Vanda Pharmaceuticals Inc (VNDA) 2024 Q4 法說會逐字稿

Hello and thank you for standing by. This time I'd like to welcome you to the Q4 2024 Vanda Pharmaceuticals Inc earnings conference call. (Operator Instructions)

您好，感謝您的支持。這次，我歡迎您參加 2024 年第四季 Vanda Pharmaceuticals Inc 收益電話會議。（操作員指令）

I would now like to turn the conference over to Mr. Kevin Moran, Vanda's Chief Financial Officer. Please go ahead, sir.

現在，我想將會議交給 Vanda 的財務長 Kevin Moran 先生。先生，請繼續。

Thank you, Jericho. Good afternoon and thank you for joining us to discuss Vanda Pharmaceuticals’ fourth-quarter and full-year 2024 performance. Our fourth-quarter and full-year 2024 results were released this afternoon and are available on the SEC's EDGAR system and on our website www.vandapharma.com. In addition, we are providing live and archived versions of this conference call on our website.

謝謝你，傑里科。下午好，感謝您加入我們討論 Vanda Pharmaceuticals 2024 年第四季和全年業績。我們的 2024 年第四季和全年業績於今天下午發布，可在美國證券交易委員會的 EDGAR 系統和我們的網站 www.vandapharma.com 上查閱。此外，我們在我們的網站上提供本次電話會議的現場和存檔版本。

Joining me on today's call is Dr. Mihales Polymeropoulos, our President, Chief Executive Officer, and Chairman of the Board; and Tim Williams, our General Counsel. Following my introductory remarks, Mihales will update you on our ongoing activities. I will then comment on our financial results before we open the lines for your questions.

參加今天電話會議的還有我們的總裁、執行長兼董事會主席 Mihales Polymeropoulos 博士；以及我們的總法律顧問 Tim Williams。在我的開場發言之後，米哈萊斯將向大家通報我們正在進行的活動。在我們開始回答你們的問題之前，我將對我們的財務結果進行評論。

Before we proceed, I would like to remind everyone that various statements that we make on this call will be forward-looking statements within the meaning of federal securities laws. Our forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances, and uncertainties.

在我們繼續之前，我想提醒大家，我們在本次電話會議上所做的各種聲明將是聯邦證券法含義內的前瞻性聲明。我們的前瞻性陳述是基於目前的預期和假設，涉及風險、情況變化和不確定性。

These risks are described in the “Cautionary Note Regarding Forward-Looking Statements”, “Risk Factors”, and “Management's Discussion and Analysis of Financial Condition and Results of Operations”, sections of our most recent annual report on Form 10-K as updated by our subsequent quarterly reports on Form 10-Q, current reports on Form 8-K, and other filings with the SEC, which are available on the SEC's EDGAR system and on our website. We encourage all investors to read these reports and our other filings. The information we provide on this call is provided only as of today, and we undertake no obligation to update or revise publicly any forward-looking statements we may make on this call on account of new information, future events, or otherwise except as required by law.

這些風險在我們最新的 10-K 表年度報告的「前瞻性陳述警示說明」、「風險因素」和「管理層對財務狀況和經營成果的討論和分析」部分中進行了描述，並由我們隨後的 10-Q 表季度報告、8-K 表當前報告和向美國證券交易委員會提交的其他文件進行了更新，這些文件可在美國證券交易委員會的 EDGAR 系統和我們的網站上查閱。我們鼓勵所有投資者閱讀這些報告和我們的其他文件。我們在本次電話會議上提供的資訊僅截至今天為止，除非法律另有規定，我們不承擔因新資訊、未來事件或其他原因而更新或公開修改我們在本次電話會議上做出的任何前瞻性陳述的義務。

With that said, I would now like to turn the call over to our CEO, Dr. Mihales Polymeropoulos.

說了這麼多，現在我想把電話轉給我們的執行長 Mihales Polymeropoulos 博士。

Thank you very much, Kevin, and good afternoon, everyone. Thank you for joining us to discuss Vanda's fourth-quarter and full-year 2024 results. As we discussed in our press release earlier this afternoon, strong revenue growth for Fanapt is putting us on a significant growth trajectory for 2025 and beyond, supported also by the commercial performance of HETLIOZ and PONVORY.

非常感謝，凱文，大家下午好。感謝您加入我們討論 Vanda 2024 年第四季和全年業績。正如我們今天下午早些時候在新聞稿中討論的那樣，Fanapt 強勁的收入增長將使我們在 2025 年及以後走上顯著的增長軌道，同時 HETLIOZ 和 PONVORY 的商業表現也將為我們提供支持。

The Fanapt long acting injectable program, the new drug application for Bysanti, milsaperidone, for bipolar disorder, and schizophrenia, along with its development for major depressive disorder, have the potential to drive future growth in our psychiatry portfolio for many years to come. Tradipitant 's new drug application for motion sickness was filed with a potential approval this year while we're pursuing approval in gastroparesis and the development of tradipitant to improve tolerability of GLP-1 analog, Wegovy.

Fanapt 長效注射計畫、Bysanti、米沙哌酮（用於治療躁鬱症和精神分裂症）的新藥申請及其用於治療重度憂鬱症的開發，有可能在未來許多年推動我們精神病學產品組合的成長。Tradipitant 用於治療暈動病的新藥申請已於今年提交，並可能獲得批准，同時我們正在尋求其用於治療胃輕癱的批准，並開發 Tradipitant 來提高 GLP-1 類似物 Wegovy 的耐受性。

Our anti-inflammatory portfolio anchored by PONVORY was strengthened with the addition of imsidolimab from Anaptys, an IL-36 receptor inhibitor for the treatment of generalized Pustular psoriasis. We plan to file a BLA later this year while we're exploring registration in Europe and Japan as well as the development of this novel drug for other inflammatory disorders with an unopposed action of the IL-36 system.

我們以 PONVORY 為基礎的抗發炎產品組合因添加了 Anaptys 公司的 imsidolimab（一種用於治療全身性膿皰型乾癬的 IL-36 受體抑制劑）而增強。我們計劃在今年稍後提交 BLA，同時我們正在探索在歐洲和日本進行註冊，以及開發這種用於治療與 IL-36 系統無對抗作用的其他發炎性疾病的新型藥物。

In 2024, we returned to revenue growth driven by the commercial launches in bipolar disorder and multiple sclerosis and advance our developing pipeline with a number of products at or near marketing applications. All this was achieved by the hard work, ingenuity, and efficiency of our organization and its wonderful people.

2024年，在躁鬱症和多發性硬化症商業發布的推動下，我們恢復了收入成長，並透過多款已進入或接近行銷應用階段的產品推進了我們正在開發的管道。這一切都歸功於我們組織及其優秀員工的辛勤工作、獨創性和高效率。

I will now turn to Fanapt. Fanapt was approved in the second quarter of 2024 for the acute treatment of bipolar I disorder. Vanda initiated the commercial launch of Fanapt in this indication in the third quarter of 2024. In the fourth quarter, as compared to the fourth quarter of '23, new patient starts as reflected by new-to-brand prescriptions or NBRx increased by over 160% and Fanapt net product sales increased by 18%. A dedicated specialty sales force of approximately 200 persons has been promoting Fanapt supported by a speaker program to improve peer-to-peer awareness. Given the successful trajectory and consistent with other peers, we're currently in the process of further expanding our sales force to 300 representatives, which will allow for increase in both reach and frequency.

現在我將談談 Fanapt。Fanapt 於 2024 年第二季獲準用於治療 I 型雙極性情感疾患的急性治療。Vanda 於 2024 年第三季啟動 Fanapt 在此適應症的商業化上市。第四季度，與 23 年第四季相比，以新品牌處方或 NBRx 反映的新患者開始數量增加了 160% 以上，Fanapt 淨產品銷售額增加了 18%。約 200 人的專業銷售團隊一直在推廣 Fanapt，並透過演講者計畫提供支持，以提高同行的知名度。鑑於成功的軌跡並與其他同行保持一致，我們目前正在將銷售團隊進一步擴大到 300 名代表，這將增加覆蓋範圍和頻率。

In January of 2025, we began our direct-to-consumer advertising to increase general consumer awareness of Fanapt. We expect product adoption to continue as more prescribers develop treatment experiences and identify candidate patients.

2025 年 1 月，我們開始直接向消費者進行廣告宣傳，以提高消費者對 Fanapt 的整體認知度。我們預計，隨著越來越多的處方人員累積治療經驗並確定候選患者，產品的採用將會持續下去。

Vanda also initiated a Phase III program for the long-acting injectable LAI formulation of Fanapt in the fourth quarter of 2024. The long-acting injectable once-a-month Fanapt is evaluated in relapse prevention for schizophrenia, where the oral formulation has already been shown to be successful and is already included in the Fanapt prescribing information.

Vanda 也於 2024 年第四季啟動了 Fanapt 長效注射 LAI 製劑的 III 期計畫。每月注射一次的長效 Fanapt 正在接受精神分裂症復發預防的評估，其中口服製劑已被證明是成功的，並且已經包含在 Fanapt 處方資訊中。

While all products so far have been developed in double-blind, placebo-controlled studies, and while Vanda and FDA have agreed on this design, an IRB, institutional review board, has objected to a placebo-controlled design for schizophrenia maintenance. We're evaluating with the FDA ways to proceed outside of a placebo-controlled study which could include a bridging study with the oral formulation. This evaluation is not specific to Vanda and the outcome of this design will likely be required of others.

