Nektar Therapeutics (NKTR) 2023 Q4 法說會逐字稿

Good day, and thank you for standing by, and welcome to the Nektar Therapeutics Fourth Quarter 2023 financial results conference call. (Operator Instructions) Once again, please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Vivian Wu. Please go ahead.

美好的一天，感謝您的耐心等待，歡迎參加 Nektar Therapeutics 2023 年第四季財務業績電話會議。（操作員指示）再次提醒您，今天的會議正在錄製中。現在我想把會議交給今天的發言人 Vivian Wu。請繼續。

Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. With us on the call are Howard Robin, our President and CEO; Dr. Jonathan Zalevsky, our Chief of Research and Development; Dr. Mary Tagliaferri, our Chief Medical Officer; Sandra Gardiner, our Chief Financial Officer; and Jennifer Ruddock, our Chief Business Officer.

謝謝克里斯托，大家下午好。感謝您今天加入我們。與我們一起參加電話會議的是我們的總裁兼執行長霍華德羅賓 (Howard Robin)；我們的研發主管 Jonathan Zalevsky 博士； Mary Tagliaferri 博士，我們的首席醫療官；桑德拉‧加德納 (Sandra Gardiner)，我們的財務長；以及我們的首席商務官 Jennifer Ruddock。

On today's call, we expect to make forward-looking statements regarding our business, including statements regarding the therapeutic potential of future development candidates and programs. The timing of the initiation of clinical studies and the availability of clinical data for drug candidates, the timing and plans for future clinical data presentations, the formation and future development plans or success of our agreement expectations following our corporate restructuring and reorganization, financial guidance and certain other statements regarding the future of our business.

在今天的電話會議上，我們希望就我們的業務做出前瞻性聲明，包括有關未來開發候選人和專案的治療潛力的聲明。臨床研究的啟動時間和候選藥物臨床數據的可用性、未來臨床數據展示的時間和計劃、公司重組和重組後協議預期的形成和未來發展計劃或成功、財務指導和有關我們業務未來的某些其他聲明。

Because forward-looking statements relate to the future, they're subject to uncertainties and risks that are difficult to predict, many of which are outside of our control. Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-Q that was filed on November 8, 2023, which is available at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. A webcast of this call will be available on the IR page of Nektar's website at arqule.

由於前瞻性陳述涉及未來，因此它們會受到難以預測的不確定性和風險的影響，其中許多是我們無法控制的。我們的實際結果可能與這些陳述有重大差異。我們於 2023 年 11 月 8 日提交的 10-Q 表格中列出了重要的風險和不確定性，該表格可在 sec.gov 上取得。我們不承擔更新任何前瞻性陳述的義務，無論是由於新資訊、未來發展或其他原因。本次電話會議的網路直播將在 Nektar 網站 arqule 的 IR 頁面上提供。

With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard?

話雖如此，我想將電話轉交給我們的總裁兼執行長霍華德羅賓。霍華德？

Thank you, Vivian, and thank you for all joining us today. 2023 was a pivotal year for Nektar, we refocused the company's development pipeline on immunology and inflammation with our primary near term goal to advance rest bags to meaningful data catalysts in the first half of 2025.

謝謝你，維維安，也謝謝大家今天加入我們。 2023 年對 Nektar 來說是關鍵的一年，我們將公司的開發管道重新集中在免疫學和發炎上，我們的近期主要目標是在 2025 年上半年將休息袋推進到有意義的數據催化劑。

REZPEG is poised to be highly disruptive in the biologic treatment landscape for atopic dermatitis by offering a novel agonistic mechanism as peg is designed to both dampen the inflammatory response and simultaneously restore immune balance by directly expanding functional T-reg cells and engaging multiple immuno regulatory pathways in patients with atopic dermatitis and other autoimmune disorders through a unique mechanism.

REZPEG 預計將在異位性皮膚炎的生物治療領域具有高度顛覆性，因為peg 旨在透過直接擴展功能性T-reg 細胞和參與多種免疫調節途徑來抑制發炎反應，同時恢復免疫平衡，從而提供一種新穎的激動機制透過獨特的機制治療異位性皮膚炎和其他自體免疫疾病患者。

REZPEG also has the potential to provide patients with superior efficacy as well as more favorable infrequent dosing. There are over 30 million people in the US alone battling this chronic skin condition and it can greatly impact quality of life and mental health for these patients.

REZPEG 還具有為患者提供卓越療效以及更有利的不頻繁給藥的潛力。僅在美國就有超過 3000 萬人正在與這種慢性皮膚病作鬥爭，它會極大地影響這些患者的生活品質和心理健康。

We made significant advancements advancements in 2023 with respect to our recipe program, most notably we regain the full rights to respect from Eli Lilly and now own the program 100% with no encumbrances. We move to quickly design the Phase IIb study in atopic dermatitis based on the promising results from the Phase Ib placebo-controlled randomized study of red bag, which showed an 83% drop in eczema skin scores after just 12 weeks of treatment.

2023 年，我們在配方計劃方面取得了重大進展，最值得注意的是，我們重新獲得了禮來公司尊重的全部權利，現在 100% 擁有該計劃，沒有任何產權負擔。基於 Red Bag 的 Ib 期安慰劑對照隨機研究的有希望的結果，我們開始快速設計異位性皮膚炎的 IIb 期研究，該研究顯示，僅治療 12 週後，濕疹皮膚評分就下降了 83%。

Our Phase IIb global study in this indication was launched in October of '23, and enrollment is on track for data readout in the first half of '25. In late 2023, we also began work designing a Phase IIb study in alopecia areata, another area of high unmet need for studies. Starting this month, there are approximately 7 million patients in the United States and 160 million people worldwide who have alopecia areata.

我們針對此適應症的 IIb 期全球研究於 23 年 10 月啟動，入組工作預計在 25 年上半年公佈數據。2023 年末，我們也開始設計針對斑禿的 IIb 期研究，這是另一個研究需求未被滿足的領域。從本月開始，美國約有 700 萬名患者，全球約有 1.6 億人患有斑禿。

JAK inhibitors are the primary treatment option for patients with alopecia, but have a significant rebound effect with treatment cessation and several black-box warning based on the data we generated to date on red bag in the skin related autoimmune condition of atopic dermatitis, psoriasis and in patients with cutaneous manifestations of lupus. We believe red peg has strong scientific rationale in the setting of alopecia. It could have the potential to be a highly differentiated treatment option with a similar remit of effect for this underserved patient population.

