Tvardi Therapeutics Inc (TVRD) 2023 Q4 法說會逐字稿

Thank you for standing by, and welcome to Cara Therapeutics fourth quarter and full year 2023 earnings conference call. (Operator Instructions) I would now like to hand the call over to Matt Murphy, Manager of Investor Relations. Please go ahead.

感謝您的支持，歡迎參加 Cara Therapeutics 2023 年第四季和全年財報電話會議。（操作員指示）現在我想將電話轉給投資者關係經理馬特·墨菲。請繼續。

Thank you, operator, and good afternoon. After market closed today, Cara issued a news release announcing the company's financial and operating results for the fourth quarter and full year 2023. Copies of this news release can be found in the Investors section of our website at caratherapeutics.com.

謝謝接線員，下午好。今天收盤後，Cara發布新聞稿，公佈了該公司2023年第四季和全年的財務和營運業績。本新聞稿的副本可在我們網站 caratherapeutics.com 的投資者部分找到。

Before we begin, let me remind you that during the course of this conference call, we will be making certain forward-looking statements about Cara and our program based on management's current plans and expectations. These statements are being made under the Private Securities Litigation Reform Act of 1995, and are subject to risks and uncertainties.

在我們開始之前，請允許我提醒您，在本次電話會議期間，我們將根據管理層目前的計劃和期望對 Cara 和我們的計劃做出某些前瞻性陳述。這些聲明是根據 1995 年《私人證券訴訟改革法》作出的，具有風險和不確定性。

Actual results may differ materially due to various factors and Cara undertakes no obligation to update or revise these statements publicly as a result of new information or future results or developments. Investors should read the risk factors set forth in Cara's 10-K for the year ended December 31, 2022, and any subsequent reports filed with the SEC, including its Form 10-Q for the quarter ended September 30, 2023.

由於各種因素，實際結果可能存在重大差異，且 Cara 不承擔因新資訊或未來結果或發展而公開更新或修改這些聲明的義務。投資者應閱讀 Cara 截至 2022 年 12 月 31 日的 10-K 報告中列出的風險因素，以及向美國證券交易委員會提交的任何後續報告，包括截至 2023 年 9 月 30 日的季度的 10-Q 表。

With that said, I'd like to turn the call over to Chris Posner, Cara's Chief Executive Officer. Chris?

話雖如此，我想將電話轉給 Cara 的執行長 Chris Posner。克里斯？

Thanks, Matt. Good afternoon and thank you for joining our call. With me today are Ryan Maynard, our Chief Financial Officer, and Dr. Joana Goncalves, our Chief Medical Officer.

謝謝，馬特。下午好，感謝您參加我們的電話會議。今天與我一起的有我們的財務長 Ryan Maynard 和我們的首席醫療官 Joana Goncalves 博士。

Significant developments in 2023 led us to sharpen Cara's strategy and focus. We announced in January of this year that we have prioritized the program with the highest likelihood of clinical and commercial success, oral difelikefalin for notalgia paresthetica or NP. Focusing all our resources on NP extends our cash runway into 2026, which allows us to reach all value inflection milestones in this program.

2023 年的重大發展促使我們加強了 Cara 的策略和重點。我們在今年 1 月宣布，我們已優先考慮最有可能取得臨床和商業成功的項目，即用於治療背痛或 NP 的口服 difelikefalin。將我們所有的資源集中在 NP 上，可以將我們的現金流延長到 2026 年，這使我們能夠達到該計劃中的所有價值拐點里程碑。

NP is a highly underserved neuropathic condition with a sizable patient population and no approved therapies. We are optimistic that oral difelikefalin, if approved, could become the first and only oral antipruritic therapy for NP.

NP 是一種嚴重缺乏治療的神經病變，患者數量龐大，但尚無核准的治療方法。我們樂觀地認為，口服difelikefalin如果獲得批准，可能成為第一個也是唯一的NP口服止癢療法。

I want to highlight why NP has such potential and detail how our late-stage oral difelikefalin clinical program can address it. Notalgia paresthetica is an unexplored neuropathy and yet, NP is relatively common. The disease is a chronic neuropathic pruritic condition characterized by pruritis of the upper back, often leading to pigment changes as a result of excessive scratching.

我想強調為什麼 NP 具有如此大的潛力，並詳細說明我們的後期口服 difelikefalin 臨床計畫如何解決這個問題。背痛異常是一種尚未被探索的神經病，但 NP 相對常見。此疾病是一種慢性神經性搔癢症，其特徵是上背部搔癢，常因過度抓癢而導致色素變化。

Notalgia paresthetica has been dramatically understudied. But as I will highlight in a bit, anecdotal evidence suggests, and we believe, that chronic neuropathic pruritus is often as onerous as chronic pain in terms of impacting the quality of life of patients. And while chronic pain has been targeted and studied extensively, chronic neuropathic pruritus has not.

