Nektar Therapeutics (NKTR) 2023 Q3 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Nektar Therapeutics third-quarter 2023 financial results conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

美好的一天，感謝您的支持。歡迎參加 Nektar Therapeutics 2023 年第三季財務業績電話會議。 （操作員指示）請注意，今天的會議正在錄製中。

I would now like to hand the conference over to your speaker today, Vivian, we'll. Please go ahead.

我現在想把會議交給今天的發言人，維維安，我們會的。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; and Jennifer Ruddock, our Chief Business Officer. Unfortunately, Sandra Gardiner, our acting Chief Financial Officer, was not able to make it on today's call due to an unexpected family emergency.

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；以及我們的首席商務官 Jennifer Ruddock。不幸的是，我們的代理財務長桑德拉·加德納（Sandra Gardiner）由於家庭突發緊急情況而未能參加今天的電話會議。

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 drug candidates and research programs, the timing of the initiation of clinical studies and the availability of clinical data for our drug candidates, the timing and plans for future clinical data presentations, the formation, future development plans, or success of our collaboration arrangements, the 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陳述，包括有關候選藥物和研究項目的治療潛力和未來開發計劃、臨床研究啟動時間以及我們的臨床數據可用性的陳述。候選藥物、未來臨床數據展示的時間和計劃、我們合作安排的形成、未來發展計劃或成功、我們公司重組和重組後的預期、財務指導以及有關我們業務未來的某些其他聲明。

Because forward-looking statements relate to the future, they are 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 August 9, 2023, which is available at SEC.gov.

由於前瞻性陳述涉及未來，因此它們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 8 月 9 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。

We undertake no obligation to update any of these 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 nektar.com.

我們沒有義務更新任何這些前瞻性陳述，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 nektar.com 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 all for joining us today. In the third quarter, we made substantial progress in advancing our development programs.

謝謝你，維維安，也謝謝大家今天加入我們。第三季度，我們的發展計畫取得了實質進展。

First, on REZPEG, we're pleased to say that we began initiating our first clinical sites in October for the Phase 2b trial of REZPEG in patients with atopic dermatitis. We expect the first data from this study on the primary endpoint of easy reduction over the 16-week induction period sometime in the first half of 2025. The strength of our data from the randomized Phase 1b study gives us much optimism that we will be successful in the Phase 2b study.

首先，關於 REZPEG，我們很高興地說，我們在 10 月開始啟動第一個臨床試驗點，針對異位性皮膚炎患者進行 REZPEG 2b 期試驗。我們預計這項研究的第一份數據將在2025 年上半年的某個時候在16 週的誘導期內輕鬆減量的主要終點。我們來自隨機1b 期研究的數據強度讓我們非常樂觀，我們將取得成功在 2b 期研究。

These data were recently presented at the 2023 EADV meeting in an oral late-breaking news Plenary session, and JZ will summarize some of the new data presented later on in this call. But importantly, we observed a consistent benefit with monotherapy REZPEG across multiple clinical efficacy endpoints and patient reported outcomes.

這些數據最近在 2023 年 EADV 會議的口頭最新新聞全體會議上提出，JZ 將總結稍後在本次電話會議中提出的一些新數據。但重要的是，我們觀察到單一療法 REZPEG 在多個臨床療效終點和患者報告的結果中具有一致的益處。

As Dr. Silverberg mentioned in his Plenary talk, the Phase 1b trial of REZPEG is the first randomized placebo-controlled study to offer an exciting proof of concept for the important role of T regulatory cells in treating autoimmune disease. And it was exciting to see that this benefit was maintained for many patients through 36 weeks after treatment ended.

正如 Silverberg 博士在全體會議演講中提到的，REZPEG 的 1b 期試驗是第一個隨機安慰劑對照研究，為 T 調節細胞在治療自體免疫疾病中的重要作用提供了令人興奮的概念證明。令人興奮的是，許多患者在治療結束後 36 週內仍保持這種益處。

The substantial benefit observed with REZPEG could eliminate the need for frequent maintenance dosing for patients with atopic dermatitis, and it positions REZPEG with its novel T-regulatory-cell mechanism as a potential new treatment option, which could be highly disruptive in the biologic treatment landscape for atopic dermatitis.

REZPEG 所觀察到的實質益處可以消除異位性皮膚炎患者頻繁地維持給藥的需要，並且它使REZPEG 以其新穎的T 調節細胞機製成為一種潛在的新治療選擇，這可能對生物治療領域具有高度破壞性用於異位性皮膚炎。

The biologic market for atopic dermatitis is a multi-billion dollar market and growing. This landscape includes many IL-13 based mechanisms which overlap with one another, and REZPEG offers the unique promise of a new mechanism in this landscape and a new treatment paradigm that is well tolerated, which is why we're so optimistic about REZPEG's potential. Our goal is to ensure enrollment proceeds on track, to deliver data from the randomized Phase 2b trial on our planned timeline in the first half of 2025.

異位性皮膚炎的生物製劑市場是一個價值數十億美元的市場，而且還在持續成長中。這一領域包括許多相互重疊的基於IL-13 的機制，而REZPEG 在這一領域提供了一種新機制的獨特前景，以及一種耐受性良好的新治療範例，這就是我們對REZPEG 的潛力如此樂觀的原因。我們的目標是確保註冊工作按計劃進行，並按計劃在 2025 年上半年交付隨機 2b 期試驗的數據。

This past quarter, we expanded our plan for a second study in alopecia areata from its original randomized Phase 2a study design in approximately 40 patients to a randomized Phase 2b study design in approximately 80 patients. This is consistent with standard studies in this area and the incremental cost of this study is still within our projected budget. Importantly, this study will readout around the same time as the atopic dermatitis study.

