Nektar Therapeutics (NKTR) 2025 Q3 法說會逐字稿

Hello, and thank you for standing by. Welcome to the Nektar Therapeutics third quarter 2025 financial results conference call. (Operator Instructions)

您好，感謝您的耐心等待。歡迎參加Nektar Therapeutics 2025年第三季財務業績電話會議。（操作說明）

Please be advised that today's conference is being recorded. I would now like to hand the conference over to Vivian Wu from Nektar Investor Relations to kick things off. Please go ahead.

請注意，今天的會議正在錄影。現在我謹將會議交給Nektar投資者關係部的Vivian Wu，由她來開始會議。請繼續。

Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. Today you will hear from Howard Robin, our President and Chief Executive Officer; Dr. Jonathan Zalevsky, our Chief Research and Development Officer; and Sandra Gardiner, our Chief Financial Officer. Dr. Mary Tagliaferri, our Chief Medical Officer, will also be available during the question-and-answer session.

謝謝你，克麗絲塔爾，大家下午好。感謝您今天蒞臨。今天您將聽到我們總裁​​兼執行長霍華德·羅賓、首席研發官喬納森·扎列夫斯基博士和財務長桑德拉·加德納的演講。我們的首席醫療官瑪麗·塔利亞費裡博士也將在問答環節中出席。

On today's call, we expect to make forward-looking statements regarding our business, including statements regarding the therapeutic potential of and future development plans for rezpegaldesleukin, the timing and plans for future clinical data presentations, and other statements regarding the future of our business. Because forward-looking statements relate to the future, they're subject to uncertainties and risks that are difficult to predict, and many of which are outside of our control. Our actual results may differ materially from these statements.

在今天的電話會議上，我們預計將就我們的業務發表前瞻性聲明，包括關於 rezpegaldesleukin 的治療潛力和未來發展計劃的聲明、未來臨床數據展示的時間和計劃，以及其他關於我們業務未來的聲明。由於前瞻性陳述涉及未來，因此存在難以預測的不確定性和風險，其中許多是我們無法控制的。我們的實際結果可能與這些說法有重大差異。

Important risks and uncertainties are set forth in our latest Form 10-K available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. The webcast of this call will be available on the IR page on Nektar's website at nektar.com. With that said, I would like to hand the call over to our President and CEO, Howard Robin.

重要風險和不確定性已列於我們最新的10-K表格中，表格可在sec.gov網站查閱。我們不承擔因新資訊、未來發展或其他原因而更新任何前瞻性陳述的義務。本次電話會議的網路直播將在Nektar公司網站nektar.com的投資者關係頁面上提供。接下來，我將把電話會議交給我們的總裁兼執行長霍華德羅賓。

Thank you, Vivian, and good afternoon, everyone. Before I start with remarks for the quarter, I'd like to take a minute to welcome Dr. Mary Tagliaferri back to the company, who has recently rejoined us as Chief Medical Officer after a need to step away for personal reasons earlier this year. Mary was instrumental in the design and execution of our successful Phase 2 program in atopic dermatitis, and we are so fortunate that she has now rejoined us as we prepare for the initiation of the Phase 3 program next year.

謝謝你，薇薇安，大家下午好。在開始對本季進行總結發言之前，我想花一分鐘時間歡迎瑪麗·塔利亞費裡博士重返公司。她因個人原因於今年稍早離職，最近已重新加入我們擔任首席醫療官。Mary 在我們成功開展的異位性皮膚炎 2 期計畫的規劃和執行中發揮了重要作用，我們非常幸運，她現在又重新加入我們，為明年啟動 3 期計畫做準備。

I'd also like to thank Brian Kotzin for his help serving as the interim CMO during the period. Brian has worked with us for nearly 10 years, and we are grateful that he will continue to serve as a medical consultant.

我還要感謝 Brian Kotzin 在此期間擔任臨時首席行銷長所給予的幫助。Brian 與我們共事近 10 年，我們非常感謝他將繼續擔任醫療顧問。

This quarter and year-to-date we've remained laser-focused on pursuing regulatory T cell science across our pipeline and preparing to advance our lead program, rezpegaldesleukin, also known as REZPEG, into Phase 3 development. Our pipeline programs are focused on stimulating Tregs in different ways to restore the proper balance between T effector cells and T regulatory cells and achieve homeostasis in the immune system.

本季及今年以來，我們始終專注於推進整個研發管線中的調節性 T 細胞科學，並準備將我們的領先專案 rezpegaldesleukin（也稱為 REZPEG）推進到 3 期開發階段。我們的研發管線計畫專注於以不同的方式刺激 Treg 細胞，以恢復 T 效應細胞和 T 調節細胞之間的適當平衡，從而實現免疫系統的穩態。

The data in atopic dermatitis reported in June and presented at EADV 2025 for REZPEG represented a powerful translation of the scientific discoveries that led to an understanding of the importance of Tregs and to the first demonstration of their clear clinical efficacy in autoimmune disease. The Nobel Prize in Physiology or Medicine was recently awarded for these discoveries that established FoxP3-positive Tregs as key enforcers of immune tolerance. We're very humbled that the Nobel Committee included the publication of the Phase 1b data for REZPEG in atopic dermatitis and psoriasis as support in the background documents for this award.

6 月報告的 REZPEG 在異位性皮膚炎方面的數據，並在 2025 年歐洲皮膚病與病毒學會 (EADV) 會議上公佈，有力地轉化了科學發現，這些發現使人們了解了 Treg 的重要性，並首次證明了 Treg 在自身免疫性疾病中的明確臨床療效。最近，諾貝爾生理學或醫學獎授予了這些發現，這些發現確立了 FoxP3 陽性 Treg 細胞作為免疫耐受的關鍵執行者。我們非常榮幸諾貝爾委員會將 REZPEG 在異位性皮膚炎和銀屑病中的 1b 期數據發表作為該獎項背景文件的支持材料。

The recognition of REZPEG was truly an honor and speaks to the journey that our Nektar scientists and clinicians have traveled over the years to turn important scientific discoveries into real potential medicines for patients.

REZPEG 獲得認可真是莫大的榮幸，這體現了我們 Nektar 的科學家和臨床醫生多年來為將重要的科學發現轉化為真正有潛力造福患者的藥物所付出的努力。

Our approach with REZPEG and stimulation of Tregs is highly differentiated in the field. We believe this is why we've been able to uniquely generate meaningful and robust clinical data that clearly support continued development of this novel modality.

我們採用 REZPEG 和刺激 Tregs 的方法在該領域具有高度差異化。我們認為，正因如此，我們才能獨特地產生有意義且可靠的臨床數據，這些數據明確支持繼續開發這種新型療法。

REZPEG was designed to closely mimic the way Tregs in our own immune system work to resolve inflammation. Its construct gets closest to emulating natural human biology, achieving this through IL-2 agonism with native sequence IL-2 receptor interactions and a validated chemistry approach, pegylation, that has led to over two dozen approved biologics.

REZPEG 的設計旨在密切模擬我們自體免疫系統中 Treg 細胞的工作原理，從而消除發炎。它的結構最接近模擬天然的人類生物學，透過 IL-2 激動劑與天然序列 IL-2 受體相互作用以及經過驗證的化學方法（聚乙二醇化）來實現這一點，該方法已經產生了二十多種獲批的生物製劑。

At the 2025 EADV Congress in September, we presented compelling results from the 16-week induction period of the 400-patient RESOLVE-AD study of REZPEG in moderate to severe atopic dermatitis. These data showcased the clinical differentiation that can be achieved with this novel MOA, and JZ will touch on this later in the call. And this weekend, at the 2025 American College of Allergy, Asthma and Immunology annual scientific meeting, we will present data from a pre-planned analysis of atopic dermatitis patients from the RESOLVE-AD study who also had a history of asthma. These data provide further basis for differentiation of REZPEG.

在 2025 年 9 月舉行的 EADV 大會上，我們展示了 REZPEG 治療中度至重度異位性皮膚炎的 400 名患者 RESOLVE-AD 研究的 16 週誘導期的令人信服的結果。這些數據展示了這種新型作用機制可以實現的臨床差異化，JZ 將在稍後的電話會議中談到這一點。本週末，在 2025 年美國過敏、氣喘和免疫學會年會上，我們將展示 RESOLVE-AD 研究中患有異位性皮膚炎且有氣喘病史的患者預先計劃的分析數據。這些數據為 REZPEG 的區分提供了進一步的依據。

Recently approved and in-development IL-13 selective pathway blockers and OX40 pathway blockers have shown limited potential to help the asthma symptoms in patients with both atopic dermatitis and asthma, which is a comorbidity in 25% of all atopic dermatitis patients. And so we're very excited about these new data.

最近核准和正在研發的IL-13選擇性通路阻斷劑和OX40通路阻斷劑在幫助同時患有異位性皮膚炎和氣喘的患者的氣喘症狀方面顯示出有限的潛力，而這種合併症在所有異位性皮膚炎患者中佔25%。因此，我們對這些新數據感到非常興奮。

In Q1, we will present 52-week maintenance and escape arm data from the RESOLVE-AD study in atopic dermatitis. The maintenance arm data in particular will be an important look at continued treatment with REZPEG in patients who have established an EASI-50 response at the end of 16 weeks of induction treatment.