JAK抑制劑是脫髮患者的主要治療選擇，但根據我們迄今為止產生的關於異位性皮膚炎、牛皮癬和皮膚相關自體免疫疾病中紅包的數據，隨著治療停止和一些黑框警告，JAK抑製劑具有顯著的反彈效應。有狼瘡皮膚表現的患者。我們相信紅色掛鉤在治療脫髮方面具有強有力的科學依據。它有可能成為一種高度差異化的治療選擇，對於服務不足的患者群體具有類似的效果。

As I stated earlier, we look forward to the Phase IIb data for our atopic dermatitis study and for our alopecia study in the first half of 2025. These will be highly meaningful data catalysts for Nektar.

正如我之前所說，我們期待在 2025 年上半年獲得異位性皮膚炎研究和脫髮研究的 IIb 期數據。這些對 Nektar 來說將是非常有意義的數據催化劑。

In addition to respect, we have another important immunology program that we're moving towards the clinic. This is a first-in-class differentiated mechanism and immunology, a TNFR2 agonist antibody, NKTR-165. TNFR2 has been shown to potentiate the suppressive effects and overall functional properties of T regs in the program is built on what we've learned through our deep experience with Red Peg and the direct field and represents a promising mechanism for treatment of autoimmune diseases, including multiple sclerosis and ulcerative colitis.

除了尊重之外，我們還有另一個重要的免疫學計畫正在走向臨床。這是一流的差異化機制和免疫學，TNFR2激動劑抗體，NKTR-165。TNFR2 已被證明可以增強T reg 的抑製作用，該計畫中的T reg 的整體功能特性是建立在我們透過Red Peg 和直接領域的深入經驗而學到的基礎上的，代表了一種治療自身免疫性疾病的有前途的機制，包括多發性硬化症和潰瘍性結腸炎。

We're currently conducting IND-enabling studies with the goal of targeting an IND submission in the first half of next year in line with our objectives to advance our immunology pipeline. Today, we announced a $30 million financing that further bolsters Vector's financial position as we head into transformative data cutoff. Importantly, we're pleased to bring on a new, high-quality, long-term investor TCG crossover, who clearly shares our belief in the potential of REZPEG. At a price of $1.20 per share, the transaction represents a premium of over 80% connectors 30 days. This puts us in a strong financial position and extends our cash runway from our previous guidance, which was the middle of 2026 to now well into the third quarter of 2026.

我們目前正在進行 IND 支持研究，目標是在明年上半年提交 IND，這符合我們推進免疫學管道的目標。今天，我們宣布了 3000 萬美元的融資，在我們邁向變革性的數據截止之際，進一步增強了 Vector 的財務狀況。重要的是，我們很高興引入一位新的、高品質的、長期的 TCG 跨界投資者，他顯然與我們一樣相信 REZPEG 的潛力。以每股 1.20 美元的價格計算，該交易代表 30 天連接器溢價超過 80%。這使我們處於強勁的財務狀況，並將我們的現金跑道從我們先前的指導（2026 年中期）延長到了 2026 年第三季。

And with that, I'll hand the call over to JZ for an R&D discussion.

接下來，我會將電話轉交給 JZ 進行研發討論。

Thank you, Howard. Let's begin today with REZPEG, which is the most advanced IL-2 based T-regs mechanism in the field across the rest peg studies that have been conducted to date, we have observed a consistent and highly predictable clinical pharmacology profile with respect to target engagement as well as the peak and duration of T-reg mobilization. It has demonstrated a well-tolerated safety profile and clear clinical efficacy in atopic dermatitis and also psoriasis and in patients with cutaneous manifestations of lupus. Our deep experience with respect to date across the totality of the clinical program gives us conviction in our ongoing Phase IIb studies in atopic dermatitis and alopecia areata. Specifically in atopic dermatitis, there are three important issues that patients with this disease continue to face.

謝謝你，霍華德。今天讓我們從REZPEG 開始，它是該領域最先進的基於IL-2 的T-regs 機制，在迄今為止進行的其餘peg 研究中，我們觀察到在標靶參與方面具有一致且高度可預測的臨床藥理學特徵以及 T-reg 動員的峰值和持續時間。它在異位性皮膚炎、牛皮癬以及有狼瘡皮膚表現的患者中表現出良好的耐受性安全性和明確的臨床療效。我們迄今為止在整個臨床計畫方面的豐富經驗使我們對正在進行的異位性皮膚炎和斑禿的 IIb 期研究充滿信心。特別是在異位性皮膚炎中，該疾病患者繼續面臨三個重要問題。

First, there is a need for great efficacy, specifically a deeper magnitude of response and rapid onset of treatment. Second, patients like durable responses and therapy free remission. Once current therapies or discontinued patients rebound rapidly. And third, treatments with favorable safety profiles are lacking. This is especially important given the chronic nature of the disease and the need for continuous dose. We believe there are major opportunities in this disease state that the differentiated profile of REZPEG could potentially address diving into our Phase Ib data in atopic dermatitis.

首先，需要良好的療效，特別是更深層的反應和快速的治療起效。其次，患者喜歡持久的反應和無需治療的緩解。一旦目前治療或停止治療，患者會迅速反彈。第三，缺乏具有良好安全性的治療方法。考慮到該疾病的慢性性質和持續給藥的需要，這一點尤其重要。我們相信，在這種疾病狀態下，REZPEG 的差異化特徵可能會解決我們對異位性皮膚炎 Ib 期數據的深入研究的重大機會。

Through the 12-week induction period, REZPEG demonstrated dose-dependent efficacy across both physician assessed, and patient reported efficacy measurements, reaching statistical significance across many of these measures. At the highest dose level, REZPEG demonstrated a very rapid onset of response with over 40% of patients achieving easy 75 by week three after only two doses of REZPEG. This rapid onset of action rivals that of JAK inhibitors, which have outperformed to pull them out of this parameter.