雖然迄今為止所有產品都是在雙盲、安慰劑對照研究中開發的，而 Vanda 和 FDA 已同意這種設計，但機構審查委員會 (IRB) 反對用於精神分裂症維持治療的安慰劑對照設計。我們正在與 FDA 一起評估在安慰劑對照研究之外進行研究的方法，其中可能包括與口服製劑的橋接研究。此次評估並非針對 Vanda，其他人也可能需要藉用此設計的結果。

Vanda plans to initiate a study for the Fanapt long-acting injectable as a once-a-month injectable for the treatment of hypertension to address both treatment resistance and treatment compliance. In the course of our extensive clinical program with Fanapt for over 20 years, we have now identified an unexpected but robust benefit in treating hypertension with Fanapt. Specifically, in a large meta-analysis of placebo-controlled studies, we have identified a rapid and sustainable effect in reducing systolic and diastolic blood pressure, especially among people with baseline hypertension.

Vanda 計劃啟動一項 Fanapt 長效注射劑的研究，作為每月注射一次的高血壓治療藥物，以解決治療抗性和治療依從性問題。在我們針對 Fanapt 開展的超過 20 年的廣泛臨床計畫過程中，我們現在已經發現了 Fanapt 在治療高血壓方面具有意想不到但強大的益處。具體而言，在安慰劑對照研究進行的大規模薈萃分析中，我們發現了降低收縮壓和舒張壓的快速和可持續的效果，尤其是對於基線高血壓患者。

The effect size is comparable to effective antihypertensives. While the exact mechanism is not known, we believe that this effect is likely due to the mixed alpha, serotonin, and dopamine receptor antagonism observed with Fanapt. We plan to initiate a study to evaluate this effect with the once-a-month injectable Fanapt LAI in people with treatment-resistant hypertension.

其效果與有效的抗高血壓藥物相當。雖然確切的機制尚不清楚，但我們認為這種影響可能是由於 Fanapt 觀察到的混合 α、血清素和多巴胺受體拮抗作用。我們計劃進行一項研究，評估每月注射一次的 Fanapt LAI 對難治性高血壓患者的影響。

It has been reported that medication non-adherence in hypertension is a significant public health risk, and as such, if we are successful in our studies, Fanapt LAI could become the first medication to address this large public health need. Additionally, Vanda submitted a marketing authorization application in Europe in the fourth quarter of 2024 for Fanapt, and that is the European Medicine Agency for bipolar I disorder and schizophrenia.

據報道，高血壓患者不遵守藥物治療是一個重大的公共衛生風險，因此，如果我們的研究成功，Fanapt LAI 可能成為第一個解決這一巨大公共衛生需求的藥物。此外，Vanda 於 2024 年第四季度在歐洲提交了 Fanapt 的上市許可申請，​​這是歐洲藥品管理局針對雙相情感障礙 I 型和精神分裂症的治療藥物。

I will now turn to Bysanti known as milsaperidone. Vanda expects to submit a new drug application for Bysanti for the treatments of acute bipolar I disorder and schizophrenia to the US Food and Drug Administration in the first quarter of 2025. Exclusivity, including pending patent applications, could extend into the 2040s.

現在我將談談被稱為米沙哌利酮 (milsaperidone) 的 Bysanti。Vanda 預計將於 2025 年第一季向美國食品藥物管理局提交 Bysanti 用於治療急性雙相情感障礙 I 型和精神分裂症的新藥申請。包括正在申請的專利在內的排他性可能會延續到 2040 年代。

Bysanti is an active metabolite of iloperidone and has been extensively studied. In the last year, we have met with the FDA and agreed upon the clinical and manufacturing requirements, and we're now prepared to submit a new drug application in the coming weeks.

Bysanti 是伊潘立酮的活性代謝物，已被廣泛研究。去年，我們與 FDA 會面並就臨床和製造要求達成一致，現在我們準備在未來幾週提交新藥申請。

Vanda initiated a Phase III clinical study for Bysanti as a once-a-day adjunctive treatment for major depressive disorder in the fourth quarter of 2024. Results are expected in 2026.

Vanda 將於 2024 年第四季啟動 Bysanti 的 III 期臨床研究，作為重度憂鬱症的每日一次輔助治療。預計結果將於 2026 年公佈。

I will now move on to HETLIOZ, tasimelteon. Vanda has initiated clinical programs in pediatric insomnia and delayed sleep phase disorder, and these programs are ongoing. Vanda's MAA for HETLIOZ and HETLIOZ LQ for Smith-Magenis syndrome is now pending with the European Medicines Agency.

我現在將討論 HETLIOZ（tasimelteon）。Vanda 已啟動兒童失眠和睡眠時間延遲障礙的臨床項目，這些項目正在進行中。Vanda 公司針對 Smith-Magenis 症候群的 HETLIOZ 和 HETLIOZ LQ 的 MAA 目前正在等待歐洲藥品管理局的批准。

In addition, Vanda has continued to pursue the approval of HETLIOZ in sleep onset insomnia and the treatment of jet lag. Vanda has completed successfully multiple studies in these indications that have demonstrated substantial evidence of efficacy and a positive benefit-risk profile. Vanda has requested an FDA hearing on the insomnia indication, and an appeals court is expected to rule in the coming months on the jet lag application.

此外，Vanda 也繼續尋求 HETLIOZ 在入睡困難型失眠和時差治療方面的批准。Vanda 已成功完成這些適應症的多項研究，這些研究已證明其具有充分的療效證據和積極的效益風險狀況。Vanda 已請求 FDA 就其治療失眠的適應症舉行聽證會，上訴法院預計將在未來幾個月內就其治療時差的申請作出裁決。

PONVORY, ponesimod. Vanda initiated the commercial launch of PONVORY for the treatment of relapsing forms of multiple sclerosis in the third quarter of 2024. A new specialty sales force is now promoting PONVORY for this indication across the United States. We believe that PONVORY's profile, when appreciated, will drive the preferences of prescribers and patients. The sales force is supported by a new speakers program for peer-to-peer awareness.

PONVORY，ponesimod。Vanda 將於 2024 年第三季啟動 PONVORY 的商業上市，用於治療復發型多發性硬化症。一支新的專業銷售隊伍目前正在美國各地推廣 PONVORY 的這種治療方案。我們相信，PONVORY 的形像一旦得到認可，將會影響醫生和病人的偏好。新的演講者計劃為銷售人員提供支持，以提高同行之間的認識。

Investigational new drug applications for PONVORY in the treatments of psoriasis and ulcerative colitis were accepted by the FDA in the fourth quarter of 2024. PONVORY has been previously shown to be effective in treating acute episodes of psoriasis as well as preventing relapse. This study was conducted by Actelion before Vanda's acquisition of the product, and the results have been published. Vanda is now finalizing the development program that could lead to a new drug application filing in this indication.

美國食品藥物管理局於 2024 年第四季接受了 PONVORY 用於治療牛皮癬和潰瘍性結腸炎的新藥研究申請。PONVORY 先前已被證明可有效治療牛皮癬急性發作以及預防復發。這項研究是由 Actelion 在 Vanda 收購產品之前進行的，結果已經公佈。Vanda 目前正處於最終開發階段，這可能會促成針對該適應症提交新藥申請。

Tradipitant. The new drug application for tradipitant for the treatment of motion sickness was submitted to the FDA in the fourth quarter of 2024. This application is supported by three positive studies in prevention of motion-induced vomiting in actual sea travel conditions. We expect an FDA decision later this year.

特拉迪皮坦。tradipitant用於治療暈動病的新藥申請已於2024年第四季向FDA提交。該應用程式已得到三項關於預防實際海上旅行條件下運動誘發嘔吐的積極研究的支持。我們預計 FDA 將在今年稍後做出決定。

Vanda has recently initiated a clinical trial to study tradipitant in the prevention of vomiting induced by a GLP-1 analog, Wegovy, that is, semaglutide, in the fourth quarter of 2024. A frequent and, at times, severe treatment emerging adverse event with GLP-1 analogs is nausea and vomiting, which requires slower titration and delayed onset of effect.

Vanda 近期啟動了一項臨床試驗，研究 tradipitant 在預防 GLP-1 類似物 Wegovy（即索馬魯肽）引起的嘔吐方面的作用，該試驗將於 2024 年第四季度進行。GLP-1 類似物治療中常見且有時嚴重的不良事件是噁心和嘔吐，這需要減慢滴定速度並延遲療效的發生。

We're evaluating whether tradipitant can prevent Wegovy-induced nausea and vomiting. And if it does, it could become a very useful product during GLP-1 analog treatment initiation.

我們正在評估 tradipitant 是否可以預防 Wegovy 引起的噁心和嘔吐。如果確實如此，它可能成為 GLP-1 類似物治療開始時非常有用的產品。

Vanda has now accepted the opportunity for a hearing with the FDA on the approvability of the NDA for tradipitant for the treatment of symptoms of gastroparesis. Vanda has identified a number of faults in the FDA review that led to a complete response letter. And we believe that if allowed to be reviewed by experts, they would also reach the conclusion that tradipitant can be a useful product in treating symptoms of gastroparesis. In the meantime, more than 50 patients are currently treated with tradipitant through the expanded access program, and many additional ones are being evaluated to initiate treatment.