第一季度，我們將公佈 RESOLVE-AD 研究在異位性皮膚炎治療中 52 週的維持治療和緩解治療數據。特別是維持治療組的數據，將對在 16 週誘導治療結束時達到 EASI-50 反應的患者繼續接受 REZPEG 治療進行重要的考察。

There remains a need for novel mechanisms beyond those available currently in the treatment landscape for atopic dermatitis patients. In the US, there are over 15 million people with moderate to severe atopic dermatitis, and fewer than 10% are receiving biologic treatments for this chronic skin disorder, with many patients not responding well to the existing agents. We believe that this market will grow with the adoption of novel mechanisms, as was seen with the introduction of new mechanisms in the evolution of the psoriasis market.

對於異位性皮膚炎患者而言，目前治療領域仍需要新的治療機制。在美國，有超過 1500 萬人患有中度至重度異位性皮膚炎，但只有不到 10% 的人接受生物製劑治療這種慢性皮膚病，而且許多患者對現有藥物的反應並不好。我們相信，隨著新機制的採用，這個市場將會成長，就像在銀屑病市場發展過程中引入新機制一樣。

We expect to hold an end-of-Phase 2 meeting with the FDA before the end of this year to review our Phase 3 plans for REZPEG in moderate to severe atopic dermatitis. Importantly, in December, we plan to present the topline results from the Phase 2b RESOLVE-AA study in patients with alopecia areata. This study enrolled approximately 90 patients with severe to very severe alopecia areata. With strong Phase 2 results in the dermatological setting of atopic dermatitis, we're optimistic about the second dermatological setting for REZPEG.

我們預計將在今年年底前與 FDA 舉行 2 期臨床試驗結束會議，以審查 REZPEG 治療中重度異位性皮膚炎的 3 期臨床試驗計劃。重要的是，我們計劃在 12 月公佈針對斑禿患者的 2b 期 RESOLVE-AA 研究的主要結果。這項研究納入了約 90 名患有重度至極重度斑禿的患者。REZPEG 在異位性皮膚炎的皮膚病治療領域取得了強勁的 2 期療效，我們對 REZPEG 在第二個皮膚病治療領域的前景充滿信心。

Nearly 7 million people in the US have or will develop alopecia areata, and over a million of these patients have severe to very severe disease. According to the 2023 population-based cohort study. Patients with severe to very severe alopecia have limited treatment options. The only FDA-approved systemic treatments for alopecia areata are JAK inhibitors, which carry multiple well-known black box warnings and are associated with high relapse rates upon discontinuation.

美國有近 700 萬人患有或將患有斑禿，其中超過 100 萬患者病情嚴重或非常嚴重。根據 2023 年基於人群的隊列研究。重度至極重度脫髮患者的治療選擇有限。目前唯一獲得 FDA 批准的斑禿全身治療方法是 JAK 抑制劑，但這類藥物帶有多個眾所周知的黑框警告，並且停藥後復發率很高。

In a 2024 survey of 131 US-based board-certified dermatologists, a majority of physicians said they were uncomfortable prescribing a JAK inhibitor, and more than half of these physicians reported they would try alternative therapies prior to prescribing a JAK inhibitor. With this backdrop, REZPEG could be introduced as the first biologic in the setting of alopecia areata, representing an additional $1 billion market opportunity. And so we look forward to these upcoming results from the 36-week treatment period of the RESOLVE-AA study expected in December of this year.

在 2024 年對 131 位美國認證皮膚科醫生進行的一項調查中，大多數醫生表示他們不願意開立 JAK 抑制劑，超過一半的醫生表示，他們會在開立 JAK 抑制劑之前嘗試其他療法。在此背景下，REZPEG 有望成為首個用於治療斑禿的生物製劑，從而帶來額外的 10 億美元市場機會。因此，我們期待 RESOLVE-AA 研究 36 週治療期的結果，預計今年 12 月公佈。

In immunology, our partner TrialNet recently initiated the Phase 2 study of REZPEG in type 1 diabetes. This study, which is funded and sponsored by TrialNet, will evaluate REZPEG in new-onset stage 3 type 1 diabetes patients. JZ will update you on our other programs as well as our lead pipeline antibody, a TNFR2 agonist that has a unique tissue-specific Treg and Breg stimulator profile.

在免疫學領域，我們的合作夥伴 TrialNet 最近啟動了 REZPEG 治療第 1 型糖尿病的第 2 期研究。這項研究由 TrialNet 資助和贊助，將評估 REZPEG 對新發 3 期 1 型糖尿病患者的療效。JZ 將向您介紹我們的其他項目以及我們的領先研發管線抗體，這是一種 TNFR2 激動劑，具有獨特的組織特異性 Treg 和 Breg 刺激劑特性。

Because of its monomeric activity, we're now building a bispecific program based upon this mechanism which combines it with validated antibody targets in immunology. Our goal is to advance one of these antibody programs into the clinic next year. With that, I'd like to turn the call over to JZ to review more details on REZPEG's ongoing Phase 2b studies and our early pipeline programs. JZ?

由於其單體活性，我們現在正在基於此機制建立雙特異性抗體程序，並將其與免疫學中已驗證的抗體目標結合。我們的目標是明年將其中一個抗體計畫推進到臨床試驗階段。接下來，我想把電話交給 JZ，讓他詳細介紹 REZPEG 正在進行的 2b 期研究和我們早期的研發管線計畫。JZ？

Thanks, Howard, and thank you everyone on the call for joining us today. To begin, I'll remind you that earlier this year, the RESOLVE-AD Phase 2b results demonstrated the promise of Nektar's novel approach to the IL-2 pathway. The global study randomized 393 patients with moderate to severe atopic dermatitis to receive subcutaneous treatment with three doses of REZPEG, a high dose of 24 mcg per kilogram every 2 weeks, a middle dose of 18 mcg per kilogram every 2 weeks, and a low dose of 24 mcg per kilogram every 4 weeks, or placebo every 2 weeks for an induction period of 16 weeks.

謝謝霍華德，也謝謝今天所有參加電話會議的朋友。首先，我要提醒大家，今年早些時候，RESOLVE-AD 2b 期試驗結果證明了 Nektar 公司針對 IL-2 通路的新方法的前景。這項全球研究隨機選取了 393 名中度至重度異位性皮膚炎患者，讓他們接受皮下注射三種劑量的 REZPEG 治療：高劑量每 2 週每公斤 24 微克，中劑量每 2 週每公斤 18 微克，低劑量每 4 週每公斤 24 微克；或接受安慰劑治療，每 2 週為 2 週。

Following week 16, REZPEG-treated patients who achieved EASI reductions of 50% or greater were re-randomized to continue at the same dose level on a Q4-week or Q12-week regimen for an additional 36-week maintenance period.

在第 16 週之後，接受 REZPEG 治療且 EASI 降低 50% 或以上的患者被重新隨機分組，繼續以相同的劑量水平接受每 4 週或每 12 週一次的治療方案，以進行額外的 36 週維持治療。

In our June data disclosure, we reported that the study achieved statistical significance on the primary endpoint at week 16 for mean percent change in EASI score from baseline for all REZPEG arms versus placebo. And the study achieved statistical significance for key secondary endpoints at week 16 of disease reduction, including EASI-75, EASI-90, HNRS, the vIGA-AD, and BSA.

我們在 6 月的數據揭露中報告稱，該研究在第 16 週的主要終點上達到了統計學意義，所有 REZPEG 組與安慰劑組相比，EASI 評分從基線到平均百分比變化均有所提高。該研究在第 16 週疾病減輕的關鍵次要終點方面達到了統計學意義，包括 EASI-75、EASI-90、HNRS、vIGA-AD 和 BSA。

Additionally, we have yet to see a plateau in the efficacy response in the REZPEG treatment arms. This study is currently ongoing with two additional upcoming data readouts that Howard mentioned. The first will be the 36-week maintenance study results which compare treatment with REZPEG at either 1-month or 3-month dosing intervals out to a full year, which would be the intended maintenance-based dosing regimens following the 16-week induction period. And the second readout will be the 1-year off-treatment data expected in the beginning of 2027, which will measure the potential remittive effect of REZPEG in atopic dermatitis.

此外，我們尚未看到 REZPEG 治療組的療效反應達到平台期。這項研究目前仍在進行中，正如霍華德所提到的，還有兩項數據即將公佈。首先將發表為期 36 週的維持治療研究結果，該研究將比較 REZPEG 以 1 個月或 3 個月的給藥間隔進行治療長達一年的效果，這將是 16 週誘導期後預期的維持治療給藥方案。第二個讀數將是預計在 2027 年初公佈的 1 年停藥數據，該數據將衡量 REZPEG 對異位性皮膚炎的潛在緩解作用。

In the meantime, we continue to add to the compelling data set from the RESOLVE-AD study, including the data we shared from the escape arm of the trial at this year's EADV Congress. As a reminder, the study design allowed for patients who originally received placebo in the 16-week induction period and achieved less than EASI-50 at week 16 to enter into an open-label treatment escape arm to receive the high-dose REZPEG regimen for a treatment period of up to 36 weeks. The data presented at EADV demonstrated a deepening of responses in these patients with continuous treatment with REZPEG and support a 24-week induction period for our Phase 3 program.

