Longboard Pharmaceuticals Inc (LBPH) 2022 Q4 法說會逐字稿

Good day and thank you for standing by. Welcome to the Longboard Pharmaceuticals conference call. (Operator Instructions) Please be advised that today's conference is being recorded. I'd now like to hand the conference over to your speaker today, Brandi Roberts, Chief Financial Officer. Please go ahead.

美好的一天，感謝您的支持。歡迎參加 Longboard Pharmaceuticals 電話會議。 （操作員指示）請注意，今天的會議正在錄製中。現在我想將會議交給今天的發言人、財務長布蘭迪羅伯茲。請繼續。

Thank you. And good afternoon, everyone. Welcome to Longboard's conference call and webcast where we will be discussing our 2022 financial results and providing a corporate review of the past year and an update on the year ahead.

謝謝。大家下午好。歡迎參加 Longboard 的電話會議和網路廣播，我們將在會議上討論 2022 年的財務業績，並提供對過去一年的公司回顧和未來一年的最新情況。

Before we begin today, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company including, without limitation, statements about the anticipated timing of commencement, enrollment, and completion of clinical trials for our product candidates; the anticipated timing of release of clinical trial data; the market opportunity for our product candidates; and the expected timeframe for funding operations with current cash, cash equivalents, and short-term investments.

在今天開始之前，我想提醒大家，本次電話會議和網路廣播將包含有關公司的前瞻性聲明，包括但不限於有關我們產品候選者臨床試驗的預期開始、註冊和完成時間的聲明;臨床試驗數據的預計發佈時間；我們的候選產品的市場機會；以及利用當前現金、現金等價物和短期投資為營運活動提供資金的預期時間表。

These statements are subject to risks and uncertainties that could cause actual results to differ. Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward looking statements are discussed in greater detail in our most recent reports filed with the SEC.

這些陳述存在風險和不確定性，可能導致實際結果有所不同。我們最近向 SEC 提交的報告中更詳細地討論了可能導致實際結果或結果與此類前瞻性陳述中表達或暗示的結果有重大差異的因素。

Please note that these forward-looking statements reflect our opinions only as of the date of this call, and we undertake no obligation to revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events.

請注意，這些前瞻性陳述僅反映我們截至本次電話會議之日的意見，我們不承擔根據新資訊或未來事件修改或公開發布這些前瞻性陳述的任何修改結果的義務。

With that, I'll hand the call over to Kevin Lind, Longboard's President and CEO. Kevin?

接下來，我會將電話轉交給 Longboard 總裁兼執行長 Kevin Lind。凱文？

Thanks, Brandi. And thank you very much to everyone joining us today on our first earnings call. We wanted to provide an update since it's been just about two years since our IPO and just over three years since we started this endeavor, I'm extremely proud of what our team has accomplished during this time. And I'm incredibly excited about the opportunity ahead of us in 2023 as we expect topline data readouts for both LP352 and LP659.

謝謝，布蘭迪。非常感謝今天參加我們第一次財報電話會議的所有人。我們想提供最新情況，因為我們的 IPO 已經過去了大約兩年，而我們開始這項工作也僅僅三年多了，我對我們的團隊在這段時間所取得的成就感到非常自豪。我對 2023 年擺在我們面前的機會感到非常興奮，因為我們預計 LP352 和 LP659 都會讀出頂線數據。

On today's call, I will provide a high level business update for our potentially best-in-class pipeline. Our Chief Medical Officer, Dr. Randall Kaye, will give key updates on LP352, and then Brandi Roberts will provide an overview of our 2022 financial results before we open the line for Q&A.

在今天的電話會議上，我將為我們潛在的一流管道提供高水準的業務更新。我們的首席醫療官 Randall Kaye 博士將提供 LP352 的重要更新，然後 Brandi Roberts 將在我們開通問答線路之前概述我們 2022 年的財務業績。

As many of you are aware, we spun out of Arena Pharmaceuticals and formed Longboard with the mission of advancing neurology assets with differentiated pharmacokinetics, pharmacodynamics, and targeted engagement. To do this, we've focused on building a world class neuroscience team, with the ability to strategically select the best indications, design the right clinical trials, and move the assets through clinical development in a differentiated way. Ultimately, our goal is for our compounds to deliver differentiated clinical outcomes that meaningfully impact the lives of patients.

正如你們許多人所知，我們從 Arena Pharmaceuticals 中分離出來，成立了 Longboard，其使命是透過差異化的藥物動力學、藥效學和有針對性的參與來推進神經病學資產的發展。為此，我們專注於建立世界一流的神經科學團隊，能夠策略性地選擇最佳適應症、設計正確的臨床試驗，並以差異化的方式將資產轉移到臨床開發中。最終，我們的目標是讓我們的化合物提供差異化的臨床結果，對患者的生活產生有意義的影響。

What is so compelling to me today is that I'm seeing a lot of the same characteristics that we saw at Arena when I joined. And what drives our team is that our assets have the attributes of great medications that have successfully helped patients.

今天對我來說如此引人注目的是，我看到了許多與我加入 Arena 時所看到的相同的特徵。推動我們團隊前進的是，我們的資產具有成功幫助患者的優質藥物的屬性。

First, each one utilizes a more precise approach, targeting a well-understood mechanism of action. Second, each one has been developed for our target patient population to remove receptor interactions that negatively impact patient safety or are not known to contribute toward efficacy. Third, each one is going after a potential billion and plus opportunity with multiple relevant multibillion dollar M&A analogs for similar mechanisms of action. And importantly, each is going after a mechanism of action where the legacy Arena discovery scientists have had success.

首先，每個方法都採用更精確的方法，針對易於理解的作用機制。其次，每一種都是針對我們的目標患者群體開發的，以消除對患者安全產生負面影響或未知對療效無貢獻的受體交互作用。第三，每個人都在尋求潛在的數十億美元以上的機會，透過多個相關的數十億美元的併購類似物來實現類似的行動機制。重要的是，每個人都在追求一種行動機制，而傳統競技場發現科學家已經成功了。

So, let's start with LP352. LP352 is an oral, highly selective, centrally acting 5-HT2C superagonist. LP352 is the only 5-HT2C receptor agonist being dose-optimized for developmental and epileptic encephalopathies, or DEEs. Given its greater selectivity and specificity, we believe that LP352 could be a treatment for individuals with DEEs who either of one, have not had access to newer therapies, or two are still searching for a safer, more efficacious, easy to add on treatment in the syndromes where current therapies are inadequate.

那麼，讓我們從 LP352 開始吧。 LP352 是一種口服、高選擇性、中樞作用的 5-HT2C 超級激動劑。 LP352 是唯一針對發育性腦病變和癲癇性腦病變 (DEE) 進行劑量優化的 5-HT2C 受體激動劑。鑑於其更高的選擇性和特異性，我們相信LP352 可以成為DEE 患者的一種治療方法，這些患者中的任何一個尚未獲得更新的療法，或者兩個仍在尋找更安全、更有效、易於添加的治療方法目前療法不足的綜合症。

We're advancing LP352 in our ongoing Phase 1b/2a PACIFIC study, which is a basket study accepting participants with a range of DEEs. And we expect to have topline data from PACIFIC in the second half of this year.