上個季度，我們將第二項斑禿研究計畫從最初約 40 名患者參與的隨機 2a 期研究設計擴大到約 80 名患者參與的隨機 2b 期研究設計。這與該領域的標準研究一致，而這項研究的增量成本仍在我們的預期預算之內。重要的是，這項研究將與異位性皮膚炎研究大約同時發表。

We believe there's an opportunity for REZPEG to become a novel biologic mechanism in alopecia, which has no currently approved biologic treatments, and JAK inhibitors are the primary treatment mechanism. We know JAK inhibitors have cardiac safety concerns and patients experience a rebound after discontinuing therapy. So there's a high unmet medical need for those patients for a new treatment option.

我們相信 REZPEG 有機會成為治療脫髮的新型生物機制，目前脫髮還沒有批准的生物治療方法，而 JAK 抑制劑是主要的治療機制。我們知道 JAK 抑制劑有心臟安全問題，且患者在停止治療後會反彈。因此，這些患者對新的治療方案的醫療需求尚未得到滿足。

With the collective data we've generated to date on REZPEG in atopic dermatitis and other autoimmune diseases, we believe there's a strong scientific rationale for REZPEG with its Treg mechanism in action to be able to address the underlying pathogenesis of alopecia, and JZ will discuss the scientific rationale for this study in a moment. We plan to submit the IND for this study to the FDA by year end, and we expect to initiate the study shortly thereafter.

根據我們迄今為止所獲得的REZPEG 在異位性皮膚炎和其他自體免疫疾病中的集體數據，我們相信REZPEG 及其Treg 機制的作用有強有力的科學依據，能夠解決脫髮的潛在發病機制，JZ 將討論稍後我們將解釋這項研究的科學原理。我們計劃在年底前向 FDA 提交這項研究的 IND，並預計不久後啟動該研究。

We're also continuing to advance our preclinical programs in immunology, including our TNFR2 agonist antibody that offers a promising mechanism for multiple sclerosis, ulcerative colitis, and other autoimmune indications as well. Our goal is to submit an IND for this antibody program in 2024.

我們也正在繼續推進我們的免疫學臨床前項目，包括我們的 TNFR2 激動劑抗體，它為多發性硬化症、潰瘍性結腸炎和其他自體免疫適應症提供了一種有前景的機制。我們的目標是在 2024 年提交該抗體計畫的 IND。

Moving on to NKTR-255, we are pleased to have recently announced our new clinical study collaboration with Cellular Biomedicine Group, also known as CBMG, to evaluate NKTR-255 in combination with CBMG's TIL therapy in lung cancer patients that don't respond to anti-PD-1 therapy. CBMG is adding NKTR-255 to its ongoing Phase 1 study being conducted at Duke University Cancer Institute and other investigator sites in the US. We're also continuing our other clinical work with NKTR-255 while we evaluate additional strategic partnership pathways for the program.

接下來是 NKTR-255，我們很高興最近宣布與 Cellular Biomedicine Group（也稱為 CBMG）開展新的臨床研究合作，以評估 NKTR-255 與 CBMG 的 TIL 療法聯合治療對肺癌患者無反應的情況。抗PD-1治療。 CBMG 正在將 NKTR-255 加入杜克大學癌症研究所和美國其他研究機構正在進行的一期研究中。我們也持續 NKTR-255 的其他臨床工作，同時評估該計畫的其他策略夥伴途徑。

We ended the quarter in a strong financial position with $373 million in cash. And as I stated earlier, we are well positioned to be able to advance our planned clinical studies while maintaining a cash runway into the middle of 2026. The goal is to reach multiple value-enhancing Phase 2 milestones for REZPEG in the first half of 2025, and we believe we are well positioned to execute on this.

本季結束時，我們的財務狀況良好，擁有 3.73 億美元的現金。正如我之前所說，我們處於有利地位，能夠推進我們計劃的臨床研究，同時保持到 2026 年中期的現金跑道。我們的目標是在 2025 年上半年實現 REZPEG 的多個增值第二階段里程碑，我們相信我們有能力執行此任務。

Since many of you have been asking about the status of our litigation with Lilly, I'll make a brief comment that we continue to actively pursue the litigation and remain confident in our legal position.

鑑於你們中的許多人一直在詢問我們與禮來公司的訴訟狀況，我將簡短地評論一下，我們將繼續積極進行訴訟並對我們的法律地位保持信心。

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

這樣，我會將電話轉交給 JZ 進行研發討論。傑茲？

Thank you, Howard. Starting off with our lead immunology program REZPEG. As Howard stated earlier, this program is uniquely positioned as the most advanced IL-2-based Treg mechanism in the clinic and has potential in multiple autoimmune diseases, including our current focus areas of atopic dermatitis and alopecia areata.

謝謝你，霍華德。從我們的領先免疫學計畫 REZPEG 開始。正如Howard 之前所說，該計畫具有獨特的定位，是臨床上最先進的基於IL-2 的Treg 機制，並且在多種自體免疫疾病方面具有潛力，包括我們目前關注的異位性皮膚炎和斑禿領域。

Last month, Dr. Jonathan Silverberg presented compelling data for REZPEG from the Phase 1b trial in atopic dermatitis during a late-breaking abstract session at the 2023 EADV Congress. This presentation of the final study results for that trial highlighted the potential of REZPEG for the treatment of atopic dermatitis. 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.

上個月，Jonathan Silverberg 博士在 2023 年 EADV 大會的最新摘要會議上展示了來自異位性皮膚炎 1b 期試驗的 REZPEG 令人信服的數據。該試驗最終研究結果的介紹強調了 REZPEG 治療異位性皮膚炎的潛力。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，在許多這些測量中達到了統計顯著性。

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. And this type of extended disease control after the end of dosing is not observed for dupilumab or for JAK inhibitors.