感覺異常性背痛的研究一直嚴重不足。但正如我稍後要強調的那樣，軼事證據表明，而且我們相信，慢性神經性搔癢在影響患者生活品質方面往往與慢性疼痛一樣嚴重。儘管慢性疼痛已成為關注的焦點並得到廣泛的研究，但慢性神經性搔癢卻尚未被廣泛研究。

An estimated 34 million US patients or 13% of the adult population suffer from chronic pruritus. And approximately $2.7 million or 8% of them have chronic neuropathic pruritus. Now out of those chronic neuropathic pruritus patients, 650,000 or 24% of are notalgia paresthetica patients under the care of a health care provider, predominantly a dermatologist. This number does not account for the many mis- or undiagnosed patients.

據估計，美國有 3,400 萬名患者或 13% 的成年人口患有慢性搔癢症。其中約有 270 萬美元或 8% 患有慢性神經性搔癢症。目前，在這些慢性神經性搔癢症患者中，有 65 萬人（佔 24%）是感覺異常性背部痛患者，需要接受醫療保健提供者（主要是皮膚科醫生）的照護。這個數字還不包括許多被誤診或未確診的患者。

Notalgia paresthetica has a significant impact on the quality of life of patients, including on their mood, sleep, and self-care activities. And yet this significant health challenge has no current treatment or wide-ranging efforts to address it. Anecdotal feedback from patients suggest that their pruritis is often constant, and is as debilitating as pain.

背痛對患者的生活品質有顯著影響，包括情緒、睡眠和自我照顧活動。然而，這項重大的健康挑戰目前尚無治療方法或廣泛的應對措施。來自患者的軼事回饋表明，他們的瘙癢症往往是持續性的，並且與疼痛一樣令人虛弱。

There are no approved treatments for notalgia paresthetica, and off-label use of other therapies, frequently topical and systemic treatments indicated for neuropathic pain, are mostly ineffective or associated with significant side effects. In market research, almost 90% of NP patients responded that the treatments that they had been offered for NP have been minimally or not at all helpful. As a result, almost 75% of responders said that they were not currently on any therapy for NP.

目前尚無核准的治療背痛的方法，而其他療法的標籤外使用（通常是針對神經性疼痛的局部和全身治療）大多無效或伴隨嚴重的副作用。在市場調查中，幾乎 90% 的 NP 患者表示，他們接受的 NP 治療效果甚微或根本沒有效果。結果顯示，近 75% 的受訪者表示他們目前沒有接受任何 NP 治療。

It is clear from the literature and our market research that there is a significant unmet need for an effective, safe, and well-tolerated treatment for NP.

從文獻和我們的市場研究中可以清楚地看出，對有效、安全且耐受性良好的 NP 治療方法存在著巨大的未滿足需求。

Our oral DFK program could lead the way to target and address notalgia paresthetica's hallmark chronic neuropathic pruritus. We believe oral DFK's neuromodulatory action presents an ideal mechanistic approach to treating chronic neuropathic pruritus. In our Phase 2 proof-of-concept study in NP, oral DFK, at a 2 mg PID dose showed a statistically significant separation from placebo on the worst itch NRS scale as early as day one.

我們的口服 DFK 計劃可以引領針對和解決背部感覺異常痛標誌性慢性神經性搔癢症的方法。我們相信口服 DFK 的神經調節作用為治療慢性神經性搔癢提供了理想的機制方法。在我們針對 NP 進行的 2 期概念驗證研究中，口服 DFK（2 毫克 PID 劑量）早在第一天就在最嚴重搔癢 NRS 量表上與安慰劑表現出統計學上顯著的差異。

It also showed sustained efficacy throughout the double-blind eight-week treatment period. The publication of these data in February 2023 New England Journal of Medicine has attracted a lot of attention from thought leaders, investigators, and patients. Highlighting this significant unmet need, this excitement has resulted in rapid enrollment in the ongoing dose-finding portion of our Phase 2/3 KOURAGE 1 study.