我們正在進行的 1b/2a 期 PACIFIC 研究中推進 LP352，該研究是一項籃子研究，接受具有一系列 DEE 的參與者。我們預計今年下半年將獲得 PACIFIC 的主要數據。

I'll now turn it over to Randall to go deeper into DEEs, the reason to believe for 352, and why we are so excited about the PACIFIC study. Randall?

現在我將把它交給 Randall，讓他更深入地探討 DEE、相信 352 的理由，以及為什麼我們對 PACIFIC 研究如此興奮。蘭德爾？

Thanks, Kevin. Good afternoon, everyone. As Kevin mentioned, we have a really unique opportunity and responsibility to patients given the value that we believe our highly selective molecules have over existing medications in the space. Let's begin with LP352.

謝謝，凱文。大家下午好。正如凱文所提到的，鑑於我們相信我們的高選擇性分子比該領域現有藥物具有的價值，我們對患者擁有真正獨特的機會和責任。讓我們從 LP352 開始。

Just as a reminder, DEEs refer to a group of severe heterogeneous epilepsies that are characterized by significant developmental delay, treatment refractory seizures, and abnormalities in brain wave function, as an example, EEGs.

提醒一下，DEE 是指一組嚴重的異質性癲癇，其特徵是明顯的發育遲緩、治療難治性癲癇發作以及腦電波功能異常（例如腦電圖）。

While there have been significant advances in the treatment of DEEs over the past decade, the unmet medical need of these patients and their families is striking. Most of you are familiar with a few of the DEEs syndromes like Dravet and Lennox-Gastaut, but beyond these two, there are over 20 other DEE syndromes that are described. And in total, only four of these DEEs actually has specifically approved therapies.

儘管過去十年 DEE 的治療取得了重大進展，但這些患者及其家人的醫療需求仍未得到滿足，這一點令人震驚。大多數人都熟悉一些 DEE 綜合徵，例如 Dravet 和 Lennox-Gastaut，但除了這兩種之外，還描述了 20 多種其他 DEE 綜合徵。總的來說，這些 DEE 中只有 4 個實際上擁有專門批准的療法。

These patients still have a significant unmet medical need and multiple seizures that interfere with their development. Physicians and caregivers are looking for a safe, efficacious, and easy to add on therapy. And we know that safety is incredibly important to this community.

這些患者的醫療需求仍然未得到滿足，並且多次癲癇發作會幹擾他們的發育。醫生和護理人員正在尋找一種安全、有效且易於添加的療法。我們知道安全對這個社區來說非常重要。

So, why do we believe that LP352 is a potential best-in-class 5-HT2C superagonist for the treatment of DEEs? Well, let's start with selectivity and precision. 352 is the only 5-HT agonist that has no detected activity at receptors that are associated with significant adverse side effects, in the case of 5-HT2B with valvular heart disease and pulmonary arterial hypertension, and in the case of 5-HT2A with psychiatric AEs such as insomnia, hallucinations and euphoria.

那麼，為什麼我們相信 LP352 是治療 DEE 的潛在同類最佳 5-HT2C 超級激動劑？好吧，讓我們從選擇性和精度開始。 352 是唯一一種在與嚴重不良副作用相關的受體上未檢測到活性的5-HT 激動劑，對於患有瓣膜性心臟病和肺動脈高壓的5-HT2B 以及對於患有精神疾病的5- HT2A不良事件如失眠、幻覺和欣快感。

Second, preclinical validation. We have reported multiple preclinical models that demonstrate significant reduction in seizure activity and epileptiform events where we expected to, and this is similar to other compounds that are in the class.

第二，臨床前驗證。我們報告了多個臨床前模型，這些模型證明癲癇發作活動和癲癇樣事件顯著減少，這與我們預期的一樣，這與該類別的其他化合物相似。

Third, clinical validation. In our Phase 1 SAD/MAD studies, 352 was demonstrated to have favorable safety and tolerability and with adverse events that are generally consistent with the expected effects of serotonergic medications.

第三，臨床驗證。在我們的 1 期 SAD/MAD 研究中，352 被證明具有良好的安全性和耐受性，且不良事件通常與血清素藥物的預期效果一致。

And fourth, clinical CSF/EEG data. We designed an interesting CNS Phase 1 study to see if we could further characterize 352 in plasma and CSF as well as get to read on EEG or brainwave function. The results confirm that plasma and CSF PK concentrations increased in a dose dependent and consistent manner, and that LP352 demonstrated effects on qEEG activity within the first few doses with a sustained dose-dependent effects on this activity after continuous dosing. This is really important because this indicates that LP352 is getting into the brain as evidenced by receptor engagement.

第四，臨床腦脊髓液/腦電圖數據。我們設計了一個有趣的 CNS 第一階段研究，看看我們是否可以進一步表徵血漿和腦脊髓液中的 352，並了解腦電圖或腦電波功能。結果證實，血漿和腦脊髓液PK 濃度以劑量依賴性和一致的方式增加，且LP352 在前幾個劑量內表現出對qEEG 活性的影響，並且在連續給藥後對該活性產生持續的劑量依賴性影響。這非常重要，因為這表明 LP352 正在進入大腦，正如受體結合所證明的那樣。

Well, let's turn to the PACIFIC study. And I'd like to start by thanking the epilepsy community as we're extremely motivated internally by the engagement that we have had with parents and caregivers, physicians, our trial sites, as well as advocacy groups. In my 30 years involved in drug development, I have never seen a more engaged community. As a dedicated company, we take an extremely hands-on approach to the conduct of our clinical trial.

好吧，讓我們轉向太平洋研究。首先，我要感謝癲癇界，因為我們與父母和照護者、醫生、我們的試驗中心以及倡導團體的合作，在內部極大地激勵了我們。在我從事藥物開發的 30 年裡，我從未見過如此積極參與的社區。作為一家專注的公司，我們採取極為實際的方法來進行臨床試驗。

We personally conduct in-person visits at every one of our participating sites. We feel this is incredibly valuable in order to ensure the speed of enrollment, as well as the consistency across the seizure analysis. We also work very closely with the epilepsy study consortium to help review every trial participant and train sites and caregivers on how to categorize and count every seizure for even greater consistency.

我們親自對每一個參與站點進行實地訪問。我們認為這對於確保登記速度以及癲癇分析的一致性非常有價值。我們也與癲癇研究聯盟密切合作，幫助審查每位試驗參與者，並培訓地點和照護者如何對每次癲癇發作進行分類和計數，以提高一致性。

In the PACIFIC study, we plan to enroll 50 participants, 40 on medication, 10 on placebo, across 30 sites in the US and Australia. And our goal is to have a mixture of patients across multiple DEEs with approximately 10 patients with Dravet, 10 patients with Lennox-Gastaut, and then a combination of 30 patients diagnosed with other DEEs.

在 PACIFIC 研究中，我們計劃在美國和澳洲的 30 個地點招募 50 名參與者，其中 40 名接受藥物治療，10 名接受安慰劑。我們的目標是混合多個 DEE 患者，其中大約 10 名 Dravet 患者、10 名 Lennox-Gastaut 患者，然後是 30 名診斷為其他 DEE 的患者。

Well, as we're out there and we're interacting with our sites, what do we hear from our study sites? Excitement, commitment, passion. And we're excited to be part of this journey. And we continue to hear that there's tremendous remaining unmet medical need across both the DEEs with approved recent medications and the DEEs without any recent approvals.

