Longboard Pharmaceuticals Inc (LBPH) 2024 Q2 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Longboard Pharmaceutical earnings and incorporate update Call. As a reminder, this conference call is being recorded.

下午好，女士們先生們，歡迎來到 Longboard Pharmaceutical 的財報並更新電話會議。謹此提醒，本次電話會議正在錄音中。

I would now like to turn the call over to Brandi Roberts, Longboard's Chief Financial Officer. You may begin.

我現在想將電話轉給 Longboard 首席財務官布蘭迪羅伯茨 (Brandi Roberts)。你可以開始了。

Thank you, and good afternoon, everyone. Welcome to Longboard's conference call and webcast where we'll be providing a corporate update, including results from our LP659 single-ascending dose study.

謝謝大家，大家下午好。歡迎參加 Longboard 的電話會議和網路廣播，我們將在其中提供公司最新信息，包括 LP659 單劑量遞增研究的結果。

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 potential of our product candidates, the anticipated timing and design of clinical trials, top line data, commercial opportunities and financial guidance. These statements are subject to risks and uncertainties that could cause actual results to differ.

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陳述，包括但不限於有關我們的產品候選者的潛力、臨床試驗的預期時間和設計、頂部的陳述線路數據、商業機會和財務指導。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。

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. 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.

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。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，我們沒有義務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。

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 during what is a very exciting time for Longboard. I'm extremely proud of what we have accomplished in 2024 across the entire organization and portfolio. I'm going to start off by providing an update on our lead asset, Bexicaserin, a highly selective and specific 5-HT2C receptor agonist and then hand it over to Dr. Kaye to provide an update on LP659, and then Brandi will give an update on our financials before we open the call for Q&A.

謝謝布蘭迪，也非常感謝今天加入我們的所有人，這對長板來說是一個非常令人興奮的時刻。我對 2024 年整個組織和產品組合所取得的成就感到非常自豪。我將首先介紹我們的主要資產 Bexicaserin（一種高選擇性和特異性 5-HT2C 受體激動劑）的最新情況，然後將其交給 Kaye 博士提供 LP659 的最新情況，然後 Brandi 將提供在我們開始在問答之前更新我們的財務狀況。

We kicked off the year with a positive top line data from our Phase 1b/2a PACIFIC study, evaluating Bexicaserin in Developmental and Epileptic Encephalopathies, or DEEs. We were incredibly pleased that Bexicaserin achieved a median reduction of countable motor seizures of approximately 60% in highly refractory participants and on top of three to four other anti-seizure medications in Dravet, Lennox-Gastaut and a number of other DEE participants.

我們以 1b/2a 期 PACIFIC 研究的積極頂線數據拉開了新的一年的序幕，該研究評估了 Bexicaserin 在發育性和癲癇性腦病 (DEE) 中的作用。我們非常高興的是，在Dravet、Lennox-Gastaut 和其他一些DEE 參與者中，Bexicaserin 與其他三到四種抗癲癇藥物相比，在高度難治性參與者中可數運動性癲癇發作的中位減少了約60%。

Then in June, we had a very busy month. First, we shared an interim analysis of our open-label extension study of PACIFIC, demonstrating a sustained response over an approximate 6-month period with continued favorable safety and tolerability as well as successful titration of all of our placebo participants on to Bexicaserin. Second, we completed our end of Phase 2 meeting. And third, the FDA granted Breakthrough Therapy designation for seizures associated with DEEs down to the age of 2.

然後到了六月，我們度過了非常忙碌的一個月。首先，我們分享了PACIFIC 開放標籤擴展研究的中期分析，顯示在大約6 個月的時間內有持續的反應，具有持續良好的安全性和耐受性，並且所有安慰劑參與者都成功滴定到Bexicaserin 。其次，我們完成了第二階段會議的結束。第三，FDA 授予了針對 2 歲以下 DEE 相關癲癇發作的突破性療法稱號。

We are the first and only company to receive this designation for DEEs. The PACIFIC Data and Breakthrough Therapy designation have been the most rewarding achievement since the founding of Longboard. Both of these support our thesis and strengthen what we believe we have been working towards, which is to treat DEEs broadly and provide more equitable access to patients that are tremendously underserved. We have been overwhelmed by the outpouring of excitement and support from caregivers, advocates and physicians.

我們是第一家也是唯一一家獲得 DEE 頭銜的公司。PACIFIC 數據和突破性療法頭銜是 Longboard 成立以來最有價值的成就。這兩者都支持我們的論點，並加強了我們相信我們一直在努力的目標，即廣泛治療 DEE 並為服務嚴重不足的患者提供更公平的治療機會。來自護理人員、倡導者和醫生的熱情和支持讓我們不知所措。

We're committed to making a difference for those living with DEEs. To that end, we are moving forward with our innovative design to study all DEEs in our global Phase 3 program. We are so pleased to have the opportunity to collaborate with the FDA with the goal of addressing the tremendous unmet medical need for this population in an optimized manner.

我們致力於為那些患有 DEE 的人帶來改變。為此，我們正在推進我們的創新設計，以研究我們全球第 3 階段計劃中的所有 DEE。我們很高興有機會與 FDA 合作，目標是以優化的方式解決該人群巨大的未滿足的醫療需求。

We are expeditiously preparing to start our Phase 3 program, which will include two pivotal studies, one for Dravet syndrome and one DEE study that will include Lennox-Gastaut and all the other DEEs. We intend to initiate our Phase 3 program in the second half of this year, and we'll provide additional details on the studies at an upcoming Investor and Analyst Day on September 16.

我們正在迅速準備啟動我們的第 3 階段計劃，其中將包括兩項關鍵研究，一項針對 Dravet 綜合徵，一項 DEE 研究將包括 Lennox-Gastaut 和所有其他 DEE。我們打算在今年下半年啟動第三階段計劃，我們將在即將舉行的 9 月 16 日投資者和分析師日上提供有關研究的更多詳細資訊。

With that, I'd like to switch over to our second clinical stage asset, LP659, a highly selective S1P1, S1P5 receptor modulator. LP659 was created and optimized by Arena's world-class GPCR research team, the same team that discovered (inaudible). LP659 was designed to be a centrally acting S1P receptor modulator with some of the same differentiating characteristics built into (inaudible)

有了這個，我想轉向我們的第二個臨床階段資產 LP659，一種高度選擇性的 S1P1、S1P5 受體調節劑。LP659 由 Arena 世界一流的 GPCR 研究團隊創建和優化，該團隊發現了（聽不清楚）。 LP659 被設計為中樞作用的 S1P 受體調節劑，具有一些相同的差異化特徵（聽不清楚）

S1P receptor modulators are considered well understood and early data has been shown to be generally predictive of clinical effectiveness. We have been doing a lot of translational work here. That, coupled with additional learnings from the I&I space has opened up several orphan CNS indications that we think could be very interesting and have attractive commercial opportunities.