它還在雙盲八週治療期間顯示出持續的療效。這些數據於2023年2月《新英格蘭醫學雜誌》上發表，引起了思想領袖、研究人員和患者的廣泛關注。突顯了這一重大的未滿足需求，這種興奮導致我們正在進行的 2/3 期 KOURAGE 1 研究的劑量探索部分迅速招募患者。

I am pleased to announce that we have completed enrollment in KOURAGE 1 Part A ahead of schedule, putting us on track to report top-line efficacy and safety results in Q3 of this year. As a reminder, KOURAGE 1 is comprised of two parts: Part A, the dose-finding portion of the study is a double-blind placebo-controlled eight-week study comparing three dosage strengths of oral DFK to placebo. We currently have 53 active sites in North America and Europe, and we plan to include additional sites for the pivotal portion of the program.

我很高興地宣布，我們已提前完成 KOURAGE 1 Part A 的註冊，這使我們能夠在今年第三季報告頂級療效和安全性結果。提醒一下，KOURAGE 1 由兩部分組成：A 部分，即研究的劑量探索部分，是一項雙盲安慰劑對照的八週研究，比較三種劑量強度的口服 DFK 與安慰劑。我們目前在北美和歐洲擁有 53 個活躍站點，並且我們計劃為該計劃的關鍵部分增加更多站點。

The primary endpoint is the proportion of patients with a greater-than four-point improvement at week eight from baseline in the worst itch NRS scale. The readout from this portion of the trial will provide key information, specifically the dose and sample size to initiate the Phase 3 pivotal portion of the program, Part B of KOURAGE 1, and the second study, KOURAGE 2.

主要終點是第八週時最嚴重搔癢 NRS 量表較基線改善超過四分的患者比例。試驗這一部分的讀數將提供關鍵信息，特別是啟動該計劃第 3 階段關鍵部分、KOURAGE 1 的 B 部分和第二項研究 KOURAGE 2 的劑量和样本量。

Ahead of these top line data, we will be hosting a panel of renowned dermatology KOLs to discuss the unmet need in NP and the potential role of oral DFK in this underserved disease and wide-open therapeutic indication. We will issue an announcement with details of this event in the coming days, and we hope you will join us.

在這些頂級數據公佈之前，我們將邀請知名皮膚病學 KOL 組成一個小組，討論 NP 中未滿足的需求以及口服 DFK 在這種服務不足的疾病和廣泛開放的治療適應症中的潛在作用。我們將在未來幾天發布有關此活動的詳細資訊的公告，希望您能加入我們。

Moving on to KORSUVA injection. In the fourth quarter of 2023, we saw a strong quarter to quarter demand growth of 22% as reflected by the vials shipped to individual clinics. This continued growth in demand is a clear testament to the value and clinical benefit KORSUVA offers to patients and their providers. However, was unfavorable reimbursement changes following the end of the TDAPA period on March 31 this year, we anticipate that DOs, dialysis organizations, will modify current treatment protocols and significantly restrict access to KORSUVA. As a result, we do not expect meaningful revenue contributions from KORSUVA going forward.

繼續進行 KORSUVA 注射。2023 年第四季度，我們看到需求較上季強勁成長 22%，這從運往各個診所的小瓶數量可以看出。需求的持續成長清楚地證明了 KORSUVA 為患者及其提供者提供的價值和臨床益處。然而，由於今年 3 月 31 日 TDAPA 期限結束後報銷政策發生了不利變化，我們預計 DO、透析組織將修改目前的治療方案並大幅限制使用 KORSUVA。因此，我們預計 KORSUVA 未來不會帶來有意義的收入貢獻。

Let me conclude by reiterating the following over the three months we have taken decisive and swift action. We have evolved our strategy and meaningfully extended our cash runway by sharpening our focus on the program with the highest potential. Notalgia paresthetica has the ingredients for a breakout program with a high probability of clinical and commercial success. I am confident and optimistic that we are on the right path to unlock Cara's growth potential and create sustainable value for all our stakeholders.

最後，我要重申我們在過去三個月所採取的果斷而迅速的行動。我們已經改進了策略，並透過更加關注最具潛力的項目，顯著延長了我們的現金流。背痛異常症具有突破性治療方案的要素，具有很高的臨床和商業成功機率。我相信並樂觀地認為，我們正走在釋放 Cara 成長潛力和為所有利害關係人創造永續價值的正確道路上。

I would now like to turn the call over to Ryan for additional details on our fourth quarter results. Over to you, Ryan.

現在我想將電話轉給瑞安，以了解有關我們第四季度業績的更多詳細資訊。交給你了，瑞安。

Thank you, Chris. I would like to first reiterate the importance of the financing transaction with health care royalty, which we completed in Q4. We were able to bring forward the value of our ex-USA and Japan royalties and add to our balance sheet in a meaningful non-dilutive manner. This, combined with our privatization announcement in January of this year, allowed us to extend our cash runway into 2026, thereby enabling us to reach all value inflection milestones in our NP program.