在 12 週的誘導期中，REZPEG 在醫生評估和患者報告的療效測量中都表現出劑量依賴性療效，在許多這些指標中達到了統計顯著性。在最高劑量水平下，REZPEG 表現出非常快速的起效，超過 40% 的患者僅在服用兩劑 REZPEG 後第三週就達到了輕鬆 75。這種快速起效的作用可與 JAK 抑制劑相媲美，JAK 抑制劑的表現優於 JAK 抑制劑，使其擺脫了此參數。

At the end of the induction period of 12 weeks, we observed a profound magnitude of efficacy and 83% reduction in percent change from baseline, easy score with the highest dose. This is the largest magnitude of change that we've seen for a biologic and outside of one JAK inhibitor Importantly, we are encouraged by the extended durability seen for REZPEG. Long after the completion of the 12-week induction period, many patients maintained durable disease control for an additional 36 weeks after the end of dosing.

在 12 週的誘導期結束時，我們觀察到顯著的療效，與基線相比變化百分比減少了 83%，最高劑量的輕鬆評分。這是我們在 JAK 抑制劑之外的生物製品中看到的最大幅度的變化。重要的是，我們對 REZPEG 延長的耐久性感到鼓舞。12 週誘導期結束後很長一段時間，許多患者在給藥結束後的 36 週內仍保持持久的疾病控制。

And this type of extended disease control after the end of dosing is not observed for daclizumab or for JAK inhibitor. Durability of the EZ 75 response was observed with approximately 70% of the EZ75 responders, maintaining that response for 36 weeks after the end of the 12-week induction period. This is a very exciting result and suggested REZPEG has the potential to be the first re-bid of therapy for atopic dermatitis.

對於達珠單抗或 JAK 抑制劑，沒有觀察到給藥結束後這種類型的延長疾病控制。大約 70% 的 EZ75 反應者觀察到 EZ 75 反應的持久性，在 12 週誘導期結束後將反應維持 36 週。這是一個非常令人興奮的結果，表明 REZPEG 有潛力成為異位性皮膚炎治療的第一個重新招標。

For both patient reported outcomes and physician assessed endpoints, we observed the same trend rapid onset of effect dose-dependent and long durability of control. Additionally, REZPEG was well tolerated and treat them with respect did not induce antidrug antibodies in patients which has been reported that some examples of the IL-2 mutant class. These promising data have us and KOLs very enthusiastic about the potential for long lasting responses and in frequent maintenance dosing.

對於患者報告的結果和醫生評估的終點，我們觀察到相同的趨勢：起效快、劑量依賴性和控制持久性長。此外，REZPEG 具有良好的耐受性，並且尊重地對待它們，不會在患者體內誘導抗藥物抗體，據報道，IL-2 突變類的一些例子。這些有希望的數據讓我們和 KOL 對持久反應和頻繁維持劑量的潛力充滿熱情。

With respect in the setting of atopic dermatitis. In October 2023, we initiated the Phase IIb study of REZPEG biologic naive atopic dermatitis patients and enrollment is well underway. Our goal is to enroll roughly 400 patients with three different regimens of REZPEG versus placebo evaluated over a 16-week induction period. After the induction period, patients that meet the threshold to advance from induction to maintenance will be re-randomized into one or two maintenance regimen at different dosages at either once a month or once-every-three-month dosing. And that schedule will continue for another 28 weeks. Our enrollment for this study is on track, and we expect data in the first half of 2025.

尊重異位性皮膚炎的情況。2023年10月，我們啟動了REZPEG生物製劑幼稚異位性皮膚炎患者的IIb期研究，入組工作正在順利進行中。我們的目標是招募約 400 名患者，在 16 週的誘導期內接受三種不同的 REZPEG 方案與安慰劑方案的評估。誘導期結束後，達到從誘導轉為維持的閾值的患者將被重新隨機分配到一種或兩種不同劑量的維持方案，每月一次或每三個月一次給藥。這個時間表還將持續 28 週。我們這項研究的招募工作正按計畫進行，預計數據將於 2025 年上半年公佈。

Moving to alopecia areata, we believe REZPEG has strong scientific rationale in this indication. Alopecia areata is also a disease of the skin where your immune system starts to attack the hair follicle, thereby weakening the ability of stem cells to grow hair with prolonged immune attack. This eventually causes that hair follicle to release the hair altogether leading to Apache hair loss. And as the disease progresses to Boulder, biologically speaking, red bag through its central pathway of T-reg rescue, which is uniquely poised to address the diversity of immunohematology, providing broad potential for targeting multiple dermal diseases, including alopecia, for example, in alopecia.

談到斑禿，我們相信 REZPEG 在這適應症方面具有強而有力的科學依據。斑禿也是一種皮膚疾病，您的免疫系統開始攻擊毛囊，從而削弱幹細胞在長期免疫攻擊下生長頭髮的能力。這最終導致毛囊完全釋放頭髮，導致阿帕契脫髮。從生物學角度來說，隨著疾病進展到博爾德，紅包透過其T-reg 救援的中央途徑，獨特地準備解決免疫血液學的多樣性，為治療多種皮膚疾病（包括脫髮）提供了廣泛的潛力。脫髮。

There are almost no immune cells in normal hair follicles, meaning the hair follicle is in immune privileged tissue. T-regs are very important in maintaining that immune privilege and people with alopecia areata, develop a breakdown for that immune privilege space. We think the T-regs mechanism of rice pay can restore immune privilege and could provide durable disease control, which we believe would be game-changing in this indication. Jacque inhibitors are the only agents approved in alopecia and they do not provide disease durability after a patient discontinued treatment with JAK inhibitors.

正常毛囊中幾乎沒有免疫細胞，這意味著毛囊處於免疫特權組織。T-regs 對於維持免疫特權非常重要，斑禿患者會破壞免疫特權空間。我們認為大米支付的 T-regs 機制可以恢復免疫特權，並可以提供持久的疾病控制，我們相信這將改變這種適應症的遊戲規則。Jacque 抑制劑是唯一被批准用於治療脫髮的藥物，並且在患者停止 JAK 抑制劑治療後，它們不能提供疾病持久性。

It can take a patient anywhere from 9 to 18 months to grow hair. And once a patient starts taking a JAK inhibitor, which may happen for a variety of reasons, including toxicity, their hair falls out again rapidly. There is a high unmet need in this patient population for tolerable treatment options that provide durable response. And we believe that restoration of immune privilege is key to obtain durability. For these reasons, we believe there's an opportunity for Westpac to become a novel biologic therapy and alopecia areata.