S1P 受體調節劑被認為是眾所周知的，早期數據已被證明通常可以預測臨床有效性。我們在這裡做了很多翻譯工作。再加上從 I&I 領域獲得的額外經驗，我們發現了一些孤兒中樞神經系統適應症，我們認為這些適應症可能非常有趣，並且具有有吸引力的商業機會。

LP659 works centrally to modulate S1P receptors, which play a crucial role in the immune and nervous systems. It exhibits a rapid onset and offset of action, making it potentially more effective and manageable in clinical settings.

LP659 的主要作用是調節 S1P 受體，而 S1P 受體在免疫和神經系統中發揮著至關重要的作用。它表現出快速的起效和抵消作用，使其在臨床環境中可能更加有效和易於管理。

Its high selectivity to S1P1 and S1P5 receptors minimizes off-target effects, enhancing its therapeutic profile and preclinical studies have shown no significant impact on S1P2 and S1P3, indicating a targeted approach. LP659 has high oral bioavailability, meaning it is effectively absorbed when taken orally, and it directly impacts CNS glial cell S1P receptors. It has shown promising results in preclinical models for various conditions.

它對 S1P1 和 S1P5 受體的高選擇性最大限度地減少了脫靶效應，增強了其治療效果，臨床前研究表明對 S1P2 和 S1P3 沒有顯著影響，這表明是一種標靶方法。LP659具有較高的口服生物利用度，這意味著口服時可以有效吸收，並且直接影響中樞神經系統膠質細胞S1P受體。它在各種條件的臨床前模型中顯示出了有希望的結果。

The market for S1P receptor modulators is substantial, with these treatments already generating significant revenue in CNS applications, primarily in multiple sclerosis. In multiple sclerosis mouse models, LP659 demonstrated lymphocyte modulation, suggesting its potential efficacy in similar human conditions.

S1P 受體調節劑的市場很大，這些治療方法已經在中樞神經系統應用（主要是多發性硬化症）中產生了可觀的收入。在多發性硬化症小鼠模型中，LP659 表現出淋巴細胞調節作用，顯示其在類似的人類條件下具有潛在功效。

However, based on advancements in our understanding of S1Ps, we believe that LP659's unique properties provided with the potential to be a best-in-class CNS-focused S1P addressing a range of orphan neurological disorders.

然而，基於我們對 S1P 理解的進步，我們相信 LP659 的獨特特性有可能成為同類最佳的專注於 CNS 的 S1P，解決一系列孤兒神經系統疾病。

With that, I'll turn it over to Randall.

有了這個，我會把它交給蘭德爾。

Good afternoon, and thanks, Kevin. Today, I'll be presenting on LP659, our promising S1P receptor modulator with broad applicability in treating various rare orphan neuro conditions.

下午好，謝謝，凱文。今天，我將介紹 LP659，這是我們很有前途的 S1P 受體調節劑，在治療各種罕見的孤兒神經疾病方面具有廣泛的適用性。

I'd like to delve into how LP659 functions by selectively modulating S1PR1. So just as a reminder, S1Ps, and more specifically on LP659 work by functionally antagonizing S1PR1, binding of these agonists to the receptor, induces receptor internalization in degradation. This disrupts the normal egress of lymphocyte subsets from the lymph nodes. So by reducing the migration of lymphocytes, LP659 decreases the release of inflammatory cytokines, thereby minimizing organ and tissue damage.

我想深入研究 LP659 如何透過選擇性調節 S1PR1 發揮作用。提醒一下，S1P，更具體地說是 LP659，透過功能性拮抗 S1PR1 發揮作用，這些激動劑與受體結合，誘導受體內化降解。這會擾亂淋巴細胞亞群從淋巴結的正常流出。因此，透過減少淋巴細胞的遷移，LP659 減少發炎細胞因子的釋放，從而最大限度地減少器官和組織損傷。

And what's important is LP659 does this while maintaining immune surveillance, ensuring that the body's defense mechanism still remain intact. In the CNS, S1P receptor 1 is expressed in astrocytes and its activation has been shown to reduce astrogliosis and support microglial cell function. In oligodendrocytes, S1P5 may play a role in myelination. These effects on the glial cells are expected to reduce neuroinflammation and enhance neuronal survival.

重要的是 LP659 在保持免疫監視的同時做到這一點，確保身體的防禦機制仍然保持完整。在 CNS 中，S1P 受體 1 在星狀細胞中表達，其活化已被證明可以減少星狀細胞增生並支持小膠質細胞功能。在少突膠質細胞中，S1P5 可能在髓鞘形成中發揮作用。這些對神經膠質細胞的影響有望減少神經發炎並提高神經元存活率。

On the next slide, the selectivity profile of LP659 is directly coupled to its potential to decrease inflammation and enhance neuroprotection in the central nervous system. There are five S1P receptors that are known in humans with the S1P receptors 1 and 5 who are mediating the anti-inflammatory and neuroprotective effects.

在下一張投影片中，LP659 的選擇性特徵與其減少發炎和增強中樞神經系統神經保護的潛力直接相關。人類中有五種已知的 S1P 受體，其中 S1P 受體 1 和 5 可以介導抗發炎和神經保護作用。

S1P4 is generally considered to be non active in the CNS. And importantly, S1P2, S1P3 have been associated with potential safety liabilities of the class, so that includes vasoconstriction, fibrosis as well as decreased blood brain barrier integrity. LP659 is a highly potent agonist of the S1P1 receptor while retaining some activity at S1P5. It does not bind or activate S1P2 or S1P3 and has little activity.

S1P4 通常被認為在 CNS 中不活躍。重要的是，S1P2、S1P3 與該類藥物的潛在安全隱患相關，包括血管收縮、纖維化以及血腦屏障完整性降低。LP659 是 S1P1 受體的高效激動劑，同時保留了 S1P5 的一些活性。它不結合或活化 S1P2 或 S1P3，且活性很小。

On the next slide, LP659 was designed to be a next-generation S1P1 receptor agonist to target the CNS-related diseases with greater precision. LP659 is designed to be the most potent agonist at S1PR1 internalization and this potency is crucial for its therapeutic effect.

在下一張投影片中，LP659被設計為下一代S1P1受體激動劑，以更精確地針對中樞神經系統相關疾病。LP659 被設計為 S1PR1 內化最有效的激動劑，這種效力對其治療效果至關重要。

So when tested for its ability to promote total S1PR1 internalization mediated by both G proteins and [betaarrestin] coupling LP659 emerges the most potent of all of the approved CNS focused S1P modulators, so when you think of other examples such as Ponesimod Ozanimod, Siponimod, as well as Fingolimod.

因此，當測試其促進由G 蛋白和[βarrestin] 偶聯介導的總S1PR1 內化的能力時，LP659 成為所有已批准的CNS 重點S1P 調節劑中最有效的，因此當您想到其他例子時，例如Ponesimod Ozanimod、Siponimod、還有芬戈莫德。

So importantly, LP659 preferentially triggers beta-arrestin signaling over G protein signaling. Beta-arrestin signaling causes internalization and functional antagonism. So therefore, this contributes to the anti-inflammatory effects of the class. The G protein signaling contributes to first dose bradycardia, this is seen clinically with a less selective S1P receptor modulators.