Vanda 現已接受 FDA 的聽證機會，以確定 tradipitant 用於治療胃輕癱症狀的 NDA 的批准情況。Vanda 發現 FDA 審查中存在多處錯誤，並因此發出了完整的回覆信。我們相信，如果讓專家進行審查，他們也會得出結論：tradipitant 可以成為治療胃輕癱症狀的有效產品。同時，目前已有 50 多名患者透過擴大獲取計畫接受 tradipitant 治療，還有許多其他患者正在接受評估以開始治療。

Imsidolimab. In February 2025, Vanda announced it entered into an exclusive global license agreement with AnaptysBio, Anaptys, for the development and commercialization of imsidolimab that is an IL-36 receptor antagonist monoclonal antibody. Vanda expects to initiate and complete the technology transfer activities in 2025 and to immediately begin preparing the biologic license application, BLA, and MAA for generalized pustular psoriasis, GPP, for the US and European Union.

伊姆斯多利單抗。2025年2月，Vanda宣布與AnaptysBio、Anaptys達成獨家全球授權協議，用於開發和商業化IL-36受體拮抗劑單株抗體imsidolimab。Vanda 預計將於 2025 年啟動並完成技術轉移活動，並立即開始為美國和歐盟準備針對全身性膿皰性乾癬 (GPP) 的生物製劑許可申請 (BLA) 和 MAA。

Generalized pustular psoriasis or GPP is a rare, severe skin disorder that is often caused by recessive mutations in the IL-36RN gene, a regulator of the IL-36 activity. The role of such mutations in heterozygous state, which are far more common, is not yet appreciated, but it may play a significant role in the pathogenesis and progression of other inflammatory skin conditions. We plan to file a BLA later this year, while we're exploring registration in Europe and Japan and as well as the development of this novel drug in other inflammatory disorders with an unopposed action of the IL-36 cytokine system.

全身性膿皰性乾癬或 GPP 是一種罕見的嚴重皮膚病，通常由 IL-36RN 基因（IL-36 活性的調節劑）的隱性突變引起。這種雜合狀態下的突變較為常見，其作用尚未被認識到，但它可能在其他發炎性皮膚病的發病機制和進展中發揮重要作用。我們計劃在今年稍後提交 BLA，同時我們正在探索在歐洲和日本進行註冊，並在對 IL-36 細胞激素系統具有無對抗作用的其他發炎性疾病中開發這種新藥。

Finally, on early-stage program highlights. VQW-765, an alpha 7 nicotinic acetylcholine receptor partial agonist is currently in clinical development for the treatment of acute performance anxiety in social situations. We have previously reported results from a Phase II study with encouraging outcomes in a model of acute performance anxiety. We plan to meet with the FDA in the coming months at the end of Phase II meeting and plan to initiate Phase III program in social anxiety disorder in 2025.

最後，談談早期專案的亮點。VQW-765 是一種 α7 菸鹼乙醯膽鹼受體部分激動劑，目前正在進行臨床開發，用於治療社交場合的急性表現焦慮。我們先前已經報告了第二階段研究的結果，該研究在急性表現焦慮模型中取得了令人鼓舞的結果。我們計劃在未來幾個月第二階段會議結束時與 FDA 會面，並計劃在 2025 年啟動社交焦慮症第三階段計劃。

The IND application for VCA-894A, an antisense oligonucleotide in the treatment of Charcot-Marie-Tooth disease, axonal type 2S, an inherited peripheral neuropathy, for which there is no available treatment was accepted by the FDA in 2024. The Phase I clinical study for VCA-894A is expected to enroll this single patient by mid-2025.

VCA-894A 是一種反義寡核苷酸，用於治療腓骨肌萎縮症（2S 型軸突性腓骨肌萎縮症，是一種遺傳性週邊神經病變，目前尚無可用的治療方法），其 IND 申請於 2024 年獲得 FDA 接受。VCA-894A 的 I 期臨床研究預計將於 2025 年中期招募這位患者。

In December 2024, Vanda announced that the FDA has granted orphan drug designation for VGT-1849A , a selective antisense oligonucleotide-based JAK2 inhibitor for the treatment of polycythemia vera, a form of a rare hematologic malignancy that is estimated to affect 1 in 2,000 Americans.

2024 年 12 月，Vanda 宣布 FDA 已授予 VGT-1849A 孤兒藥資格，VGT-1849A 是一種基於反義寡核苷酸的選擇性 JAK2 抑制劑，用於治療真性紅血球增多症，這是一種罕見的血液系統惡性腫瘤，估計每 2,000 名美國人中就有 1 名患有此病。

I will just review the key regulatory milestones. Tradipitant NDA for motion sickness submitted in Q4 2024, Fanapt MAA in Europe for bipolar I disorder and schizophrenia submitted in Q4 2024, HETLIOZ MAA in Europe for Smith-Magenis syndrome submitted in Q4 2024, Bysanti new drug application for bipolar I disorder and schizophrenia expected to be submitted in Q1 2025, and imsidolimab BLA in generalized pustular psoriasis, expect to be submitted in 2025.

我僅回顧一下關鍵的監管里程碑。Tradipitant 用於治療暈動病的新藥申請 (NDA) 已於 2024 年第四季度提交，Fanapt 用於治療 I 型雙相情感障礙和精神分裂症的歐洲 MAA 已於 2024 年第四季度提交，HETLIOZ 用於治療 Smith-Magenis 綜合徵的歐洲 MAA 已於第 2024 年第 2024 年第256436歲精神分裂症，Bys 2024 年心理障礙limab BLA 用於治療全身性膿皰性乾癬，預計 2025 年提交。

With that, I'll turn now to Kevin to discuss our financial results. Kevin?

說完這些，我現在將轉向凱文討論我們的財務表現。凱文？

Thank you, Mihales. I'll first discuss the results for the full year 2024 before turning to the fourth quarter of 2024.

謝謝你，米哈萊斯。我將先討論 2024 年全年的業績，然後再討論 2024 年第四季的業績。

Total revenues for the full year 2024 were $198.8 million, a 3% increase compared to $192.6 million for the full year of 2023. As Mihales mentioned, this increase was primarily due to increased Fanapt revenue as a result of the bipolar commercial launch and the introduction of PONVORY revenue following our acquisition of the product in December of 2023, partially offset by decreased HETLIOZ revenue as a result of generic competition.

2024 年全年總營收為 1.988 億美元，較 2023 年全年的 1.926 億美元成長 3%。正如 Mihales 所提到的，這一增長主要是由於雙相情感障礙藥物的商業化推出導致 Fanapt 收入增加，以及我們於 2023 年 12 月收購該產品後引入 PONVORY 收入，但部分被仿製藥競爭導致的 HETLIOZ 收入下降所抵消。

Let me now break this down by product. Fanapt net product sales were $94.3 million for the full year 2024, a 4% increase compared to $90.9 million for the full year 2023. The increase in net product sales relative to the full year 2023 was attributable to increased volume and increased price net of deductions.

現在讓我按產品分解。Fanapt 2024 年全年淨產品銷售額為 9,430 萬美元，較 2023 年全年的 9,090 萬美元成長 4%。與 2023 年全年相比，淨產品銷售額的成長歸因於銷售增加和扣除扣除額後價格上漲。

HETLIOZ net product sales were $76.7 million for the full year 2024, a 23% decrease compared to $100.2 million for the full year 2023. The decrease relative to the full year 2023 was the result of continued generic competition in the US. HETLIOZ net product sales, as reported for the first quarter of 2023, reflected higher unit sales as compared to recent prior periods. The higher unit sales during the first quarter of 2023 resulted in a significant increase of inventory stocking at specialty pharmacy customers at March 31, 2023.

HETLIOZ 2024 年全年淨產品銷售額為 7,670 萬美元，較 2023 年全年 1.002 億美元下降 23%。與 2023 年全年相比的下降是由於美國仿製藥競爭持續存在。根據 2023 年第一季報告顯示，HETLIOZ 淨產品銷售額反映與近期相比更高的單位銷售額。2023 年第一季單位銷售增加導致 2023 年 3 月 31 日專業藥局客戶的庫存大幅增加。

During the remainder of 2023, although there was continued destocking at specialty pharmacy customers, inventory levels remained elevated relative to inventory levels prior to the entrance of generic competition and continued to remain elevated throughout 2024. Going forward, HETLIOZ net product sales may reflect lower unit sales as a result of reduction of the elevated inventory levels and specialty pharmacy customers or may be variable depending on when specialty pharmacy customers need to purchase again. Further, HETLIOZ net product sales will likely decline in future periods, potentially significantly related to continued generic competition in the US.