同時，我們繼續為 RESOLVE-AD 研究的引人注目的數據集添加數據，包括我們在今年的 EADV 大會上分享的試驗逃脫組的數據。提醒一下，研究設計允許最初在 16 週的誘導期內接受安慰劑治療，並在第 16 週達到 EASI-50 以下的患者進入開放標籤治療逃脫組，接受高劑量 REZPEG 方案治療，治療期最長可達 36 週。在 EADV 會議上公佈的數據表明，這些患者持續接受 REZPEG 治療後，療效得到加深，並支持我們 3 期計畫採用 24 週的誘導期。

As Howard stated earlier, we are presenting additional data in patients with asthma from RESOLVE-AD in a late-breaking oral presentation at the ACAAI meeting being held in Orlando, Florida this weekend. In addition to the asthma data that I'll discuss in a moment, that presentation will also give an update on the placebo crossover data, where now all but one patient have crossed 24 weeks of treatment with 24 mcg per kilogram REZPEG Q2 weeks. We will also cover additional endpoints such as EASI-90 and HNRS. In addition, the presentation will show a forest plot demonstrating the consistency of REZPEG efficacy across multiple subgroups. This important finding prepares us for Phase 3.

正如 Howard 之前所說，我們將在本週末於佛羅裡達州奧蘭多舉行的 ACAAI 會議上，以最新口頭報告的形式，展示 RESOLVE-AD 研究中哮喘患者的更多數據。除了我稍後將要討論的氣喘數據之外，該報告還將更新安慰劑交叉數據，目前除一名患者外，所有患者均已接受每公斤體重 24 微克 REZPEG 每 2 週治療 24 週。我們也將介紹其他終點指標，例如 EASI-90 和 HNRS。此外，簡報還將展示一張森林圖，以證明 REZPEG 在多個亞組中的療效一致性。這項重要發現為我們進入第三階段做好了準備。

Given that 1 in 4 patients with atopic dermatitis also have asthma, we designed the study in advance to evaluate its effect on symptoms of asthma using the validated 5-point asthma control questionnaire, also known as the ACQ-5. And these data include a pre-specified exploratory endpoint for the subset of patients in RESOLVE-AD that also had asthma, including those with moderate and uncontrolled asthma at baseline.

鑑於 1/4 的異位性皮膚炎患者同時患有氣喘，我們預先設計了這項研究，以使用經過驗證的 5 分氣喘控制問卷（也稱為 ACQ-5）來評估其對氣喘症狀的影響。這些數據包括 RESOLVE-AD 中患有氣喘的患者子集的預先指定的探索性終點，其中包括基線時患有中度氣喘和未控制氣喘的患者。

The ability to improve comorbid conditions is a substantial factor in clinical treatment decisions for atopic dermatitis and could expand the potential market opportunity for REZPEG in this setting. We know that beyond Dupixent, neither lebrikizumab nor rilzabrutinib has been able to show an improvement in asthma symptoms in patients with atopic dermatitis. And this extends to the OX40 programs in late-stage development as well.

改善合併症的能力是異位性皮膚炎臨床治療決策中的重要因素，並且可能會擴大 REZPEG 在此領域的潛在市場機會。我們知道，除了 Dupixent 之外，lebrikizumab 和 rilzabrutinib 都未能改善異位性皮膚炎患者的氣喘症狀。這也適用於處於後期開發階段的 OX40 專案。

And now turning to alopecia areata, we are on track and look forward to reporting data from the Phase 2b study in December of this year. A positive outcome here would reinforce the potential of REZPEG to provide a completely new treatment paradigm for patients with chronic dermatological diseases.

現在來說說斑禿，我們進展順利，期待今年 12 月公佈 2b 期研究的數據。如果取得正面成果，將進一步證明 REZPEG 有潛力為慢性皮膚病患者提供一種全新的治療模式。

The RESOLVE-AA trial was initiated in March 2024. A total of 94 patients with severe to very severe alopecia areata who have not received a JAK inhibitor or other biologic were randomized to two different dose regimens of REZPEG, 24 micrograms per kilogram every 2 weeks and 18 mcg per kilogram every 2 weeks, or placebo. Patients were recruited across approximately 30 sites globally, with two-thirds of patients enrolled in Europe and the rest from North America.

RESOLVE-AA 試驗於 2024 年 3 月啟動。總共 94 名患有嚴重至極嚴重斑禿且未接受過 JAK 抑制劑或其他生物製劑治療的患者被隨機分配到兩種不同的 REZPEG 劑量方案組，分別為每 2 週每公斤 24 微克和每 2 週每公斤 18 微克，或安慰劑組。患者招募工作在全球約 30 個地點進行，其中三分之二的患者來自歐洲，其餘患者來自北美。

As a reminder, patient eligibility for the study was determined using the SALT score, both at screening and randomization. Patients who experienced an unstable course of alopecia areata over the last 6 months per investigator assessment were excluded from the study, and patients with diffuse alopecia and other forms of alopecia were also excluded. The primary efficacy endpoint of this study will evaluate mean percent change in the Severity of Alopecia Tool, or SALT score, at the end of the 36-week induction period.

提醒一下，患者是否符合研究條件是根據 SALT 評分確定的，無論是在篩選還是隨機分組時。根據研究者的評估，在過去 6 個月中出現斑禿病情不穩定的患者被排除在研究之外，患有瀰漫性脫髮和其他類型脫髮的患者也被排除在外。本研究的主要療效終點將評估在 36 週誘導期結束時，脫髮嚴重程度工具 (SALT) 評分的平均百分比變化。

Secondary endpoints include proportion of patients achieving SALT 20, which is an absolute SALT score of less than or equal to 20, mean percent improvement in SALT score at other assessed time points, and proportion of participants with greater than or equal to 50% reduction in SALT score at week 36 and other assessed time points. Importantly, SALT 20, the responder analysis, is also the established regulatory endpoint for Phase 3 trials.

次要終點包括達到 SALT 20 的患者比例（即 SALT 絕對評分小於或等於 20 分）、其他評估時間點 SALT 評分的平均改善百分比，以及在第 36 週和其他評估時間點 SALT 評分降低 50% 或以上的參與者比例。重要的是，SALT 20（應答者分析）也是第 3 期試驗的既定監管終點。

As Howard mentioned, the only available systemic therapies that are FDA-approved for the treatment of alopecia areata are JAK inhibitors, which contain a number of black box warnings, and many patients experience hair loss after treatment cessation. With the limited treatment options available in alopecia areata, we believe there's opportunity for a novel mechanism like REZPEG, especially when the therapeutic is shown to be safe and well tolerated.

正如霍華德所提到的，目前唯一獲得 FDA 批准用於治療斑禿的全身療法是 JAK 抑制劑，但這些藥物包含許多黑框警告，許多患者在停止治療後會出現脫髮。由於斑禿的治療選擇有限，我們認為像 REZPEG 這樣的新機制有機會，尤其是在證明該療法安全且耐受性良好的情況下。

When comparing the outcomes from RESOLVE-AA to the approved JAKs, we see low-dose ritlecitinib as the appropriate benchmark. In its two Phase 3 trials, the approved 2 mg dose of ritlecitinib showed that 15% to 16% of patients achieved SALT 20 on a placebo-adjusted basis at week 36, and the mean improvement in SALT scores from baseline was 24% to 26% on a placebo-adjusted basis.

將 RESOLVE-AA 的結果與已批准的 JAK 藥物進行比較時，我們認為低劑量利特西替尼是合適的基準。在兩項 3 期試驗中，獲準的 2 毫克劑量利特西替尼在第 36 週時，15% 至 16% 的患者在安慰劑調整的基礎上達到了 SALT 20，並且 SALT 評分從基線到平均改善了 24% 至 26%（以安慰劑調整為基礎）。

Note that the placebo response rate in these trials is relatively low at 3% to 5% for the SALT 20 endpoint and 4% to 9% on the mean reduction endpoint. Because of our differentiated mechanism of action compared to the JAK inhibitors and our safety profile, we see a very clear market opportunity for REZPEG in alopecia areata if REZPEG achieves these benchmarks.

請注意，這些試驗中安慰劑反應率相對較低，SALT 20 終點為 3% 至 5%，平均減少終點為 4% 至 9%。由於我們與 JAK 抑制劑相比具有不同的作用機制和安全性，如果 REZPEG 達到這些標準，我們認為 REZPEG 在斑禿治療領域具有非常明顯的市場機會。

We look forward to sharing the topline data from the 36-week treatment period of the RESOLVE-AA study in December and defining the potential for REZPEG in this new indication. Similar to atopic dermatitis, with positive results from Phase 2b, we would move very quickly into Phase 3 preparations, taking advantage of our fast-track designation in the alopecia areata indication.

我們期待在 12 月分享 RESOLVE-AA 研究 36 週治療期的主要數據，並確定 REZPEG 在該新適應症中的潛力。與異位性皮膚炎類似，如果 2b 期試驗取得積極結果，我們很快就會進入 3 期試驗階段，利用我們在斑禿適應症方面獲得的快速通道資格。

A quick few words on type 1 diabetes, another autoimmune disease where REZPEG has great potential as a T regulatory mechanism. We believe REZPEG can potentially slow the progressive loss of insulin-producing beta cells, which are the target of the patient's overactive immune cells in this disease. As Howard mentioned, TrialNet has initiated and is funding an investigator-sponsored Phase 2 clinical trial evaluating REZPEG in 66 patients with new-onset type 1 diabetes.