謝謝你，克里斯。我想首先重申與醫療保健特許權使用費的融資交易的重要性，我們在第四季度完成了該交易。我們能夠提前實現美國和日本以外的特許權使用費的價值，並以有意義的非稀釋性方式增加我們的資產負債表。結合我們今年 1 月宣布的私有化，這使我們能夠將現金流延長至 2026 年，使我們能夠達到 NP 計劃中的所有價值拐點里程碑。

Now I'd also like to highlight how the HCR Agreement is reflected in our financial statements. In Q4, we recorded the total net proceeds as a long-term liability on our balance sheet. Royalties received from CSL and Maruishi under this agreement are recorded as noncash other revenue on our P&L. We also recorded non-cash imputed interest. As a reminder, if the royalty payments received by HCR under this agreement exceed two times HCR's initial contribution before 2029, then the royalties thereafter would then revert back to us.

現在我還想強調一下 HCR 協議如何反映在我們的財務報表中。在第四季度，我們將總淨收益記錄為資產負債表上的長期負債。根據本協議從 CSL 和丸石收到的特許權使用費在我們的損益表中記錄為非現金其他收入。我們也記錄了非現金估算利息。提醒一下，如果 HCR 根據本協議收到的特許權使用費在 2029 年之前超過 HCR 初始貢獻的兩倍，那麼此後的特許權使用費將歸還給我們。

Now onto the Q4 results. In the fourth quarter of 2023, KORSUVA injection generated net sales of $5 million. We reported revenue of $3 million for the three months ended December 31, 2023, compared to $3.3 million for the same period in 2022.

現在來看看第四季的業績。2023年第四季度，KORSUVA注射液的淨銷售額為500萬美元。我們報告稱，截至 2023 年 12 月 31 日的三個月的收入為 300 萬美元，而 2022 年同期的收入為 330 萬美元。

Revenue this quarter consisted of $2.3 million of collaborative revenue related to our profit from CSL Vifor's sales of KORSUVA injection, and $0.7 million of other revenue related to royalties and milestone payments related to the HCR agreement. Demand for KORSUVA continued to grow in Q4 with wholesaler shipments to dealers reaching 110,000 vials, which was a 22% increase from the prior quarter. The majority of these vials were inventory that was reallocated within the Fresenius network of clinics and therefore did not translate into incremental revenue for Cara.

本季度收入包括與我們從 CSL Vifor 銷售 KORSUVA 注射液中獲得的利潤相關的 230 萬美元合作收入，以及與 HCR 協議相關的特許權使用費和里程碑付款相關的 70 萬美元其他收入。第四季度，KORSUVA 的需求持續成長，批發商向經銷商的出貨量達到 11 萬瓶，比上一季成長了 22%。這些藥瓶中的大部分都是在費森尤斯診所網絡內重新分配的庫存，因此並沒有轉化為 Cara 的增量收入。

Cost of goods sold was $0.6 million for the three months ended December 31, 2023, compared to $2.1 million for the same period in 2022. Cost of goods sold this quarter included mainly inventory adjustment charges rather than actual vials shipped to CSL Vifor.

截至 2023 年 12 月 31 日的三個月，銷售成本為 60 萬美元，而 2022 年同期為 210 萬美元。本季銷售成本主要包括庫存調整費用，而不是運送至 CSL Vifor 的實際小瓶。

Research and development expenses were $28.4 million for the three months ended December 31, 2023, compared to $26 million in the same period of 2022. The higher R&D expenses in '23 were primarily due to increases in clinical trial costs related to our three late-stage development programs, partially offset by a decrease in stock-based compensation expense.

截至 2023 年 12 月 31 日的三個月，研發費用為 2,840 萬美元，而 2022 年同期為 2,600 萬美元。23 年研發費用增加主要是由於與我們三個後期開發項目相關的臨床試驗成本增加，但股票薪酬費用的減少部分抵消了這一影響。

R&D expense in the three months ended December 31, 2023 included a $1.7 million expense related to an agreement for manufacturing commitments that are no longer needed due to the reduced demand expectations of KORSUVA in the United States.

截至 2023 年 12 月 31 日的三個月的研發費用包括一筆 170 萬美元的費用，該費用與製造承諾協議有關，由於美國對 KORSUVA 的需求預期下降，該協議不再需要。

G&A expenses were essentially flat at $6.6 million for the three months ended December 31, 2023, compared to $6.4 million last year. Cash, cash equivalents and marketable securities at December 31, 2023, totaled $100.8 million compared to $156.7 million for the same period in 2022. The decrease in the balance primarily resulted from $92.1 million of cash used in operating activities, offset by the $36.5 million of net proceeds received from HCR.