好吧，當我們在外面與我們的網站互動時，我們從我們的研究網站聽到了什麼？興奮、承諾、熱情。我們很高興能成為這趟旅程的一部分。我們不斷聽說，最近獲得批准的藥物的 DEE 和最近沒有任何批准的 DEE 都存在大量未滿足的醫療需求。

We are looking forward to the completion of the enrollment of the PACIFIC study in the first half of this year and presenting topline data in the second half of this year. Let's now pass it back over to Kevin.

我們期待在今年上半年完成 PACIFIC 研究的入組工作，並在今年下半年公佈頂線數據。現在讓我們把它傳回給凱文。

Thanks, Randall. As you can tell, we're very enthusiastic about 352. But this is also an important year for LP659. A significant reason why we started Longboard because we saw the striking results generated by etrasimod and realized that there remained a tremendous opportunity for more selective, next generation S1P receptor modulators with optimized pharmacology, PK, and target engagement.

謝謝，蘭德爾。正如您所看到的，我們對 352 非常熱情。但這對 LP659 來說也是重要的一年。我們啟動Longboard 的一個重要原因是，我們看到了etrasimod 產生的驚人結果，並意識到對於具有優化藥理學、PK 和標靶參與作用的更具選擇性的下一代S1P 受體調節劑仍然存在巨大的機會。

In this case, LP659 was designed to be a centrally acting S1P receptor modulator focused on the modulation of the S1P1 and P5 receptors that are known to contribute towards efficacy while having no observable impact on the S1P2 and P3 receptors that have safety concerns or/and are involved in some of the potential off-target effects, including renal injury, hypertension, pulmonary issues, and macular edema. We believe LP659 could have potential in a number of inflammatory neurological conditions, and we look forward to initiating our Phase 1 shortly.

在這種情況下，LP659被設計為一種中樞作用的S1P受體調節劑，專注於調節已知有助於療效的S1P1和P5受體，同時對存在安全問題或/和的S1P2和P3受體沒有可觀察到的影響涉及一些潛在的脫靶效應，包括腎損傷、高血壓、肺部問題和黃斑水腫。我們相信 LP659 在許多發炎性神經系統疾病中具有潛力，我們期待很快啟動我們的第一階段。

So, why do we think 2023 will be an important year for LP659? Typically, Phase 1 data are not particularly telling. But in this Phase 1, we think we will see some really interesting potential data which could highlight certain differentiating characteristics of 659.

那麼，為什麼我們認為 2023 年對 LP659 來說將是重要的一年呢？通常，第一階段的數據並不特別有說服力。但在第一階段，我們認為我們將看到一些非常有趣的潛在數據，這些數據可以突出 659 的某些差異化特徵。

First, we obviously will be looking at safety and tolerability. Secondly, we expect to see rapid reduction in lymphocytes, as well as rapid recovery of lymphocytes, which we have seen in preclinical models. Of note, this was a significant advantage that etrasimod has seen over some of the other S1P receptor modulators. We look forward to sharing that SAD data later this year and framing the opportunity and thoughts on initial indications as we get closer to advancing the compound beyond healthy volunteers and into patients.

首先，我們顯然會考慮安全性和耐受性。其次，我們期望看到淋巴細胞的快速減少，以及淋巴細胞的快速恢復，這我們在臨床前模型中已經看到了。值得注意的是，這是 etrasimod 相對於其他一些 S1P 受體調節劑的顯著優勢。我們期待在今年稍後分享該 SAD 數據，並隨著我們越來越接近將該化合物從健康志願者推廣到患者的目標，框架對初步適應症的機會和想法。

With that, I'll pass the call to Brandi to review our financial results. Brandi?

這樣，我會將電話轉給布蘭迪，以審查我們的財務表現。布蘭迪？

Thanks, Kevin. We ended the year with $67.6 million in cash, cash equivalents, and short-term investments. Our 2022 operating expenses were just under $45 million. R&D expenses were $34.6 million for 2022 compared to $19.8 million in 2021. Our 2022 R&D expenses increased over 2021 levels as we progressed both of our programs and added headcount to our team.

謝謝，凱文。截至年底，我們的現金、現金等價物和短期投資為 6,760 萬美元。我們 2022 年的營運費用略低於 4,500 萬美元。 2022 年的研發費用為 3,460 萬美元，而 2021 年為 1,980 萬美元。隨著我們兩個專案的進展和團隊人數的增加，我們 2022 年的研發費用比 2021 年增加。

G&A expenses were $10.2 million for 2022 compared to $8.1 million in 2021. Our 2022 G&A expenses increased over 2021 levels as we continue to build out support functions as appropriate for a public company of our size.

2022 年的一般管理費用為 1,020 萬美元，而 2021 年為 810 萬美元。隨著我們繼續建立適合我們規模的上市公司的支援職能，我們 2022 年的一般管理費用比 2021 年的水準有所增加。

Net loss was $43.9 million or $2.56 per share for the full year 2022 compared to $27.8 million or $1.93 per share for the full year 2021.

2022 年全年淨虧損為 4,390 萬美元，即每股 2.56 美元，而 2021 年全年淨虧損為 2,780 萬美元，即每股 1.93 美元。

We expect that our expenses will trend upwards during 2023 as we continue the development of LP352 and advance LP659 into the clinic.

我們預計，隨著我們繼續開發 LP352 並將 LP659 推進臨床，我們的費用將在 2023 年呈上升趨勢。

We are providing expected guidance for 2023 operating expenses to be in the range of $57 million to $63 million, excluding stock-based compensation.

我們預計 2023 年營運支出將在 5,700 萬美元至 6,300 萬美元之間，不包括股票薪酬。

We are focused on spending responsibly as we progress our programs. We have built a very solid team with a lot of expertise, and they are able to do a tremendous amount of work.

在推進計劃的過程中，我們注重負責任地支出。我們建立了一支非常堅實的團隊，擁有豐富的專業知識，他們能夠完成大量的工作。

As we prepare for our Phase 3 program with LP352 and, down the road, a Phase 2 for LP659, we are planning for the resources we will need both internally and externally and we'll bring them onboard at the appropriate time. We want to be able to move our programs through clinical development as quickly and efficiently as possible.

當我們準備 LP352 的第 3 階段計劃以及 LP659 的第 2 階段計劃時，我們正在規劃內部和外部所需的資源，並將在適當的時間將它們引入。我們希望能夠盡可能快速有效地推動我們的專案進入臨床開發階段。

I also wanted to take this opportunity to provide a little bit more color on our recent financing. In February, we completed a $23 million follow-on public offering of our common stock. This financing was the result of receiving several reverse inquiries from strong institutional funds that indicated interest in building a position in our stock. We are happy that we were able to bring some new funds into the Longboard family, as well as increased investments from some of our existing holders who have strongly supported us through our Series A financing in October of 2020, our IPO in 2021, and now our follow-on offering. We are focused on creating long-term value for those who believe in our technology and are supporting us through our journey.

我還想藉此機會為我們最近的融資提供更多的資訊。 2 月份，我們完成了 2,300 萬美元普通股的後續公開發行。此次融資是收到來自強大機構基金的多次反向詢問的結果，這些基金表明有興趣在我們的股票中建倉。我們很高興能夠為 Longboard 家族帶來一些新資金，以及一些現有持有人的增加投資，他們透過 2020 年 10 月的 A 輪融資、2021 年的 IPO 以及現在對我們的大力支持我們的後續產品。我們致力於為那些相信我們的技術並在我們的旅程中支持我們的人創造長期價值。

We believe that the proceeds from this financing along with our cash, cash equivalents, and short-term investments as of year-end 2022 will be sufficient to fund our current planned operations into mid-2024 and, importantly, through our PACIFIC data later this year.