重要的是，LP659 優先觸發 β-arrestin 訊號而不是 G 蛋白訊號。β-抑制蛋白訊號傳導導致內化和功能拮抗。因此，這有助於該類的抗發炎作用。G 蛋白訊號傳導導致首劑心搏過緩，這在臨床上使用選擇性較低的 S1P 受體調節劑觀察到。

And then furthermore, LP659 demonstrated the greatest selectivity for S1PR1 over S1PR5. You're seeing this on the right-hand side of the screen when tested for activity at beta-arrestin signaling alone. So LP659's potency at S1P1 internalization positions it as a pioneering treatment with significant potential from managing CNS related and autoimmune diseases.

此外，LP659 對 S1PR1 的選擇性高於 S1PR5。當單獨測試 β-抑制蛋白訊號傳導的活性時，您會在螢幕右側看到這一點。因此，LP659 在 S1P1 內化方面的功效使其成為一種開創性的治療方法，在治療 CNS 相關疾病和自體免疫疾病方面具有巨大潛力。

On the next slide, LP659 reduces circulating T and B cells without effect on natural killer cells and monocytes. So thus, this is what's in the immuno-surveillance. Those alternative cells are responsible for combating infection. This is data that I'm showing you from a preclinical model. This uses the EAE rats that are dosed with LP659 for 2 weeks, and this is compared to vehicle EAE rats. LP659 demonstrate potent in (inaudible) activity. It effectively lowers as seen on the left-hand side of the strain, T and B cell populations.

在下一張投影片中，LP659 減少了循環 T 細胞和 B 細胞，但對自然殺手細胞和單核細胞沒有影響。因此，這就是免疫監視的內容。這些替代細胞負責對抗感染。這是我向您展示的臨床前模型數據。這使用了給予 LP659 2 週的 EAE 大鼠，並將其與載體 EAE 大鼠進行比較。LP659 表現出強大的（聽不清楚）活性。如菌株左側所示，它有效地降低了 T 細胞和 B 細胞群。

Importantly, LP659 increases the proportion of the regulatory T cells, we'll call them T-regs over total CD4 cells. T-regs are a class of T cells that have anti-inflammatory effects and their function has been found to be beneficial in autoimmune and neurodegenerative disease. Now it's notable, I described before, LP659 does not have significant effect on natural killer cells on monocytes, and this indicates a selective modulation of immune cells.

重要的是，LP659 增加了調節性 T 細胞的比例，我們稱之為 T-regs 佔總 CD4 細胞的比例。T-reg 是一類具有抗發炎作用的 T 細胞，其功能已被發現對自體免疫和神經退化性疾病有益。現在值得注意的是，我之前描述過，LP659對單核細胞上的自然殺手細胞沒有顯著影響，這表明對免疫細胞的選擇性調節。

So therefore, in a preclinical model, LP659 promoted market suppression of the CD3-positive T cells, a significant reduction of B cells and an increase in T-reg frequency. These effects are consistent with the mechanism of action of this drug class, and these preclinical data confirm that LP659 improved in vitro profile while increased selectivity is expected to maintain clinical efficacy.

因此，在臨床前模型中，LP659促進了CD3陽性T細胞的市場抑制、B細胞的顯著減少和T-reg頻率的增加。這些作用與該類藥物的作用機轉一致，這些臨床前數據證實 LP659 改善了體外特性，同時增加的選擇性可望維持臨床療效。

So next what we're going to discuss is the Phase 1 SAD trial as well as its subsequent data. This slide represents the design and key study objectives of the 101 study. This is a first-in-human clinical trial. It's a Phase 1 single ascending dose. We call these SAD studies, adult healthy volunteers. And just to call your attention to the cohorts, cohorts 1 and 2 and 4 on day one, they're administered formulation 1 after an overnight fast, and this is followed by a discharge on day one.

接下來我們要討論的是第一階段 SAD 試驗及其後續數據。這張投影片展示了 101 研究的設計和主要研究目標。這是首次人體臨床試驗。這是第一階段單次遞增劑量。我們將這些 SAD 研究稱為成人健康志願者。為了引起您的注意，第一天的隊列 1、2 和 4，他們在禁食過夜後服用配方 1，然後在第一天出院。

And in Cohort 3, day 1, administration of Formulation 1 after an overnight fasting, they stay in clinic and on day 8, they're administered for, they have a washout and they're administered formulation to, I'm sorry, their administered formulation 2 following a 1-week washout of Formulation 1, and then they're subsequently discharged on day 15.

在第 3 組中，第 1 天，在禁食過夜後服用配方 1，他們留在診所，在第 8 天，他們接受了清洗，他們被服用配方，對不起，他們的在配方1 1 週沖洗後施用配方2，然後在第15 天出院。

So the key study objectives are to assess the safety and tolerability of a single ascending dose of LP659 to determine the PK profile of LP659 and its metabolites in single ascending doses and to determine the PD profile of LP659 in a single ascending dose.

因此，關鍵研究目標是評估單次遞增劑量 LP659 的安全性和耐受性，以確定單次遞增劑量中 LP659 及其代謝物的 PK 曲線，並確定單次遞增劑量中 LP659 的 PD 曲線。

So next, I'm going to give an overview. We'll focus first on the safety aspects of the Phase 1 study. LP659 was generally safe and well tolerated by the study participants. All adverse events were of mild severity. Importantly, no treatment-emergent adverse events led to a discontinuation of the study nor did we observe serious adverse events during the study period. The impact on heart rate was consistently low throughout the study duration and notably, there were no instances of first-dose bradycardia, which is often a concern in similar treatments.

那麼接下來，我將概述一下。我們將首先關注第一階段研究的安全性面向。LP659 總體上是安全的，並且研究參與者的耐受性良好。所有不良事件的嚴重程度均為輕度。重要的是，沒有治療引起的不良事件導致研究中止，我們在研究期間也沒有觀察到嚴重的不良事件。在整個研究期間，對心率的影響始終較低，值得注意的是，沒有首劑心搏過緩的情況，而這在類似治療中通常是一個問題。

Our ECG assessment showed no abnormalities including no cases of atrioventricular block, echocardiograms also were normal, indicating no functional adverse cardiac events, pulmonary function tests, including spirometry, showed no abnormalities, pelagic assessments were normal with no adverse event findings reported, and we observed no infections among the study populations highlighting the treatment favorable safety profile in this regard. So overall, LP659 demonstrated a very encouraging safety profile.