在 2023 年剩餘時間內，儘管專科藥房客戶繼續去庫存，但庫存水準相對於仿製藥競爭進入之前的庫存水準仍然較高，並且在 2024 年全年仍將保持高位。展望未來，HETLIOZ 淨產品銷售額可能反映由於庫存水準和專業藥房客戶減少而導致的單位銷售額下降，或者可能根據專業藥房客戶何時需要再次購買而發生變化。此外，HETLIOZ 淨產品銷售額在未來一段時間內可能會下降，這可能與美國持續的仿製藥競爭有很大關係。

Additionally, the company constrained HETLIOZ net product sales for the year ended December 31, 2024 and 2023, to an amount not probable of significant revenue reversal. As a result, HETLIOZ net product sales could experience variability in future periods as the remaining uncertainties associated with variable consideration related to inventory stocking by specialty pharmacy customers are resolved.

此外，該公司將 HETLIOZ 截至 2024 年 12 月 31 日和 2023 年 12 月 31 日止年度的淨產品銷售額限制在不太可能出現重大收入逆轉的數額。因此，隨著與專業藥房客戶庫存相關的變動對價的剩餘不確定性得到解決，HETLIOZ 淨產品銷售額在未來期間可能會出現波動。

PONVORY net product sales were $27.8 million for the full year 2024 and include approximately $3 million of variable consideration that may be subject to dispute, but that the company believes is not probable of significant revenue reversal. As a reminder, we completed the acquisition of the US and Canadian rights to PONVORY in December of 2023. As such, this represents the fourth full quarter of PONVORY revenue recognition at Vanda and significant progress in diversifying our product mix with innovative and value-generating products.

PONVORY 2024 年全年的淨產品銷售額為 2780 萬美元，其中包括約 300 萬美元的可變對價，該對價可能會產生爭議，但公司認為不太可能出現重大的收入逆轉。提醒一下，我們在 2023 年 12 月完成了對 PONVORY 美國和加拿大權利的收購。因此，這代表 PONVORY 在 Vanda 實現了第四個完整季度的收入確認，並且在透過創新和創造價值的產品實現產品組合多樣化方面取得了重大進展。

For the full year 2024, Vanda recorded a net loss of $18.9 million compared to net income of $2.5 million for the full year 2023. The net loss for the full year 2024 included an income tax benefit of $4 million as compared to an income tax provision of $3.8 million for the full year [2023] (corrected by company after the call).

2024 年全年，Vanda 淨虧損為 1,890 萬美元，而 2023 年全年淨收入為 250 萬美元。2024 年全年淨虧損包括 400 萬美元的所得稅收益，而全年所得稅撥備為 380 萬美元[2023]（本公司於通話後更正）。

Of note on the tax side, the company assesses the need for a valuation allowance against its deferred tax asset each quarter through the review of all available positive and negative evidence. The company generated a pre-tax loss for the year ending December 31, 2024. If the company continues to generate pre-tax losses and/or if the company's projections indicate pre-tax losses in future periods, the conclusion about the appropriateness of the valuation allowance could change in a future period. An increase in the valuation allowance would result in a non-cash income tax expense during the period of change.

值得注意的是，在稅務方面，公司每季都會透過審查所有可用的正面和負面證據來評估其遞延所得稅資產的估值準備的必要性。該公司截至 2024 年 12 月 31 日的年度產生了稅前虧損。如果公司繼續產生稅前虧損和/或公司預測表明未來期間將出現稅前虧損，則關於提列準備金適當性的結論可能會在未來期間發生變化。估價準備的增加將導致變更期間產生非現金所得稅費用。

Operating expenses for the full year 2024 were $239.4 million compared to $206.6 million for the full year 2023. The $32.8 million increase was primarily driven by higher SG&A expenses related to spending on Vanda's commercial products as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis and legal and other corporate activities, as well as higher intangible asset amortization expense due to the amortization recorded on the PONVORY intangible asset.

2024 年全年營運費用為 2.394 億美元，而 2023 年全年營運費用為 2.066 億美元。3,280 萬美元的增幅主要由於：由於 Fanapt 在治療 I 型雙相情感障礙和 PONVORY 在治療多發性硬化症方面的商業發布，與 Vanda 商業產品支出相關的銷售、一般和行政費用增加，以及由於 PONVORY 無形資產攤銷導致的無形資產攤銷費用增加。

During 2024, we commenced a host of activities as part of our commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis, including an expansion of our sales force and the development of prescriber awareness and comprehensive marketing programs. SG&A expenses may increase in future periods as a result of the continued ongoing commercial efforts around Fanapt in bipolar I disorder and PONVORY in multiple sclerosis.

2024 年，我們開展了一系列活動，作為 Fanapt（用於治療雙相情感障礙 I 型）和 PONVORY（用於治療多發性硬化症）商業發布的一部分，包括擴大銷售團隊和開發處方意識和綜合行銷計劃。由於 Fanapt（用於治療 I 型雙相情感障礙）和 PONVORY（用於治療多發性硬化症）持續進行商業努力，未來銷售、一般及行政開支可能會增加。

Vanda's cash, cash equivalents and marketable securities referred to as cash, as of December 31, 2024, was $374.6 million, representing a decrease of $1.6 million compared to September 30, 2024, and a decrease of $13.6 million compared to December 31, 2023.

截至 2024 年 12 月 31 日，Vanda 的現金、現金等價物和有價證券（稱為現金）為 3.746 億美元，與 2024 年 9 月 30 日相比減少 160 萬美元，與 2023 年 12 月 31 日相比減少 1,360 萬美元。

Turning now to our quarterly results, total revenues for the fourth quarter of 2024 were $53.2 million, a 17% increase compared to $45.3 million for the fourth quarter of 2023, and a 12% increase compared to $47.7 million in the third quarter of 2024. The increase as compared to the fourth quarter of 2023 was primarily due to the introduction of PONVORY revenue, following our acquisition of the product in December of 2023 and increased Fanapt revenue.

現在來看看我們的季度業績，2024 年第四季的總營收為 5,320 萬美元，比 2023 年第四季的 4,530 萬美元成長 17%，比 2024 年第三季的 4,770 萬美元成長 12%。與 2023 年第四季相比，成長主要歸因於 PONVORY 收入的引入，這是我們在 2023 年 12 月收購該產品之後引入的，並且 Fanapt 收入也增加了。

Fanapt net product sales were $26.6 million for the fourth quarter of 2024, an 18% increase compared to $22.6 million in the fourth quarter of 2023. The increase in Fanapt revenue between the fourth quarter of 2024 and the fourth quarter of 2023 was primarily attributable to an increase in volume, which was driven by increased prescription demand or TRxs as reported by IQVIA Xponent, and inventory stocking at the wholesalers. Historically, Fanapt inventory at wholesalers has ranged between three and four weeks on hand as calculated based off trailing demand. As of the end of the fourth quarter of 2024, Fanapt inventory at wholesalers was just above four weeks on hand.

Fanapt 2024 年第四季的淨產品銷售額為 2,660 萬美元，較 2023 年第四季的 2,260 萬美元成長 18%。2024 年第四季至 2023 年第四季之間 Fanapt 收入的成長主要歸因於銷售量的成長，這受到 IQVIA Xponent 報告的處方需求或 TRxs 增加以及批發商的庫存儲備的推動。從歷史上看，根據過去的需求計算，批發商處的 Fanapt 庫存量在三到四周之間。截至 2024 年第四季末，批發商處的 Fanapt 庫存略多於四周。

Fanapt prescriptions in the fourth quarter of 2024 increased by approximately 9% compared to the fourth quarter of 2023. And Fanapt new patient starts in the fourth quarter of 2024 as reflected by new to brand prescriptions, or NBRx, increased by over 160% compared to the fourth quarter of 2023.

2024 年第四季的 Fanapt 處方與 2023 年第四季相比增加了約 9%。2024 年第四季度，Fanapt 新患者的數量（以新品牌處方或 NBRx 為代表）與 2023 年第四季相比增加了 160% 以上。

Fanapt net product sales in the fourth quarter of 2024 increased by 11% as compared to $23.9 million in the third quarter of 2024. Fanapt prescriptions in the fourth quarter of 2024 increased by approximately 7% compared to the third quarter of 2024.

Fanapt 2024 年第四季的淨產品銷售額與 2024 年第三季的 2,390 萬美元相比成長了 11%。2024 年第四季的 Fanapt 處方與 2024 年第三季相比增加了約 7%。

Turning now to HETLIOZ, HETLIOZ net product sales were $20 million for the fourth quarter of 2024, a 5% decrease compared to $21.1 million in the fourth quarter of 2023. The decrease in net product sales relative to the fourth quarter of 2023 was attributable to a decrease in price net of deductions, partially offset by an increase in volume. HETLIOZ net product sales in the fourth quarter increased by 12% as compared to $17.9 million in the third quarter of 2024.

現在來看看 HETLIOZ，HETLIOZ 2024 年第四季的淨產品銷售額為 2,000 萬美元，與 2023 年第四季的 2,110 萬美元相比下降了 5%。與 2023 年第四季相比，淨產品銷售額的下降歸因於扣除扣除額後價格的下降，但部分被銷售的增加所抵銷。HETLIOZ 第四季的淨產品銷售額與 2024 年第三季的 1,790 萬美元相比成長了 12%。

And finally turning to PONVORY. PONVORY net product sales were $6.5 million in the fourth quarter of 2024, an increase of 11% compared to $5.9 million in the third quarter of 2024. The increase in net product sales was attributable to an increase in volume of units sold, partially offset by a decrease in price net of deductions.