患者可能需要 9 至 18 個月才能長出頭髮。一旦患者開始服用 JAK 抑制劑（可能由於多種原因（包括毒性）而發生這種情況），他們的頭髮就會再次迅速脫落。此患者族群對可提供持久反應的可耐受治療方案的需求尚未得到滿足。我們相信，恢復免疫特權是獲得持久性的關鍵。基於這些原因，我們相信西太平洋銀行有機會成為治療斑禿的新型生物療法。

We are initiating a Phase 2b study of REZPEG in alopecia. This the Phase IIb study plans to recruit roughly 80 patients with severe to very severe alopecia who will be randomized to REZPEG or placebo. Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total. Our primary endpoint for this study is the mean percent improvement in SALT for the Severity of Alopecia Tool at week 36, which is the validated outcome measure used for regulatory approval. We will also be looking at a number of other secondary endpoints, including proportion of patients who saw a reduction.

我們正在啟動 REZPEG 治療脫髮的 2b 期研究。這項 IIb 期研究計劃招募約 80 名患有嚴重至極嚴重脫髮的患者，他們將被隨機分配到 REZPEG 或安慰劑組。患者將接受 36 週的治療，總共觀察長達 60 週。我們這項研究的主要終點是第 36 週時脫髮嚴重程度工具的 SALT 平均改善百分比，這是用於監管批准的經過驗證的結果測量。我們還將研究許多其他次要終點，包括減少的患者比例。

Now turning to NLTR0165, our TNFR2 agonist antibody. TNFR2 is highly expressed on T-regs myeloid suppressor cells, regulatory B cells, neuronal cells and others. And TNFR2 agonism has been shown to potentiate the suppressive effect and overall functional properties of T-regs. And these other suppressive cell populations. If TNFR2 is absent it is associated with autoimmunity and other genetic conditions that resemble FoxP three loss of function.

現在轉向 NLTR0165，我們的 TNFR2 激動劑抗體。TNFR2 在 T-reg 骨髓抑制細胞、調節性 B 細胞、神經元細胞等高表現。TNFR2 激動劑已被證明可以增強 T 調節細胞的抑製作用和整體功能特性。還有這些其他抑制性細胞群。如果 TNFR2 缺失，則與自體免疫和其他類似 FoxP 3 功能喪失的遺傳狀況有關。

In contrast, its presence has been associated with immuno regulatory function and protective effects for multiple cell populations and tissues in the body. This TNFR2agonist program in our pipeline is built upon many years of direct experience gained from REZPEG. For example, we know that essential T-regs such as timing T regs require substantial checks that signal that is physiologically provided by the IL-2 receptor pathway. And this is essential theme and the mechanism of action of REZPEG.

相反，它的存在與免疫調節功能和對體內多個細胞群和組織的保護作用有關。我們管道中的 TNFR2 激動劑項目是建立在從 REZPEG 獲得的多年直接經驗的基礎上的。例如，我們知道重要的 T 調節因子（例如定時 T 調節因子）需要大量檢查，以檢測由 IL-2 受體途徑生理提供的訊號。這是REZPEG的基本主題和作用機制。

In contrast, T-regs that leave the central compartment and infiltrate the distal organs and tissues, they are less dependent on the jacks that pathway and instead shift their reliance onto NF-kappa B pathway engagement for their maintenance of suppressive function.

相較之下，離開中央區室並滲透遠端器官和組織的 T-reg 較少依賴於該通路的傑克，而是將其依賴轉移到 NF-κ B 通路的參與上來維持抑制功能。

TNFR2 is the most abundant TNF superfamily member expressed on T-regs and the key driver of NF-kappa B signaling and those dots and consequently, a bona fide TNFR2 agonist would be an incredibly exciting addition to our pipeline. Examples of indications that could be addressed by TNFR2 agonism include multiple sclerosis, mucosal immunology conditions such as alternative colitis of the GI or other oral mucosal diseases and even dermal autoimmune diseases like vitiligo, we have identified several the TNFR2 two antibody programs from an artificial intelligence-based antibody discovery campaign with our partner biologic design.

TNFR2 是在T-reg 上表達最豐富的TNF 超家族成員，也是NF-kappa B 訊號傳導和這些點的關鍵驅動因素，因此，真正的TNFR2 激動劑將是我們管道中令人難以置信的令人興奮的補充。TNFR2 激動劑可以解決的適應症包括多發性硬化症、黏膜免疫學病症（例如胃腸道替代性結腸炎）或其他口腔黏膜疾病，甚至皮膚自體免疫疾病（例如白斑症），我們已經從人工智慧中識別出幾種TNFR2 兩種抗體方案是基於我們的合作夥伴生物設計的抗體發現活動。

The lead antibody is called NKTR0165, and it has highly desirable properties, including exquisite TNFR2, selectivity, TNFR2 agonism and primary human cells activity in multiple preclinical efficacy models and a very well tolerated profile and early non-GLP toxicology. We have developed a manufacturing cell line for Lilly and are conducting upstream and downstream process development with the aim to enter the clinic for this program in the first half of 2025.

先導抗體稱為NKTR0165，它具有非常理想的特性，包括多種臨床前功效模型中精緻的TNFR2、選擇性、TNFR2 激動作用和原代人類細胞活性，以及​​良好的耐受性和早期非GLP毒理學。我們已經為禮來公司開發了生產細胞系，並正在進行上下游製程開發，目標是在2025年上半年進入臨床。

Later this year, we plan to present the first preclinical data of NKTR0165 at an upcoming medical conference. As we move forward with our IND-enabling studies, there is growing interest for a novel selective TNFR2 agonist like NKTR0165. And thus, we remain open to the opportunity of working with companies that have interest in these areas to strategize on the best path forward.

