is from Tim Lugo with William Blair.

我們的下一個問題來自蒂姆·盧戈和威廉·布萊爾。

This is Lachlan on for Tim. So I was wondering with what sounds like potentially several launches across the European markets next year. Do you already have the commercial infrastructure you'll need in those markets in place? Or are you going to be building that out as you sort of get closer to the reimbursement decisions there? And then, secondly, I was wondering for the CDKL5 study, are you comfortable sharing any details around the powering of that and maybe some of the assumptions you used there?

這是拉克蘭替提姆發言。所以我想知道明年可能會在歐洲市場推出幾款產品。您是否已具備這些市場所需的商業基礎設施？或者當你接近那裡的報銷決定時你會建立這個嗎？其次，我想知道關於 CDKL5 研究，您是否願意分享有關該研究的動力的任何細節，以及您在那裡使用的一些假設？

I can take those for you. With respect to powering, we haven't really publicly talked about that. But the type of powering that we use for our Dravet syndrome is where I would need you as opposed to the powering that we needed for LGS. The reason for that is that CDKL5 is a monogenetic epilepsy, very similar to Dravet syndrome. And we feel comfortable with the equals 40 per group that will be able to hit significance. And just remind me of your first question again.

我可以幫你拿走那些。關於供電，我們還沒有真正公開討論過。但是我們用於 Dravet 綜合症的供電類型正是我需要您的地方，而不是我們用於 LGS 所需的供電類型。原因是 CDKL5 是一種單基因癲癇，與 Dravet 症候群非常相似。我們對每組 40 人感到滿意，這將能夠達到顯著效果。再次提醒我你的第一個問題。

I was wondering -- I think you said you have a market in Europe with reimbursement expectations. Do you already have the commercial infrastructure built out in those countries? Or are you going to be building that out between now and when you would...?

我想知道 - 我想你說過你在歐洲有一個有報銷預期的市場。你們已經在這些國家建立了商業基礎建設嗎？或者你打算從現在到你…的時候建造它？

Yes. We are -- yes, we are playing very much a stage approach. So we have certain functions which are centralized and important for Europe based in Maidenhead in the U.K. and then, we are building our presence in various countries as and when the product becomes commercialized there. So for example, today, we have a presence in Germany, where we've launched at the beginning of this year, as you know, we have about 10 employees in Germany. And that's probably the largest country office that we will have in Germany. So we will build out these country presences once we have reimbursement approved.

是的。我們——是的，我們正在以一種舞台方式進行表演。因此，我們在英國梅登黑德擁有一些對歐洲來說集中且重要的職能，然後，當產品在這些國家商業化時，我們正在各個國家建立我們的業務。舉例來說，今天，我們在德國設立了辦事處，我們於今年年初在德國設立了辦事處，如您所知，我們在德國約有 10 名員工。這可能是我們在德國設立的最大的國家辦事處。因此，一旦報銷獲得批准，我們將擴大這些國家的業務。

The next question is from Danielle Brill with Raymond James.

下一個問題是丹妮爾·布里爾和雷蒙德·詹姆斯提出的。

This is Alex on for Danielle. So correct me if I'm wrong, my notes for Mt1621 said that we'd be getting data by year-end and that the NDA was looking to be submitted by first half '22. And today, you're now guiding to second half '22. Could you share the reason for this delay? And then, was that informed by anything that came up in the FDA Type B meeting? And then, additionally, quickly, forgive me if I missed this, how many doctors are now enrolled in the REMS program?

這是亞歷克斯為丹妮爾代言。如果我錯了，請糾正我，我的 Mt1621 筆記說我們將在年底前獲取數據，並且 NDA 預計在 22 年上半年提交。今天，您將帶領大家進入 22 年下半年。能分享一下延遲的原因嗎？那麼，FDA B 類會議上提出的任何內容是否告知了這一點？另外，如果我錯過了這一點，請盡快原諒我，現在有多少醫生參加了 REMS 計劃？

Brad, you want to take that? The question on Study 107 being in the right spec to the NDA submission.

布拉德，你想接受嗎？關於研究 107 是否符合新藥申請提交的規範的問題。

Yes. So in our meeting, there are no -- in our Type B meeting there are no studies, as I mentioned earlier, the delay is due to Study 107 which is identifying patients outside so generic sponsoring studies, both untreated and treated patients. And the delay is going due to the pandemic, the sites having delays in the IRB meetings and they're signing clinical trial agreements. And that's, as you know, a problem across the industry. And that's why it's pushed out one quarter.