我們的心電圖評估顯示沒有異常，包括沒有房室傳導阻滯病例，超音波心動圖也正常，顯示沒有功能性不良心臟事件，肺功能測試，包括肺活量測定，顯示沒有異常，中上層評估正常，沒有不良事件發現報告，我們觀察到研究族群中沒有出現感染，凸顯了治療在這方面有利的安全性。總的來說，LP659 表現出了非常令人鼓舞的安全性。

Let's get to the good stuff. So the graph that I'm about to show you is going to look at the mean percent change from baseline in absolute lymphocyte counts and I'll coat it as ALC. This is looked at over a 24 hour period. And just to remind you, this is just a single dose study, not continuous dosing. The different lines that we're presenting here represent varying doses as well as formulations of LP659 as well as a pooled placebo group.

讓我們來看看好東西。因此，我將向您展示的圖表將顯示絕對淋巴細胞計數相對於基線的平均百分比變化，我將其標記為 ALC。這是在 24 小時內進行的觀察。只是提醒您，這只是單劑量研究，而不是連續給藥。我們在這裡展示的不同系列代表了 LP659 的不同劑量和配方以及安慰劑組。

It's important to note and to reiterate that lymphocyte reduction is an anticipated on-target effect of S1P modulators. It's indicative of the drug's mechanism of action is functioning as expected. I'll just overview the mean percent changes. In the ALC's, we're just going to highlight right at our six post-dosed. That's an important time point, Dose A, 3.5% reduction, B, 0.9%, OC, 18.8%, and here's where we're starting to see the effect that we're hoping to see is in Dose C formulation to 58.9% in dose D Formulation 1, a decrease of 48% with a pooled placebo cohort of 4.1%.

重要的是要注意並重申，淋巴細胞減少是 S1P 調節劑的預期中標效應。這表明藥物的作用機制正在如預期般發揮作用。我將概述平均百分比變化。在 ALC 中，我們將重點放在六次服藥後的情況。這是一個重要的時間點，劑量A，降低3.5%，劑量B，降低0.9%，OC，降低18.8%，在這裡我們開始看到我們希望看到的效果，即劑量C 配方中的降低58.9% 。

This data suggests that LP659 has a dose and formulation dependent effect on reducing ALC with higher doses showing greater reductions. This reduction in lymphocyte is a crucial parameter as we evaluate our drug's potential effectiveness as well as safety profile. Further analysis and studies will continue to assess the long-term effects in optimizing dosing strategies.

此數據表明，LP659 在降低 ALC 方面具有劑量和配方依賴性效應，劑量越高，顯示的降低幅度越大。當我們評估藥物的潛在有效性和安全性時，淋巴球的減少是至關重要的參數。進一步的分析和研究將繼續評估優化給藥策略的長期影響。

So now we get to the point, what does this all mean? How do we start to bring this information together and where do we go from here? What are the opportunities in immune and inflammatory conditions? There's been a lot of innovation in the I&E space since the approval of Fingolimod and the development of the other approved mods. The list of potential indications is continuing to grow. To that end, we have conducted preclinical studies of LP659 in three broad areas of interest, autoimmune, neuro inflammation and proteinopathies.

現在我們進入正題，這一切又意味著什麼？我們如何開始將這些資訊整合在一起以及我們下一步該何去何從？免疫和發炎狀況下有哪些機會？自從芬戈莫德獲得批准以及其他批准模組的開發以來，I&E 領域出現了許多創新。潛在適應症的清單正在不斷增加。為此，我們對 LP659 在自體免疫、神經發炎和蛋白質疾病這三個廣泛感興趣的領域進行了臨床前研究。

This slide outlines the primary disease areas that LP659 could potentially target. Each condition is characterized by its unique pathology and the role of T and, or B cells in disease progression. LP659 shows promise in targeting these indications due to its selective action on S1PR1 and its ability to modulate T and B cell behavior, thereby potentially reducing neuroinflammation and promoting better clinical outcomes.

這張投影片概述了 LP659 可能針對的主要疾病領域。每種疾病都有其獨特的病理學以及 T 和/或 B 細胞在疾病進展中的作用。LP659 由於其對 S1PR1 的選擇性作用以及調節 T 和 B 細胞行為的能力，從而有可能減少神經發炎並促進更好的臨床結果，因此在針對這些適應症方面顯示出了前景。

We continue to believe that the best path forward for LP659 will be in an indication where there's a high unmet medical need, where there is a strong preclinical data set and, or clinical support and whereby clinical studies can be conducted that are practical and that are feasible. In order to finalize that decision, we want to see the results of our anticipated Phase 1 MAD study, which we expect to initiate in the first quarter of 2025.

我們仍然相信，LP659 的最佳前進道路將是在存在高度未滿足的醫療需求的情況下，在存在強大的臨床前數據集和/或臨床支持的情況下，並且可以進行實用且符合要求的臨床研究。為了最終確定這一決定，我們希望看到預期的第一階段 MAD 研究的結果，我們預計該研究將於 2025 年第一季啟動。

And with that, I'll turn it over to Brandi to review our financials.

這樣，我會將其交給布蘭迪來審查我們的財務狀況。

Thanks, Randall. I'd like to take this opportunity to provide a bit more color on our Q2 results, our cash runway, scaling for our Phase 3 programs and our strategy for bringing programs forward.

謝謝，蘭德爾。我想藉此機會為我們第二季度的業績、我們的現金跑道、第三階段計劃的擴展以及我們推進計劃的策略提供更多資訊。

We ended the second quarter with approximately $305 million in cash and investments, and this reflects a cash burn of about $19 million for the quarter. Our second quarter expenses were higher than our first quarter expenses due to increased R&D activities, primarily related to Bexicaserin and a smaller amount for LP659. These expenses were in accordance with our internal expectations.

第二季末，我們擁有約 3.05 億美元的現金和投資，反映出該季度約 1,900 萬美元的現金消耗。由於研發活動增加，我們第二季的支出高於第一季的支出，主要與 Bexicaserin 相關，而 LP659 的支出較少。這些費用符合我們的內部預期。

For Bexicaserin, we had continued activities for our open label extension study as well as significant activities to prepare for our Phase 3 program. We expect that our expenses will continue to trend slightly upwards during 2024 as we continue to build out our world class organization, focused on elucidating the potential best-in-class clinical and commercial characteristics of Bexicaserin and continue to make progress on LP659.

對於 Bexicaserin，我們繼續進行開放標籤延伸研究活動，並進行重要活動，為我們的第 3 階段計畫做準備。我們預計，隨著我們繼續建立世界一流的組織，專注於闡明 Bexicaserin 潛在的一流臨床和商業特性，並繼續在 LP659 上取得進展，我們的費用將在 2024 年繼續略有上升。

That means scaling our team and building out our infrastructure in order to make sure our global Phase 3 program for Bexicaserin and roles at a pace that's acceptable to our organization, exploring additional clinical and non-clinical studies to differentiate our portfolio and taking advantage of the opportunity to interact with the DEE community and educate the broader community about the tremendous unmet need for DEE patients, their caregivers, loved ones and health care specialists. We are very excited about the opportunity ahead of us for Bexicaserin and LP659.