重要的是，我們對 REZPEG 在 12 週誘導期結束後很長一段時間內的持久性感到鼓舞。許多患者在給藥結束後的 36 週內仍保持持久的疾病控制。 Dupilumab 或 JAK 抑制劑在給藥結束後沒有觀察到這種類型的延長疾病控制。

Time to response was rapid with over 40% of atopic dermatitis patients achieving EC75 by week three after only two doses of REZPEG at the highest dose level. REZPEG's rapid onset of action rivals that of JAK inhibitors which have outperformed dupilumab in head-to-head studies to date in this regard.

反應時間很快，超過 40% 的異位性皮膚炎患者僅在最高劑量服用兩劑 REZPEG 後，在第三週就達到了 EC75。 REZPEG 起效迅速，可與 JAK 抑制劑相媲美，迄今為止，在這方面的頭對頭研究中，JAK 抑制劑的表現優於 dupilumab。

Durability of the EC75 response was also observed with approximately 70% of these 75 responders maintaining their 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 remittive therapy for atopic dermatitis.

也觀察到了 EC75 反應的持久性，這 75 名反應者中約 70% 在 12 週誘導期結束後將其反應維持了 36 週。這是一個非常令人興奮的結果，顯示 REZPEG 有潛力成為異位性皮膚炎的第一個緩解療法。

Additionally, REZPEG was well tolerated and treatment with REZPEG did not induce antidrug antibodies in patients, which has been reported with some examples in the IL-2 mutein class. Compared with placebo, there were sustained increases in absolute numbers of circulating total and CD25 bright Tregs in the REZPEG treatment arms. The peak increase in CD25 bright Treg number was 10 fold above baseline at the highest REZPEG dose group.

此外，REZPEG 具有良好的耐受性，且 REZPEG 治療不會在患者體內誘導產生抗藥物抗體，這已在 IL-2 突變蛋白類的一些例子中得到報導。與安慰劑相比，REZPEG 治療組中循環總 Treg 和 CD25 Bright Tregs 的絕對數量持續增加。在最高 REZPEG 劑量組中，CD25 Bright Treg 數量的峰值增加是基線的 10 倍。

Despite a shorter-than-typical induction period of 12 weeks as compared with a 16 to 24 week induction period for most other biologics, there were clear improvements for all efficacy endpoints, including EC scores, the vIGA, BSA, itch NRS, DLQI, and POEM. These improvements begin as early as weeks 2 to 4 and continued through week 12 of treatment.

儘管大多數其他生物製劑的誘導期為 16 至 24 週，但其誘導期為 12 週，但所有療效終點均有明顯改善，包括 EC 評分、vIGA、BSA、癢 NRS、DLQI、和 POEM。這些改善早在治療第 2 至 4 週就開始出現，並持續到治療第 12 週。

To give you some perspective, with historical studies in atopic dermatitis at the lower dose levels of REZPEG, the improvements we saw were similar to those observed for biologic therapies. And at the higher dose level, REZPEG demonstrated a comparable activity to those reported with JAK inhibitors. The 83% improvement in EC score from baseline observed at only 12 weeks of induction with REZPEG was superior to what was seen at the dupilumab studies after 16 weeks. These promising data have us and KOLs very enthusiastic about the potential for a long-lasting responses in a frequent maintenance dosing with REZPEG in the setting of atopic dermatitis.

為了給您一些視角，根據 REZPEG 較低劑量水平對異位性皮膚炎的歷史研究，我們看到的改善與生物療法觀察到的改善相似。在較高劑量水平下，REZPEG 表現出與 JAK 抑制劑報告的活性相當的活性。 REZPEG 誘導僅 12 週時觀察到的 EC 評分較基線提高 83%，優於 16 週後 dupilumab 研究中觀察到的結果。這些有希望的數據讓我們和 KOL 對頻繁維持劑量 REZPEG 在異位性皮膚炎中產生持久反應的潛力充滿熱情。

The results we have obtained so far with REZPEG are significant for a number of reasons. Firstly, before this work was conducted, relatively little was known about the ability to restore Treg function to reverse immunological pathogenesis and improve the severity of dermal or cutaneous diseases. Now with REZPEG and its Treg mechanism, we have demonstrated clinical efficacy against the cutaneous manifestations of lupus, psoriasis, and atopic dermatitis.

到目前為止，我們透過 REZPEG 獲得的結果具有重要意義，原因有很多。首先，在進行這項工作之前，人們對恢復 Treg 功能以逆轉免疫發病機制和改善皮膚疾病嚴重程度的能力知之甚少。現在，透過 REZPEG 及其 Treg 機制，我們已經證明了對狼瘡、牛皮癬和異位性皮膚炎的皮膚表現的臨床療效。

These results begin to validate the Treg mechanism for the treatment of multiple pathologies of the skin. REZPEG's attractive mechanism employs the body's own immune system to restore tolerance by inducing the Treg pathway and presents a novel approach differing from the available broad or targeted strategies to block inflammatory pathways in dermal diseases such as atopic dermatitis.

這些結果開始驗證 Treg 治療多種皮膚病理的機轉。 REZPEG 的有吸引力的機制利用人體自身的免疫系統透過誘導Treg 路徑來恢復耐受性，並提出了一種不同於現有廣泛或靶向策略的新方法，用於阻斷特應性皮膚炎等皮膚疾病的發炎路徑。

Secondly, our hypothesis is that administration of the agonist drug, REZPEG, induces Treg expansion and engages multiple immunoregulatory mechanisms to facilitate immune tolerance and regulation by attenuating TH1, TH2, and TH17 effector T cells, suppressing antigen-presenting cell activity and fostering tolerogenic dendritic cells. We believe the science translate to the durability of response we observed in the atopic dermatitis trial and is the differentiating element that allows us to pursue an every-three-month dosing regimen in our ongoing Phase 2b atopic dermatitis study.