我們相信，截至 2022 年底，本次融資的收益以及我們的現金、現金等價物和短期投資將足以為我們目前計劃的運營提供資金到 2024 年中期，重要的是，透過我們今年晚些時候的太平洋數據年。

I'll now turn the call back to the operator to open the line for Q&A. Operator?

現在，我將把電話轉回給接線員，以開通問答線路。操作員？

(Operator Instructions) Neena Bitritto-Garg, Citi.

（操作員指示）Neena Bitritto-Garg，花旗銀行。

Hi guys. Thanks for taking my question. I was just wondering if you could remind us of a few things on the PACIFIC study design. So, first, appreciate you giving updates on the number of patients with Dravet and LGS that you expect to have in the study. But can you remind us if you will have both active and placebo patients in each of those subgroups that we can potentially see a difference there? And then, also thinking about what you would consider to be a success from the PACIFIC study, can you lay out for us what sort of reduction in seizure frequency you would consider to be a success on the topline? Thanks.

嗨，大家好。感謝您提出我的問題。我只是想知道您能否提醒我們有關太平洋研究設計的一些事情。因此，首先，感謝您提供您預計參與研究的 Dravet 和 LGS 患者數量的最新資訊。但是您能否提醒我們，如果每個亞組中都有活性治療患者和安慰劑患者，我們可能會看到其中的差異？然後，同時考慮一下您認為 PACIFIC 研究的成功之處是什麼，您能否向我們列出您認為哪種類型的癲癇發作頻率降低才是成功的？謝謝。

Thanks, Neena. Happy to take those questions. Randall, do you want to take both of them in terms of study design, active and placebo?

謝謝，妮娜。很高興回答這些問題。 Randall，您想在研究設計方面同時採用活性藥物和安慰劑嗎？

Sure. So, we put, as we noted, 10 patients with Dravet, approximately 10 with Lennox-Gastaut, and a mixture of the other DEEs. We have not stratified in this design because of the size of the study. Statistically, we'd expect to see equal numbers of placebo and drug in each of the groups, but that would be the general hope.

當然。因此，正如我們所指出的，我們輸入了 10 名 Dravet 患者，大約 10 名 Lennox-Gastaut 患者，以及其他 DEE 的混合。由於研究規模的原因，我們沒有在此設計中進行分層。從統計數據來看，我們預計每組中安慰劑和藥物的數量相同，但這只是普遍的希望。

In terms of efficacy expectations, remember, primarily, this is a safety and tolerability study as the most important of the endpoints. We are looking in the primary endpoint position at reductions in seizure frequency relative to baseline. We haven't put out a number of what the expectations are. What we're looking to see is, our hypothesis is that the reduction in seizure frequency is similar qualitatively across the DEE spectrum. And I think that's something that we would be looking more closely at once we actually know what the mixture is per se of different DEEs.

就療效預期而言，請記住，這主要是一項安全性和耐受性研究，是最重要的終點。我們正在研究主要終點位置，即癲癇發作頻率相對於基線的減少。我們還沒有給出一些期望。我們希望看到的是，我們的假設是，在整個 DEE 譜系中，癲癇發作頻率的減少在質量上是相似的。我認為一旦我們真正知道不同 DEE 的混合物本身是什麼，我們就會更仔細地研究這一點。

(multiple speakers) I was just going to add, remember, the placebo effect across most of these DEE studies has been in a fairly acceptable band, in the 7% to 20% range along the way. And so, we didn't feel that it was necessary to stratify.

（多個發言者）我只是想補充一點，請記住，大多數 DEE 研究中的安慰劑效應一直處於相當可接受的範圍內，一直在 7% 到 20% 的範圍內。因此，我們認為沒有必要進行分層。

Got it. Okay, that's super helpful. And then can you just remind us as well of what we should expect and what you're looking for on the AE side? I know you're not doing any cardiovascular monitoring in the study, but anything in particular that we should be looking out for there.

知道了。好的，這非常有幫助。那麼您能否提醒我們我們應該期待什麼以及您在 AE 方面尋找什麼？我知道您在研究中沒有進行任何心血管監測，但我們應該特別注意其中的任何事情。

Hey, it's Randall here. The AE profile that we've seen so far has been relatively benign. The most common adverse event has been headache; to some degree, some mild GI symptomatology. We'd expect to continue to see that to some degree. Again, we're focusing more on tolerability, can we get patients on an initial starting dose and maintain them during the overall maintenance period.

嘿，我是蘭德爾。到目前為止，我們看到的 AE 情況相對良好。最常見的不良事件是頭痛；在某種程度上，有一些輕微的胃腸道症狀。我們預計在某種程度上會繼續看到這種情況。同樣，我們更關注耐受性，我們能否讓患者接受初始劑量並在整個維持期內維持劑量。

And thanks for bringing up the point about other adverse events. Since our compound, 352, does not interact with the 5-HT2B receptor, we do not anticipate the typical cardiovascular risks that are associated with other medications out there, such as Fintepla. In fact, in our study protocol, FDA did not require us to do echocardiogram. So, we're just doing routine monitoring.

感謝您提出其他不良事件的觀點。由於我們的化合物 352 不會與 5-HT2B 受體相互作用，因此我們預計不會出現與 Fintepla 等其他藥物相關的典型心血管風險。事實上，在我們的研究方案中，FDA 並沒有要求我們做超音波心臟檢查。所以，我們只是進行例行監控。

Yeah, so, remember, from a long-term perspective, we fundamentally believe safe and easy to add on to current standard of care is going to be incredibly important. At the same time, we're balancing out that this is the only 5-HT2C that's being dose optimized for these patients. And so, what we're trying to do is, really, in this study, figure out where do we want to push, how do we want to push, how do we want to get patients to that optimal dose where we're balancing both that safety profile that we hope to have as well as that efficacy that comes from dose optimization.

是的，所以，請記住，從長遠來看，我們從根本上相信，安全且易於添加到當前的護理標準將非常重要。同時，我們正在平衡，這是唯一針對這些患者進行劑量優化的 5-HT2C。因此，我們真正想做的是，在這項研究中，找出我們想要推動的方向，我們想要如何推動，我們想要如何讓患者達到我們平衡的最佳劑量我們希望擁有的安全性以及劑量優化帶來的功效。

Got it. Appreciate it. [I'll go ahead,] thanks.

知道了。欣賞它。 [我會繼續，]謝謝。

Josh Schimmer, Evercore ISI.

喬許‧施默 (Josh Schimmer)，Evercore ISI。

Thanks for taking the question. First on 352, would you consider a switch study from patients on Fintepla? And if so, any thoughts on what that might look like?

感謝您提出問題。首先，關於 352，您會考慮對 Fintepla 患者進行轉換研究嗎？如果是這樣，你有什麼想法嗎？

And then for 659, as you're considering potential indications there, there are a number of indications that S1P modulators already addressed, such as MS and ulcerative colitis. Would you be inclined to pursue those or find new territories and what might your thinking be to identify the best applications of this mechanism? Thanks.