截至 2023 年 12 月 31 日的三個月，一般及行政費用基本持平，為 660 萬美元，去年同期為 640 萬美元。截至 2023 年 12 月 31 日的現金、現金等價物及有價證券總額為 1.008 億美元，而 2022 年同期為 1.567 億美元。餘額減少主要由於經營活動所用現金 9,210 萬美元，但被從 HCR 收到的 3,650 萬美元淨收益所抵銷。

Now finally, we expect that our current unrestricted cash, cash equivalents, and available-for-sale marketable securities will be sufficient to fund our currently anticipated operating plan into 2026. Our current operating plan reflects the impact of our prioritization announcement in January of 2024, which includes costs related to our planned pivotal program for NP.

最後，我們預計我們目前的非限制性現金、現金等價物和可供出售的有價證券將足以資助我們目前預期的 2026 年營運計畫。我們目前的營運計劃反映了我們在 2024 年 1 月宣布的優先事項的影響，其中包括與我們為 NP 計劃的關鍵計劃相關的成本。

Now I'll turn it back to Chris.

現在我將話題轉回給克里斯。

Thanks, Ryan. Cara is fundamentally a development company. By sharpening our strategic focus on notalgia paresthetica, we have set Cara on a path to becoming a pioneer in the field of medical dermatology. Based on preclinical and clinical data, oral DFK is uniquely suited to address the unmet medical need in this highly underserved disease, and we look forward to sharing the data from the dose-finding portion of the Phase 2/3 trial with you in Q3.

謝謝，瑞安。Cara 本質上是一家開發公司。透過加強對背部感覺異常痛的策略關注，我們已使 Cara 走上了成為醫學皮膚病學領域先驅的道路。根據臨床前和臨床數據，口服 DFK 非常適合解決這種嚴重缺乏治療的疾病中未滿足的醫療需求，我們期待在第三季度與您分享 2/3 期試驗劑量探索部分的數據。

With that, Ryan, Jo, and I will be happy to take your questions. So operator, if you could please open the line for Q&A.

因此，Ryan、Jo 和我很樂意回答您的問題。接線員，請開通問答專線。

(Operator Instructions) Annabel Samimy, Stifel.

（操作員指示）Annabel Samimy，Stifel。

Hi, thanks for taking my questions. So obviously, NP looks like a pretty attractive category for the difelikefalin mechanism. How large a clinical program do you think this could be in Phase 3? And when you think about the dose to take forward, what you want -- only one dose to take forward? Would you look for a couple of doses just for that optionality for the patient?

你好，謝謝你回答我的問題。因此顯然，NP 對於 difelikefalin 機制來說看起來是一個非常有吸引力的類別。您認為第三階段的臨床計畫規模有多大？當您考慮要服用的劑量時，您想要什麼—只服用一劑？您是否會為了提供患者選擇性而尋找幾種劑量？

And then separately, given the rapid enrollment and clearly the high interest from the community that you've got after the journal publication, do you think that you could partner -- you would want to partner this opportunity even in the late stages development rather just for commercialization? And so just I know that -- I realize that you're a development company, but given that interest, I'm just wondering if you're getting expressions of interest from those publications. Thanks.

另外，考慮到期刊出版後您的研究註冊人數迅速增加以及社區的濃厚興趣，您是否認為您可以合作——您是否願意在後期開發階段就抓住這個機會，而不僅僅是為了商業化？所以我所知道的是——我知道你們是一家開發公司，但考慮到這種興趣，我只是想知道你們是否從這些出版物中得到了興趣表達。謝謝。

Thanks, Annabel. Let me turn the first part to Jo, and then I'll tackle the second part of your question.

謝謝，安娜貝爾。讓我先把第一部分交給喬，然後我會解決你問題的第二部分。

Yeah. Thanks, Annabel. So just to address how large the pot be in the pivotal program will be, and this will be based upon our results from Part A. We'll take the results together with our comfort data into account when assessing the size of the study. So more to come once we get that data. As far as how many doses, ideally always it's best to take one dose forward. It just makes a simpler pivotal program. So that will be our aim.