其次，我們的假設是，激動劑藥物REZPEG 的施用會誘導Treg 擴增，並參與多種免疫調節機制，透過減弱TH1、TH2 和TH17 效應T 細胞、抑制抗原呈現細胞活性和培養耐受性樹突來促進免疫耐受性和調節。細胞。我們相信科學轉化為我們在異位性皮膚炎試驗中觀察到的反應的持久性，並且是使我們能夠在正在進行的2b 期異位性皮膚炎研究中追求每三個月一次的給藥方案的差異化因素。

Biologically speaking, REZPEG, through its central pathway of Tregs rescue, is uniquely poised to address a diversity of immune pathologies, giving a broad potential for targeting multiple dermal diseases, including atopic dermatitis, alopecia areata and others.

從生物學角度來說，REZPEG 透過其拯救Tregs 的中心途徑，具有獨特的能力來解決多種免疫病理學問題，為治療多種皮膚疾病（包括異位性皮膚炎、斑禿等）提供了廣泛的潛力。

In October, we initiated the Phase 2b study of REZPEG in biologic naive atopic dermatitis patients. Our goal is to enroll roughly 400 patients with three different regiments of REZPEG versus placebo evaluated over a 16-week induction period. After the induction period, patients that meet a threshold to advance from induction to maintenance will be re-randomized into one of two maintenance regimens at different dosages at either once a month or once every three month dosing schedule that will continue for another 28 weeks. We expect the study will take approximately 54 weeks to conduct, and we expect data in the first half of 2025.

10 月，我們啟動了 REZPEG 在生物性異位性皮膚炎患者中的 2b 期研究。我們的目標是招募約 400 名患者，接受三種不同的 REZPEG 方案與安慰劑方案，並在 16 週的誘導期內進行評估。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兩種不同劑量的維持方案中的一種，每月一次或每三個月一次的給藥方案，將持續另外28 週。我們預計研究將需要大約 54 週的時間進行，並預計在 2025 年上半年獲得數據。

We also plan to initiate a Phase 2b study of REZPEG in alopecia areata later in early next year. Alopecia areata is an indication with a high clinical unmet need for a biologic as the only approved agents are JAK inhibitors, which come with a black box warning and lack durability after cessation of dosing. For these reasons, we believe there's an opportunity for REZPEG to become a novel biologic therapy in alopecia areata. And as I just mentioned, we believe that REZPEG and its Treg mechanism of action has great potential for addressing this indication which is essentially a dermal disease of the scalp.

我們也計劃於明年初啟動 REZPEG 治療斑禿的 2b 期研究。斑禿是一種臨床上對生物製劑的需求未被滿足的適應症，因為唯一批准的藥物是 JAK 抑制劑，該抑制劑帶有黑框警告，並且在停止給藥後缺乏持久性。基於這些原因，我們相信 REZPEG 有機會成為斑禿的新型生物療法。正如我剛才提到的，我們相信 REZPEG 及其 Treg 作用機制在解決這一本質上是頭皮皮膚疾病的適應症方面具有巨大潛力。

Across all of our studies with nearly 600 people treated, REZPEG demonstrates a consistent and highly predictable Tred cell pharmacodynamic profile in different autoimmune disease pathologies and even in healthy volunteers. Taken together, we believe there's strong rationale for REZPEG for the treatment of alopecia.

在我們對近 600 名接受治療的人進行的所有研究中，REZPEG 在不同的自體免疫疾病病理學甚至健康志願者中表現出一致且高度可預測的 Tred 細胞藥效學特徵。綜上所述，我們相信 REZPEG 治療掉髮有充分的理由。

The Phase 2b study plans to recruit roughly 80 patients with moderate to severe alopecia and will be randomized to REZPEG or placebo. As Howard mentioned, while it was previously our plan to run a Phase 2a trial with roughly 40 patients, after reviewing historical trials in this indication, we decided to increase the size of our study to achieve a Phase 2b design at minimal incremental costs.

2b 期研究計畫招募約 80 名中度至重度脫髮患者，並將隨機分配至 REZPEG 或安慰劑組。正如 Howard 所提到的，雖然我們之前計劃對大約 40 名患者進行 2a 期試驗，但在回顧了該適應症的歷史試驗後，我們決定擴大研究規模，以最小的增量成本實現 2b 期設計。

The patients will be treated for a period of 36 weeks and observed up to 48 weeks in total. Our primary endpoint for this study is mean percent improvement in SALT or the Severity of Alopecia Tool at week 36, which is very standard in the field. We will also be looking at a number of other secondary endpoints, including proportion of patients who saw a reduction in SALT.

患者將接受 36 週的治療，總共觀察長達 48 週。我們這項研究的主要終點是第 36 週時 SALT 或脫髮嚴重程度工具的平均改善百分比，這在該領域是非常標準的。我們還將關注許多其他次要終點，包括 SALT 降低的患者比例。

Now turning to our lead immunology research program, a TNFR2 agonist antibody program. TNFR2 is highly expressed on Tregs, neuronal cells, and others. And TNFR2 agonism has been shown to potentiate the suppressive effect and overall functional properties of Tregs. If TNFR2 is absent, it is associated with autoimmunity and other genetic conditions, resembling FOXP3 loss of function. In contrast, its presence has been associated with immunoregulatory function and protective effects for multiple cell populations and tissues in the body.