然後對於 659，當您考慮那裡的潛在適應症時，S1P 調節劑已經解決了許多適應症，例如 MS 和潰瘍性結腸炎。您傾向於追求這些目標或尋找新的領域？您可能會如何考慮確定機制的最佳應用？謝謝。

Sure. Thanks, Josh. 659, we think that there's tremendous unmet need beyond MS and ulcerative colitis. Again, the unique characteristics of 659 lend themselves towards these neurological conditions, given the central action that occurs. We do have a license with Pfizer to make sure we don't compete with them in ulcerative colitis and Crohn's and some of the areas they're going after. So that's not even possible.

當然。謝謝，喬許。 659，我們認為，除了多發性硬化症和潰瘍性結腸炎之外，還有巨大的未滿足需求。同樣，考慮到所發生的中樞作用，659 的獨特特徵使其適合這些神經系統疾病。我們確實擁有輝瑞公司的許可，以確保我們不會在潰瘍性結腸炎和克羅恩病以及他們所追求的一些領域與他們競爭。所以這根本不可能。

But we think there's tremendous unmet need in these orphan neurological conditions where lymphocyte reduction, T-cell trafficking, all these things that we've seen with these S1Ps over the last 10 years to 15 years could be incredibly valuable to patients who have tremendous unmet needs. So, that's more we're thinking about for 659.

但我們認為，在這些孤兒神經系統疾病中，存在著巨大的未滿足需求，其中淋巴細胞減少、T 細胞販運，以及我們在過去10 年到15 年中透過這些S1P 看到的所有這些事情，對於那些尚未滿足巨大需求的患者來說可能非常有價值需求。所以，我們對 659 的考慮更多。

Randall, do you want to take a first cut at the switch study?

蘭德爾，你想參加轉換研究的第一次嗎？

Sure, So, a switch study from Fintepla over to LP352, so I'm going to answer this as a clinician. I'm not sure you'd need to do that. You have a medication that has one of the most restrictive REMS that are out there in the marketplace in a patient population that is fragile and challenging. So just what might sound simple as doing an echocardiogram prior to treatment and echos throughout, I don't think you need to do a switch study. I think you will get natural movement over to our compound. It would be intrinsically obvious that LP352 would be safer and would be a right thing to switch without the study. But it's a provoking question. We'll think about it a little bit more.

當然，所以，從 Fintepla 到 LP352 的轉換研究，所以我將以臨床醫生的身份來回答這個問題。我不確定你是否需要這樣做。您所擁有的藥物是市場上限制性最強的 REMS 藥物之一，適用於脆弱且具有挑戰性的患者群體。因此，聽起來很簡單，例如在治療前做超音波心動圖並在整個過程中進行迴聲，我認為您不需要進行轉換研究。我想你會自然地移動到我們的庭院。本質上很明顯，LP352 會更安全，並且在不進行研究的情況下轉換是正確的選擇。但這是一個發人深省的問題。我們會再考慮一下。

Yeah, something we've been thinking a lot. And it gets down to how do we want to handle Dravet, given fenfluramine usage there? But as of right now, we're not seeing a tremendous uptake with fenfluramine in even Dravet alone, let alone in Lennox-Gastaut, such that we think it's necessary, but it's something we've been kicking around for a while as a potential after we see PACIFIC data.

是的，我們一直在想很多事情。考慮到芬氟拉明的使用情況，這取決於我們如何處理 Dravet？但截至目前，我們還沒有看到芬氟拉明在 Dravet 中的巨大應用，更不用說在 Lennox-Gastaut 中，因此我們認為這是必要的，但這是我們已經考慮了一段時間的潛在藥物。在我們看到太平洋數據之後。

Okay, got it. And do you feel like you've got the resources, capital wise, to potentially advance both the programs simultaneously? Or do you feel like you, at some point, may have to choose which to prioritize?

好，知道了。您是否覺得自己擁有資源（從資本角度來看）可以同時推動這兩個專案？或者您覺得在某些時候可能必須選擇優先考慮哪一個？

We think we are going to be able to have the resources. As Brandi mentioned, this last financing was not about funding the Phase 3s for LP352 and the Phase 2 for LP659. This was really a bunch of folks who could not find volume in our stock wanting to get into the name and so using financing in a formal setting as opposed to using the ATM.

我們認為我們將能夠擁有資源。正如布蘭迪所提到的，最後一次融資並不是為 LP352 的第 3 階段和 LP659 的第 2 階段提供資金。這實際上是一群找不到我們股票交易量的人想要進入這個名字，因此在正式場合使用融資而不是使用 ATM。

And so, our hope is that we can continue to finance as necessary. And we are going to try to be prudent in how much dilution we want to take along the way, knowing that there has been this movement towards the haves versus the have nots, but we don't think we need to raise massive amounts of capital to really be still considered to have.

因此，我們希望能夠繼續提供必要的融資。我們將盡量謹慎地對待我們想要採取的稀釋程度，因為我們知道已經出現了向富人和窮人傾斜的趨勢，但我們認為我們不需要籌集大量資金真算還是有的。

Brandi, do you want to add anything?

布蘭迪，你想補充什麼嗎？

No, I just want to say that I think we've really done a great job at building a lot of talent in the organization as well. We've grown from just three employees back in 2022 to 33 at the end of 2022 and have brought in a lot of people with great epilepsy and neurology experience. And I think we plan to capitalize on that and continue to move these programs forward ourselves.

不，我只是想說，我認為我們在組織內培養大量人才方面也確實做得很好。我們的員工數量從 2022 年的 3 名員工增加到 2022 年底的 33 名員工，並引進了許多具有豐富的癲癇和神經病學經驗的人員。我認為我們計劃利用這一點並繼續推動這些項目。

Thanks very much. Good luck with the updates this year.

非常感謝。祝今年的更新好運。

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯，坎托菲茨杰拉德。

Yes. Good afternoon, Kevin and team. Thanks for the [good kins] and the update and taking our questions. I had a couple of questions on 352. I'm just wondering if you could provide us a little bit more color on the types of patients that are really joining into this study. Can you tell us whether or not they're skewed to the younger ages? And I note that exclusion criteria include the use of fenfluramine. Is that forever in a Dravet patient completely naive or could some of those people have been exposed to fenfluramine in the past?

是的。下午好，凱文和團隊。感謝[好親戚]和更新並回答我們的問題。我對 352 有幾個問題。我只是想知道您是否能為我們提供更多有關真正參與這項研究的患者類型的信息。您能告訴我們他們是否傾向於年輕化嗎？我注意到排除標準包括使用芬氟拉明。對 Dravet 患者來說，這種情況是否永遠是天真的？或者其中一些過去是否曾接觸過芬氟拉明？

Yeah, Randall, do you want to take that?

是的，蘭德爾，你想接受嗎？

Yeah. Hey Charles, it's Randall. Thanks for those questions. So, we have opened up the study originally starting as an adult population, 18 and above, and then dropped the population as additional confirmatory preclinical safety data emerged.

是的。嘿查爾斯，我是蘭德爾。謝謝你提出這些問題。因此，我們最初從 18 歲及以上的成年人開始進行這項研究，然後隨著更多驗證性臨床前安全數據的出現而放棄了該族群。

So, we felt comfortable moving into the adolescent population down to 12. We are seeing patients coming into the study within the adolescent population. We haven't put specific numbers out. So, it'd be hard to answer your question about skewing towards, but we're satisfied that we're getting a nice balance of patients.