是的。謝謝，安娜貝爾。因此，只需解決關鍵計劃中的資金規模有多大的問題，這將基於我們 A 部分的結果。在評估研究規模時，我們將結合舒適度數據來考慮結果。一旦我們獲得這些數據，就會有更多資訊。至於服用多少劑量，理想情況下最好提前服用一劑。它只是使一個關鍵程序變得更簡單。這就是我們的目標。

Yeah. And Annabel, the second part of your question on partnering. As you know, this asset is totally unencumbered, which is great. And given the strategic prioritization we did in the beginning of this year, we have the cash available into early '26 to complete all the key clinical programs. So right now, our intent is to continue the development of NP. Like you said, we're super excited at what we saw in the rapid enrollment. It is certainly indicative, we believe, of the large unmet need spurred by the New England Journal, but also by the physician interest now, and we intend to continue down this path.

是的。安娜貝爾，你的問題的第二部分是關於合作的。如您所知，這項資產完全不受任何限制，這很好。鑑於我們在今年年初制定的策略重點，我們有足夠的現金到 26 年初完成所有關鍵的臨床專案。所以現在，我們的目的是繼續開發 NP。正如您所說，我們對快速入學的情況感到非常興奮。我們相信，這無疑顯示了《新英格蘭雜誌》所激發的巨大未滿足需求，也是醫生現在的興趣，我們打算繼續沿著這條道路前進。

Okay. And if I could just follow up with one question for Jo. I know right now it's BD -- is this was there ever any thought to exploring the once daily schedule for this or it was never an option in any other (multiple speakers)

好的。我是否可以繼續問喬一個問題？我知道現在這是 BD——有沒有想過探索每天一次的時間表，或者在任何其他情況下都沒有這個選擇（多位發言者）

Yeah, good question, Annabel. As you know, the drug is predominantly excreted by the kidneys and based on the PK profile with the healthy patient population, twice daily is what is needed for this patient population. So it'll remain as a BD dose.

是的，安娜貝爾，問得好。如您所知，該藥物主要透過腎臟排泄，根據健康患者群體的 PK 特徵，該患者群體每天需要服用兩次。因此它將保留為 BD 劑量。

Okay. Got it. Thank you.

好的。知道了。謝謝。

(technical difficulty)

（技術難度）

Joseph Stringer, Needham & Company.

約瑟夫·斯金格，Needham & Company。

Hi. Thanks for taking our questions. Just a few on the expectations on the Part A readout. In the Phase 2A NP trial at the 2 mg dose on that key efficacy endpoint, the four-point responder analysis that we gave, you had around, I think it was 41% response for KORSUVA, and around 18% for placebo. So I guess is this what you consider a reasonable bar for success for -- and what you'd consider a win when the Part A data come out? And what gives you confidence that you can replicate this data in Part A?

你好。感謝您回答我們的問題。關於 A 部分讀數的期望只有幾點。在 2A 期 NP 試驗中，以 2 毫克劑量針對該關鍵療效終點進行研究時，我們給出的四點反應者分析顯示，我認為 KORSUVA 的反應率為 41%，安慰劑的反應率為 18% 左右。所以我想，這是您認為成功的合理標準嗎？當 A 部分數據出來時，您會認為這是勝利嗎？是什麼讓您有信心可以在 A 部分複製這些資料？

Yes, Jo (multiple speakers)

是的，喬（多位發言者）

Yeah. Thanks, Joey. And so yeah, we were incredibly pleased with the data we got from concept. And we do have to keep in mind that the study now has slightly different design in that we have three active arms versus one placebo. So the three-to-one randomization -- mostly sites as well, greater awareness through the New England Journal as well as our late-breaker. So we anticipate that the placebo response may be slightly higher. We still expect within the same range, but likely a little bit higher than what we've seen. So we have to take all of that into account when setting our expectations for the Part A.

是的。謝謝，喬伊。是的，我們對從概念中獲得的數據感到非常滿意。我們必須記住，現在的研究設計略有不同，我們有三個活性組和一個安慰劑組。因此，三比一的隨機化——大多數網站也是如此，透過《新英格蘭雜誌》和我們的最新消息提高了知名度。因此我們預期安慰劑反應可能會略高一些。我們仍然期望在同一範圍內，但可能比我們看到的要高一點。因此，我們在設定對 A 部分的期望時必須考慮到所有這些因素。

So with that, what we hope to see is that we do have separation with one of the doses from placebo. Remember that this has not been powered to show statistical significance versus placebo. Really, we're aiming to see separation and to be able to select the dose that demonstrates the most favorable benefit risk profile. It is really our aim to be able to move forward into our pivotal program. So that's what we hope to see.

因此，我們希望看到的是，我們確實將其中一種劑量與安慰劑區分開來。請記住，這並不能顯示出與安慰劑相比的統計意義。實際上，我們的目標是看到分離並能夠選擇表現出最有利的效益風險狀況的劑量。我們的目標確實是能夠推進我們的關鍵計劃。這就是我們希望看到的。

Great. Thank you for taking our questions.