這意味著擴大我們的團隊規模並建立我們的基礎設施，以確保我們的Bexicaserin 全球3 期計劃和作用以我們組織可接受的速度進行，探索更多的臨床和非臨床研究來區分我們的產品組合，並利用與 DEE 社區互動的機會，並教育更廣泛的社區了解 DEE 患者、他們的護理人員、親人和醫療保健專家尚未滿足的巨大需求。我們對 Bexicaserin 和 LP659 面臨的機會感到非常興奮。

We take our responsibility for managing resources very seriously. We want every dollar to matter. So when we consider plans for additional studies for either program, we are constantly evaluating the risk, reward and whether we believe that level of spend is the best course of action for the company and our shareholders. Our goal is to continue to build value and the approximately $305 million in cash and investments that we have as of June 30, 2024, gives us the ability to execute on our vision into 2027.

我們非常重視管理資源的責任。我們希望每一美元都發揮作用。因此，當我們考慮對這兩個項目進行額外研究的計劃時，我們會不斷評估風險、回報以及我們是否認為該支出水準是公司和股東的最佳行動方案。我們的目標是繼續創造價值，截至 2024 年 6 月 30 日，我們擁有約 3.05 億美元的現金和投資，使我們有能力實現 2027 年的願景。

This concludes the prepared remarks from this afternoon's call, and I'll now turn the call back to the operator to open the line for Q&A, where I'll be rejoined by Kevin and Randall. Operator?

今天下午的電話會議準備好的演講到此結束，我現在將電話轉回給接線員，打開問答線路，凱文和蘭德爾將重新加入我的行列。操作員？

(Operator instructions)

（操作員說明）

Laura Chico, Wedbush.

勞拉·奇科，韋德布希。

Good afternoon and thanks very much for taking the question. Congratulations on the progress, guys. I have one question just with respect to the Bexicaserin Phase 3 efforts and then just one on LP659. With respect to the Bexicaserin pivotal program, wondering if you could just expand a little bit on the sizing of the respective studies. And just wondering if there are any kind of minimal numbers of certain types of DEEs that need to be represented on a patient number basis.

下午好，非常感謝您提出問題。恭喜你們取得了進步。我有一個關於 Bexicaserin 第三階段工作的問題，還有一個關於 LP659 的問題。關於 Bexicaserin 關鍵計劃，想知道您是否可以稍微擴展各自研究的規模。只是想知道是否存在需要以患者數量為基礎表示的某些類型 DEE 的最小數量。

With respect to LP659, thank you, Randall, for all that commentary. Just wondering if you could kind of walk through the decision matrix a little bit in terms of indication selection for next steps. Thanks very much, guys.

關於 LP659，謝謝蘭德爾的所有評論。只是想知道您是否可以在下一步的指示選擇方面稍微瀏覽一下決策矩陣。非常感謝，夥計們。

Yes, hey, thanks, Laura. Appreciate the questions. On the Phase 3 program for Bexicaserin, we want to make sure we roll it all out at the right time, not piecemeal. And so look forward to a fulsome disclosure of what we're planning to do around the R&D Day that we're scheduling for September 16.

是的，嘿，謝謝，勞拉。感謝您提出的問題。在 Bexicaserin 的第三階段計劃中，我們希望確保在正確的時間全面推出，而不是零敲碎打。因此，我們將在 9 月 16 日的研發日全面揭露我們計劃要做的事情。

With regards to your second question on the decision matrix, I'm happy to take it. It's a combination of three things. So we've been talking about this for a while. It's commercial opportunity. Is this something we can do? Is this something that is attractive? Do we like the risk reward on the commercial side? The competitive landscape on clinical feasibility, can we find patients, can we enroll the studies, can we do this in a time-efficient manner and a cost-efficient manner?

關於你關於決策矩陣的第二個問題，我很樂意回答。這是三件事的結合。所以我們已經討論這個問題有一段時間了。這是商業機會。這是我們能做的嗎？這就是有魅力的東西嗎？我們喜歡商業方面的風險報酬嗎？臨床可行性的競爭格局，我們能否找到患者，我們能否招募研究，我們能否以一種省時且經濟的方式做到這一點？

And then the last piece is translational science. Can we look at preclinical models as well as data generated from the other mods to help us elucidate other indications to go after? And the interesting thing is that over-time that, that translational area, the data we can glean from other mods has really expanded the potential indications we could go after because of all the learnings in I&I. And so I think when we started talking to folks when we did the IPO, we were kind of triangulating around a couple of indications.

最後一部分是轉譯科學。我們可以查看臨床前模型以及其他模型產生的數據來幫助我們闡明其他需要遵循的適應症嗎？有趣的是，隨著時間的推移，由於 I&I 中的所有學習，我們可以從其他模組收集的數據確實擴展了我們可以追蹤的潛在跡象。因此，我認為，當我們在首次公開募股時開始與人們交談時，我們正在圍繞一些跡象進行三角測量。

As we have progressed and learning more about LP659, as we have run it through additional preclinical models, as we have done additional literature searches that lens has really opened wider. And so where we are today is we have a good sense of what we want to see in the MAD to help us make that final decision, but I think it's a little premature to pick that indication until we see how the drug performs at steady state.

隨著我們取得進展並了解更多有關 LP659 的信息，隨著我們通過其他臨床前模型運行它，隨著我們進行其他文獻檢索，鏡頭確實開闊了。因此，我們今天所處的位置是，我們對MAD 中希望看到的內容有很好的了解，以幫助我們做出最終決定，但我認為在我們看到藥物在穩定狀態下的表現之前選擇該適應症還為時過早。

And so while we were hoping to roll out the indication a little bit earlier and frankly, if you had asked me when we did the IPO, when would we have selected that indication, I would have said it would be done by now. But the really interesting thing is we're continuing to learn a lot about this and expanding our potential indications. So my sense is we'll probably roll it out closer to the end of MAD or after MAD and as we move closer to the Phase 2 or our expected Phase 2.

因此，雖然我們希望早一點推出該指示，但坦白說，如果你問我我們什麼時候進行 IPO，我們什麼時候會選擇該指示，我會說現在就會完成。但真正有趣的是我們正在繼續了解許多這方面的知識並擴大我們的潛在適應症。所以我的感覺是，當我們接近第二階段或我們預期的第二階段時，我們可能會在接近 MAD 結束時或在 MAD 之後推出它。

Does that answer your question?

這能回答你的問題嗎？

Yes. It does. Thanks very much.

是的。確實如此。非常感謝。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Great. Congrats on the progress and thanks for taking the questions. The first one is on Bexicaserin. I think the most common question I've been getting from investors since the breakthrough therapy destination is how large is the DEE opportunity? Are you able to share anything about your market research on that?

偉大的。恭喜您的進展，並感謝您提出問題。第一個是 Bexicaserin。我認為，自從突破性治療目的地以來，我從投資者那裡得到的最常見的問題是 DEE 機會有多大？能分享一下您對此的市場研究嗎？

Yes. So we'll talk a little bit more about that in September. I think where we are today, there's a lot still left to learn. We're trying to make sure we're not double counting by including patients who have a diagnosis for Lennox-Gastaut plus a genetic diagnosis or one of the other DEEs. We're trying to look at patients who will have their indication potentially migrate over the course of their life. But what we will say what we do feel comfortable with saying is we think the market is very big.