最後轉向 PONVORY。PONVORY 2024 年第四季的淨產品銷售額為 650 萬美元，較 2024 年第三季的 590 萬美元成長 11%。淨產品銷售額的成長歸因於銷售單位數量的增加，但部分被扣除費用後價格的下降所抵銷。

The increase in volume in the fourth quarter of 2024 was partially attributable to a temporary inventory destocking in the third quarter at the specialty distributors and pharmacies due to the transition of distribution from Janssen to Vanda. As a reminder, we completed the acquisition of the US and Canadian rights to PONVORY in December of 2023.

2024 年第四季銷售增加部分歸因於第三季度由於分銷從 Janssen 轉向 Vanda 導致專業分銷商和藥局暫時庫存減少。提醒一下，我們在 2023 年 12 月完成了對 PONVORY 美國和加拿大權利的收購。

For the fourth quarter of 2024, Vanda recorded a net loss of $4.9 million compared to a net loss of $2.4 million for the fourth quarter of 2023. The net loss for the fourth quarter of 2024 included an income tax benefit of $1.6 million as compared to an income tax provision of $0.7 million for the fourth quarter of 2023.

2024 年第四季，Vanda 淨虧損為 490 萬美元，而 2023 年第四季淨虧損為 240 萬美元。2024 年第四季的淨虧損包括 160 萬美元的所得稅收益，而 2023 年第四季的所得稅準備金為 70 萬美元。

Operating expenses in the fourth quarter of 2024 were $63.5 million compared to $52.4 million in the fourth quarter of 2023. The $11.1 million increase was primarily driven by higher SG&A expenses related to spending on Vanda's commercial products as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis and legal and other corporate activities, partially offset by a decrease in R&D expense, primarily driven by lower spend on our tradipitant development programs.

2024 年第四季的營運費用為 6,350 萬美元，而 2023 年第四季的營運費用為 5,240 萬美元。1,110 萬美元的成長主要由於：由於 Fanapt 在治療 I 型躁鬱症和多發性硬化症方面上市以及法律和其他公司活動，與 Vanda 商業產品支出相關的銷售、一般和行政費用增加；但研發費用減少（主要由於我們在傳統藥物開發項目上的支出減少）部分抵消了這一增長。

Operating expenses in the fourth quarter of 2024 increased by $4.8 million as compared to $58.7 million in the third quarter of 2024. This increase is primarily driven by higher R&D spend due in large part to increased expenses on our psychiatry programs and increased spending on Vanda's commercial products as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis.

2024 年第四季的營運費用與 2024 年第三季的 5,870 萬美元相比增加了 480 萬美元。這一增長主要得益於研發支出的增加，這在很大程度上是由於我們在精神病學項目上的支出增加，以及由於用於治療雙相情感障礙 I 型的 Fanapt 和用於治療多發性硬化症的 PONVORY 的商業化推出而導致的用於 Vanda 商業產品的支出增加。

During 2024, we commenced a host of activities as a result of the commercial launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis, including an expansion of our sales force and the development of prescriber awareness and comprehensive marketing programs. SG&A expenses may increase in future periods as a result of the continued ongoing commercial efforts around Fanapt in bipolar I disorder and PONVORY in multiple sclerosis.

2024 年，隨著 Fanapt（用於治療 I 型雙相情感障礙）和 PONVORY（用於治療多發性硬化症）的商業化推出，我們開展了一系列活動，包括擴大銷售團隊、提高處方意識和開展綜合行銷計劃。由於 Fanapt（用於治療 I 型雙相情感障礙）和 PONVORY（用於治療多發性硬化症）持續進行商業努力，未來銷售、一般及行政開支可能會增加。

With regards to the launches of Fanapt in bipolar I disorder and PONVORY in multiple sclerosis, as I mentioned, the launches were initiated in 2024, and we expect to continue to build out our full commercial infrastructure with the impact of these commercial efforts expected to contribute to revenue growth in 2025 and beyond.

關於 Fanapt（用於治療 I 型雙相情感障礙）和 PONVORY（用於治療多發性硬化症）的上市，正如我所提到的，這些上市計劃於 2024 年開始，我們預計將繼續構建我們的完整商業基礎設施，這些商業努力的影響預計將有助於 2025 年及以後的收入增長。

We have already seen significant progress in our commercial activities. Several lead indicators suggest a strong initial market response to our commercial launch of Fanapt in bipolar I disorder, including new patient starts as reflected by NBRx increasing by over 160% in the fourth quarter of 2024 as compared to the fourth quarter of 2023.

我們的商業活動已經取得重大進展。多項領先指標表明，市場對我們在雙相情感障礙 I 型中商業推出的 Fanapt 的初步反應強烈，包括新患者的開始，這反映在 2024 年第四季度與 2023 年第四季度相比，NBRx 增長了 160% 以上。

Our Fanapt sales force continues to expand. Currently, our sales force has grown to over 200 persons, and we have now initiated a further expansion, as Mihael mentioned. In addition to our Fanapt sales force, we have established a specialty sales force to market PONVORY to neurology prescribers around the country. The expansion has allowed us to significantly increase our reach and frequency with prescribers, and we've now had over 700 Fanapt prescriber awareness programs completed in 2024, and the PONVORY prescriber awareness program continues to expand, with over 4 times as many programs completed in the fourth quarter of 2024 as compared to the third quarter of 2024.

我們的 Fanapt 銷售團隊不斷擴大。目前，我們的銷售團隊已經發展到 200 多人，而且正如 Mihael 所提到的，我們現在已經開始進一步擴張。除了 Fanapt 銷售隊伍外，我們還建立了一支專業銷售隊伍，向全國各地的神經病學處方人員推銷 PONVORY。此次擴展使我們能夠顯著提高與處方醫師的聯繫範圍和頻率，目前，我們已經在 2024 年完成了 700 多個 Fanapt 處方醫師意識計劃，PONVORY 處方醫師意識計劃也在繼續擴展，2024 年第四季度完成的計劃數量是 2024 年第三季度的 4 倍多。

Before turning to our financial guidance, I would like to remind folks that with Fanapt, HETLIOZ, and PONVORY already commercially available, the tradipitant NDA for motion sickness submitted to the FDA, the Bysanti NDA for bipolar I disorder and schizophrenia expected to be submitted in the coming weeks, and a BLA for imsidolimab expected to be submitted later this year, Vanda could have six products commercially available in 2026.

在談到我們的財務指導之前，我想提醒大家，由於 Fanapt、HETLIOZ 和 PONVORY 已經上市，用於治療暈動病的 tradipitant NDA 已提交給 FDA，用於治療 I 型雙相情感障礙和精神分裂症的 Bysanti NDA 預計將在未來幾週提交，而 imsidolimab 的 BLA 預計將於今年有六種產品，VLA 60 2006 年。

Turning now to our financial guidance, Vanda expects to achieve the following financial objectives in 2025: total revenues from Fanapt, HETLIOZ, and PONVORY of between $210 million and $250 million. This revenue range would imply revenue growth in 2025 of between 6% and 26% as compared to full year 2024 revenue. It is worth commenting that the quarterization of revenue in 2025 will be impacted by several items, including the Medicare benefit redesign portion of the Inflation Reduction Act, which went into effect as of January 1, 2025. The implementation of the benefit redesign is expected to negatively impact gross to net for the Medicare payer segment of our products, more significantly on Fanapt and HETLIOZ. Note that this change is not linked specifically to Vanda but is an industry-wide change, which will have varying impacts on pharmaceutical companies. Insurance plan transitions, as patients adjust to new insurance plans to start the year, there may be some disruption in the first quarter. This is also a typical industry-wide occurrence. And as I previously mentioned, Fanapt inventory levels as of December 31, 2024, were higher than typical levels based on trailing demand. If wholesalers adjust their inventory to historical levels, this could have a short-term negative impact on revenue in the period in which the destocking occurs.

現在談到我們的財務指導，Vanda 預計在 2025 年實現以下財務目標：Fanapt、HETLIOZ 和 PONVORY 的總收入在 2.1 億美元至 2.5 億美元之間。這一收入範圍意味著 2025 年的收入將比 2024 年全年收入增長 6% 至 26% 之間。值得一提的是，2025年的收入季度化將受到幾項因素的影響，其中包括《通膨削減法案》中關於醫療保險福利重新設計的部分，該法案於2025年1月1日生效。福利重新設計的實施預計將對我們產品的醫療保險支付方部分的毛利與淨利產生負面影響，對 Fanapt 和 HETLIOZ 的影響更為顯著。請注意，這項變更並非專門針對 Vanda，而是整個產業的變化，將對製藥公司產生不同的影響。保險計劃轉變，隨著患者在年初適應新的保險計劃，第一季可能會出現一些混亂。這也是全行業的典型現象。正如我之前提到的，截至 2024 年 12 月 31 日，Fanapt 的庫存水準高於基於後續需求的典型水準。如果批發商將庫存調整到歷史水平，這可能會對去庫存期間的收入產生短期負面影響。

Given the conditional investments that Vanda is currently making to facilitate future revenue growth, both in the form of R&D investments and potentially outsized commercial investments, which could increase depending on the success of these commercial strategies, Vanda is not providing 2025 cash guidance at this time. Vanda will continue to evaluate its ability to provide cash guidance in future periods.