是的。因此，在我們的會議中，沒有——在我們的B 類會議中，沒有研究，正如我之前提到的，延遲是由於研究107 造成的，該研究正在識別通用資助研究之外的患者，包括未經治療和已治療的患者。由於大流行，這些地點推遲了 IRB 會議，但他們正在簽署臨床試驗協議。如您所知，這是整個行業的一個問題。這就是為什麼它被推遲了四分之一。

Okay. Great. And then, just on the REMS registration. Do you have an updated number on this?

好的。偉大的。然後，就進行 REMS 註冊。您有這方面的更新號碼嗎？

Yes. At the end of last quarter, there were over 720 prescribers that were enrolled in the REMS program. And approximately half of those were writing prescriptions for FINTEPLA.

是的。截至上季末，有超過 720 名處方者註冊了 REMS 計畫。其中大約一半是為 FINTEPLA 開處方。

(Operator Instructions) Our next question is from Bhavin Patel with Bank of America.

（操作員指示）我們的下一個問題來自美國銀行的 Bhavin Patel。

This is Bhavin Patel on for Jason Gerberry. So first, on the LGS filing for FINTEPLA with a few weeks left ahead of the 60-day deadline to get priority review. I just wanted to hear your thoughts on what degree of confidence you have that you'll be granted the priority review? And then, I also wanted to ask with regards to getting new physicians REM certified, if you could quantify the number of docs certified at the end of 3Q? And so, it looks like you had 720 you just mentioned at the end of 2Q. So how likely are you to meet or even exceed the goal of 1,400 by year-end? Given, you've mentioned identifying and adding more prescribers to your call is as well. And then, finally, on MT1621, I just wanted to get your thoughts on the path to market for that asset? And what can you tell us about any data that we can expect at the event next Monday?

我是巴文‧帕特爾 (Bhavin Patel)，代表傑森‧格伯里 (Jason Gerberry)。首先，LGS 向 FINTEPLA 提交申請，距離獲得優先審查的 60 天截止日期還有幾週。我只是想聽聽您對獲得優先審查的信心有多大？然後，我還想問一下，關於讓新醫生獲得 REM 認證，您是否可以量化第三季末獲得認證的醫生數量？因此，看起來您剛剛提到的第二季末有 720 個。那麼，到年底您達到甚至超過 1,400 人的目標的可能性有多大呢？鑑於您也提到了識別並向您的電話中添加更多處方者也是如此。最後，關於 MT1621，我只是想了解您對該資產的市場路徑的看法？您能告訴我們下週一活動中我們可以期待的數據嗎？

Thanks for your questions. Gail, would you like to take the LGS question?

感謝您的提問。 Gail，您願意回答 LGS 問題嗎？

Sure. As you know, getting a priority review is an FDA decision. And there are a number of other products that are approved for LGS. However, listening to the patient community, there is still great unmet medical need among the community to have better treatment options. And FINTEPLA with the unique mechanism of action would provide a brand new alternative. Importantly, this study, the LGS pivotal study, meets the requirements of a pediatric written request from FDA and the standard review time for a submission in response to a pediatric written request is 6 months. So we believe that we would be granted or have a good chance of having granted the priority review timing because of this response characterization.

當然。如您所知，獲得優先審查是 FDA 的決定。還有許多其他產品獲得 LGS 批准。然而，在聽取患者社區的意見後，社區中仍然存在巨大的未滿足的醫療需求，需要更好的治療選擇。而FINTPLA以其獨特的作用機制將提供全新的選擇。重要的是，這項 LGS 關鍵研究符合 FDA 兒科書面請求的要求，並且回應兒科書面請求提交的標準審查時間為 6 個月。因此，我們相信，由於這種回應特徵，我們將被授予或很有可能獲得優先審查時間。

Okay. And just in case I misspoke, the number of certified doctors in the REMS program was over 720 at the end of September. And so at the end of Q3. Maybe, Ashish, you can talk about what we're doing to increase the number of subscribers into the REMS program?