簡單介紹一下第 1 型糖尿病，這是另一種自體免疫疾病，REZPEG 作為一種 T 調節機制具有很大的潛力。我們相信 REZPEG 有可能減緩胰島素分泌 β 細胞的進行性喪失，而這些 β 細胞正是這種疾病中患者過度活躍的免疫細胞的目標。正如霍華德所提到的，TrialNet 已經啟動並資助了一項由研究者發起的 2 期臨床試驗，該試驗評估 REZPEG 對 66 名新發 1 型糖尿病患者的療效。

Lastly, on our pipeline progression, NKTR-0165, our TNFR2 agonist, remains on track. This molecule has very high specificity for signaling through TNFR2 on Tregs to enhance and optimize their ability to regulate the immune system.

最後，關於我們的研發管線進展，我們的 TNFR2 激動劑 NKTR-0165 仍然按計劃進行。此分子對透過 Treg 細胞上的 TNFR2 訊號傳導具有非常高的特異性，可增強和優化 Treg 細胞調節免疫系統的能力。

NKTR-0165 has also shown that a strong signal can be generated through a single-arm monovalent antibody, making it a perfect candidate for inclusion in bispecific and trispecific constructs. Our goal is to advance one of these antibody programs into the clinic next year. We look forward to sharing more on these sophisticated antibody engineering programs in future earnings calls. And I'll now turn it over to Sandy for the financials. Sandy.

NKTR-0165 也表明，單臂單價抗體可以產生強烈的訊號，使其成為雙特異性和三特異性構建體的理想候選物。我們的目標是明年將其中一個抗體計畫推進到臨床試驗階段。我們期待在未來的財報電話會議上與大家分享更多關於這些先進的抗體工程項目的資訊。接下來我將把財務部分交給桑迪。沙。

Thank you, JZ, and good afternoon, everyone. On today's call, I'll briefly review our quarterly financials and share updates to our financial guidance for 2025. We ended the third quarter of 2025 with $270.2 million in cash and investments and with no debt on our balance sheet.

謝謝JZ，大家下午好。在今天的電話會議上，我將簡要回顧我們的季度財務狀況，並分享我們對 2025 年財務指引的最新資訊。截至 2025 年第三季末，我們擁有 2.702 億美元的現金和投資，資產負債表上沒有任何債務。

As discussed in our Q2 earnings call, this end-of-third-quarter cash balance includes the completion of the secondary public offering in July with net proceeds of approximately $107 million. It also includes additional net proceeds of $34.3 million we raised in September from our existing ATM facility.

正如我們在第二季財報電話會議上所討論的，第三季末的現金餘額包括7月完成的二次公開發行，淨收益約為1.07億美元。其中還包括我們在 9 月透過現有 ATM 設施籌集的 3,430 萬美元淨收益。

We now expect to end the year with approximately $240 million in cash and investments, up from our prior guidance of $100 million to $185 million. This increased year-end guidance also includes $38.3 million of net proceeds from additional sales of our ATM facility in October. Based upon our higher year-end cash balance, we are extending our cash runway guidance into the second quarter of 2027.

我們現在預計年底現金和投資約為 2.4 億美元，高於我們先前預期的 1 億美元至 1.85 億美元。此次上調後的年終業績預期還包括 10 月出售 ATM 設施所得的 3,830 萬美元淨收益。鑑於我們年末現金餘額較高，我們將現金儲備預期延長至 2027 年第二季。

Now turning to the income statement. Our non-cash royalty revenue was $11.5 million for the third quarter of 2025. We still expect our non-cash royalty revenue to total approximately $40 million for the full year. Our R&D expense was $27.3 million for the third quarter of 2025, and we still anticipate full-year R&D expense to range between $125 million and $130 million, including approximately $5 million to $10 million of non-cash depreciation and stock-based compensation expense.

現在來看損益表。2025年第三季度，我們的非現金特許權使用費收入為1,150萬美元。我們預計全年非現金版稅收入總額約為 4,000 萬美元。2025 年第三季度，我們的研發費用為 2,730 萬美元，我們仍然預計全年研發費用將在 1.25 億美元至 1.3 億美元之間，其中包括約 500 萬美元至 1,000 萬美元的非現金折舊和股票選擇權費用。

Our G&A expense was $16.1 million for the third quarter. We still expect G\&A for the full year of 2025 to be between $70 million and $75 million, including approximately $5 million to $10 million of non-cash depreciation and stock-based compensation expense.

第三季我們的管理費用為1,610萬美元。我們仍預計 2025 年全年的 G&A 費用將在 7,000 萬美元至 7,500 萬美元之間，其中包括約 500 萬美元至 1,000 萬美元的非現金折舊和股票選擇權費用。

Non-cash interest expense for the third quarter was $6 million, and we still expect non-cash interest expense for the full year to total approximately $20 million. Our non-cash loss from equity method investment was $500,000 in the third quarter of 2025, and we still expect non-cash loss of approximately $10 million for the full year 2025.

第三季非現金利息支出為 600 萬美元，我們仍然預期全年非現金利息支出總額約為 2,000 萬美元。2025 年第三季度，我們因權益法投資產生的非現金損失為 50 萬美元，我們仍然預計 2025 年全年非現金損失約為 1000 萬美元。

As an equity investor in Gannet BioChem, we have no commitment to contribute cash to Gannett. Our net loss for the third quarter was $35.5 million, or $1.87 basic and diluted net loss per share. And as I stated earlier, we now expect to end the year with approximately $240 million in cash and investments, with our cash runway extending into the second quarter of 2027.

作為 Gannet BioChem 的股權投資者，我們沒有義務向 Gannett 投入現金。第三季淨虧損為 3,550 萬美元，即每股基本及攤薄淨虧損 1.87 美元。正如我之前所說，我們現在預計到年底將擁有約 2.4 億美元的現金和投資，我們的現金儲備可以維持到 2027 年第二季。

Finally, as we head into our December data reporting, we intend to enter into a quiet period for the month of December until we report the topline results for the REZPEG alopecia study. And with that, we'll now open the call for questions. Operator.

最後，在我們即將發布 12 月數據報告之際，我們打算在 12 月進入一段平靜期，直到我們公佈 REZPEG 脫髮研究的主要結果。接下來，我們將開始接受提問。操作員。

(Operator Instructions) Yasmine Rahimi, Piper Sandler.

（操作說明）Yasmine Rahimi，Piper Sandler。

Hi, congrats on a great quarter. This is Dominic on for Yasmine Rahimi. We just had a quick question on the upcoming ACAAI data that will be presented. Could you help us understand what you hope to report in the presentation in patients with AD and asthma, and then moving forward, how would you expect this data to, I guess, impact development in asthma? Thank you.

您好，恭喜您本季業績優異。這是Dominic替Yasmine Rahimi報道。我們剛剛收到一個關於即將發布的ACAAI數據的簡短問題。您能否幫助我們理解您希望在報告中介紹的關於 AD 和氣喘患者的信息，以及您預計這些數據將如何影響氣喘的發展？謝謝。

Well, let me, I'll have JZ answer that, but I would tell you that at this point we're not pursuing an asthma indication. I think, however, it's important to recognize that in atopic dermatitis, the fact that we have an important drug that potentially solves that comorbidity issue is very exciting. And as I said earlier, 25% of the patients who have atopic dermatitis also have asthma as a comorbidity.

嗯，這個問題我讓 JZ 來回答吧，但我可以告訴你，目前我們還沒有考慮將其作為氣喘適應症。但我認為，重要的是要認識到，在異位性皮膚炎方面，我們有一種重要的藥物有可能解決這種合併症問題，這非常令人興奮。正如我之前所說，25% 的異位性皮膚炎患者同時患有氣喘這種合併症。

So I think it's a very important component of differentiating REZPEG, although we don't have a plan to run an asthma study. JZ, would you like to help with the rest of the question?

所以我認為這是 REZPEG 的一個非常重要的差異化因素，儘管我們目前還沒有進行氣喘研究的計畫。JZ，你願意幫忙回答剩下的問題嗎？

Sure, yeah, thanks for the question, Dominic. So at the ACAAI presentation, we're presenting the results of a pre-planned exploratory analysis that was included in the study. There's a validated questionnaire instrument that is a patient-reported outcome called the ACQ-5, which stands for the Asthma Control Questionnaire.

當然，謝謝你的提問，多明尼克。因此，在 ACAAI 的演講中，我們將展示一項預先計劃的探索性分析的結果，該分析已納入研究之中。有一種經過驗證的問卷調查工具，稱為 ACQ-5，它是氣喘控制問卷的縮寫，是一種患者報告的結果。

And with that, you can assess the comorbidity symptoms of asthma in patients that have both atopic dermatitis as well as asthma. That allows you to look at the total improvement in the ACQ-5 scores over time, but it also lets you isolate on patients that have more severe, for example, uncontrolled asthma at baseline. That's a subset of people that have higher scores on ACQ-5 at baseline.