鑑於 Vanda 目前為促進未來收入成長而進行的有條件投資，包括研發投資和潛在的超大規模商業投資，這些投資可能會根據這些商業策略的成功而增加，因此 Vanda 目前不提供 2025 年現金指引。Vanda 將繼續評估其在未來時期提供現金指導的能力。

It is worth noting that the quarterization of cash balances will be impacted by several items, including payments totaling $15 million which were made to Anaptys in the first quarter of 2025 upon entering into the global license agreement for imsidolimab, fees and costs associated with the filing of our applications with regulatory agencies in the US and Europe, including the Bysanti NDA for bipolar I disorder and schizophrenia, and the standard timing of certain items paid in the first quarter each year.

值得注意的是，現金餘額的季度化將受到多項項目的影響，包括在 2025 年第一季度簽訂 imsidolimab 全球許可協議時向 Anaptys 支付的總計 1500 萬美元的款項、向美國和歐洲監管機構提交申請相關的費用和成本，包括針對 I 型雙相情感障礙和精神分裂症的 BysantiNDA 以及每年第一季度支付某些標準的標準。

Given the significant progress made during 2024 on establishing our commercial infrastructure and the commercial investments we expect to make in coming periods, Vanda is providing 2030 revenue targets. For the psychiatry portfolio alone, Vanda is targeting annual revenue in excess of $750 million in 2030, assuming the potential approval of Bysanti for the treatments of acute bipolar I disorder and schizophrenia in early 2026, the potential approval of Bysanti for the treatment of MDD, and the potential approval of Fanapt LAI.

鑑於我們在 2024 年建立商業基礎設施方面取得的重大進展以及我們預計在未來進行的商業投資，Vanda 制定了 2030 年的收入目標。僅就精神病學產品組合而言，Vanda 的目標是到 2030 年實現年收入超過 7.5 億美元，假設 Bysanti 可能在 2026 年初獲得批准用於治療急性雙相情感障礙 I 型和精神分裂症，Bysanti 可能獲得批准用於治療 MDD，並且 Fanapt LAI 可能獲得批准。

Vanda is also targeting total annual revenue in excess of $1 billion in 2030. It is worth noting that the revenue economics for Bysanti are expected to be significantly favorable relative to the current revenue economics for Fanapt. The potential market opportunity for our growing psychiatry portfolio is significant and necessitates the increased investments we are currently making to enhance the commercial profile of Fanapt, bring Bysanti and Fanapt LAI to market, and expand the Bysanti label to include major depressive disorder.

Vanda 也設定了 2030 年年總收入超過 10 億美元的目標。值得注意的是，Bysanti 的收入經濟效益預計會比 Fanapt 目前的收入經濟效益明顯更高。我們不斷成長的精神病學產品組合具有巨大的潛在市場機會，這需要我們加強投資，以提升 Fanapt 的商業形象，將 Bysanti 和 Fanapt LAI 推向市場，並擴大 Bysanti 標籤以涵蓋重度憂鬱症。

With that, I'll now turn the call back to Mihales.

說完這些，我現在將電話轉回給米哈萊斯。

Thank you, Kevin. At this time, we would like to answer any questions you may have.

謝謝你，凱文。現在，我們想回答您可能提出的任何問題。

Thank you. We will now begin the question-and-answer session. (Operator Instructions)

謝謝。我們現在開始問答環節。（操作員指令）

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯、康托菲茨傑拉德。

Hey. Good afternoon, Mihales and team. Congrats on a good year of seeing the commercial turn, as well as a ton of things going on with the pipeline, so lots of productivity.

嘿。下午好，米哈萊斯和團隊。恭喜您度過了一個商業轉型的豐收年，同時管道方面也有大量工作正在進行，生產力也大幅提升。

I had a question, first, on commercial and then pipeline. With regard to Fanapt, I guess I'm wondering, as you see that Q-on-Q growth, where do you think you're picking up traction, and what types of prescribers?

我首先有一個關於商業的問題，然後是關於管道的問題。關於 Fanapt，我想知道，當您看到季度環比增長時，您認為您在哪些方面獲得了發展動力，以及有哪些類型的處方者？

And then I wanted to ask you about that 300 reps, the 50% growth in the sales force. I'm wondering if you think that'll be sufficient to compete with potentially larger pharma companies coming in in marketing, obviously COBENFY, but also perhaps J&J in the future with CAPLYTA.

然後我想問您關於那 300 位銷售代表，銷售隊伍成長 50% 的情況。我想知道您是否認為這足以與潛在的大型製藥公司在市場上競爭，顯然是 COBENFY，但未來也可能是強生公司的 CAPLYTA。

Yeah. Thank you very much, Charles. So in terms of where the growth is coming from, the prescribers that are coming to Fanapt are prescribers that have patients with bipolar disorder. And this is a difference from the smaller group of psychiatrists and psychiatric nurses that serve schizophrenia patients. So it seems that the growth is exclusively coming outside of schizophrenia.

是的。非常感謝，查爾斯。因此，就成長來源而言，來 Fanapt 開藥的醫生都是為患有躁鬱症的患者開藥的醫生。這與為精神分裂症患者服務的精神科醫生和精神科護士的人數較少有所不同。因此看起來，這種增長完全來自於精神分裂症之外。

In terms of the size of the sales force, as you know very well, this is a highly promotionally sensitive class of drugs, and we have very recent examples of successful commercialization from some of our peers. Whether this is the right size sales force, I would venture to say likely it's going to be on the lower side. But certainly, you want to build rapidly, but at the same time, don't jeopardize the quality and very important training of the sales force.

就銷售團隊的規模而言，正如您所知，這是一類對促銷高度敏感的藥物，我們最近從一些同行那裡獲得了成功商業化的案例。無論這支銷售隊伍的規模是否合適，我敢說，很可能規模會比較小。但當然，你想快速建設，但同時，不要危及銷售隊伍的品質和非常重要的培訓。

Now we do see the potential competition by more deep-pocketed big pharma, of course, BMS with COBENFY, at this time, they will be primarily focused on the only indication that they have, schizophrenia. And that is not our main focus now. And in terms of J&J, if they complete the acquisition of Intra-Cellular, certainly, there's going to be a lot of strength, but it seems that the people there will be in patients with major depression if they succeed in securing the approval in that indication, which seems quite possible given the very nice data they have.

現在我們確實看到了更多財力雄厚的大型製藥公司的潛在競爭，當然，BMS 和 COBENFY 目前，他們將主要關注他們唯一的適應症，即精神分裂症。而這不是我們現在關注的重點。就強生公司而言，如果他們完成對 Intra-Cellular 的收購，肯定會有很大的優勢，但如果他們成功獲得該適應症的批准，那麼那裡的患者似乎會是重度憂鬱症患者，考慮到他們擁有非常好的數據，這似乎是很有可能的。

Very good, Mihales. That's helpful. Makes sense. With regard to the DTC that you started in January, I assume that's targeting then the bipolar patients. Do you think that those patients are amenable to picking up the messaging of the DTC and perhaps bringing that to their prescribers and talking about Fanapt?

非常好，米哈萊斯。這很有幫助。有道理。關於您在一月啟動的 DTC，我認為其目標客戶是躁鬱症患者。您是否認為這些患者願意接受 DTC 的訊息並將其傳達給他們的處方醫生並談論 Fanapt？

Yeah. Thank you. Yes, the target is specifically for people with bipolar I disorder. And, certainly we don't have to guess on the effectiveness in that before us, there have been others -- almost every other, drug recently, the category, they have advertised to DTC which increased, not just awareness but also confidence of support of the drug among patients, but we're also finding, it is actually intriguing to prescribers themselves. So we believe that is a very effective way to increase awareness.

是的。謝謝。是的，該目標專門針對患有 I 型雙相情感障礙的人。當然，我們不必猜測其有效性，因為在我們之前已經有其他藥物——最近幾乎所有其他藥物，該類別的藥物，都已向 DTC 做了廣告，這不僅提高了患者對該藥物的認知度，還提高了患者對該藥物的支持信心，但我們也發現，這對處方者來說實際上很有趣。因此我們相信這是提高認識的非常有效的方法。

And I would point out that Vanda has a significant track record in efficiently launching a DTC campaign and buying media. And I think that's going to become very important in the coming months.

我想指出的是，Vanda 在高效啟動 DTC 活動和購買媒體方面擁有卓越的業績記錄。我認為這在接下來的幾個月裡將變得非常重要。

I would like to underscore what Kevin suggested that, at this time, we did not give a cash guidance, and this is primarily driven by trying to gauge what is the right size direct-to-consumer and you buy as you go. So we, unlike some large companies, we're not doing pre-buys at this time. We buy on demand, and we're very carefully evaluating the return on our investment. So it is a measured approach, but we are prepared to make a significant investment provided a good ROI on the other side.

我想強調凱文所說的，目前，我們還沒有給出現金指導，這主要是為了試圖判斷直接面向消費者的正確規模以及隨時購買的規模。因此，與一些大公司不同，我們目前不進行預購。我們根據需求購買，並且非常仔細地評估我們的投資回報。因此，這是一種謹慎的方法，但是為了獲得良好的投資回報率，我們也準備進行大量投資。

Thank you for that information. On Bysanti if I could ask a quick question, I'm intrigued with the one-per-day MDD study that you started towards the end of last year. I'm wondering if you have specific information on either Fanapt or milsaperidone that suggests that it may have activity in MDD as well as perhaps depressed patients with bipolar. What is the kind of rationale behind that Phase III?