偉大的。感謝您回答我們的問題。

Thanks, Joey.

謝謝，喬伊。

Dennis Ding, Jefferies.

丹尼斯丁，傑富瑞。

Hi. Thanks for taking our questions. If we can ask two questions on the NP data in Q3. You made comments earlier around expecting placebo effect to be a little bit higher than we have seen previously; were there any changes to the inclusion-exclusion criteria? Or what exactly drove that comment?

你好。感謝您回答我們的問題。如果我們可以針對 Q3 中的 NP 數據提出兩個問題。您之前曾評論說，安慰劑效應預計會比我們之前看到的要高一點；納入排除標準有任何變化嗎？或者究竟是什麼促使了你發表這樣的評論？

And then number two, around quality of life in your previous Phase 2, it seems like it's just getting better, but doesn't really have any impact on quality of life. Can you help frame that for us? And will you be measuring that as well in the upcoming data? Thank you.

第二，關於您之前第二階段的生活質量，看起來只是在變好，但實際上並沒有對生活品質產生任何影響。您能幫我們構思一下嗎？您是否也會在即將公佈的數據中對此進行測量？謝謝。

Yeah. So my comment to -- and thank you, Dennis. My comments regarding placebo was not due to any design elements in this Part A program. The design is pretty much the same as what we had for comfort. But as I mentioned, and I'll just reiterate the key factors that may contribute to a higher placebo. These are three-to-one randomization. So patients may feel that they are on active when they're on a placebo arm. That's different to what we had before, it was one-to-one.

是的。所以我的評論是——謝謝你，丹尼斯。我對安慰劑的評論並不是源自於 A 部分計畫中的任何設計元素。設計與我們為舒適而設計的設計幾乎相同。但正如我所提到的，我只想重申可能導致安慰劑效應更高的關鍵因素。這些是三比一的隨機化。因此，患者在接受安慰劑治療時可能會感覺自己處於活躍狀態。這與我們以前的做法不同，以前是一對一的。

This is a larger study with more study sites. So they naturally -- naturally is variability when you have more sites included. And then, of course the greater win, so if you take all those factors into account, we are anticipating that the placebo response will be slightly higher. So that's where that comment came from.

這是一項規模更大的研究，涉及更多的研究地點。因此，當你包含更多網站時，它們自然而然地就會變得多樣化。然後，當然是更大的勝利，所以如果考慮到所有這些因素，我們預計安慰劑反應會略高一些。這就是那條評論的由來。

And then regarding your second question, regarding quality of life and impact on quality of life. Compared with the first time we -- anyone had conducted a robust randomized study, and we're still trying to understand what quality of life endpoints are most appropriate for this NP patient population.

然後關於你的第二個問題，關於生活品質及其對生活品質的影響。與我們第一次進行的強有力的隨機研究相比，我們仍在試圖了解哪些生活品質終點最適合該 NP 患者群體。

And so, we still navigate that. We're still navigating through that and understanding what that is. They -- the tools that are used for other dermatological conditions, not necessarily -- are not necessarily relevant to NP. And that's what we understood from our Phase 2 data. And that's what we continue to work through as we move forward to our pivotal program.

因此，我們仍在探索這一方向。我們仍在探索並理解它是什麼。它們——用於治療其他皮膚病的工具，不一定——與 NP 不一定相關。這就是我們從第二階段數據中了解到的。這正是我們在推進關鍵計畫時將繼續努力的方向。

Thank you.

謝謝。

[Kyle Kwan], Canaccord Genuity.

[Kyle Kwan]，Canaccord Genuity。

Hi, this is Kyle Kwan for Sumant. Two questions related -- the first is regarding the readout happening in 3Q. Are you guys planning on disclosing any granular details on the safety of the different doses? And then second question is on the highest dose. What are the safety expectations you're expecting? And what are potential limitations? thanks.

大家好，我是 Sumant 的 Kyle Kwan。兩個相關問題－第一個問題與第三季的讀數有關。你們打算揭露有關不同劑量安全性的詳細資訊嗎？第二個問題是關於最高劑量。您對安全有何期望？潛在的限制是什麼？謝謝。

Hey, Scott. Well, the first one, yeah. We're going to disclose top line efficacy and safety results in Q3 that will be with the Part A readout. So the first answer to your question is yes, we will be disclosing top-line efficacy and safety. And the second part, Jo, I'll turn it to you.