這樣，你就可以評估同時患有異位性皮膚炎和氣喘的患者的氣喘合併症狀。這樣一來，你就可以觀察 ACQ-5 評分隨時間推移的整體改善情況，也可以將研究對象集中在病情較嚴重的患者身上，例如基線時氣喘控制不佳的患者。這是基線時 ACQ-5 得分較高的族群的子集。

For us, this is really interesting because like we discussed, roughly 25% of patients have that, so roughly 100 people in our study also had asthma in addition to atopic dermatitis. This allows us to assess the effect of REZPEG on asthma control and even potentially the improvement of those asthma symptoms in patients that also had atopic dermatitis.

對我們來說，這真的很有趣，因為正如我們討論的那樣，大約 25% 的患者患有這種情況，因此，我們研究中大約有 100 人除了患有異位性皮膚炎外，還患有氣喘。這使我們能夠評估 REZPEG 對氣喘控制的影響，甚至有可能改善同時患有異位性皮膚炎的患者的氣喘症狀。

One of the things that's so important about that is that when you are faced with treatment decisions as a physician and you know you have patients with atopic disease, and atopic constantly includes other organs, that's why such a high proportion of atopic dermatitis patients also have asthma. That starts to influence some of the treatment decisions.

其中非常重要的一點是，當你作為一名醫生面臨治療決策時，你知道你的病人患有特應性疾病，而特應性疾病通常會累及其他器官，這就是為什麼特應性皮膚炎患者中哮喘患者的比例如此之高的原因。這開始影響一些治療方案的選擇。

Right now, Dupixent is really the drug that's gone to for people with comorbidity, as Dupixent has demonstrated activity in both asthma and atopic dermatitis and in patients that express both symptoms as well as each indication separately. That's really likely due to the IL-4 component of its mechanism. But the other agents in the class approved for atopic dermatitis don't have nearly the level of effect that Dupixent does. So this is a differentiating element of the Treg mechanism of REZPEG.

目前，Dupixent 確實是合併症患者的首選藥物，因為 Dupixent 已證明對氣喘和異位性皮膚炎均有效，並且對同時表現出這兩種症狀以及分別表現出每種適應症的患者也有效。這很可能是由於其作用機制中的 IL-4 成分所致。但其他獲準用於治療異位性皮膚炎的同類藥物，其療效遠不及 Dupixent。所以這是 REZPEG 的 Treg 機制的一個區別性要素。

We do think it differentiates REZPEG further from the other molecules in the class and the other molecules in development, as well as the approved agents like IL-13 selective antagonists and the OX40 classes. We think it's something that has potential to really further build upon with REZPEG and something that we'll be exploring and thinking a lot about in the future, both in the setting of the comorbidity and, as Howard said, even beyond. Thanks, Dominic.

我們認為，這使得 REZPEG 與其他同類分子、其他正在研發的分子以及已獲批准的藥物（如 IL-13 選擇性拮抗劑和 OX40 類藥物）進一步區別開來。我們認為它有潛力與 REZPEG 進一步發展，我們將在未來對此進行深入探索和思考，無論是在合併症的背景下，還是如 Howard 所說，甚至在其他方面。謝謝你，多米尼克。

Julian Harrison, BTIG.

Julian Harrison，BTIG。

Hi, thank you for taking the questions and congrats on all the recent progress. It looks like you've had a few months now to socialize with the medical community the initial RESOLVE-AD results and REZPEG's potential here. I'm wondering if you have a good sense now for the level of interest for a therapy that potentially has a truly remittive effect. To what extent do you think that could emerge as a differentiator for REZPEG in atopic derm?

您好，感謝您回答問題，並祝賀您最近的所有進展。看來您已經有幾個月的時間與醫學界交流 RESOLVE-AD 的初步結果以及 REZPEG 在這方面的潛力。我想知道您現在是否對這種可能真正具有緩解作用的療法的興趣程度有了比較清晰的認識。您認為這在多大程度上可以成為 REZPEG 在異位性皮膚炎治療中的差異化優勢？

And then switching to alopecia areata, JZ, I heard your comments around the ritlecitinib low-dose magnitude of efficacy potentially setting the bar. Do you see maybe an opportunity for use if efficacy is even lower than that, just given how presumably safe REZPEG is, potentially free of box warnings compared to JAK inhibitors?

然後，JZ，我聽過你關於利妥昔單抗低劑量療效可能成為衡量斑禿的標準的評論。如果療效甚至低於這個水平，考慮到 REZPEG 的安全性可能很高，而且與 JAK 抑制劑相比可能沒有黑框警告，您是否認為存在使用 REZPEG 的機會？

Oh, Julian, I'll take the first part of the question. Look, clearly this mechanism, the Treg mechanism, has received a lot of attention, especially with the Nobel Prize in Physiology or Medicine. And I think given this very strong data we have in atopic dermatitis and the rescue data or the escape arm data, I should say, where patients who failed to see any response on placebo did exceptionally well when they were crossed over to drug, I think that's incredibly compelling data. And we're very proud of that.

哦，朱利安，我來回答問題的第一部分。顯然，這種機制，即 Treg 機制，已經受到了廣泛關注，尤其是獲得了諾貝爾生理學或醫學獎。我認為，鑑於我們在異位性皮膚炎方面擁有的非常強有力的數據，以及救援數據或逃逸組數據（應該說是補救組數據），即那些在安慰劑治療中沒有看到任何反應的患者，在交叉接受藥物治療後表現得非常好，我認為這是非常有說服力的數據。我們為此感到非常自豪。

The combination of that data with what we now see in the comorbidity of asthma, I think sets apart REZPEG from a number of different drugs in treating atopic dermatitis. So yes, to answer your question more directly, there's a lot of interest in it. There's a lot of inbound interest in it, and I think it's going to have very good prospects. I'll let JZ handle the rest of the question.

我認為，將這些數據與我們現在看到的氣喘合併症結合起來，使 REZPEG 在治療異位性皮膚炎方面與其他許多不同的藥物區分開來。所以，更直接回答你的問題，是的，很多人對此很感興趣。很多人對此很感興趣，我認為它前景非常好。剩下的問題就交給 JZ 來回答吧。

Yeah, thanks, Howard and Julian. So, I mean, in the context of the benchmarks, I think what's really important is that REZPEG has the potential to be a truly differentiated mechanism in alopecia areata by numerous factors, and one of those is especially given its safety profile. Right now, there are no approved biologics in the alopecia areata space, and there's really been no therapy that's demonstrated a sustained treatment effect.

是啊，謝謝霍華德和朱利安。所以，我的意思是，就基準而言，我認為真正重要的是，REZPEG 有可能透過多種因素成為斑禿治療中真正差異化的機制，其中一個因素尤其體現在其安全性上。目前，斑禿領域還沒有核准的生物製劑，也沒有任何療法能夠證明其具有持續的治療效果。

What I mean by that is even a short-term interruption in a JAK course can cause hair thinning. It's really quick to wear off. So you have the ability to address so many features that both affect the disease and then the convenience factor for the patient and substantially the comfort level for the physician. In a drug that doesn't have a black box warning, which is one of the issues and limitations of the JAK inhibitors. There's no question that those are great drugs for reducing inflammation and reducing inflammation quickly.

我的意思是，即使JAK療程短暫中斷也會導致頭髮稀疏。它的效果很快就會消失。因此，您可以解決許多影響疾病本身、患者的便利性以及醫生舒適度的因素。對於一種沒有黑框警告的藥物來說，這是 JAK 抑制劑的問題和限制之一。毫無疑問，這些藥物是減輕發炎和快速消炎的良藥。

They're just very difficult drugs to take for a long period of time, and these are chronic conditions. So it's really the challenge with a drug like that. But with REZPEG, you can turn the whole problem on its side. And we have done a lot of the market research. We've tested the profile, and the profile of low-dose ritlecitinib, we find, is very competitive given all of the other elements, features of the mechanism of action, and the differentiated safety profile.

這些藥物很難長期服用，而且這些都是慢性疾病。所以，這才是這類藥物真正的挑戰。但有了 REZPEG，你就可以徹底改變這個問題。我們已經做了大量的市場調查。我們已經測試了該藥物的特性，我們發現，考慮到所有其他因素、作用機制的特徵以及差異化的安全性，低劑量利特西替尼的特性非常具有競爭力。

We know that there's space there. To your point, Julian, we're using that as a reasonable kind of proxy benchmark for now. It is an approved drug and an approved dose, but there is some space around that, to your point.

我們知道那裡有空間。朱利安，你說得對，我們目前將其作為合理的代理基準。它是一種核准的藥物，劑量也是獲準的，但正如你所說，這其中還有一些迴旋餘地。

Thanks. Excellent, thank you. That's all very helpful.

謝謝。太好了，謝謝。這都很有幫助。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Hi, this is John on the line for today. Thanks for taking the question and congrats on the program. Maybe speaking to the AA, I'm just wondering how fast you can maybe start the Phase 3 program, and are you planning to move the program by yourself or you may seek a partnership if the December data is positive?