因此，我們對進入 12 歲以下的青少年群體感到放心。我們看到青少年群體中的患者進入研究。我們還沒有公佈具體數字。因此，很難回答你關於偏向的問題，但我們很滿意我們在病人方面取得了良好的平衡。

Your second question, let me clarify. We exclude patients who have failed conforming. Failure would mean they had no discernible treatment response to fenfluramine, or they had an adverse event profile or a side effect profile that would preclude its use. So, if a patient, let's say, had been on fenfluramine, but insurance wasn't covering it, or the parents didn't like the inconvenience of regular echos, then that would be a subject that would potentially be included.

你的第二個問題，讓我澄清一下。我們排除未能遵守規定的患者。失敗意味著他們對芬氟拉明沒有明顯的治療反應，或者他們有不良事件或副作用，無法使用芬氟拉明。因此，如果一個病人，比如說，服用了芬氟拉明，但保險不承保，或者父母不喜歡定期迴聲帶來的不便，那麼這將是一個可能被包括在內的主題。

Okay, that's helpful. And then in terms of the actual conduct of the study, are you allowing down titration during the maintenance phase? Or is that just not necessary? Are you not seeing any of that over the course of the study so far?

好的，這很有幫助。然後就研究的實際進行而言，您是否允許在維持階段下調滴定？或者這只是沒有必要？到目前為止，您在研究過程中還沒有看到這些嗎？

Yes, it's an interesting question. So, the way the protocol is written, we use the up-titration portion to get them on a dose that they're tolerating. So, start at six, go up to nine, go up to 12. But we're going up by tolerability. We're not forcing and pushing everyone up to 12. So, the expectation is, when they get into the maintenance period, they're tolerating 352 well.

是的，這是一個有趣的問題。因此，按照方案的編寫方式，我們使用向上滴定部分來讓他們接受他們能夠耐受的劑量。所以，從 6 點開始，增加到 9 點，再增加到 12 點。但我們是根據耐受性來提高的。我們不會強迫每個人都達到 12。因此，我們的預期是，當他們進入維護期時，他們能夠很好地容忍 352。

Our expectation is that they will stay on that dose for that time period. Would we theoretically allow some flexibility? I guess we could protect potentially, but generally, the approaches that we'll have them on the right dose so they can tolerate and stay on that during the maintenance period.

我們的期望是他們將在這段時間內保持該劑量。理論上我們會允許一定的彈性嗎？我想我們可以潛在地保護他們，但一般來說，我們會讓他們服用正確的劑量，這樣他們就可以忍受並在維持期間堅持下去。

Okay, got it. Last question quickly is, if you considered success, I think the first analyst asked a question about seizure reduction frequency. Is anything beyond just simple seizure reduction that you would be looking at from an efficacy standpoint that you'd be intrigued with, being able to show, particularly given the safety profile of the drug, and seeing, I guess, compliance or dose density over time? What would intrigue you?

好，知道了。最後一個問題是，如果你考慮成功，我認為第一位分析師問了一個關於癲癇發作頻率減少的問題。除了簡單的減少癲癇發作之外，您還會從功效的角度來考慮，您會對此感興趣，能夠展示，特別是考慮到藥物的安全性，並且我猜，您會看到依從性或劑量密度超過時間？什麼會引起您的興趣？

I think it's important to frame this as a safety and tolerability study and also proof of concept that you can treat a heterogeneous group of patients across the DEE spectrum. So, success would be safe, well tolerated, and some comparable seizure reduction. I'd love to start to talk about some of the other potential areas that you can start to look at in the larger studies, such as quality of life, clinical global improvement, and so forth. But that's just going to have to wait until we move into pivotal studies next year.

我認為將其作為一項安全性和耐受性研究以及可以治療跨 DEE 譜系的異質患者群體的概念證明非常重要。因此，成功是安全的、耐受性良好的，癲癇發作也有一定程度的減少。我很樂意開始談談您可以在更大規模的研究中開始關注的其他一些潛在領域，例如生活品質、臨床整體改善等等。但這只能等到明年我們進入關鍵研究。

Okay, [good to know]. Thanks for taking the questions.

好的，[很高興知道]。感謝您提出問題。

Laura Chico, Wedbush.

勞拉·奇科，韋德布希。

Hi. Good afternoon. Thanks for taking my question. I've got two more strategic questions for you, I guess. The first one, assuming success with PACIFIC, I'm wondering how we should be thinking about the potential or the feasibility of using a basket registrational study kind of expanding on the PACIFIC design, if you would.

你好。午安.感謝您提出我的問題。我想我還有兩個策略問題想問你。第一個，假設 PACIFIC 取得成功，我想知道我們應該如何考慮使用籃子註冊研究來擴展 PACIFIC 設計的潛力或可行性（如果您願意的話）。

Secondarily, Kevin, maybe from a strategic perspective, wondering if you could take a step back for us and comment on what gives you confidence in the market opportunity within the DEE space specifically? Thanks very much.

其次，Kevin，也許從策略角度來看，您是否可以為我們退後一步，評論一下是什麼讓您對 DEE 領域的市場機會充滿信心？非常感謝。

Yeah, thanks Laura. Great question. Look, I think from a company perspective, from a philosophical perspective, we would like to get to a broad DEE approval because we think it's the right thing for patients in the community and the caregivers. We think that it's tremendously unfair -- Rare Disease Day was earlier this week, and we think it's tremendously unfair that some of these DEEs and these families and these patients with DEEs don't have access to some of these newer medications. And we think that the current development pathway leave certain people behind unnecessarily.

是的，謝謝勞拉。很好的問題。聽著，我認為從公司的角度、從哲學的角度來看，我們希望獲得 DEE 的廣泛批准，因為我們認為這對社區患者和照護者來說是正確的事情。我們認為這是非常不公平的——罕見疾病日是在本週早些時候，我們認為其中一些 DEE、這些家庭和這些 DEE 患者無法獲得一些較新的藥物，這是非常不公平的。我們認為，目前的發展道路不必要地將某些人拋在後面。

So, from a philosophical perspective, we really would like to do that. And we think that there's a tremendous market opportunity there well beyond Dravet and Lennox-Gastaut, well beyond what has been seen with Epidiolex or fenfluramine, or some of these other [sanovimed] that are more niche. And so, we would like to get there.

所以，從哲學的角度來看，我們真的很想這麼做。我們認為，除了 Dravet 和 Lennox-Gastaut 之外，還有巨大的市場機會，遠遠超出 Epidiolex 或芬氟拉明或其他一些更小眾的 [sanovimed] 所看到的。因此，我們希望實現這一目標。

From a practical perspective, we want to make sure we do the right thing for this molecule. And we want to do the right thing for our shareholders because the last thing we want to do is create a development path forward that doesn't work with regulators. That doesn't help anyone. And so, we are going to continue to work on this messaging and this strategy over time. And I think the most important thing we're going to see that will impact whether we go down the individual indication route versus the broader basket route is the data from PACIFIC.

從實際角度來看，我們希望確保我們對這個分子做正確的事。我們希望為股東做正確的事情，因為我們最不想做的就是創造一條不與監管機構合作的發展道路。這對任何人都沒有幫助。因此，隨著時間的推移，我們將繼續致力於這項訊息傳遞和這項策略。我認為我們將看到的最重要的事情是來自太平洋的數據，這將影響我們是否走個體指示路線還是更廣泛的籃子路線。

And so, that's why we're so excited about that this year. Because, right now, we can have great conversations with KOLs and patient advocacy groups and walk through why we think this will be so transformative, but until we see that data set, we can't make that call. And frankly, it's all theoretical.