今年晚些時候，我們計劃在即將舉行的醫學會議上展示 NKTR0165 的第一個臨床前數據。隨著我們推進 IND 研究，人們對 NKTR0165 這樣的新型選擇性 TNFR2 激動劑越來越感興趣。因此，我們仍然願意與對這些領域感興趣的公司合作，以製定最佳的前進道路策略。

Now let's switch gears to our IL-15 based oncology program, NKTR255. NKTR255 is IL-15 based mechanism of action holds great promise as a combination agent with cell therapies and other mechanisms such as checkpoint inhibitors. And we are exploring the best partnering paths for continued development for this drug candidate.

現在讓我們轉向基於 IL-15 的腫瘤學計畫 NKTR255。NKTR255 是基於 IL-15 的作用機制，作為細胞療法和檢查點抑制劑等其他機制的組合藥物，前景看好。我們正在探索該候選藥物持續開發的最佳合作途徑。

Our Nectar sponsored trial combining NKTR255 with the approved CD19 CAR-T use Breyanzi and use Karta for treatment of patients with large B-cell lymphoma has enrolled 15 patients in the dose escalation portion of the study combination of NKTR255 in Breyanzi is also being studied in a separate investigator-sponsored trial at Fred Hutch. We are targeting the potential submission of data from these studies at medical meetings in the second half of this year.

我們的Nectar 贊助的試驗將NKTR255 與已批准的CD19 CAR-T 結合使用Breyanzi 和Karta 來治療大B 細胞淋巴瘤患者，已在Breyanzi 的NKTR255 組合研究的劑量遞增部分招募了15 名患者，該研究組合也正在研究中Fred Hutch 進行的另一項由研究者資助的試驗。我們的目標是在今年下半年的醫學會議上提交這些研究的數據。

A clinical trial in non-small cell lung cancer sponsored and funded by April data, which evaluates the combination enables that as tumor infiltrating lymphocytes cell therapy plus NKTR255 and checkpoint inhibitor is also ongoing and enrolling patients. And with our partner, Merck KGA, we have also been evaluating NKTR255 in combination with Philadelphia versus single agent Bavencio in the Phase two JAVELIN bladder memory study. And that study is on track to potentially report interim PFS data later this year. And with that, I will turn the call over to Sandy for a review of our financial guidance. Sandy?

由 4 月的數據贊助和資助的一項非小細胞肺癌臨床試驗評估了這種組合，使得腫瘤浸潤淋巴細胞療法加上 NKTR255 和檢查點抑製劑也正在進行中並招募患者。我們也與我們的合作夥伴 Merck KGA 一起，在第二階段 JAVELIN 膀胱記憶研究中評估了 NKTR255 與 Philadelphia 聯合用藥與單藥 Bavencio 的聯合用藥。該研究預計將在今年稍後報告中期 PFS 數據。接下來，我將把電話轉給桑迪，以審查我們的財務指導。沙？

Thank you, JZ, and good afternoon, everyone. We ended the year in a very strong financial position with $329.4 million in cash and investments and with no debt on our balance sheet. As Howard stated earlier, today's announcement of a $30 million financing further strengthens our cash position. Our revenue was $23.9 million for the fourth quarter of 2023 and $90.1 million for the full year of 2023.

謝謝你，JZ，大家下午好。年底，我們的財務狀況非常強勁，擁有 3.294 億美元的現金和投資，資產負債表上沒有任何債務。正如霍華德之前所說，今天宣布的 3000 萬美元融資進一步增強了我們的現金狀況。2023 年第四季我們的營收為 2,390 萬美元，2023 年全年營收為 9,010 萬美元。

Our operating costs and expenses for the fourth quarter of 2023 were $57.4 million and $353.8 million for the full year 2023. Our nonoperating expenses for the fourth quarter of 2023 were $8.6 million and $12.6 million for the full year 2023.

2023 年第四季我們的營運成本和費用為 5,740 萬美元，2023 年全年營運成本和費用為 3.538 億美元。我們 2023 年第四季的非營運支出為 860 萬美元，2023 年全年的非營運支出為 1,260 萬美元。

Q4 2023 included a non-cash charge of $6.1 million or $0.03 per share for the reclassification of the foreign currency translation adjustment to income related to the wind-down of our India legal entity. As a reminder, our India facility was sold in December 2022 for approximately $12 million with the wind-down of the entity occurring in 2023.

2023 年第四季包括 610 萬美元或每股 0.03 美元的非現金費用，用於將外幣換算調整重新分類為與印度法人實體解散相關的收入。需要提醒的是，我們的印度工廠於 2022 年 12 月以約 1,200 萬美元的價格出售，該實體將於 2023 年逐步關閉。

Our net loss for the fourth quarter of 2023 was $42.1 million or $0.22 per share. For the full year of 2023, our net loss was $276.1 million or $1.45 per share, excluding $111.8 million in noncash goodwill and other impairment charges. Net loss on a non-GAAP basis for the full year 2023 was $164.3 million or $0.86 basic and diluted loss per share.

我們 2023 年第四季的淨虧損為 4,210 萬美元，即每股 0.22 美元。2023 年全年，我們的淨虧損為 2.761 億美元，即每股 1.45 美元，不包括 1.118 億美元的非現金商譽和其他減損費用。2023 年全年非 GAAP 淨虧損為 1.643 億美元，即每股基本虧損及攤薄虧損 0.86 美元。

Looking forward to 2024 and beyond, our financial position remains strong in part, reflecting the cost savings initiatives we undertook last year. We plan to end 2024 with $200 million to $225 million in cash and investments. In addition to the $30 million pipe we announced this morning, our 2024, our cash guidance also includes [$15 million], resulting from an amendment executed today on a former 2020 agreement with certain entities of health care royalty.

展望 2024 年及以後，我們的財務狀況在某種程度上仍然強勁，這反映了我們去年採取的成本節約措施。我們計劃在 2024 年底前擁有 2 億至 2.25 億美元的現金和投資。除了今天早上宣布的 3000 萬美元管道外，我們的 2024 年現金指導還包括 [1500 萬美元]，這是今天對與某些醫療保健特許權實體簽訂的 2020 年前協議執行的修訂產生的。

Our cash runway now still extends well into the third quarter of 2026, which will take us through key value-generating milestones, including Phase two risk take data in a topic, dermatitis and alopecia areata. Our revenue for the full year of 2024 is expected to be between $75 million and $85 million, which includes $55 million to $65 million in noncash royalties and $20 million to $25 million in product sales.