是的。因此，我們將在九月進一步討論這一點。我認為我們今天所處的位置，還有很多東西要學習。我們試圖確保我們不會重複計算，將診斷為 Lennox-Gastaut 加上基因診斷或其他 DEE 之一的患者納入其中。我們正在嘗試尋找那些在其一生中其適應症可能發生遷移的患者。但我們可以放心地說的是，我們認為市場非常大。

We're excited about that opportunity to really be able to address a number of DEEs and a number of patients who don't have access to the latest clinical trials and don't have access to the latest standard of care. And to us, that is tremendously exciting. So more to come on exact numbers, but we think that there's a real opportunity here to do something with that designation in that indication.

我們很高興有機會真正能夠解決許多 DEE 和許多無法獲得最新臨床試驗和最新護理標準的患者的問題。對我們來說，這是非常令人興奮的。因此，更多的確切數字仍有待公佈，但我們認為，這裡確實有機會利用該指示中的指定來做一些事情。

Okay. That's helpful. A then a question on LP659. On the slides presented today, it looked like there was 2 formulations tested with quite a large difference in those 2 formulations. Are you able to share anything about what that formulation is or at least how much you'll be testing different formulations in the MAD study?

好的。這很有幫助。然後是關於 LP659 的問題。在今天展示的幻燈片上，看起來有 2 種配方經過測試，這 2 種配方之間存在很大差異。您能否分享有關該配方是什麼的任何信息，或者至少您將在 MAD 研究中測試不同配方的程度？

Yes. A great question. I think in the MAD study, we have triangulated on some variation of formulation too. Formulations will potentially adjust slightly on the margin, but we think formulation too gets into the plasma much better and has less variability. Obviously, you can see the impact on lymphocytes. And so formulation too is the path forward for the MAD. And I'm going to pass it over to Randall to add something.

是的。這是一個很好的問題。我認為在 MAD 研究中，我們也對配方的一些變化進行了三角測量。配方可能會略有調整，但我們認為配方也能更好地進入血漿，且變異性較小。顯然，您可以看到對淋巴細胞的影響。因此，制定方案也是 MAD 的前進之路。我將把它交給蘭德爾來補充一些東西。

Yes. Just a point to add is both the formulations and doses have got us to where we wanted to be in terms of the preliminary findings. The target was to show a reduction in absolute lymphocyte counts. We were in that 50% to 60% range.

是的。需要補充的一點是，配方和劑量都使我們達到了初步結果所希望的水平。目標是顯示絕對淋巴細胞計數的減少。我們處於 50% 到 60% 的範圍內。

That's great from an early content development standpoint in SAD. So an important thing to keep in mind is in a multiple ascending dose study with multiple doses, one would anticipate that, that decrease in absolute lymphocyte counts will continue to decrease to get the best benefit of the product. But these are terrific early findings in both formulations.

從 SAD 早期內容開發的角度來看，這非常棒。因此，要記住的一件重要的事情是，在多次劑量遞增的劑量研究中，人們預計，絕對淋巴細胞計數的減少將繼續減少，以獲得產品的最佳益處。但這些都是這兩種配方的出色的早期發現。

Thank you.

謝謝。

Gavin Clark Gartner, Evercore.

加文·克拉克·加特納 (Gavin Clark Gartner)，Evercore。

Hey, guys. Congrats on all the progress and thanks for taking the questions. I'll follow the form of doing one Bexi and one S1P question. First, just on Bexi, could you just comment on the status of discussions with global regulators on the potential for the broad DEE path since it sounds like you're clearly aligned with the FDA already?

嘿，夥計們。恭喜所有進展並感謝您提出問題。我會按照做一道Bexi題和一道S1P題的形式。首先，就 Bexi 而言，您能否評論一下與全球監管機構就廣泛 DEE 路徑的潛力進行討論的情況，因為聽起來您已經明確與 FDA 保持一致？

Sure. Randall, do you want to take this one ?

當然。蘭德爾，你想拿這個嗎？

Sure. Well, we're planning a global Phase 3 program. We're going to talk about all the details about that in September. We have initiated our discussions with global regulatory authorities. One would anticipate that our breakthrough therapy designation will set precedent in other areas will, and as part of our discussions, believe it or not, regulatory authorities do talk with each other across the globe, and they are aware of the Breakthrough Therapy designation and the reasoning and the thinking behind it. We do share that information across. So we would expect that our discussions with other regulatory authorities will go in a similar positive fashion.

當然。嗯，我們正在計劃一個全球性的第三階段計劃。我們將在九月討論所有細節。我們已開始與全球監管機構進行討論。人們預計我們的突破性療法認定將在其他領域開創先例，並且作為我們討論的一部分，無論您相信與否，監管機構確實在全球範圍內相互交談，他們知道突破性療法認定和推理及其背後的思考。我們確實分享這些資訊。因此，我們預計與其他監管機構的討論將以類似的積極方式進行。

Awesome. That makes sense. And on the S1P, I'm just wondering what the half-life of LP659 in humans is, and at the 1 dose where you saw the largest ALC impact, what was the heart rate or the QTC impact there? Thanks, guys.

驚人的。這是有道理的。在 S1P 上，我只是想知道 LP659 在人體中的半衰期是多少，在 1 劑量時，您看到 ALC 影響最大，心率或 QTC 影響是多少？謝謝，夥計們。

Yes, let me pass it to Randall.

是的，讓我把它轉給蘭德爾。

Yes. So the question on heart rate changes and ALC numbers, we did not see a clinically significant decrease in heart rate in any of the formulations tested. I also made a note that there were no abnormal EKG finding. So, I can't comment on the QTC numbers because they were all normal. We did not see. I think you're implying (inaudible) any QTC prolongation and we did not.

是的。因此，關於心率變化和 ALC 數字的問題，我們沒有看到任何測試的製劑中心率出現臨床顯著下降。我還記下心電圖沒有發現異常。所以，我無法對 QTC 數字發表評論，因為它們都是正常的。我們沒有看到。我認為您是在暗示（聽不清楚）任何 QTC 延長，但我們沒有。

Half life?

半衰期？

Half-life, way better to have that discussion with a multiple ascending dose study. The half-life that you do see is only the half-life after a single dose. They sometimes depending on the product, can be misleading. I'm not implying that there's a positive or negative here. I just think in general, we want to wait until you have a multiple ascending dose until you talk about the typical PK parameters such as half-life [Cmax, Tmax], AUCs and so forth.

半衰期，最好透過多次劑量遞增研究來討論。您看到的半衰期只是單次劑量後的半衰期。有時，根據產品的不同，它們可能會產生誤導。我並不是暗示這裡有正面或負面的一面。我只是認為一般來說，我們要等到你有多次遞增劑量，直到你談論典型的 PK 參數，例如半衰期 [Cmax、Tmax]、AUC 等。

Thanks. Congrats on the progress again.