嘿，斯科特。嗯，第一個，是的。我們將在第三季公佈與 A 部分讀數一起發布的頂級功效和安全性結果。所以對你的問題的第一個答案是肯定的，我們將揭露最重要的功效和安全性。喬，第二部分我交給你。

Yeah. And just to add with the topline safety. To what we typically present -- so your adverse events, most common discontinuations, so just typical safety data. And then your second question regarding the highest dose and expectations. With the highest dose at the 2 milligram twice daily, which was used in our KOMFORT study. And so we would anticipate a similar readout of the safety as we saw there. And in fact, that remains very consistent with what we've seen throughout all our programs with AP and with NP. So we feel very comfortable with that profile. And it's a very acceptable one.

是的。並且僅添加頂級安全性。我們通常會呈現的是您的不良事件、最常見的停藥情況，因此只是典型的安全資料。然後你的第二個問題是關於最高劑量和期望。最高劑量為每天兩次，每次 2 毫克，這是我們在 KOMFORT 研究中採用的劑量。因此，我們預計會出現與我們在那裡看到的類似的安全讀數。事實上，這與我們在所有 AP 和 NP 項目中看到的情況非常一致。因此，我們對該簡介感到非常滿意。這是非常可以接受的。

Of course, you've got two lower doses. And so the expectation is that the tolerability may be better with the lower doses. But I want to reiterate that the highest dose was a very good profile. And so we see the same. We'll be very pleased with it.

當然，你有兩種較低的劑量。因此，預期較低劑量的耐受性可能會更好。但我想重申，最高劑量的效果非常好。我們看到的也是同樣的情況。我們會非常高興。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

Hey, there. Kind of wanted to switch gears and dig into your comments about being a core development company. I guess with that in mind, just looking away from NP, do you have any thoughts on other potential settings for oral DFK I guess if we're in a perfect world where resources weren't an issue?

嘿。有點想換個話題，深入探討你關於成為核心開發公司的評論。我想考慮到這一點，只是把目光從 NP 移開，如果我們處在一個資源不是問題的完美世界中，您對口服 DFK 的其他潛在設置有什麼想法嗎？

And then secondly, with the cash runway being what it is to '26, is there anything early stage out there that you might be looking at that you might be mining the world for, so to speak, in terms of bringing anything in just to think of the business beyond oral DFK? And just how are you thinking about biz dev just in general? Thank you.

其次，隨著現金流到 26 年的到來，您是否正在考慮在早期階段開展什麼業務，或者說，您是否正在挖掘世界上的什麼東西，是否正在引入任何東西，只是為了考慮口服 DFK 以外的業務？那麼，您對於業務開發的整體看法是怎樣的呢？謝謝。

Yeah, thanks, David. Great to hear from you. So the first part of your question around are we looking at other things? I mean, our goal with our prioritization in January was to focus our cash and resources on neuropathic pruritus i.e., notalgia paresthetica. We want to be really disciplined there. And what we're able to do now is fund that program through a succession of key milestones, which is great. So we're -- that's our sole focus right now.

是的，謝謝，大衛。很高興收到你的來信。那麼你的問題的第一部分是關於我們是否在考慮其他事情？我的意思是，我們在一月份確定的優先目標是將我們的資金和資源集中在神經性搔癢症，即背部感覺異常痛。我們希望在那裡真正做到紀律嚴明。我們現在能夠做的是透過一系列關鍵里程碑來為該計劃提供資金，這很棒。所以——這是我們目前唯一的關注點。

You asked the question of biz dev. I mean, certainly we do look at assets. And our focused strategy gives us options to potentially leverage the value inflection points in the NP program to add more value to the company in due course.

您問的是業務開發的問題。我的意思是，我們確實會關注資產。我們的重點策略為我們提供了選擇，可以利用 NP 計劃中的價值拐點在適當的時候為公司增加更多價值。

So right now, again, we have our streamlined organization aligned to the strategy of preserving our cash to make sure we can execute the NP program with the cash we have. That's our focus.

因此，現在，我們再次精簡了組織結構，以符合保留現金的策略，確保我們能夠利用現有現金執行 NP 計劃。這就是我們的重點。

Okay. Helpful. Thanks.

好的。很有幫助。謝謝。

Thanks, David.

謝謝，大衛。

Thank you. I would now like to turn the conference back to Chris Posner for closing remarks. Sir?

謝謝。現在我想請克里斯·波斯納 (Chris Posner) 致閉幕詞。先生？

Yeah, thank you very much. And thanks again, everyone, for joining us today. And I wish everyone a great afternoon. With that, I'll close the call.

是的，非常感謝。再次感謝大家今天的參與。祝大家下午愉快。就這樣，我結束了通話。

This concludes today's conference call. Thank you for participating and you may now disconnect.

今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。