因此，這就是我們今年對此感到如此興奮的原因。因為，現在，我們可以與 KOL 和患者權益團體進行良好的對話，並解釋為什麼我們認為這將具有如此大的變革性，但在我們看到該資料集之前，我們無法做出決定。坦白說，這都是理論上的。

So, what gives me confidence today is we haven't seen these molecules work in one indication and fail in another. Remember, Lennox-Gastaut is really a catch all basket. If these molecules were just working in SCN1A patients, then that's a very, very different thing. We already are starting to see that with some molecules in TSC that are more focused on the tumor side versus the epilepsy side.

因此，今天給我信心的是，我們還沒有看到這些分子在一種適應症中起作用而在另一種適應症中失敗。請記住，Lennox-Gastaut 確實是個包羅萬象的籃子。如果這些分子只對 SCN1A 患者有效，那就是完全不同的事了。我們已經開始看到 TSC 中的一些分子更關注腫瘤一側而不是癲癇一側。

So, for us, we think this molecule has this tremendous opportunity. But what we have to do is make sure it gets to patients. And whether we can get it to the broadest group of patients is our hope and our dream, but we need to see the PACIFIC data.

因此，對我們來說，我們認為這種分子具有巨大的機會。但我們要做的就是確保它到達患者手中。能否將其推廣到最廣泛的患者群體是我們的希望和夢想，但我們需要看到太平洋地區的數據。

Did I answer your question?

我回答你的問題了嗎？

Yes, it does. Thanks, Kevin.

是的，它確實。謝謝，凱文。

Yatin Suneja, Guggenheim Partners.

蘇內賈 (Yatin Suneja)，古根漢合夥人事務所。

Kevin, could you expand a little bit more on the dose optimization point that you make? I think it is our understanding that Fintepla was never dose optimized. So, I'm just curious to understand from you, what you are seeing on a PK/PD perspective in terms of CNS exposure that gives you confidence that the molecule is better optimized than, let's say, Fintepla. So that's first question.

凱文（Kevin），您能否進一步闡述您所做的劑量優化點？我認為我們的理解是 Fintepla 從未進行過劑量優化。所以，我只是想從您那裡了解您從 PK/PD 角度所看到的中樞神經系統暴露情況，這讓您相信該分子比 Fintepla 更好地優化。這是第一個問題。

The second one is what work you might be doing on the formulation to bring it, currently, it's TID, so maybe do a QD or a BID, if you can comment on these two questions. Thanks.

第二個問題是你可能會在配方方面做哪些工作來帶來它，目前，它是 TID，所以如果你能對這兩個問題發表評論，也許可以做 QD 或 BID。謝謝。

Sure. So, look, remember, fenfluramine was the weight loss dose arbitrarily cut by some folks in Belgium, great outcome for the molecule, but we really don't know what's the optimal safety to efficacy balance with that molecule. Along the way, we saw some dose responses between the low dose and the high dose in a number of their studies, but we didn't ever really see where the top is. Lorcaserin, whether that drug ever makes it to market or not, we don't know. But again, that's the weight loss dose just carried over.

當然。所以，請記住，芬氟拉明是比利時一些人任意削減的減肥劑量，對於該分子來說效果很好，但我們真的不知道與該分子功效平衡的最佳安全性是什麼。在這個過程中，我們在許多研究中看到了低劑量和高劑量之間的一些劑量反應，但我們從未真正看到頂部在哪裡。氯卡色林，這種藥物是否會上市，我們不知道。但同樣，這只是剛剛延續的減肥劑量。

And so, for 352, what we're excited about is the opportunity to really figure out how much receptor engagement do we really want to have, and it's why we got so excited about the 102 data.

因此，對於 352，我們感到興奮的是有機會真正弄清楚我們真正想要有多少受體參與，這就是為什麼我們對 102 數據如此興奮。

So, Randall, do you want to walk through the 102 data for a second?

那麼，Randall，您想瀏覽 102 個資料嗎？

Sure. So, in our 102 data, we learned that there was good solid dose proportionality between the oral dose given, what appeared in the plasma, and probably most importantly, what ended up in CSF. We compared the CSF dose concentrations that we observed relative to the KI or the dissociation constant. And what we found is that we were getting at or, in most cases, well above the KI at our top dose at 12 milligrams TID. And we also found that, even at 6 milligrams, which is the start of the titration, we're getting great receptor engagement, somewhere around 70% or so of the KI.

當然。因此，在我們的 102 數據中，我們了解到，口服劑量、血漿中出現的劑量以及可能最重要的是腦脊髓液中最終出現的劑量之間存在良好的固體劑量比例。我們將觀察到的 CSF 劑量濃度與 KI 或解離常數進行了比較。我們發現，在 12 毫克 TID 的最高劑量下，我們達到了或在大多數情況下遠高於 KI。我們也發現，即使在滴定開始時的 6 毫克劑量下，我們也能獲得良好的受體結合，大約是 KI 的 70% 左右。

So, what that tells us is, that means you can dose optimize, you can modify, you can adjust as we go into further clinical studies next year that we can go up and down based on the data that we're seeing. And that is the opposite of what you can do with Fintepla currently.

所以，這告訴我們的是，這意味著你可以優化劑量，你可以修改，你可以調整，因為我們明年將進入進一步的臨床研究，我們可以根據我們看到的數據上下調整。這與目前 Fintepla 所能做的相反。

At a point in time, as these patients go from young children to adolescents and older, as they gain weight, you will cap out. So, you cannot continue to increase the level of fenfluramine in order to match the increasing weight. You just can't dose optimize a drug that has a restrictive REMS.

在某個時間點，當這些患者從幼兒變成青少年和老年人，隨著他們體重增加，你就會達到上限。因此，您不能為了適應體重的增加而繼續增加芬氟拉明的劑量。您無法對具有限制性 REMS 的藥物進行劑量優化。

And then on the second question, the BID formulation, again, we are focused on making sure we have that BID for the Phase 3. There's some intellectual property involved in that, that we're not ready to disclose at this point and work through, but we remain on track for BID for the Phase 3.

然後，關於第二個問題，即投標書的製定，我們的重點是確保我們有第三階段的投標書。其中涉及一些知識產權，我們目前不准備披露並解決這些問題，但我們仍在按計劃進行第3 階段的投標。

Okay. Thank you.

好的。謝謝。

Patrick Trucchio, H.C. Wainwright.

特魯基奧 (Patrick Trucchio)，H.C.溫賴特。

Thanks. Good afternoon. I'm wondering, first, if you can tell us if there's any evidence that the 5-HT2C mechanism could be complementary or synergistic with that of cannabidiol? And would you expect a portion of patients enrolled in PACIFIC to be on cannabidiol background treatment? And if so, what portion of those patients?

謝謝。午安.首先，我想知道您能否告訴我們是否有任何證據表明 5-HT2C 機制可以與大麻二酚的機制互補或協同？您是否期望參加 PACIFIC 的一部分患者接受大麻二酚背景治療？如果是這樣，這些患者的比例是多少？

Hey, Patrick. It's Randall. Great question. Thanks for that. I probably should have discussed them earlier. So, we do allow patients to have background of cannabidiol of Epidiolex as long as they've been on a stable dose. I don't have specific numbers for you. It's hard to say whether they'll be synergistic. I'd like to describe it somewhat differently.