謝謝。再次恭喜你取得了進步。

Kalpit Patel, B. Riley Securities.

卡爾皮特‧帕特爾 (Kalpit Patel)，B. 萊利證券 (Riley Securities)。

Yes, hey, good afternoon and congrats on the regulatory alignment. You mentioned that you have an other DEE component included into the LGS study. I guess if you can comment before the (inaudible) next month, how many different DEEs are you aiming to address in that other DEE component?

是的，嘿，下午好，恭喜監管協調。您提到 LGS 研究中包含了另一個 DEE 組件。我想如果您可以在下個月（聽不清楚）之前發表評論，您打算在其他 DEE 組件中解決多少個不同的 DEE？

Yes, hey, great question. I think it's almost actually the reverse. The 301 study is going to be a DEE study that includes Lennox-Gastaut. And a great question, though, but we want to be very clear on that. It truly is a DEE study that includes Lennox-Gastaut patients.

是的，嘿，好問題。我認為實際上幾乎是相反的。301 研究將是一項 DEE 研究，其中包括 Lennox-Gastaut。這是一個很好的問題，但我們希望對此說得非常清楚。這確實是一項 DEE 研究，其中包括 Lennox-Gastaut 患者。

We haven't disclosed yet how many potential DEEs will be in there. The number of DEEs continues to go up as more generic data has been generated. So we have a number in mind, but we'll probably roll that number out around the R&D Day. We did see a number of DEEs in the PACIFIC study, and that gives us comfort that we can study the entire DEE population in this 301 study as we move forward.

我們尚未透露其中將有多少潛在的 DEE。隨著更多通用資料的產生，DEE 的數量持續增加。所以我們心裡有個數字，但我們可能會在研發日前後公佈這個數字。我們確實在 PACIFIC 研究中看到了許多 DEE，這讓我們感到欣慰的是，隨著我們的進展，我們可以在這項 301 研究中研究整個 DEE 群體。

Randall, do you want to add something?

蘭德爾，你想補充一下嗎？

So we haven't disclosed the individual DEEs from the PACIFIC study. But we know there are 19 patients in that study. And when asked before, I said it was a bunch of onesies and twosies. So if you want to do the math, you could imagine that there is a significant amount of heterogeneity in different DEEs that we observed in the PACIFIC study. We'd expect that to move forward in a much larger study conducted in the DEE population. And stay tuned for September, and we'll go through some more exciting details then.

因此，我們尚未揭露 PACIFIC 研究中的各個 DEE。但我們知道研究中有 19 名患者。當之前被問到時，我說這是一堆連身衣和兩件套。因此，如果您想做數學計算，您可以想像我們在 PACIFIC 研究中觀察到的不同 DEE 之間存在顯著的異質性。我們期望在 DEE 人群中進行的一項更大規模的研究中能夠取得進展。請繼續關註九月，屆時我們將介紹一些更令人興奮的細節。

Okay. And then for the open-label extension late-breaker data next month, what sort of analysis are we expecting? Is there more follow-up data or is the same cutoff data as what we have seen?

好的。那麼對於下個月的開放標籤擴展遲到數據，我們期待什麼樣的分析？是否有更多的後續數據或與我們所看到的相同的截止數據？

Yes. So a lot of the data that will be presented there, much of which we have presented, and that is data for the 6 month cutoff. So that will provide the percent reduction in countable motor seizures at that time point as well as the full safety data set for the cohort that has reached that point.

是的。因此，我們將在那裡提供大量數據，其中大部分數據是我們已經提供的，即 6 個月截止日期的數據。因此，這將提供該時間點可計數運動性癲癇發作的減少百分比以及已達到該點的隊列的完整安全數據集。

We were pleased to see that it was accepted as an open-label extension study, and it will allow us to have a more in-depth discussion with our potential investigators. The beauty of this is, it's in Europe, it gives us a great opportunity to start to engage with our potential European investigators.

我們很高興看到它被接受為開放標籤擴展研究，這將使我們能夠與潛在的研究人員進行更深入的討論。這樣做的好處在於，它是在歐洲，它為我們提供了一個很好的機會來開始與潛在的歐洲調查人員接觸。

Okay. And then one last one for LP659. I guess, where do you guys stand on the partial clinical hold there? And what do you need to resolve if it's already not resolved?

好的。然後是 LP659 的最後一張。我想，你們對於部分臨床擱置的立場是什麼？如果尚未解決，您需要解決什麼？

Great. So with regards to the partial clinical hold, it is still in place, and our plan is to move forward with a complete response to the partial clinical hold that will be coupled with the proposal for the multiple ascending dose study, and so we would anticipate resolving that soon.

偉大的。因此，關於部分臨床擱置，它仍然存在，我們的計劃是繼續對部分臨床擱置做出全面的反應，這將與多次劑量遞增研究的提議相結合，因此我們預計很快就能解決這個問題。

Okay, wonderful. Thanks for taking the questions.

好吧，太棒了。感謝您提出問題。

David Hoang, Citigroup.

大衛黃，花旗集團。

Hi there. Thanks for taking my question. So first, I just wanted to ask about, again, the indication selection. I think you had the slide up and you showed quite a number of indications across a few different therapeutic areas. Should we really be thinking about it as, I guess, selecting just a single indication or could you think about maybe going after more than one indication and let's say, even having the potential to potentially partner and try to access larger indications? And then I had one follow-up.

你好呀。感謝您提出我的問題。首先，我想再次詢問適應症的選擇。我認為您已經完成了幻燈片，並且在幾個不同的治療領域中展示了相當多的適應症。我想，我們真的應該考慮只選擇一個適應症嗎？然後我進行了一項後續行動。

Yes, great question. I think we are waiting to decide how many potential indications we could take into Phase 2. And so we're going to continue to look at that along the way. The one challenge to be honest with everyone is that the patent life on LP659 is a little bit limited.

是的，很好的問題。我認為我們正在等待決定可以將多少潛在跡象納入第二階段。因此，我們將繼續關注這個問題。老實說，一個挑戰是 LP659 的專利壽命有點有限。

We have composition matter to 2031 plus patent term extension. So it's helping us continue to think about orphan indications as we build out the entire intellectual property portfolio. That doesn't mean we can't go after broader, bigger indications, but we want to make sure we think about it in the right way.

我們的組合物到 2031 年還有專利期限延長。因此，它幫助我們在建立整個智慧財產權組合時繼續考慮孤兒適應症。這並不意味著我們不能追求更廣泛、更大的適應症，但我們希望確保以正確的方式思考它。

Great. Really helpful. And then I just wanted to ask quickly on the overall safety profile of the LP659 molecule. You talked a lot about cardiac and not seeing anything there. But if you think about other physiological systems, ocular and such, how would you say LP659 compares to other S1P molecules in the class?