好的。萬一我說錯了，截至 9 月底，REMS 計劃中獲得認證的醫生人數已超過 720 名。第三季末也是如此。 Ashish，您也許可以談談我們正在採取哪些措施來增加 REMS 計劃的訂閱者數量？

Yes. So one other thing I'll say is that our focus is on getting more patients prescribed FINTEPLA at the top of the funnel. And in terms of getting number of physicians certified and as we said in a few quarters back, the physicians get certified once they have a patient and once they realize the value of FINTEPLA. So what we focus on, on a day-to-day basis is getting to all these physicians who have Dravet patients, and we have just expanded that list from 1,400 to almost 3,600. And the goal is to get to them, educate them on the transformational efficacy in Dravet syndrome. And once they are educated and then they decide to prescribe, and that's the time they get certified. Certification is a pretty easy process, which people can do it on a cell phone. But our focus is now more on getting physicians to write the product and getting more patients on the top of the funnel, and that's something we have been focused on in the last few months. But one thing I can tell you is that between Q2 and Q3, we increased the number but -- more than 75 physicians came on certified for the REMS. And in terms of number of physicians, we have more than 44 new physicians started prescribing in Q3, along with the physicians who are already prescribing. I hope that answers your question.

是的。因此，我要說的另一件事是，我們的重點是讓更多患者在通路頂部接受 FINTEPLA 處方。在獲得認證的醫生數量方面，正如我們在幾個季度前所說的那樣，一旦醫生有了患者並且意識到了 FINTEPLA 的價值，他們就會獲得認證。因此，我們每天關注的重點是聯繫所有擁有 Dravet 患者的醫生，我們剛剛將名單從 1,400 名擴大到近 3,600 名。我們的目標是接觸他們，教育他們了解 Dravet 症候群的轉化功效。一旦他們接受了教育，然後他們決定開處方，那就是他們獲得認證的時間。認證是一個非常簡單的過程，人們可以在手機上完成。但我們現在的重點更多是讓醫生編寫產品並讓更多的患者進入漏斗的頂部，這是我們過去幾個月一直在關注的事情。但我可以告訴您的一件事是，在第二季度和第三季度之間，我們增加了數量，但是 - 超過 75 名醫生獲得了 REMS 認證。就醫生數量而言，第三季有超過 44 名新醫生開始開處方，以及已經開處方的醫生。我希望這能回答你的問題。

And then, just one finally on the MT1621. Just what can you tell us about any data that we can expect at the event next Monday?

然後，最後只有 MT1621 上的一個。您能告訴我們下週一的活動中我們可以期待的數據嗎？

Yes. Thanks for allowing me to advertise. I won't give it all away. But the KOLs, one from U.S. and one from Europe, both who are investigators will be showing their own patient videos, pre and post-treatment, which are -- you will see, I went to view and quite impressive. In addition, I'll be -- presenting some nonsurvival data. But in addition, as I mentioned, so Study 107 is delayed until next year. And also, we'll be analyzing the prospective Study 102. Next year, there'll be a lot more non-survival data as well. So a lot more to come to all be presenting in the KOLs next Monday. The ongoing flow of great data coming out.

是的。謝謝你允許我做廣告。我不會放棄這一切。但是KOL，一位來自美國，一位來自歐洲，都是研究人員，將展示他們自己的患者治療前和治療後的視頻，這些視頻——你會看到，我去看了，非常令人印象深刻。此外，我將展示一些非生存數據。但除此之外，如我所提到的，Study 107 被推遲到明年。此外，我們還將分析前瞻性研究 102。明年，還將有更多的非生存數據。下週一，還有更多內容將在 KOL 中呈現。大量數據不斷湧現。

The next question is from Neena Bitritto-Garg with Citi.

下一個問題來自花旗銀行的 Neena Bitritto-Garg。

So I was just wondering if you could clarify, how many patients were actually on drug actively at the end of September? And then, also if you could provide the number of total cumulative starts since launch as of the end of September? That would be great.

所以我想知道您能否澄清一下，截至 9 月底，有多少患者實際上正在積極服用藥物？然後，您能否提供自 9 月底推出以來的累積啟動總數？那太好了。

Ashish, I'll hand that to you.

阿希什，我會把它交給你。

Yes. Yes, I'll take that. So Neena, we didn't mention on the call the number of patients, but we continue to add on a monthly basis patients, and we will continue to do that in the foreseeable future. The focus is for us to get them on the top of the funnel. And we know that once they are prescribed FINTEPLA, almost all of them, if not every one of them gets positive determination, and we are able to ship the product in 2 to 4 weeks. In terms of the new patient starts, I think that was your second question. We are around 130 started in the Q3. And in terms of cumulative start, that number is well over 860.