我們的現金跑道現在仍然延伸到 2026 年第三季度，這將帶領我們實現關鍵的價值創造里程碑，包括皮膚炎和斑禿主題的第二階段風險承擔數據。我們2024年全年的收入預計在7500萬至8500萬美元之間，其中包括5500萬至6500萬美元的非現金特許權使用費和2000萬至2500萬美元的產品銷售。

We anticipate full year R&D expense will range between $120 million and $130 million dollars. This includes approximately $5 million to $10 million of noncash depreciation and stock-based compensation. The increase in R&D spend for 2024 over 2023 represents an increased investment into red bag Phase IIb studies in atopic dermatitis and alopecia areata as well as IND enabling studies for our antibody program, NKTR0165. This increase is partially offset by decreased spending on NKTR0255 clinical studies and cell therapy, which are completing in 2024.

我們預計全年研發費用將在 1.2 億美元至 1.3 億美元之間。這包括約 500 萬至 1,000 萬美元的非現金折舊和股票薪酬。2024 年研發支出較 2023 年增加意味著對異位性皮膚炎和斑禿的紅袋 IIb 期研究以及我們抗體項目 NKTR0165 的 IND 研究的投資增加。這一增長被 NKTR0255 臨床研究和細胞治療支出的減少部分抵消，這些研究和細胞治療將於 2024 年完成。

The remaining ongoing clinical studies for NKTR255 are primarily funded by our external partners. We expect G&A expense for the full year of 2024 to be between $70 million and $75 million, which includes $5 million to $10 million of noncash depreciation and stock-based compensation expense.

NKTR255 剩餘的正在進行的臨床研究主要由我們的外部合作夥伴資助。我們預計 2024 年全年的一般管理費用將在 7,000 萬至 7,500 萬美元之間，其中包括 500 萬至 1,000 萬美元的非現金折舊和股票薪酬費用。

Our full year non-cash interest expense is expected to be between $20 million and $25 million. As I stated earlier, we expect to end this year with $200 million to $225 million in cash and investments. And with that, we will now open the call for questions. Crystal?

我們全年非現金利息支出預計在 2,000 萬至 2,500 萬美元之間。正如我之前所說，我們預計今年底將擁有 2 億至 2.25 億美元的現金和投資。現在，我們將開始提問。水晶？

(Operator Instructions) Jay Olson, OpCo.

（操作員說明）Jay Olson，OpCo。

Oh, hey, this is John on the line for Jay. Thank you for taking the question and congrats on the progress. And maybe just a REZPEG 80 study. I'm wondering if you can talk about the initial feedback from doctors and patients participating in the study are especially in a context that there are many other competing trials out there? And also if you also could comment on the recruitment progress thus far versus your internal expectation, that will be great. And I have a quick follow-up question after that.

哦，嘿，我是約翰，正在接聽傑伊的電話。感謝您提出問題並祝賀取得的進展。也許只是一項 REZPEG 80 研究。我想知道您是否可以談談參與研究的醫生和患者的初步回饋，特別是在還有許多其他競爭性試驗的情況下？此外，如果您還可以根據您的內部期望對迄今為止的招募進度進行評論，那就太好了。之後我有一個快速的後續問題。

Mary, you want to take that question?

瑪麗，你想回答這個問題嗎？

Yes, sure, Howard. Thank you. Hi, Joe. This is Mary Tagliaferri here. When we look at the aggregate data from site activation screening activities and enrollment, we are on track to have our top line induction data from the IDE study in the first half of 2025. And in terms of the feedback, we're really pleased with the type of screening we're seeing and we believe this is driven by the data that was presented by Jonathan Silverberg as the APB. 2023 to the doctors really do see that one ReadyTech has a very rapid onset of action.

是的，當然，霍華德。謝謝。嗨，喬。我是瑪麗‧塔利亞費裡。當我們查看網站啟動篩選活動和註冊的匯總資料時，我們預計在 2025 年上半年獲得 IDE 研究的頂線歸納資料。就回饋而言，我們對所看到的篩選類型非常滿意，我們相信這是由 APB 喬納森·西爾弗伯格 (Jonathan Silverberg) 提供的數據推動的。 2023 年，醫生確實看到 ReadyTech 的起效非常迅速。

Number two, the depth of response that was seen with the mean percent change in easy after only 12 weeks of treatment. When most studies looking at the induction period of 16 weeks for doctors have been very impressed with. And then certainly for the benefit of their patients, they really love the durability that we saw when patients were off treatment for nine consecutive months and they were able to maintain that very deep response and easy. This is all very, very attractive for recruiting for the study. So we're doing very well. I have heard on that other side there. It's with enrollment and we're not experiencing that.

第二，治療僅 12 週後，隨 Easy 平均百分比變化可見的反應深度。大多數研究都對 16 週的誘導期印象深刻。當然，為了患者的利益，他們真的很喜歡我們在患者連續九個月停止治療時所看到的持久性，並且他們能夠保持非常深入的反應和輕鬆。這對於招募該研究人員來說非常非常有吸引力。所以我們做得很好。我在那邊聽說過。這是與註冊有關的，我們沒有經歷過這種情況。

Got it. Thank you. And just a quick follow-up. I'm just wondering to what extent you can leverage the clinical sites for the AD study for the upcoming alopecia areata initiation. So can you just use the same sites or are there some other a layer of working to do?

知道了。謝謝。只是快速跟進。我只是想知道您可以在多大程度上利用 AD 研究的臨床站點來啟動即將到來的斑禿。那麼您可以只使用相同的網站還是還有其他一些工作要做？

So we are going to use 12 sites that are participating in the AD study in our alopecia study. And those physicians are very excited to have an opportunity for a second skin disease to evaluate risk pick in alopecia areata. And again, they're really eager to see and durability of response because, of course, when they treat their patients with Check inhibitors, and the growth back phone immediately. They start to lose their hair once they discontinue treatment with the JAK inhibitor. So the promise have an age of durability and restore immune privilege is definitely really encouraging and exciting to that since I've been speaking to that.