現在轉向我們的主要免疫學研究項目，即 TNFR2 激動劑抗體項目。 TNFR2 在 Tregs、神經元細胞等上高表現。 TNFR2 激動劑已被證明可以增強 Tregs 的抑製作用和整體功能特性。如果 TNFR2 缺失，則與自體免疫和其他遺傳性疾病有關，類似於 FOXP3 功能喪失。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。

Building upon what we know of the potential of regulatory-T-cell mechanisms, this makes this program incredibly exciting to us. Nektar has identified two lead antibodies that we have now validated for selective TNFR2 binding cell type specificity and TNFR2 agonism in primary human cell-based assays. We believe that a selective TNFR2 agonist holds great promise for the treatment of multiple autoimmune diseases and are aggressively pursuing this program and on track to submit our IND in 2024.

基於我們對調節性 T 細胞機制潛力的了解，這使得這個計畫對我們來說非常令人興奮。 Nektar 已鑑定出兩種先導抗體，我們現在已驗證它們在基於人類細胞的初級檢測中的選擇性 TNFR2 結合細胞類型特異性和 TNFR2 激動作用。我們相信選擇性 TNFR2 激動劑在治療多種自體免疫疾病方面具有廣闊的前景，並且正在積極推進這一項目，並有望在 2024 年提交我們的 IND。

And now I'd like to turn the call over to Mary to provide a brief update on our NKTR-255 program in oncology and our recent collaboration with CBMG. Mary?

現在我想將電話轉給 Mary，她簡要介紹了我們在腫瘤學方面的 NKTR-255 計畫以及我們最近與 CBMG 的合作。瑪麗？

Thank you, JZ. Moving to NKTR-255, we are continuing our work with NKTR-255 while we evaluate strategic partnering pathways. We believe there's a potential broad application for NKTR-255 to enhance the efficacy of cellular therapies. And to that end, as Howard mentioned earlier, we are pleased to have recently announced our new clinical study collaboration with a leading cell therapy company Cellular Biomedicine Group to evaluate NKTR-255 in combination with their TIL therapy, known as C-TIL051.

謝謝你，JZ。轉向 NKTR-255，我們將繼續與 NKTR-255 合作，同時評估策略合作途徑。我們相信 NKTR-255 具有潛在的廣泛應用，可增強細胞療法的功效。為此，正如 Howard 之前提到的，我們很高興最近宣布與領先的細胞治療公司 Cellular Biomedicine Group 合作進行新的臨床研究，以評估 NKTR-255 與其 TIL 療法（稱為 C-TIL051）的結合。

The study, which is being conducted by and fully funded by CBMG, is in advanced non-small cell lung cancer patients who do not respond to anti-PD-1 therapy. With few treatment options for these individuals, we are excited about the potential for this regimen to help patients.

研究由 CBMG 進行並全額資助，研究對象為對抗 PD-1 療法沒有反應的晚期非小細胞肺癌患者。由於這些人的治療選擇很少，我們對這種療法幫助患者的潛力感到興奮。

Preclinical and early clinical data suggests that IL-15 can improve proliferation and persistence of cellular therapies such as TIL to increase specific anti-tumor activity. The first investigator site is at Duke University with a leader in the lung cancer research field, Dr. Scott Antonia. Positive data from this study could lead to exploration of a pathway for accelerated approval by our partner CBMG.

臨床前和早期臨床數據表明，IL-15 可以改善 TIL 等細胞療法的增殖和持久性，從而增加特異性抗腫瘤活性。第一個研究地點位於杜克大學，由肺癌研究領域的領導者 Scott Antonia 博士擔任。這項研究的正面數據可能會導致我們的合作夥伴 CBMG 探索加速批准的途徑。

Our other studies are continuing in cell therapy, and we expect that we could see data reported next year from these trials, including the Phase 2 JAVELIN Bladder Medley study, which is being conducted and funded by our partner, Merck KGaA. Because of its unique potential as a combination agent with cell therapies and other mechanisms, we are exploring the best partnering and development path for continued development of NKTR-255.

我們在細胞療法方面的其他研究仍在繼續，我們預計明年可以看到這些試驗報告的數據，包括由我們的合作夥伴 Merck KGaA 進行和資助的 2 期 JAVELIN Bladder Medley 研究。由於其作為細胞療法和其他機制聯合用藥的獨特潛力，我們正在探索 NKTR-255 持續開發的最佳合作和開發路徑。

And with that, I will turn the call over to Jennifer for a review of our financial guidance. Jennifer?

接下來，我將把電話轉給詹妮弗，以審查我們的財務指導。詹妮弗？

Thank you, Mary, and good afternoon, everyone. We ended the third quarter with $373 million in cash and investments with no debt on our balance sheet. We now expect to end this year with at least $320 million in cash and investments, slightly higher than our prior projection of $315 million.

謝謝瑪麗，大家下午好。第三季末，我們擁有 3.73 億美元的現金和投資，資產負債表上沒有債務。我們現在預計今年底將擁有至少 3.2 億美元的現金和投資，略高於我們先前預測的 3.15 億美元。

As we had previously announced earlier this year, we reduced our San Francisco-based workforce by approximately 60%. And this personnel reduction represents approximately $30 million a year in operating expense reduction. The costs related to the restructuring were substantially paid in June. We will fully realize annual savings in 2024 as a result of this restructuring, and our financial position remains strong with a cash runway that extends into the middle of 2020. Importantly, this runway will take us through several key value-generating milestones for our pipeline.