嘿，派崔克。這是蘭德爾。很好的問題。感謝那。我可能應該早點討論它們。因此，我們確實允許患者有 Epidiolex 大麻二酚的背景，只要他們服用穩定的劑量。我沒有具體的數字給你。很難說它們是否會產生協同作用。我想以不同的方式描述它。

When you think about these complicated patients with these developmental and epileptic encephalopathies, multiple modality treatment with the right medication is going to make sense. So, I can see a time -- and I'll try to refer to this as precision and targeted treatment of patients where the clinician is going to the shelf and saying I want to have the best, safest, efficacious cannabidiol, and I think they're also going to be reaching up to that shelf in the DEE space for the most efficacious and safest 5-HT2C.

當您想到這些患有發育性腦病變和癲癇性腦病變的複雜患者時，使用正確的藥物進行多種方式治療將是有意義的。所以，我可以看到一個時間- 我會嘗試將其稱為對患者的精確和有針對性的治療，臨床醫生將上架並說我想要最好的，最安全的，有效的大麻二酚，我認為他們還將前往 DEE 空間的貨架購買最有效、最安全的 5-HT2C。

So, I can't say whether they'd be synergistic, but they certainly -- one would expect them to be to be complementary.

因此，我不能說它們是否會協同作用，但人們肯定會期望它們是互補的。

Yeah, that's helpful. And then how big of a concern is the Fintepla black box on adoption among clinicians and patients and what would need to be demonstrated in LP352 program to avoid having a similar black box warning on the label?

是的，這很有幫助。那麼 Fintepla 黑盒子對於臨床醫生和患者的採用有多大的擔憂，以及需要在 LP352 計畫中證明什麼才能避免標籤上出現類似的黑盒子警告？

I wouldn't expect to have a black box warning. We've had the discussion with the agency. Our compound does not interact with the 5-HT2B receptor. So a priori, there's no expectation to do the kind of work that was required with Fintepla. So, we asked the FDA specifically about conducting echocardiograms, they're not required by this program, and we wouldn't anticipate that that would be part of it.

我沒想到會有黑框警告。我們已經與該機構進行了討論。我們的化合物不與 5-HT2B 受體相互作用。因此，我們並不期望完成 Fintepla 所需的工作。因此，我們專門向 FDA 詢問了有關進行超音波心動圖的問題，該計劃並不要求進行超音波心動圖檢查，而且我們預計這不會成為其中的一部分。

To answer your question more clinically, what I'm hearing from other clinicians, these are really complicated patients. And they're very, very fragile. Adding on the component of an echocardiogram, getting it scheduled, it's not like it's right down the hall in these clinics, it could be in another building. These are not the most mobile of patients.

為了更臨床地回答你的問題，我從其他臨床醫生那裡聽到的，這些都是非常複雜的病人。而且它們非常非常脆弱。加上超音波心動圖的組成部分，安排它，它不像是在這些診所的大廳裡，它可能在另一棟大樓裡。這些患者並不是流動性最強的患者。

So, it's very, very inconvenient. And they have to continue getting echocardiograms for the duration of their therapy, and then one more if they do choose to discontinue it.

所以，這是非常非常不方便的。在治療期間，他們必須繼續接受超音波心臟檢查，如果他們選擇停止治療，他們需要再接受一次超音波心臟檢查。

We've heard numerous instances across the country where echocardiograms are available, but they're not readily available. There'll be a waiting list in order to obtain one. I think it's a significant challenge for patients. And we feel really confident in the approach of interaction with 5-HT2C, but you've got to do it in a way where it's going to be safe and convenient for patients. We think that's what LP352 has the promise of.

我們聽說全國各地都有很多可以使用超音波心動圖的例子，但它們並不容易取得。為了獲得一個，將會有一個等待名單。我認為這對患者來說是一個重大挑戰。我們對與 5-HT2C 相互作用的方法非常有信心，但必須以對患者安全且方便的方式進行。我們認為這就是 LP352 所承諾的。

Yeah, and again, congrats to everyone involved in the fenfluramine approval and launch. I don't want to speak negatively about them. But UCB just mentioned that they expect peak sales of that molecule to be about EUR800 million. And if you back into what that translates to from a patient perspective, patient number perspective, based on their current pricing, it doesn't appear that UCB expects to even get a large percentage of the Dravet market, let alone if you add the Dravet market on top of the Lennox-Gastaut market.

是的，再次恭喜所有參與芬氟拉明批准和上市的人。我不想對他們說負面的話。但 UCB 剛剛提到，他們預計該分子的峰值銷售額約為 8 億歐元。如果你從病人的角度、病人數量的角度來看這意味著什麼，根據他們目前的定價，UCB 似乎並不希望獲得 Dravet 市場的很大一部分份額，更不用說如果你添加 Dravet 了Lennox-Gastaut 市場上方的市場。

And so, we're not hearing a lot of feedback from the community, I don't have any patients for you because all of my patients are on fenfluramine. We're not hearing a lot of feedback that, oh, my gosh, I don't know how you're going to beat fenfluramine in the marketplace. That gives us great and tremendous hope for our molecule and hope for these patients to make these parents, these caregivers' lives easier. And we think a safer molecule does that.

因此，我們沒有聽到社區的太多回饋，我沒有任何患者適合您，因為我所有的患者都在服用芬氟拉明。我們沒有聽到很多反饋，哦，天哪，我不知道你將如何在市場上擊敗芬氟拉明。這給我們的分子帶來了巨大的希望，並希望這些患者能讓這些父母、這些照護人員的生活變得更輕鬆。我們認為更安全的分子可以做到這一點。

And it's back to that conversation that we were having based on Josh's question, which is, do we even need a switch study. And I think that's going to be an interesting one along the way. And the good news is we can see this specific data and see the continued launch trajectory of fenfluramine and then make that decision down the road. But fenfluramine has now been on the market for two-and-a-half years and the sales are what they are. And so, I think we're not overly concerned about our ability to differentiate ourselves and hopefully have a preferred molecule on the market down the road.

回到我們根據喬許的問題進行的對話，即我們是否需要進行轉換研究。我認為這將是一個有趣的過程。好消息是我們可以看到這些具體數據並看到芬氟拉明的持續推出軌跡，然後做出決定。但芬氟拉明現在已經上市兩年半了，銷售量也是。因此，我認為我們並不過度擔心我們區分自己的能力，並希望未來在市場上有一個首選分子。

That's great. Thank you very much.

那太棒了。非常感謝。

Thank you. This concludes our Q&A session. I would now like to turn the conference back to Kevin for closing remarks.

謝謝。我們的問答環節到此結束。現在我想請凱文致閉幕詞。

Thanks, operator. And I want to thank everyone for joining the call today and for sharing in our enthusiasm in the Longboard story as we approach data readouts across our pipeline in the second half of this year. Have a great day.

謝謝，接線生。我要感謝大家今天加入電話會議，並在今年下半年我們在整個管道中進行數據讀出時分享我們對 Longboard 故事的熱情。祝你有美好的一天。

Thanks.

謝謝。

This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。大家，祝你有美好的一天。