感謝您的資訊。關於 Bysanti，我可以問一個簡單的問題嗎？我對您在去年年底開始的每天一次的 MDD 研究很感興趣。我想知道您是否有關於 Fanapt 或米沙哌利酮的具體信息，表明它可能對 MDD 以及患有躁鬱症的抑鬱症患者有效。第三階段背後的理由是什麼？

Yeah. So of course, you know that we have a lot of experience on Fanapt, iloperidone, with twice a day, but we also have experience in the utilization across different doses. So our studies have been primarily done on the higher dose side, 12 milligrams a day divided dose or 24 milligrams a day as a divided dose. But our observations so far that a large number of patients have been prescribed a monthly doses which reflect a total in the day of approximately 12 milligrams on average.

是的。因此，您當然知道我們在每天兩次使用 Fanapt（伊潘立酮）方面擁有豐富的經驗，但我們在不同劑量的使用方面也有經驗。因此，我們的研究主要在較高劑量方面進行，即每天分劑量 12 毫克或每天分劑量 24 毫克。但到目前為止，我們的觀察發現，大量患者被處方的每月劑量平均為一天總劑量約 12 毫克。

And we know that based on the pharmacokinetics and steady state levels that once a day 12 milligrams does not present any significant issues of peak-to-trough intolerability. And the combination of all this suggested to us that a once-a-day administration of Bysanti will be a good approach in major depressive disorder and as you can guess, it happens also to be likely more convenient than a twice-a-day dosing.

我們知道，根據藥物動力學和穩態水平，每天服用一次 12 毫克不會出現任何嚴重的峰穀不耐受問題。所有這些因素結合起來告訴我們，每天服用一次 Bysanti 是治療重度憂鬱症的好方法，而且正如你所猜測的，它也可能比每天服用兩次更方便。

For sure. Look forward to that. Final question, imsidolimab, congrats on the recent in-licensing. I'm intrigued with that program. BLA later on this year. But I think Anaptys -- and I'm not going to ask you to defend Anaptys -- but I think they spoke about a BLA as early as October 20, 2023, as having already been filed. So I'm wondering if you have a sense of what the delay in filing and if a pre-BLA has been conducted. Or is that all the kind of stuff that you'll do once you fully accept all the information from them?

一定。非常期待。最後一個問題，imsidolimab，祝賀最近獲得許可。我對那個程式很有興趣。BLA 將在今年稍後推出。但我認為 Anaptys——我不會要求你為 Anaptys 辯護——但我認為他們早在 2023 年 10 月 20 日就談到了 BLA，因為已經提交了。所以我想知道您是否了解提交延遲的原因以及是否已經進行了預先 BLA。或者說，這些都是你完全接受他們提供的所有資訊後會做的事情？

Yeah, I cannot comment on the first part of the question. But a pre-BLA for a meeting with the FDA on the GPP indication has been conducted, and upon review of this information, we're confident that we have in hand what needs to be had for filing. So of course, we're only a few days away. That, I would say, Anaptys is a great partner on this. Transition is ongoing quickly of materials. So we're confident we'll be able to file this BLA within this year.

是的，我無法對問題的第一部分發表評論。但已經與 FDA 就 GPP 適應症舉行了一次 BLA 前會議，在審查了這些資訊後，我們有信心我們已經掌握了提交申請所需的資訊。當然，只剩幾天時間了。我想說，Anaptys 在這方面是一位很棒的合作夥伴。材料的轉變正在快速進行。因此我們有信心在今年內提交這份 BLA。

And I have to say, Charles, that -- maybe we get an opportunity at a future call -- we're intrigued by the mechanism of action. And we believe that the IL-36 cytokine system is a perhaps not fully explored therapeutic in a number of autoimmune inflammatory conditions. And of course, we understand the role in keratinocytes in generalized pustular psoriasis.

查爾斯，我不得不說 - 也許我們在未來的電話會議中有機會 - 我們對這種作用機制很感興趣。我們認為，IL-36 細胞激素系統在許多自體免疫發炎疾病中可能是一種尚未充分探索的治療方法。當然，我們了解角質形成細胞在全身性膿皰型乾癬中的作用。

As I pointed out in my discussion, GPP is caused by two bad genes, a recessive disorder. But of course, there is a much larger portion of the population that are heterozygous carriers of a null mutation, which under some circumstances, it may lead to a relatively unopposed action of IL-36. And there are theories of what this population may be. They may be a class of people with atopic dermatitis or psoriasis or actually other inflammatory conditions where IL-36 is important in monitoring intruders at barrier tissues. But more to be discussed in the future.

正如我在討論中指出的那樣，GPP 是由兩個不良基因引起的，是一種隱性疾病。但當然，人口中有很大一部分是無效突變的雜合攜帶者，在某些情況下，這可能導致 IL-36 相對不受阻礙的作用。目前存在著關於這一人群的具體理論。他們可能是患有異位性皮膚炎或牛皮癬或其他發炎疾病的人，其中 IL-36 在監測屏障組織中的入侵者方面發揮著重要作用。但未來還有更多內容需要討論。

Big pipeline, lot's going on. Thanks for taking the questions. Congrats on the progress.

管道很大，有很多事情要做。感謝您回答這些問題。祝賀你取得進展。

Raghuram Selvaraju, H.C. Wainwright.

拉古拉姆·塞爾瓦拉朱（Raghuram Selvaraju），H.C.溫賴特。

Hi, thanks so much for taking my questions and congrats on all the recent progress. First of all, I wanted to start with a question around your anticipated timing for the development of the iloperidone long acting injectable. So specifically, I wanted to ask when you anticipate enrolling the first patient in that pivotal program and how long you expect enrollment to take, as well as if you can provide any kind of updated outlook on the competitive landscape given the fact that this appears to be changing quite rapidly, although it obviously is also reflective of steadily expanding broader total addressable market. Thank you.

你好，非常感謝您回答我的問題，並祝賀你最近的進展。首先，我想先問一個問題，關於您對伊潘立酮長效注射劑的預計開發時間。因此，具體來說，我想問一下您預計何時在該關鍵項目中招募第一位患者，以及您預計招募需要多長時間，以及您是否可以提供任何關於競爭格局的最新展望，因為這種格局似乎正在迅速變化，儘管它顯然也反映了穩步擴大的更廣泛的總目標市場。謝謝。

Yeah. Thank you very much for the question. And at the bottom, I would say we agree with you that there appears to be a lot of need and large commercial opportunity around injectable antipsychotics and especially new entrants of molecules that have not been translated from oral to a long-acting injectable like Fanapt.

是的。非常感謝您的提問。總而言之，我想說，我們同意您的觀點，注射抗精神病藥物似乎存在很大的需求和商業機會，尤其是那些還未從口服藥物轉化為長效注射劑（如 Fanapt）的分子新藥。

In terms of the program, we are ready to go. And in fact, that program can be initiated imminently. The initial treatment period is about 12-week period of stabilization before we lead to the re-randomization relapse prevention. And what I mentioned, Ram, is that the question from the IRB was that they felt no one should be running placebo-controlled studies on a relapse prevention mode. And they offer that placebo people may be at some risk.

從計劃上來說，我們已經準備就緒。事實上，該計劃可以立即啟動。在我們進行重新隨機復發預防之前，初始治療期約為 12 週的穩定期。我提到的是，拉姆，IRB 的問題是，他們認為沒有人應該對復發預防模式進行安慰劑對照研究。他們認為服用安慰劑的人可能會面臨一定的風險。

We disagree with that, but nonetheless, it is the IRB. And we are in total agreement with the FDA on what protocol is needed. And in fact we are in agreement that this study, if successful, which we expect it to be, is the pivotal study required for registration.

我們對此不同意，但無論如何，它就是 IRB。我們完全同意 FDA 對所需協議的要求。事實上，我們一致認為，這項研究如果成功的話（我們期望它會成功），將是註冊所需的關鍵研究。

So we are actually waiting. We've launched this question to the FDA, and they're working, I guess, on their policy side to see what this shift in the IRB means and what type of study may be required. But be it as it may, the placebo is the most involved study. And we could end up with a more simple design, where there is a bridging of sorts with the oral formulation. So, no matter what it is, we can start the study very quickly.

所以我們實際上正在等待。我們已經向 FDA 提出了這個問題，我猜他們正在從政策方面研究 IRB 的這種轉變意味著什麼以及可能需要進行哪些類型的研究。但無論如何，安慰劑研究是最複雜的。我們最終可能會得到一個更簡單的設計，其中存在與口服製劑之間的某種銜接。所以，不管是什麼，我們都可以很快開始研究。

Now in terms of timing to enrollment, as you know that's hard to evaluate given the difficulty recruiting in general, but this study is a long study. Recruitment in large could take up to one year, and that means, I think we've discussed before, that we will not expect results but in some time in 2027.

現在就入學時間而言，正如您所知，由於招募通常很困難，因此很難評估，但這項研究是一項長期研究。大規模招募可能需要長達一年的時間，這意味著，我想我們之前已經討論過，我們不會期待結果，但會在 2027 年的某個時候。

Okay. And then with respect to the guidance that you provided today with -- on potential revenue in 2025, can you confirm that even the upper end of that guidance range does not actually include projected contribution from tradipitant in any indication or imsidolimab. Is that correct?