正如我們今年稍早宣布的那樣，我們將舊金山的員工人數減少了約 60%。此次人員削減意味著每年營運費用減少約 3,000 萬美元。與重組相關的費用已於6月大量支付。透過此次重組，我們將在2024 年完全實現年度節省，並且我們的財務狀況仍然強勁，現金跑道將延伸到2020 年中期。重要的是，這條跑道將帶領我們實現管道的幾個關鍵的價值創造里程碑。

In Q3, we recorded a $10 million non-cash impairment charge for real estate leased assets in San Francisco, which contributed $0.05 to our net loss per share in the quarter. As a result, for the full year, we now expect to recognize restructuring, impairment, and cost of terminated programs of approximately $50 million to $55 million, which includes $37 million of non-cash impairment charges recognized through the first nine months of 2023. There is more detail on this in our Form 10-Q, which is being filed this afternoon.

第三季度，我們為舊金山的房地產租賃資產記錄了 1,000 萬美元的非現金減損費用，這為我們本季的每股淨虧損貢獻了 0.05 美元。因此，我們現在預計全年將確認約 5,000 萬至 5,500 萬美元的重組、減損和終止計畫成本，其中包括 2023 年前 9 個月確認的 3,700 萬美元非現金減損費用。我們今天下午提交的10-Q 表格中有更多詳細資訊。

We now expect G&A operating expense for the full year of 2023 to be between $80 million and $85 million, which includes approximately $15 million to $20 million of non-cash [appreciation] and stock comp expense. Our GAAP revenue for full year 2023 is still expected to be between $80 million and $90 million. This revenue includes $65 million to $70 million in non-cash royalties and $15 million to $20 million in product sales.

我們現在預計 2023 年全年的 G&A 營運費用將在 8,000 萬至 8,500 萬美元之間，其中包括約 1,500 萬至 2,000 萬美元的非現金[增值]和股票補償費用。我們 2023 年全年的 GAAP 收入預計仍將在 8,000 萬美元至 9,000 萬美元之間。該收入包括 6,500 萬至 7,000 萬美元的非現金特許權使用費和 1,500 萬至 2,000 萬美元的產品銷售收入。

We anticipate full-year GAAP R&D operating expenses will range between $105 million and $115 million, which includes approximately $15 million to $20 million of non-cash depreciation and stock comp expense. 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 at least $320 million in cash and investments.

我們預計全年 GAAP 研發營運費用將在 1.05 億美元至 1.15 億美元之間，其中包括約 1,500 萬美元至 2,000 萬美元的非現金折舊和股票補償費用。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至少 3.2 億美元的現金和投資。

And with that, we will now open the call for questions. Crystal?

現在，我們將開始提問。水晶？

Thank you. (Operator Instructions)

謝謝。 （操作員說明）

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Oh, hey, congrats on the progress, and thanks for providing this update. Can you talk about the Phase 2b trial in atopic dermatitis -- and congrats on the initiation of that study -- can you just talk about the feedback you're hearing from investigators? When do you expect to provide some guidance on enrollment rates and when do you expect to complete recruiting for that study?

哦，嘿，恭喜您取得了進展，並感謝您提供此更新。您能談談異位性皮膚炎的 2b 期試驗嗎？恭喜研究的啟動——您能談談您從研究人員那裡聽到的回饋嗎？您預計何時提供一些有關入學率的指導以及預計何時完成研究的招募？

Yeah, thanks, Jay. I'm going to ask Mary as she's been meeting with a lot of these investigators over the past couple of months to comment on that. Mary?

是的，謝謝，傑伊。我要問瑪麗，因為她在過去幾個月會見了很多調查人員，對此發表評論。瑪麗？

Thank you, Jennifer, and thank you, Jay, for asking the question. We recently attended EADV in Berlin, and we were able to meet with 30 different investigators, mostly from Europe. And we're going to recruit this trial at 100 different clinical sites in the United States, Canada, Europe, and Australia. And I could tell you that the investigators are very excited about REZPEG, the mechanism of action, and its application in the atopic dermatitis.

謝謝你，詹妮弗，謝謝你，傑伊，提出這個問題。我們最近參加了在柏林舉行的 EADV，並會見了 30 名不同的調查人員，其中大部分來自歐洲。我們將在美國、加拿大、歐洲和澳洲的 100 個不同的臨床中心招募這項試驗。我可以告訴你，研究人員對 REZPEG、其作用機制及其在異位性皮膚炎中的應用感到非常興奮。

The presentation that Dr. Jonathan Silverberg made was very well attended and very well received. And Jonathan Silverberg mentioned that for many years, we've known the importance of T regulatory cells, but we had never seen any data from a drug that actually expands T-regulatory cells to improve dermal indications such as the atopic dermatitis. And with a 83% reduction in the mean EC score from baseline, this was what he calls best in industry. So there is a widespread enthusiasm from the investigators.

Jonathan Silverberg 博士的演講受到了廣泛關注和好評。喬納森·西爾弗伯格（Jonathan Silverberg）提到，多年來，我們都知道調節性T細胞的重要性，但我們從未見過任何藥物的數據能夠真正擴大調節性T細胞以改善特異性皮膚炎等皮膚適應症。平均 EC 分數較基線降低了 83%，這就是他所說的行業最佳成績。因此，調查人員普遍熱情高漲。

I will tell you that a couple of other things that are found very compelling about our clinical trial -- are the following. Number one, we have a very good safety profile. Our drug is highly tolerable, and we've now shown that in roughly 600 patients. Number two, they really like the idea in the maintenance setting that we're going to evaluate a monthly and a three monthly maintenance regimen. And number three, the fact that their patients are going to be able to continue to receive REZPEG beyond the induction period of 16 weeks is very attractive to their patients and to the investigators as well.

我將告訴您，我們的臨床試驗中發現的其他一些非常引人注目的事情如下。第一，我們有非常好的安全狀況。我們的藥物具有很高的耐受性，我們現在已經在大約 600 名患者身上證明了這一點。第二，他們真的很喜歡維護設定中的想法，即我們將評估每月和三個月的維護方案。第三，他們的患者將能夠在 16 週的誘導期之後繼續接受 REZPEG，這一事實對於患者和研究人員來說都非常有吸引力。

So we feel that we will absolutely be able to deliver this trial on track and on time with data -- top-line data available in the first half of 2025. Hope that answers your question.