大家好，我是約翰，今天為您服務。感謝您回答這個問題，也恭喜您成功推出這個計畫。或許可以和AA談談，我只是想知道你們多久能啟動第三階段項目，你們是打算自己推進這個項目，還是如果12月份的數據是積極的，你們會尋求合作夥伴？

And separately, I'm also wondering, in the Phase 2b study, are there any patients with alopecia areata comorbidities, and if so, any color you can share on those patients? Thank you.

另外，我還想知道，在第 2b 期研究中，是否有患有斑禿合併症的患者？如果有，您能否分享一下這些患者的狀況？謝謝。

Well, I think I got the first part of your question. I didn't hear it all clearly, but I think the first part of your question -- I'll let JZ take the second part. The first part was when do we think we could start a study in alopecia areata? I think, depending on the data that we receive in December, we certainly would look forward to starting it next year.

嗯，我想我明白你問題的第一部分了。我沒聽清楚，但我認為你問題的第一部分——第二部分就交給 JZ 來回答吧。第一部分是：我們認為什麼時候可以開始研究斑禿？我認為，根據我們12月收到的數據，我們當然期待明年開始這項工作。

I think it's important because, as we talked about, the only current therapy is a JAK inhibitor, and they come with lots of concerns and warnings. As I described, out of physician surveys that we've conducted, physicians are somewhat reluctant to use a JAK inhibitor to treat alopecia, given the safety concerns.

我認為這很重要，因為正如我們討論過的，目前唯一的治療方法是 JAK 抑制劑，而這類藥物有很多令人擔憂的問題和警告。正如我之前描述的那樣，在我們進行的醫生調查中，由於安全方面的擔憂，醫生們不太願意使用 JAK 抑制劑來治療脫髮。

So I think if we have a new modality to treat such a very serious disease and a condition that causes extreme depression in people, I think it could be very important. And consequently, we do plan to start that study next year. I'll let JZ comment on the rest.

所以我認為，如果我們有一種新的方法來治療這種非常嚴重的疾病，以及這種會導致人們極度憂鬱的病症，我認為這將非常重要。因此，我們計劃明年啟動這項研究。剩下的就讓JZ來評論吧。

Yeah, thanks, John. So we did look at multiple comorbidities in the atopic dermatitis Phase 2b study. Asthma was by far the largest patient population. As I mentioned, roughly 100 people had both atopic dermatitis and asthma in that study, and they'll be presented at ACAAI this weekend.

謝謝你，約翰。因此，我們在異位性皮膚炎 2b 期研究中檢視了多種合併症。氣喘患者群體是迄今為止最大的患者群體。正如我之前提到的，那項研究中大約有 100 人同時患有異位性皮膚炎和氣喘，他們將在本週末的 ACAAI 會議上發表研究結果。

In terms of alopecia, I also looked at vitiligo, for example, very few people. So really not a large enough patient population to isolate out a subgroup. Like a handful of people in alopecia that had both of the diseases.

就脫髮而言，我還研究了白斑症，例如，病例非常少。所以，患者群體規模真的不夠大，無法從中分離出一個亞群。就像少數患有脫髮症的人同時患有這兩種疾病一樣。

Obviously, our Phase 2b results in alopecia, which read out next month, that is by far a more definitive data set. Much larger sample size. Obviously, a patient population enrolled where that is their primary disease, and then of course we'll be looking at the treatment effect in that patient population reported next month.

顯然，我們針對脫髮的 2b 期試驗結果將於下個月公佈，這無疑是一個更確鑿的數據集。樣本量更大。顯然，我們招募的患者群體以該疾病為主要病症，然後我們當然會在下個月公佈該患者群體的治療效果。

Thank you.

謝謝。

Cha Cha Yang, Jefferies.

Cha Cha Yang，傑富瑞。

Hi, this is Cha Cha on for Roger Song. I was wondering, in addition to low-dose ritlecitinib, are there any therapeutics that are in development -- biologics for alopecia that you think would be an appropriate benchmark?

大家好，這裡是Cha Cha，為您帶來Roger Song的報道。我想知道，除了低劑量利特西替尼之外，還有哪些正在研發中的治療脫髮的生物製劑，您認為可以作為合適的基準？

And then my second question is, are there any IL-2 specific studies that you think could provide read-through to REZPEG in alopecia?

我的第二個問題是，您認為是否有任何針對 IL-2 的研究可以為 REZPEG 在脫髮治療中的應用提供參考？

JZ, you want to cover that?

JZ，你想報道這件事嗎？

Yeah, hi, please. Sure. Hey, Cha Cha. Yeah, so there are a couple of biologics in development for alopecia, and we discussed them. It's like an IL-7 receptor and other kinds of agents. So I think that those -- there are some earlier data sets.

是啊，你好，謝謝。當然。嘿，恰恰。是的，目前有幾種治療脫髮的生物製劑正在研發中，我們也討論過它們。它類似於IL-7受體和其他類型的藥物。所以我認為，有一些更早的數據集。

Our goal is we're doing a much larger study than those earlier programs. As we described, 94 people were enrolled and randomized in the Phase 2b alopecia study that we're doing. We also have multiple doses, so a much larger study that gives a chance to really assess the treatment effect, which I think is going to be more informative than a lot of the single-arm or much smaller studies that have been done to date. But it's certainly an area that people are exploring.

我們的目標是開展比以往計畫規模更大的研究。正如我們所描述的，我們正在進行的 2b 期脫髮研究招募並隨機分配了 94 人。我們還有多個劑量，因此可以進行更大規模的研究，從而有機會真正評估治療效果，我認為這將比迄今為止進行的許多單臂或規模小得多的研究更有參考價值。但這無疑是人們正在探索的一個領域。

Tregs remain a very important mechanism that is invoked from a lot of translational studies in patients with alopecia areata. We know that there are low levels and deficiencies in Treg function. We also know Tregs are necessary for hair growth and for hair moving through the hair growth cycle. The actual anagen phase that is associated with the elongation of the hair once it attaches down at the root actually requires Treg signaling to the stem cell compartment.

Tregs 仍然是斑禿患者許多轉化研究中提到的一個非常重要的機制。我們知道 Treg 細胞功能水平較低且有缺陷。我們也知道，Treg細胞對於頭髮生長和頭髮經歷生長週期是必要的。毛髮在根部附著後，其伸長所伴隨的實際生長期，實際上需要 Treg 向幹細胞區室發出信號。

So we know that those are multiple key mechanisms, and those are one of the big reasons why we're so excited in conducting the study that we'll be reading out the topline data for next month.

所以我們知道這些都是多個關鍵機制，這也是我們對進行這項研究感到非常興奮的原因之一，我們將在下個月公佈主要數據。

And then in terms of IL-2 specific studies, there have only been a few studies that have been published with IL-2. One was a case study and one was a small randomized study. The main situation is low-dose IL-2 is really not a good proxy for REZPEG.

至於 IL-2 的專項研究，目前已發表的 IL-2 的研究還很少。其中一項是案例研究，另一項是小型隨機研究。主要情況是低劑量 IL-2 真的不能很好地替代 REZPEG。

With REZPEG, we induce such a higher amount of Tregs, much, much higher than low-dose IL-2 could ever achieve—a much greater duration of Treg elevation from a given dose and the ability to treat for a very long time. As we've now treated patients for over a year, for example, for a 52-week period in the Phase 2b study in atopic dermatitis. So it's definitely a surrogate in the sense of a Treg-elevating agent, but really REZPEG substantially exceeds anything that low-dose IL-2 has been able to present across multiple indications.

使用 REZPEG，我們可以誘導產生比低劑量 IL-2 所能達到的更高的 Treg 數量，比低劑量 IL-2 所能達到的要高得多——在給定劑量下，Treg 水平的提升持續時間更長，並且能夠進行非常長時間的治療。例如，我們已經對患者進行了一年多的治療，在異位性皮膚炎的 2b 期研究中進行了 52 週的治療。因此，從某種意義上說，它是一種 Treg 提升劑的替代療法，但實際上，REZPEG 在多種適應症中都顯著優於低劑量 IL-2 所展現的療效。

Thanks. Thanks so much for the color.

謝謝。非常感謝您提供的顏色。

Mayank Mamtani from B. Riley Securities. Your line is open.

來自 B. Riley Securities 的 Mayank Mamtani。您的線路已開通。

Yes, good afternoon. Thanks for taking your questions and congrats on a productive quarter. On the alopecia topline data analysis, would you have any off-treatment responder rate you plan to report on, given some patients may have been past that 36-week treatment period?

是的，下午好。感謝您回答我的問題，並祝賀您度過了一個碩果累累的季度。在脫髮主要數據分析中，鑑於一些患者可能已經超過了 36 週的治療期，您是否計劃報告任何停藥反應率？

And if you could remind us if there's an escape arm option here for the placebo nonresponders to cross over. Obviously, wonder from your AD experience, the peak efficacy from the EADV data, you didn't get until 24, 44 weeks even, so just wonder what's your plan to assess if efficacy increases beyond that 36-week period. What's the kind of plan there? And then I have a quick follow-up.

請問是否有針對安慰劑無反應者的退出方案，可以交叉到其他組別進行試驗？顯然，根據你的 AD 經驗，EADV 數據顯示，療效高峰直到 24 週甚至 44 週才出現，所以我想知道你打算如何評估療效是否會在 36 週後有所提高。那裡的計劃是什麼類型的？然後我還有一個簡短的後續問題。

Sure, yeah. So firstly, in the kind of information that we would present at the end in December, we'll be presenting data from the 36-week induction period in the study. The primary endpoint is the mean percent reduction in SALT score from baseline, and then the key secondary endpoints that are really meaningful are the proportion of people that achieve SALT 20 and also SALT 10.