是的。是的，我會接受的。 Neena，我們沒有在電話中提及患者數量，但我們繼續每月增加患者數量，並且在可預見的未來我們將繼續這樣做。我們的重點是讓他們到達漏斗的頂部。我們知道，一旦他們開了 FINTEPLA 處方，幾乎所有的人（如果不是每個人）都會得到積極的決定，我們能夠在 2 到 4 週內發貨。就新患者開始而言，我認為這是你的第二個問題。我們在第三季啟動了大約 130 個專案。就累計啟動而言，這個數字遠遠超過 860。

We have a follow-up call -- question from Yatin Suneja with Guggenheim Securities.

我們有一個後續電話——來自古根漢證券公司 (Guggenheim Securities) 的 Yatin Suneja 的問題。

Just quickly, you guided last quarter for about 50 patient adds per month. And given you just sort of missed that slightly this quarter. I was wondering, for 4Q, if you're still consistently thinking about 50 patients per month or more of a consistent to 3Q numbers?

很快，您在上個季度指導了每月增加約 50 名患者。鑑於您本季度稍微錯過了這一點。我想知道，對於第四季度，您是否仍然始終認為每月有 50 名或更多患者與第三季度的數字一致？

I'll take that, Steve. So I think, one thing I'll say is that in Q3, we are really happy with what we -- in number of adds because of the resurgence of COVID that we have experienced significantly in July as well as in August. And those new patients, when you normalize for that have been consistent with the prior quarters. And in Q4, as you know, we have expanded our team. And the reason for that expansion was we wanted to reduce the geographies, which will allow for more face-to-face interaction. This will also be -- we have expanded our call list and the list of prescribers because we are finding more prescribers are caring for Dravet patients, and we want to call on them. And because of COVID we couldn't call on them because the large geographies, that expansion helped them. It's very early, but what we are seeing the impact that our ability to make this face-to-face call with that NCP is increasing. We are educating them on FINTEPLA, especially through the speaker programs, but also our one-on-one visits. And we are very encouraged by the progress we have made and progress made by the team since the start of this quarter. And we do see -- and we do expect to see a very meaningful impact of this expansion in the coming months, in Q4 and beyond.

我會接受的，史蒂夫。所以我想，我要說的一件事是，在第三季度，我們對新增數量感到非常滿意，因為我們在 7 月和 8 月經歷了新冠疫情的復甦。當你將這些新患者標準化時，這些新患者與前幾季是一致的。如您所知，在第四季度，我們擴大了我們的團隊。這種擴張的原因是我們希望減少地理，這將允許更多的面對面互動。這也將是——我們擴大了我們的電話名單和處方者名單，因為我們發現更多的處方者正在照顧 Dravet 患者，我們想要拜訪他們。由於新冠疫情，我們無法拜訪他們，因為地域廣闊，這種擴張對他們有幫助。現在還為時過早，但我們看到，我們與 NCP 進行面對面通話的能力正在增強。我們正在對他們進行 FINTEPLA 教育，特別是透過演講者計劃以及我們的一對一訪問。自本季開始以來，我們和團隊的進展讓我們深受鼓舞。我們確實看到了——我們確實預計這種擴張將在未來幾個月、第四季及以後產生非常有意義的影響。

This concludes the question-and-answer session. I'd like to turn the conference back over to Dr. Stephen Farr for closing remarks.

問答環節到此結束。我想把會議轉回給史蒂芬法爾博士做閉幕詞。

Thank you for joining us on today's call and particularly appreciate the questions that you addressed, that you asked as well. I'm very happy to report on a strong quarter, our growing FINTEPLA sales, submission of the sNDA for our second indication and close to initiating a Phase 3 trial in the third indication for FINTEPLA. I'm also very pleased to cover MT1621 today and especially excited to have our first mitochondrial disease focused investor event next Monday. I hope you're all able to attend this meeting virtually. And thank you all again, and enjoy the rest of your day. Goodbye.

感謝您參加今天的電話會議，特別感謝您提出的問題。我很高興地報告強勁的季度業績、不斷增長的 FINTEPLA 銷售額、提交第二個適應症的 sNDA 以及即將啟動 FINTEPLA 第三個適應症的 3 期試驗。我也很高興今天報道 MT1621，並且特別高興能在下週一舉辦我們的首場以粒線體疾病為重點的投資者活動。我希望大家能夠以虛擬方式參加這次會議。再次感謝大家，祝您有個愉快的一天。再見。

This concludes today's conference call. You may disconnect your lines. Thank you for participating, and have a pleasant day.

今天的電話會議到此結束。您可以斷開線路。感謝您的參與，祝您有個愉快的一天。