因此，我們認為我們絕對能夠按時按時交付這項試驗，並提供數據——2025 年上半年可獲得的頂線數據。希望這能回答您的問題。

Yeah. That's super helpful. Thank you so much for the details, and we'll look forward to future updates.

是的。這非常有幫助。非常感謝您提供的詳細信息，我們期待未來的更新。

On the Phase 2b study of REZPEG in alopecia areata, can you just talk about how you're thinking about dosing and then what's the bar there to initiate a Phase 3 study? And how would you compare the performance of REZPEG with recently approved oral drugs in alopecia?

關於 REZPEG 治療斑禿的 2b 期研究，您能否談談您對劑量的看法，以及啟動 3 期研究的障礙是什麼？您如何比較 REZPEG 與最近核准的口服藥物治療掉髮的效果？

Mary or JZ, would you like to take that?

Mary 或 JZ，你願意接受嗎？

Sure. I'm happy to address that.. So the JAK inhibitors, as you know, are efficacious. We see an effect after roughly 36 weeks of treatment. There are, as you know, many problems with JAK inhibitors. One, when you stop taking the JAK inhibitors, patients very rapidly lose their hair. And of course, you're well aware that there are black box warnings with the JAK inhibitors.

當然。我很高興能解決這個問題。因此，如您所知，JAK 抑制劑是有效的。我們在大約 36 週的治療後看到了效果。如您所知，JAK 抑制劑存在許多問題。第一，當停止服用 JAK 抑制劑時，患者會很快脫髮。當然，您很清楚 JAK 抑制劑存在黑框警告。

We very closely looked at the baricitinib data, and we believe if we have efficacy similar to baricitinib but don't accompany two things -- one, a rapid loss of hair after cessation of treatment or the ability to have -- again, just like we're looking at in atopic dermatitis -- a maintenance regimen that is far more convenient and favorable for the patients -- we believe that a biologic would have great appeal in the area of alopecia areata.

我們非常仔細地研究了巴瑞替尼的數據，我們相信，如果我們的療效與巴瑞替尼相似，但不伴隨兩件事——一是停止治療後頭髮迅速脫落，或者有能力——再次，就像我們正在研究異位性皮膚炎——一種對患者來說更加方便和有利的維持方案——我們相信生物製劑在斑禿領域具有巨大的吸引力。

We are going to look at two different doses versus placebo, and we will evaluate this at 36 weeks. And again, I think analogous or better efficacy than has been seen with the JAK inhibitors with an improved safety profile, tolerability profile and without the company, black box warnings would make REZPEG highly competitive in this space.

我們將比較兩種不同劑量與安慰劑的對比，並將在 36 週時進行評估。再說一遍，我認為與 JAK 抑制劑相比具有類似或更好的功效，具有改進的安全性、耐受性，並且如果沒有該公司的黑盒警告，將使 REZPEG 在該領域具有高度競爭力。

Great. Thank you for that super comprehensive responses, and congrats again on all the progress.

偉大的。感謝您非常全面的回复，並再次祝賀所有的進展。

Thank you very much, Jay.

非常感謝你，傑伊。

(Operator Instructions) Chris Shibutani, Goldman Sachs.

（操作員指令）Chris Shibutani，高盛。

Hi, everyone. This is Charlie on for Chris. Thanks so much for taking our questions, and congrats on the progress as well. Just couple of quick ones from us. First, on the 255 plans for strategic partnership. Wondering if there's any update on the expected timeline for that partnership? I know year end 2023 was the previous target. Wondering if that was still the case or if we had a new timeline in mind at this point?

大家好。這是查理為克里斯代言的。非常感謝您提出我們的問題，也祝賀我們的進展。我們只提供幾個快速的。一是關於255個策略夥伴關係計畫。想知道該合作關係的預期時間表是否有任何更新？我知道 2023 年底是之前的目標。想知道情況是否仍然如此，或者我們此時是否有一個新的時間表？

And then on the subsequent pipeline with the TNFR2 IND coming next year, wondering if there's any update on the PEG-CSF1 program and whether we should expect an IND from that program more on the 2025 sort of scale. Thank you.

然後，在明年即將推出的 TNFR2 IND 的後續管道中，想知道 PEG-CSF1 計劃是否有任何更新，以及我們是否應該期望該計劃在 2025 年獲得更大規模的 IND。謝謝。

So I'm going to have Howard take the first part of that question on 255. And then JZ, will you take the question on the preclinical programs?

所以我將讓 Howard 回答關於 255 的問題的第一部分。然後 JZ，你會回答關於臨床前計畫的問題嗎？

So yeah, sure. Good question. Look, NKTR-255 is a potentially very exciting program. We're talking to a number of companies. You see that we just completed a collaboration with CBMG in combination with TIL therapy. We have a collaboration with Merck KGA in bladder cancer. So there's a lot going on with 255. We also have our own study running at the Fred Hutchinson Cancer Center in cell therapy.

所以是的，當然。好問題。看，NKTR-255 是一個可能非常令人興奮的項目。我們正在與許多公司進行洽談。你看我們剛剛完成了與 CBMG 聯合 TIL 療法的合作。我們與 Merck KGA 在膀胱癌方面有合作。因此，255 正在發生很多事情。我們也在 Fred Hutchinson 癌症中心進行了自己的細胞治療研究。

So there are companies that are interested. I think we would like to complete a strategic collaboration for NKTR-255. Our focus as a company is in immunology now although I think this is a very exciting asset. And I can't give you specifics as to as to when and how a collaboration will get done, but we're making great progress there. And as you can see with the CBMG collaboration, we've just added another exciting potential application for NKTR-255.