當然，是的。首先，在 12 月底我們將展示的資訊中，我們將展示該研究中 36 週導入期的數據。主要終點是 SALT 評分從基線到平均百分比降低，而真正有意義的關鍵次要終點是達到 SALT 20 和 SALT 10 的人數比例。

SALT 20 is a registrational endpoint in the US and SALT 10 in Europe. And then I mentioned earlier in the presentation also the additional secondary endpoints, some of the time-dependent endpoints and some of the proportional increases in the kind of hair regrowth, right, as metrics. And then the other things that kind of round out the baseline demographics, the safety profile, all the other things.

SALT 20 是美國的註冊終點，SALT 10 是歐洲的註冊終點。然後，我在前面的演示中還提到了一些額外的次要終點，一些與時間相關的終點以及毛髮再生比例的增長，對吧，作為指標。然後還有其他一些因素，例如基本人口統計、安全狀況等等。

But importantly, Mayank, right, the study is still going to be ongoing. So, the way we designed the study is, people that reached week 36 that are experiencing benefits such as hair regrowth, for example, but that have not yet reached a SALT 20 metric, they have the opportunity to take an additional 16 weeks of treatment to 52 weeks for a full year. So there's a proportion of people that will be ongoing. And also the study design has a 24-week off-drug observation period.

但重要的是，Mayank，對吧，這項研究還將繼續進行。因此，我們設計的研究是，達到第 36 週並體驗到諸如頭髮再生等益處，但尚未達到 SALT 20 指標的人，有機會接受額外的 16 週治療，直至 52 週，為期一年。所以有一部分人會一直這樣下去。此外，研究設計還包括 24 週的停藥觀察期。

So whenever a patient completes treatment, whether that's at 9 months or at 12 months, they're then followed for that additional 24-week period of time. And that's really designed to assess that if you grew hair, can you keep hair, right, which is a significant differentiating element from a JAK mechanism of action where the hair loss is really rapid when the drug dosing is stopped.

因此，無論患者是在 9 個月還是 12 個月後完成治療，之後都會進行額外的 24 週追蹤。而這其實是為了評估，如果你長出了頭髮，你能保持頭髮嗎？這與 JAK 作用機制有一個顯著的區別，因為在 JAK 作用機制中，當停止用藥時，脫髮會非常迅速。

So because the study is still ongoing, we can't say yet the totality, but definitely the 36-week endpoint, which is the primary analysis with the entire population crossing the 36 weeks, is going to be the main subject of that topline presentation.

由於研究仍在進行中，我們還不能說全部結果，但可以肯定的是，36 週終點（即所有受試者均達到 36 週的主要分析）將是此次主要報告的主題。

Escape arm, JZ, is there an escape arm here?

JZ，這裡有逃生臂嗎？

No, there's no escape arm in the study.

不，這項研究沒有設置對照組。

Okay, thank you. And on the autoinjector development, how far along are you? And is that going to be at the start of your Phase 3 study, and is that kind of part of the protocol as you get into the end-of-Phase 2 discussion? Thanks for taking my question.

好的，謝謝。自動噴射器的研發進度如何？那會是你們第三階段研究的開始階段嗎？那會是你們在第二階段研究結束時討論的方案的一部分嗎？謝謝您回答我的問題。

Sure, yeah. So, the autoinjector development is ongoing, and our goal and plan is to have the autoinjector available at the time of launch of REZPEG. The Phase 3 studies will be conducted in the same way the Phase 2 studies were, where the drug will be used in a vial. And for us, we maintain that really for speed, because this allows us to start the Phase 3 studies as quickly as possible, relative to when we presented the topline data in June of this year.

當然，是的。因此，自動注射器的開發正在進行中，我們的目標和計劃是在 REZPEG 發佈時提供自動注射器。第三階段研究將以與第二階段研究相同的方式進行，藥物將裝在小瓶中使用。對我們來說，我們堅持這樣做確實是為了加快速度，因為這使我們能夠盡快開始 3 期研究，相對於我們今年 6 月公佈的初步數據而言。

And then, in terms of your other question, just contextually, at the end-of-Phase 2 meeting, you really discuss everything in the plan to your BLA. So that includes not just the Phase 3 clinical development program, the registrational and pivotal studies, it also includes the CMC. So yes, we have presented our plans for the final presentation of the product, the autoinjector, and then all the work that we do during the Phase 3 studies into the BLA to have that available for launch.

至於你的另一個問題，就背景而言，在第二階段結束時的會議上，你實際上會向你的 BLA 討論計劃中的所有內容。因此，這不僅包括 3 期臨床開發計劃、註冊研究和關鍵性研究，還包括 CMC。是的，我們已經展示了我們最終產品（自動注射器）的展示計劃，以及我們在 3 期研究期間所做的所有工作，並將這些工作納入生物製品許可申請 (BLA)，以便產品能夠上市。

Arthur Hee, H.C. Wainwright. Your line is now open.

亞瑟·希，H.C. 溫賴特。您的線路已開通。

Hey, good afternoon. How are you, team? Sir, I apologize if the question has been asked before. So, given the coming readout for the alopecia, JZ, maybe could you tell us a little bit more like what the potential REZPEG can offer compared to the JAK inhibitor here for the alopecia patients?

嘿，下午好。各位團隊成員，你們好嗎？先生，如果這個問題之前有人問過，我深感抱歉。鑑於即將公佈的脫髮治療結果，JZ，您能否詳細介紹一下，與JAK抑制劑相比，REZPEG能為脫髮患者帶來哪些潛在益處？

Yeah, it's a great question. I mean, I think that one of the situations with the JAK inhibitors, and we touched a little bit on this earlier, is that they definitely are effective at reducing inflammation. Like if you have common gamma chain uses of multiple cytokines, use any either homo or heterodimers of JAKs.

是的，這是一個很好的問題。我的意思是，JAK抑制劑的一個特點（我們之前也稍微提到過），就是它們確實能有效減輕發炎。例如，如果您有多種細胞激素的共同γ鏈用途，則可以使用JAK的同源二聚體或異源二聚體。

And it's an important part of the signaling cascade in response to multiple cytokines, and they're well known as effective ways of lowering inflammation and quite quickly. But the challenge with using a JAK inhibitor in any indication where it's approved is that long-term use carries with it some disadvantages, right? So the drugs have black box warnings, they have other significant limitations, they require monitoring. There's just a number of things that make them a little bit more delicate to use. And in the dermatological setting, some of those things are a little bit undesirable.

它是響應多種細胞因子而發出的信號級聯反應的重要組成部分，眾所周知，它們是降低發炎的有效且快速的方法。但是，在任何已批准的適應症中使用 JAK 抑制劑的挑戰在於，長期使用會帶來一些缺點，對吧？因此，這些藥物帶有黑框警告，有其他重大局限性，需要監測。只是有一些因素使得它們在使用時需要更加小心。在皮膚科領域，其中一些做法是不太理想的。

One of the things that REZPEG can offer is if the efficacy profile, as we discussed, reaches a benchmark such as a low-dose JAK in, say, the ritlecitinib setting, it already brings with it a completely different risk profile, right? It would not have a black box warning. It would have a completely different and much better safety profile and really has a safety profile that's much more aligned with being a very long-term chronic use drug.

REZPEG 的優點之一在於，正如我們討論的那樣，如果其療效達到基準，例如在利特西替尼治療中達到低劑量 JAK 的療效，那麼它就具有完全不同的風險特徵，對嗎？它不會有黑框警告。它將具有完全不同且更好的安全性，其安全性更符合長期慢性用藥的標準。

Also, the potential of being the first biologic in this space gives it a real tremendous advantage because that starts to really open access. We've learned from multiple studies that physicians are not necessarily excited to try JAKs as a first option for patients with the disease. So having another alternative that's available could take a significant opportunity advantage.

此外，作為該領域首個生物製劑，它具有巨大的優勢，因為這將真正打開獲取途徑。我們從多項研究中了解到，醫生不一定熱衷於 JAK 抑制劑作為治療該疾病患者的首選方案。因此，擁有另一種可行的替代方案可能會帶來巨大的機會優勢。

And then the last one really comes down to that potential of maintenance. JAK inhibitors really lose their effect very quickly, and it can be very psychologically difficult for patients because if you spend weeks and months regrowing hair that you didn't have in a really long time. And then any need to interrupt the JAK, whether it's a safety signal or other reason or liver enzyme elevation or something, then that can lead to loss of all that hair that you've grown, which can further drive the depression cycle that's a component of this disease.

最後一個問題實際上取決於維護的潛力。JAK 抑制劑的效果很快就會消失，這對患者來說在心理上會非常痛苦，因為如果你花了數週甚至數月的時間才重新長出很久以前就失去的頭髮。然後，任何需要中斷 JAK 的情況，無論是安全訊號、其他原因、肝臟酵素升高或其他情況，都可能導致你長出的所有頭髮脫落，這會進一步加劇憂鬱循環，而憂鬱循環是這種疾病的一個組成部分。

With REZPEG, there's the potential of maintaining the hair that was grown, having interruptions in drug dosing that would not be a problem, and that would be completely transformational. So these are all things that we think contribute to a very substantial opportunity for REZPEG in alopecia areata.