因此，我們將在脫髮研究中使用參與 AD 研究的 12 個站點。這些醫生非常高興有機會評估第二種皮膚病的斑禿風險選擇。再說一遍，他們真的很渴望看到反應的持久性，因為，當然，當他們用檢查抑制劑治療患者時，生長會立即恢復。一旦停止 JAK 抑制劑治療，他們就會開始脫髮。因此，自從我一直在談論這一點以來，具有持久性和恢復免疫特權的承諾絕對是非常令人鼓舞和令人興奮的。

Roger Song, Jefferies.

羅傑·宋，杰弗里斯。

Hi team. This is Kambiz on for Roger, on maybe just following up on the alopecia areata study on how many total clinical sites will be enrolling and what's kind of the geographic distribution of those sites and then what are some key baseline characteristics for the patients in those studies will be on most of them be a JAK inhibitor refractory on any detail there would be appreciated. (multiple speakers)

大家好。這是羅傑 (Roger) 的 Kambiz，可能只是跟進斑禿研究，了解總共將有多少臨床中心入組，這些中心的地理分佈是什麼樣的，然後這些研究中患者的一些關鍵基線特徵是什麼其中大多數是JAK 抑制劑，對任何細節都難以控制，我們將不勝感激。（多個發言者）

Yeah, thanks, Howard. We have slightly over [30 sites]. We're going to be in Canada in the United States and in Poland from you as you may imagine when you're in Poland, they definitely have an access issue. And also it takes a very long time for those patients to get into see a dermatologist. So it's actually a very favorable environment to enroll patients. These patients on are going to be JAK inhibitor naive patients. And then our key inclusion criteria is severe to very severe alopecia and so these patients all have to have a salt greater than or equal to 50. And of course, this is the same patient population where baricitinib endoleaks jacket and into Pfizer's JAK inhibitor and eligibility criteria for their pivotal trial.

是的，謝謝，霍華德。我們已經稍微超過了[30 個站點]。我們將前往加拿大、美國和波蘭，正如您可以想像的那樣，當您在波蘭時，他們肯定有訪問問題。而且這些患者需要很長時間才能去看皮膚科。所以這其實是一個非常有利的招募病患的環境。這些患者將是未接受 JAK 抑制劑的患者。然後我們的關鍵納入標準是嚴重到非常嚴重的脫髮，因此這些患者的鹽分都必須大於或等於 50。當然，這也是巴瑞克替尼內漏進入輝瑞 JAK 抑制劑的同一患者群體，並且符合其關鍵試驗的資格標準。

Jessica Fye, JPMorgan.

潔西卡法耶，摩根大通。

For the Phase IIb atopic derm trial, what's the threshold efficiencies need to be considered a responder and be randomized at week 16? And then also curious, what's your latest thinking on whether the agency or the alopecia trial will readout first and why?

對於 IIb 期特異性皮膚試驗，需要在第 16 週被視為有反應者並進行隨機分組的閾值效率是多少？然後也很好奇，您對機構或脫髮試驗是否會首先讀出的最新想法是什麼？為什麼？

Yes, Hi, Jessica. It's Mary. So to be re-randomized, the patient has to have EC 50s, four of when they are rebranded to the maintenance. And once a month or once every three months, they will be on the same dose that they were randomized to in the induction period and you have a second question?

是的，嗨，潔西卡。是瑪麗。因此，要重新隨機化，患者必須有 EC 50，其中 4 次重新命名為維持治療。每月一次或每三個月一次，他們將接受與誘導期隨機分配的相同劑量，您還有第二個問題嗎？

Just the timing of alopecia versus AD data?

只是脫髮時間與 AD 數據的比較？

Yes. So we expect the AD trial read out first.

是的。因此，我們預計 AD 審判將首先宣讀。

Julian Harrison, BTIG.

朱利安·哈里森，BTIG。

Hi. Congrats on the progress and thank you for taking my questions on. I'm curious if you could remind us how you're thinking about efficacy beyond 12 weeks of dosing with breast peg in the atopic derm. How do you expect to plateau at some point? Or do you expect response rates to maybe be progressive through 44 weeks of dosing.

你好。恭喜您的進展，並感謝您回答我的問題。我很好奇您能否提醒我們您如何看待在異位性皮膚中使用胸栓給藥超過 12 週後的功效。您預計如何在某個時刻達到穩定狀態？或者您預計緩解率在 44 週的用藥期間可能會有所提高。

And then with regards to the Lilly litigation, sorry if I miss it, I'm wondering if you could comment on its current status and timing of next steps?

關於禮來公司的訴訟，抱歉，如果我錯過了，我想知道您是否可以對其目前的狀況和下一步的時間表發表評論？

Mary why don't you take the first part and I'll take the second part?

瑪莉為什麼你不參加第一部分而我參加第二部分呢？

Yes, you know, I definitely think that as we have extend our induction period from 12 to 16 weeks, we're going to see a greater number of patients experienced a deeper response. And so I very much look forward to seeing what the mean percent changes. As you know, the mean percent change from baseline to 12 weeks was 83%. And as such, greater than any other biologic agents, if you look at UP or odd per year, lebri or Maemo are Roca. We definitely saw the deepest response, but I do believe that we'll probably see more patients who experience the EC75 and even [EC9], as we go out four weeks in the induction period.

是的，你知道，我絕對認為，隨著我們將誘導期從 12 週延長至 16 週，我們將看到更多的患者經歷更深層的反應。所以我非常期待看到平均百分比的變化。如您所知，從基線到 12 週的平均百分比變化為 83%。因此，如果你看看 UP 或每年的奇數，lebri 或 Maemo 比任何其他生物製劑都更適合 Roca。我們確實看到了最深刻的反應，但我確實相信，當我們在誘導期進行四週時，我們可能會看到更多經歷 EC75 甚至 [EC9] 的患者。

With regard to Lilly Lilly, after after we filed our complaint in federal courts, Lilly tried to convince the federal court judge dismissed the case. As you know, and last week, the federal judge refused Lilly's request and the judge agreed to allow Nicolas claims primary claims to move forward, and we expect the judge to set a trial date in 2025. The court also ordered the parties to engage in mediation within the next three months to tried to resolve the issue. And so we're very, very happy the cases moving forward. The judge did not dismiss the case, and we look forward to indicating ourselves through the litigation process Excellent.