所以有些公司對此感興趣。我認為我們希望完成 NKTR-255 的策略合作。作為一家公司，我們現在的重點是免疫學，儘管我認為這是一項非常令人興奮的資產。我無法向您提供有關何時以及如何完成合作的具體信息，但我們正在這方面取得巨大進展。正如您在 CBMG 合作中所看到的，我們剛剛為 NKTR-255 添加了另一個令人興奮的潛在應用。

So we'll keep you posted. I don't know that it's going to be end of this year, next year -- can't say for sure. But clearly, we're focused on that, and I do think it will get done.

所以我們會及時通知您。我不知道會是今年年底還是明年——不能確定。但顯然，我們專注於這一點，而且我確實認為它會完成。

JZ, would you handle the up the PEG-CSF1 question?

JZ，您能解決 PEG-CSF1 問題嗎？

Certainly. Yeah. Thanks for the question. So at this time, we've really prioritized our efforts on the TNFR2 program, and that's really for a couple of reasons. The first is that TNFR2 builds on a complementary pathway around Treg targeting that's distinct from the IL-2 pathway that REZPEG engages.

當然。是的。謝謝你的提問。因此，目前我們確實優先考慮了 TNFR2 項目，這實際上有幾個原因。首先，TNFR2 建立在圍繞 Treg 靶向的互補途徑之上，該途徑與 REZPEG 參與的 IL-2 途徑不同。

So for example, you know that TNFR2 is a TNF superfamily member is really one of the strongest signals that induces NF-kappa B in cells like Tregs. And it's also one of the strongest signals for controlling FOXP3 expression, which is a critical enzyme for both suppressive and differentiated and strong T-reg responses, right? You know that loss of FOXP3 causes dedifferentiation of Tregs.

例如，您知道 TNFR2 是 TNF 超家族成員，實際上是在 Tregs 等細胞中誘導 NF-κ B 的最強訊號之一。它也是控制 FOXP3 表現的最強訊號之一，FOXP3 是抑制、分化和強烈 T reg 反應的關鍵酶，對嗎？您知道 FOXP3 的缺失會導致 Tregs 去分化。

So it's really a target that's very, very sought at this time. It is really built off of what we know and have learned through our deep experience with REZPEG and the Treg field. And it also lets us leverage all that knowledge and advance our prioritized efforts into TNFR2. And so that's where we're really focused at this time. The PEG-CSF program, we will work on in the future, but it's really TNFR2, where we're focused on right now.

所以這確實是目前非常非常尋求的目標。它確實建立在我們透過 REZPEG 和 Treg 領域的豐富經驗所了解和學習的知識之上。它還讓我們能夠利用所有這些知識，將我們的優先工作推進到 TNFR2 領域。這就是我們目前真正關注的地方。我們將來會致力於 PEG-CSF 項目，但我們現在重點關注的實際上是 TNFR2。

I'll also say that as we've had the opportunity to discuss that program with some other outside entities, we have received a lot of interest around the program. We're finding many companies like pharmas and large biotechs and others that have really allocated time for TNFR2 into their strategy. So much is known around TNF inhibition with drugs like Humira, golimumab, infliximab, Enbrel and so on that have had such a profound effect on rheumatology.

我還要說，由於我們有機會與其他一些外部實體討論該計劃，因此我們對該計劃產生了很多興趣。我們發現許多公司，如製藥公司和大型生物技術公司以及其他公司，都在其策略中真正為 TNFR2 分配了時間。人們對修美樂（Humira）、戈利木單抗（golimumab）、英夫利西單抗（infliximab）、恩利（Enbrel）等藥物的TNF 抑製作用了解甚多，這些藥物對風濕病學產生了深遠的影響。

And through that period of time, we've understood about the TNFR1, TNFR2 receptor axes and what's missing. Would you just block all TNF-alpha signaling, which includes also blocking the TNFR2 pathway? So this is something that we're very excited about. We like all of the interest and where we're really prioritizing our energy.

透過那段時間，我們已經了解了 TNFR1、TNFR2 受體軸以及缺失的部分。您是否會阻斷所有 TNF-α 訊號傳導，其中還包括阻斷 TNFR2 路徑？所以這是我們非常興奮的事情。我們喜歡所有的興趣以及我們真正優先考慮我們的精力的地方。

We're very excited that we're on track. We're moving into our cell line stage aiming into the manufacturing setting, and we're on track to be submitting our IND next year in 2024 for that program.

我們很高興我們走上了正軌。我們正在進入細胞系階段，目標是進入製造環境，我們預計在明年 2024 年提交該專案的 IND。

Great. That's helpful. Thank you all so much.

偉大的。這很有幫助。非常感謝大家。

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

謝謝。我的電話線路上沒有再提出任何問題。現在我想將會議轉回霍華德·羅賓（Howard Robin）發表閉幕詞。

Well, thank you everyone for joining us today. And we remain focused on executing on the development of REZPEG in our immunology-focused research programs. And I think we have a clearly defined path forward.

好的，謝謝大家今天加入我們。我們仍然專注於在我們以免疫學為重點的研究項目中執行 REZPEG 的開發。我認為我們有明確的前進道路。

I'd like to thank all of our employees for their efforts and their hard work. And I want to thank our shareholders for their continued support. So we look forward to providing you with updates on our progress. Stay tuned, and thanks for joining us today.

我要感謝我們所有員工的努力和辛勤工作。我要感謝我們的股東一直以來的支持。因此，我們期待向您提供我們的最新進展。請繼續關注，感謝您今天加入我們。

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。每個人都度過了美好的一天。