偉大的。真的很有幫助。然後我只想快速詢問 LP659 分子的整體安全性。你談論了很多關於心臟的事情，但沒有看到任何東西。但如果您考慮其他生理系統（如眼部等），您會認為 LP659 與同類中的其他 S1P 分子相比如何？

It's Randall. Thanks for asking that. I went through that early on. It's the boring part of what I go through the safety profile of a drug. In the mods, you do have to actually look more closely, not just at the cardiovascular system, but ocular macular edema is a not uncommon finding, impact on pulmonary function is a not uncommon finding.

這是蘭德爾。謝謝你這麼問。我很早就經歷過這一點。這是我了解藥物安全性最無聊的部分。在mods中，你確實必須更仔細地觀察，不僅僅是心血管系統，但眼部黃斑水腫是一個並不罕見的發現，對肺功能的影響也是一個並不罕見的發現。

So this is a single ascending dose study. It's our initial data set, but we did not see abnormalities in the other organ systems that are typically seen, but it's a big caveat. It's just a single ascending dose study. We'll continue, obviously, to monitor pulmonary cardiovascular and ocular findings plus the what I had mentioned at the very, very end is infections is an interesting aspect of the mods.

所以這是一項單次劑量遞增研究。這是我們的初始資料集，但我們沒有看到其他器官系統中常見的異常情況，但這是一個很大的警告。這只是一項單次劑量遞增研究。顯然，我們將繼續監測肺部心血管和眼部檢查結果，加上我在最後提到的感染是該模組的一個有趣的方面。

You do want to have lymphocyte reduction, but you want to be kind of selective. You don't want to totally shut down the immune system and immune surveillance. So it's important to follow the potential for infections and opportunistic infections. We saw no infections. I'm in this data set, and we'll continue to monitor that for that adverse event as well. Appreciate you asking that question.

你確實想要減少淋巴細胞，但你想要有選擇性。您不想完全關閉免疫系統和免疫監視。因此，追蹤感染和機會性感染的可能性非常重要。我們沒有看到感染。我在這個資料集中，我們也將繼續監控該不良事件。感謝您提出這個問題。

Thanks a lot.

多謝。

Yatin Suneja, Guggenheim Securities.

Yatin Suneja，古根漢證券公司。

Thank you for taking my questions. Maybe two from me. In terms of the endpoint, if you go for the broader DEE indication, could you talk about how would you harmonize those endpoint across different subsets of DEEs? So that's one.

感謝您回答我的問題。也許是我的兩個。就端點而言，如果您尋求更廣泛的 DEE 指示，您能否談談如何在不同的 DEE 子集之間協調這些端點？這就是其中之一。

And then the second one on the S1P molecule. I might have missed it. Is there a food effect that you are observing? So that's sort of one. And then maybe if you can specify what you want to see in the MAD specifically, that will be helpful. Thank you so much.

然後是 S1P 分子上的第二個。我可能錯過了。您觀察到食物有影響嗎？這就是其中之一。如果您可以具體指定您希望在 MAD 中看到的內容，也許會有所幫助。太感謝了。

Sure. Do you want to take the first one? (inaudible)

當然。你想拿第一個嗎？（聽不清楚）

Yes. So on endpoint, again, we'll go through this in a lot more detail in our research call, but the primary endpoint that we utilized in the PACIFIC study was countable motor seizures. I would anticipate that as the likely endpoint that would be utilized in our subsequent studies.

是的。因此，關於終點，我們將在研究電話會議中更詳細地討論這一點，但我們在太平洋研究中使用的主要終點是可數運動性癲癇發作。我預計這可能是我們後續研究中使用的終點。

We anticipate that can be harmonized across the global study because this is an endpoint that has been commonly used with other medications that have been approved in this space. I wouldn't anticipate this being a surprise or something unanticipated plus as you can imagine, we have been having ongoing discussions with regulatory authorities outside the US.

我們預計這一點可以在全球研究中得到協調，因為這是經常與該領域已批准的其他藥物一起使用的終點。我預計這不會是一個驚喜或意料之外的事情，而且正如你可以想像的那樣，我們一直在與美國以外的監管機構進行持續的討論。

Then on LP659 food effect?

那麼LP659食物的效果如何呢？

We don't analyze food effect in a single ascending dose study. Those are best done as separate studies, and I can't comment today because I don't remember if that would be a component of the multiple ascending dose study.

我們不會在單次劑量遞增研究中分析食物的影響。這些最好是作為單獨的研究進行，我今天無法發表評論，因為我不記得這是否是多次劑量遞增研究的一部分。

And then what would we like to see in the MAD? Obviously, I think we would like to see continued safety. That's the first and foremost. Obviously, on the cardiovascular side, the other mods have used a combination of dose titration as well as monitoring to avoid cardiovascular risks.

那麼我們希望在 MAD 中看到什麼呢？顯然，我認為我們希望看到持續的安全。這是首要的。顯然，在心血管方面，其他mods結合使用劑量滴定和監測來避免心血管風險。

Etrasimod didn't have to do either, whether or not we'll have that final answer based on the MAD, unknown. Obviously, we will have to keep an eye on that all the way through the development of LP659. We're going to want to see lymphocyte reduction over-time, and we're going to want to look at that from a sustained perspective that tends to be the data set that folks look at.

Etrasimod 也不必這樣做，無論我們是否會根據 MA​​D 得到最終答案，未知。顯然，我們必須在 LP659 的開發過程中始終關注這一點。我們將希望看到淋巴細胞隨著時間的推移而減少，我們將希望從持續的角度來看待這一點，這往往是人們查看的數據集。

We're obviously incredibly pleased to that. We were able to see significant lymphocyte reduction in the single ascending dose tends to get a little bit better with the MAD. But we didn't see broad immune suppression, which obviously is important for the S1P space. So those were kind of the things we would be looking for from the MAD to make the decision to move the molecule forward.

我們顯然對此感到非常高興。我們能夠看到單次遞增劑量中淋巴球顯著減少，MAD 後往往會好一些。但我們沒有看到廣泛的免疫抑制，這顯然對 S1P 領域很重要。因此，我們希望從 MAD 那裡得到這些訊息，以便做出推動分子向前發展的決定。

Does that answer your question, Yatin?

這能回答你的問題嗎，Yatin？

Yes. Thank you so much,

是的。太感謝了，

Thank you for the questions.

謝謝你的提問。

That concludes our Q&A session. I will now turn the conference back over to Mr. Kevin Lind for closing remarks.

我們的問答環節到此結束。我現在將會議轉回凱文·林德先生致閉幕詞。

I want to thank everyone for joining the call today and for sharing in our enthusiasm in the Longboard story. We'll continue to execute, deliver and think differentially about clinical development and how we can best serve patients, the community and our stakeholders. Have a great day.

我要感謝大家今天加入電話會議並分享我們對長板故事的熱情。我們將繼續執行、交付和以不同的方式思考臨床開發以及如何最好地為患者、社區和利害關係人服務。祝你有美好的一天。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。