使用 REZPEG，有可能維持已經長出的頭髮，即使藥物劑量中斷也不會造成問題，這將是徹底的改變。因此，我們認為這些因素共同促成了 REZPEG 在斑禿治療領域中具有非常大的發展前景。

Thanks, JZ. So another question is, given the data there, how should we think about the primary endpoint for the approval in the future? Do you think the SALT 20 still could do the job, or we probably should look into the SALT 10 or even SALT 0 there for the future draw for the alopecia?

謝謝，JZ。那麼另一個問題是，根據這些數據，我們應該如何看待未來審批的主要終點？您認為 SALT 20 還能勝任嗎？或者我們應該考慮使用 SALT 10 甚至 SALT 0 來應對未來的脫髮問題？

Yeah, well, I mean, the health authorities set the registrational endpoints, right, and so right now those are defined as SALT 20 in the US and SALT 10 in Europe. But obviously every study measures multiple secondaries, right, including eyelash, including SALT 0 and so on.

是的，我的意思是，衛生部門設定了註冊終點，對吧，所以目前在美國被定義為 SALT 20，在歐洲被定義為 SALT 10。但顯然每項研究都會測量多個次要指標，對吧，包括睫毛、SALT 0 等等。

So I think that we leave that in the hands of the regulators. In terms of JAK efficacy, I mean, I think everywhere that there are multiple JAK inhibitors approved, ritlecitinib seems to always win, right? It just consistently produces the greatest amount of efficacy compared when it goes head-to-head against other agents, and I think we've seen that in multiple indications, Arthur, right, not just in this one. It does carry with it a little bit more of a safety profile, which is related more on-target and more on-target tox in addition to other things.

所以我認為應該把這件事交給監管機構來處理。就 JAK 療效而言，我的意思是，我認為在有多種 JAK 抑制劑獲準的情況下，利妥昔單抗似乎總是勝出，對吧？與其他藥物相比，它始終能產生最大的療效，而且我認為我們已經在多種適應症中看到了這一點，亞瑟，對吧，不僅僅是這一種。它的安全性確實更高一些，這與靶向性更強、靶向毒性更大以及其他方面有關。

But I do think as compared to the other JAK inhibitors, ritlecitinib is going to be very important, probably take a significant position against the other JAK inhibitors. But we don't really see that as impacting the biologic, right? Again, there are numerous indications where biologics and small molecules, JAKs and non-JAKs coexist. Atopic dermatitis is a great example. In psoriasis, you have TYK2 mechanisms coexisting with others, and there's really a large enough patient share and the need for multiple mechanisms that always makes plenty of room for multiple mechanisms in this indication.

但我認為，與其他 JAK 抑制劑相比，利特西替尼將會非常重要，可能會在與其他 JAK 抑制劑的競爭中佔據重要地位。但我們不認為這會對生物學產生影響，對吧？再次，有許多跡象表明生物製劑和小分子藥物、JAK 抑制劑和非 JAK 抑制劑可以共存。異位性皮膚炎就是一個很好的例子。在乾癬中，TYK2 機制與其他機制並存，而且患者群體非常龐大，需要多種機制，因此在這個適應症中總是有足夠的空間容納多種機制。

All right, thanks very much for taking my question.

好的，非常感謝您回答我的問題。

Andy Hsieh from William Blair. Your line is open.

來自威廉布萊爾的安迪謝。您的線路已開通。

Oh, great. Thanks for taking our questions. Mary, it's great to have you back. So, we have two questions. For the RESOLVE-AD study, I believe you spent a lot of time and resources to ensure that the placebo rate is low. So have you gotten a chance to review that initiative so that you can be best positioned for the positive Phase 3 outcome?

哦，太好了。謝謝您回答我們的問題。瑪麗，你回來真是太好了。所以，我們有兩個問題。我相信，在 RESOLVE-AD 研究中，您投入了大量的時間和資源來確保安慰劑率較低。那麼，您是否有機會審查該項計劃，以便為第三階段的積極成果做好充分準備？

And then the second question, maybe for Howard, what's your current manufacturing footprint? I figured given the intense interest in REZPEG, it would be really nice if you can secure one of those national priority vouchers. Thank you.

那麼第二個問題，或許可以問霍華德，你們目前的生產規模如何？鑑於大家對 REZPEG 的濃厚興趣，我想如果你能拿到一張國家優先券，那就太好了。謝謝。

I'll take the second part first, and Mary can continue. Look, we are looking at a number of different options here. We sold our pegylation manufacturing facility to Gannett Biochem, but we have a priority position there and we certainly have a guaranteed source of those raw materials.

我先做第二部分，瑪麗可以繼續。你看，我們現在考慮了很多不同的方案。我們已將聚乙二醇化生產設施出售給 Gannett Biochem，但我們在那裡享有優先權，我們肯定有這些原料的可靠來源。

And we have a number of different contract manufacturing companies, very well-known companies, that we work with, so I'm not concerned at this point about the ability to successfully manufacture REZPEG. And we are looking at the vouchers, etc. I will let Mary talk to you about the other part of your question.

我們與許多不同的合約製造公司合作，這些公司都是非常知名的公司，所以我目前並不擔心能否成功生產 REZPEG。我們正在查看代金券等相關事宜。關於您問題的另一部分，我會讓瑪麗來和您談談。

Thanks, Howard, and really great to hear your voice too, Andy, and I'm really happy to be back. I mean, as you said, the data from RESOLVE-AD are very exciting, and I've also had the opportunity to speak to multiple dermatologists since I've been back who are also very excited about the totality of the data, the speed of onset, and the excellent safety profile.

謝謝你，霍華德，也很高興聽到你的聲音，安迪，我很高興能回來。我的意思是，正如你所說，RESOLVE-AD 的數據非常令人振奮，而且自從我回來後，我也有機會與多位皮膚科醫生交談，他們也對數據的整體情況、起效速度和出色的安全性感到非常興奮。

So it's very exciting to move this forward. And certainly in our Phase 3 program, we have every plan to implement the exact same procedures that we did to minimize the placebo effect. Some of those are, of course, ensuring that we have board-certified dermatologists participating in our clinical trials. We also make sure that the eligibility criteria is met both in the screening and right before patients are randomized. And so we took multiple actions. Also, in our Phase 2b, we had quite a large size of our placebo group, and we will of course have the same when we proceed forward in a larger Phase 3 study.

所以推進這項工作令人非常興奮。當然，在我們的第三階段項目中，我們已製定了所有計劃，以實施與先前完全相同的程序，從而最大限度地減少安慰劑效應。當然，其中一些措施包括確保我們有認證的皮膚科醫生參與我們的臨床試驗。我們還確保在篩選階段和患者隨機分組之前都符合入選標準。因此，我們採取了多項措施。此外，在我們的 2b 期試驗中，安慰劑組的規模相當大，當然，當我們繼續進行更大規模的 3 期試驗時，安慰劑組的規模也會很大。

So we were very pleased that we were able to implement multiple different procedures and activities in order to ensure our placebo effect is very low, and we believe we will continue to be very successful in our Phase 3 as well. So we look forward to moving forward. We've been doing a lot of planning. We're going to have our end-of-Phase 2 meeting with the FDA by the end of this year, and so we'll have a clear path forward to a BLA.

因此，我們非常高興能夠實施多種不同的程序和活動，以確保安慰劑效應非常低，我們相信在第三階段也將繼續取得巨大成功。我們期待著向前邁進。我們做了很多規劃工作。我們將在今年年底前與 FDA 舉行第二階段結束會議，屆時我們將有明確的路徑獲得生物製品許可申請 (BLA)。

Well, great. Good luck with that. Thanks.

太好了。祝你好運。謝謝。

Thank you. And this does conclude our question-and-answer session for today's conference. I'd like to turn the call back over to Howard Robin for any closing remarks.

謝謝。今天的問答環節到此結束。我想把電話轉回給霍華德·羅賓，請他作總結發言。

Well, thank you, Crystal, and thank you everyone for joining us today. We greatly appreciate your continued support. And I want to thank all of the patients and their caregivers that have trusted and continue to trust Nektar to treat their disease.

謝謝你，克麗絲塔爾，也謝謝今天所有到場的各位。我們非常感謝您一直以來的支持。我還要感謝所有信任Nektar並繼續信任我們治療疾病的患者及其照護者。

None of this research would be possible without them. And I also want to thank our employees for their dedication and extremely hard work. We look forward to delivering data from our REZPEG program in alopecia areata in December and additional results from the program in atopic dermatitis in the first quarter of next year. So please stay tuned. Thanks for joining us.

如果沒有他們，所有這些研究都不可能進行。我還要感謝我們的員工，感謝他們的奉獻和辛勤工作。我們期待在 12 月公佈 REZPEG 計畫在斑禿方面的數據，並在明年第一季度公佈該計畫在異位性皮膚炎方面的更多結果。敬請期待。謝謝您的參與。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線了。祝大家今天過得愉快。