好的。然後，關於您今天提供的有關 2025 年潛在收入的指導，您能否確認，即使是該指導範圍的上限實際上也不包括 tradipitant 在任何適應症或 imsidolimab 中的預計貢獻。那正確嗎？

That is correct. The range guidance we're giving is solely based on the commercialized products today in the commercialized indications. And of course, we could be pleasantly surprised towards the upper end, depending on the Fanapt trajectory and PONVORY gaining speed. On HETLIOZ, given the generic contribution, we have more tamed expectations.

正確。我們提供的範圍指導完全基於目前商業化適應症中的商業化產品。當然，我們可能會對上限感到驚喜，這取決於 Fanapt 軌跡和 PONVORY 的速度。對於 HETLIOZ，考慮到通用貢獻，我們有更溫和的期望。

To what extent do you anticipate there to be a significantly larger number of generic competitors -- generic purveyors of tasimelteon by the end of 2025 versus the end of 2024?

您預計，到 2025 年底，仿製藥競爭對手（tasimelteon 的仿製藥供應商）的數量將比 2024 年底增加多少？

At this time, we do not expect that field to change outside of the three approved ones.

目前，我們預計除了已批准的三個領域之外，該領域不會發生變化。

Okay. And then, the last question is with respect to broader reimbursement changes. Any specific developments of note that you anticipate taking effect in 2025 that could significantly impact gross to nets?

好的。最後一個問題是關於更廣泛的報銷變化。您預計 2025 年將有哪些值得注意的具體發展會對毛收入與淨收入產生重大影響？

Yeah. Hey, Ram. It's Kevin. So on the main one, which we talked about in the scripted portion of it, is the introduction of the Medicare benefit redesign, which went into effect at the beginning of January. And the reminder there is previously where there was the donut hole concept and the manufacturer had a portion of that contribution until the patient had moved through the donut hole for the year, the benefit redesign has a different structure where for the catastrophic portion of the coverage, the manufacturer has an either 10% or 20% contribution to that with some exceptions for different types of manufacturers and different types of patient populations. So that went into effect at the beginning of January, as I mentioned, and was factored into our projections for 2025.

是的。嘿，拉姆。是凱文。因此，我們在腳本部分討論的主要內容是醫療保險福利重新設計的引入，該設計於 1 月初生效。需要提醒的是，之前有甜甜圈洞概念，製造商貢獻了一部分，直到患者在當年突破甜甜圈洞為止，福利重新設計具有不同的結構，對於災難性部分的保險，製造商貢獻 10％ 或 20％，但不同類型的製造商和不同類型的患者群體有一些例外。正如我所提到的那樣，這項政策於 1 月初生效，並被納入我們對 2025 年的預測中。

Andrew Tsai, Jefferies.

傑富瑞 (Jefferies) 的 Andrew Tsai。

Hey. Thanks, good afternoon. I appreciate all the updates. First question is about the 2030 guidance. What exactly compelled you guys to provide that guidance today? And then within that $1 billion dollar guidance, of course, $750 million is coming from psychiatry. How much of that $750 million is based on products or indications that have yet to be approved as opposed to currently approved products? Thanks.

嘿。謝謝，下午好。我感謝所有的更新。第一個問題是關於 2030 年指導方針。是什麼促使你們今天提供這樣的指導？當然，在這 10 億美元的指導經費中，有 7.5 億美元來自精神病學。相對於目前已核准的產品，這 7.5 億美元中有多少是基於尚未核准的產品或適應症？謝謝。

Thanks, Andrew. Yeah. So maybe starting with the psychiatry portfolio, first. Obviously with Fanapt currently on the market doing about $100 million this year and with the commercial investments we're making, hoping to see growth as we obviously head into next year and beyond. But then even beyond that, we noted that -- included in that 2030 projection is the approval of Bysanti for bipolar I disorder and schizophrenia, hopefully, next year, and then potentially a label expansion there in MDD beyond that as well as the approval of Fanapt in LAI.

謝謝，安德魯。是的。因此也許先從精神科組合開始。顯然，Fanapt 目前在市場上的銷售額今年約為 1 億美元，加上我們正在進行的商業投資，我們希望在明年及以後看到成長。但除此之外，我們注意到 - 2030 年的預測包括 Bysanti 預計在明年獲準用於治療 I 型雙相情感障礙和精神分裂症，然後可能在此基礎上擴展其在 MDD 中的標籤，以及 Fanapt 在 LAI 中的批准。

So and the one thing I also made note of in the script that's an important piece to that is that milsaperidone is expected to have -- or Bysanti rather is expected to have very different economics than Fanapt currently has. And at a minimum, that's due to the price reset that we would experience under Medicaid with a new drug application being approved.

因此，我在劇本中也提到了一件很重要的事情，那就是米沙哌利酮預計會具有——或者更確切地說，Bysanti 預計會具有與 Fanapt 目前非常不同的經濟效益。至少，這是由於在新的藥品申請獲得批准後，我們將在醫療補助計劃下經歷價格重置。

So all of those -- obviously, we didn't provide kind of a breakout of the contributions of those individual factors, but hopefully that gives you a sense of what contributions would go into the $750 million from existing product indications, future product indications. And then on the balance, obviously with HETLIOZ and PONVORY on the market, Helioz, as Mihales mentioned, where our expectations are a bit more tamed, at least on the short term, and with PONVORY, growing and hopefully even more so in the years to come. And also the possibility that we mentioned of an additional three products being on the market next year, including milsaperidone but also tradipitant and imsidolimab, those products also provide some of the bridge between the $750 million and $1 billion.

因此，所有這些 — — 顯然，我們沒有提供這些單一因素的貢獻的細分，但希望這可以讓您了解現有產品適應症和未來產品適應症對 7.5 億美元的貢獻。然後從總體上看，顯然隨著 HETLIOZ 和 PONVORY 進入市場，正如 Mihales 所提到的，Helioz 的預期至少在短期內有所緩和，而隨著 PONVORY 的不斷發展，希望在未來幾年能有更大的發展。而且我們提到，明年可能會有另外三種產品上市，包括米沙哌利酮、tradipitant 和 imsidolimab，這些產品也為 7.5 億美元和 10 億美元之間的收入橋樑提供了一些幫助。

Thanks. And when we think about your overall business, where or when should we think the trough year is in terms of revenue and your total cash balance? Said another way, do you think the trough year already happened, or could it be somewhere in 2025 or a little bit later?

謝謝。當我們考慮您的整體業務時，我們應該認為收入和總現金餘額的低谷年份在哪裡或何時？換句話說，您認為低谷年已經到來了嗎，還是會是在 2025 年的某個時候，或者稍晚一點？

Yeah. Thanks for the question there, Andrew. So obviously with our reported revenue for this year being growth from the year before, so we saw growth from about $193 million up to about $199 million in the most recent year, and the midpoint of our guidance being $230 million, which would imply about a 15% growth on 2024, I would say that the trough here, as you kind of expressed it, is over the shoulder. And our expectation is that we're growing revenue from here both with the existing products and indications, but obviously all the products and indications that we're planning on bringing to the market in the short term and the long term.

是的。謝謝你的提問，安德魯。因此顯然，我們報告的今年的收入比前一年有所增長，所以我們看到從約 1.93 億美元增長到最近一年的約 1.99 億美元，而我們預期的中點是 2.3 億美元，這意味著到 2024 年將增長約 15%，我想說，正如您所表達的那樣，這裡的低谷已經過去了。我們的預期是，我們不僅能透過現有的產品和適應症來增加收入，而且顯然還能透過我們計劃在短期和長期內推向市場的所有產品和適應症來增加收入。

Okay, thanks. And the last question is for HETLIOZ, if we stripped out the indications where generics -- where you're facing generics, how much sales are you generating from the other formulations or indications where HETLIOZ is not facing genericization? So I guess the liquid formulation and the EU component, how much are those sales currently? Thank you.

好的，謝謝。最後一個問題是，對於 HETLIOZ，如果我們去掉仿製藥的適應症——您面臨的仿製藥，您從 HETLIOZ 沒有面臨仿製藥的其他配方或適應症中獲得了多少銷售額？所以我猜測液體配方和歐盟成分目前的銷售額是多少？謝謝。

Yeah. So Andrew, we haven't gotten into a breakout by geography or by indication. So I can't provide any further kind of color to that.

是的。因此，安德魯，我們還沒有在地理或跡象方面取得突破。因此我無法對此提供任何進一步的說明。

There are no further questions at this time. I'll turn the call back over to the team.

目前沒有其他問題。我會把電話轉回給團隊。

Well, thank you very much for joining us on this call. We'll see you on a future earnings call. Thank you.

好吧，非常感謝您參加我們的電話會議。我們將在未來的收益電話會議上見到您。謝謝。

This concludes today's call. Thank you for joining. You may now disconnect.

今天的電話會議到此結束。感謝您的加入。您現在可以斷開連線。

[EJ1]Intended to say 2023. How do you propose we edit this?

[EJ1] 預計是 2023 年。您建議我們如何編輯它？