關於禮來（Lilly）禮來，在我們向聯邦法院提出申訴後，禮來（Lilly）試圖說服聯邦法院法官駁回此案。如您所知，上週聯邦法官拒絕了禮來公司的請求，法官同意允許尼古拉斯的主要索賠繼續推進，我們預計法官將審判日期定在 2025 年。法院也命令雙方在未來三個月內進行調解，試圖解決問題。因此，我們對案件的進展感到非常非常高興。法官沒有駁回此案，我們期待透過訴訟過程表明自己的優秀。

Andy Hsieh, William Blair.

安迪謝，威廉布萊爾。

I have two quick ones for us. One is can you talk about this ebbs and flow dynamic of associate with hair loss and alopecia, would you be enrolling kind of severe and really severe patients kind of mitigate that variability? And the second question has to do with the TNF receptor 165 program and we know that the receptor family is a trimer. So I guess to maximally agonize this receptor, you might have to have like a like a trimer design. I'm just curious if that's kind of a part of the design that goes into clone 165 and downstream from there, there's also kind of clustering. So is that also a part of the design of the molecule?

我有兩個快速的給我們。一是你能談談與脫髮和脫髮相關的這種起起落落的動態嗎？你會招募一些嚴重和真正嚴重的患者來減輕這種變異性嗎？第二個問題與 TNF 受體 165 程序有關，我們知道該受體家族是一個三聚體。所以我想為了最大程度地刺激這種受體，你可能必須有類似的三聚體設計。我只是好奇這是否是克隆 165 及其下游設計的一部分，也有某種集群。那麼這也是分子設計的一部分嗎？

Mary, do you want to take the hair loss and then JZ can take the TNF one?

瑪麗，你想接受脫髮然後JZ可以接受TNF嗎？

So, hi, Andy, it's Mary. So you're exactly right. Once patients go into the severe and very severe, generally speaking, there is not a regrowth of hair and that you're exactly right, but that's why the eligibility criteria and even for the threshold for approval by the FDA is this patient and it does patients to start out with some experience, the catchy hair loss. But as the disease progresses, certainly the hair becomes more extreme and even towards baldness. But once a patient loses their hair, it's very soon or they tend to have regrowth of their hair without some sort of medical intervention and an old pass over the second question to Jay.

所以，嗨，安迪，我是瑪麗。所以你是完全正確的。一旦患者進入嚴重和非常嚴重的階段，一般來說，頭髮就不會再生長，你是完全正確的，但這就是為什麼 FDA 批准的資格標準甚至門檻都是這個患者，而且確實如此患者先從一些經歷開始，脫髮的朗朗上口。但隨著疾病的進展，頭髮肯定會變得更加嚴重，甚至是禿頭。但是，一旦患者脫髮，很快就會脫髮，或者他們往往會在沒有某種醫療幹預的情況下重新長出頭髮，也不需要向傑伊提出第二個問題。

Thanks, Mary, and thanks, Andy, for your question. So you are right to TNF proteins or drivers. But as we've learned more and more about the biophysics of the receptors and the way the plot domains, right, which are the cystine which domains I hold together the receptor subunits, they actually work to create dimers receptors. And then a trimer comes along and clusters, six receptors or three pairs of dimers.

謝謝瑪麗，也謝謝安迪提出的問題。所以您對 TNF 蛋白或驅動程式的選擇是正確的。但是，隨著我們對受體的生物物理學以及繪圖域的方式了解得越來越多，右圖是將受體亞基結合在一起的胱氨酸域，它們實際上可以產生二聚體受體。然後一個三聚體出現並聚集，六個受體或三對二聚體。

So and then you can get additional clustering and some of this ultra structure has been published and some structural studies have been done well, we've come to understand a through learning about the cell biology of these receptors. The way these divers, the TIL multiple arise. And the way the apoptosis for binding to the receptor to work is that the epitope is actually fundamentally important.

因此，您可以獲得額外的聚類，並且一些超結構已經發表，並且一些結構研究已經完成，我們已經透過了解這些受體的細胞生物學來了解。這些潛水者的方式，TIL倍數出現。而細胞凋亡與受體結合發揮作用的方式是抗原決定位其實是非常重要的。

One of the things we discovered with NKTR0165 is that it's an episode that has its own unique properties and it can signal in a completely cluster independent fashion. For example, it doesn't need FC. It doesn't even these balances. That's one of the things that's really unique and highly differentiated about the antibodies that we've created and keeping in mind all of these ultra structural forms of the receptor and then the different states that the receptor can occupies is obviously one of the key things that's important for developing a success.

我們透過 NKTR0165 發現的一件事是，它是一個具有自己獨特屬性的事件，並且它可以以完全獨立於集群的方式發出信號。例如，它不需要FC。它甚至沒有這些平衡。這是我們創建的抗體真正獨特且高度差異化的事情之一，並牢記受體的所有這些超結構形式，然後受體可以佔據的不同狀態顯然是關鍵的事情之一對於發展成功很重要。

And I am showing no further questions from the phone lines. And I'd like to turn the conference back over to Howard Robin for any closing remark.

我在電話線上沒有再提出任何問題。我想將會議轉回霍華德·羅賓（Howard Robin）發表結束語。

I will say thank you, everyone, for joining us today. And as we stated on our call, we really remain focused on executing the development of REZPEG in our immunology focus research programs. I'd like to thank all of our employees for their very hard work and thank all of our shareholders, new and existing for their continued support. And we look forward to providing you with updates on our progress. So stay tuned, and thanks for joining us again.

我要感謝大家今天加入我們。正如我們在電話會議中所說，我們確實仍然專注於在我們的免疫學重點研究計畫中執行 REZPEG 的開發。我要感謝我們所有員工的辛勤工作，並感謝所有新舊股東的持續支持。我們期待向您提供我們的最新進展。請繼續關注，感謝您再次加入我們。

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

謝謝。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，每個人都有美好的一天。