Nektar Therapeutics (NKTR) 2025 Q1 法說會逐字稿

Good day and thank you for standing by. Welcome to the Nectar Therapeutics first quarter 2025 Financial results conference call.

您好，感謝您的支持。歡迎參加 Nectar Therapeutics 2025 年第一季財務業績電話會議。

(operator instruction)

（操作員指令）

I would now like to hand the conference over to your speaker today, Corinne Franklin and Nectar Investor Relations, who is filling in for Vivian Wu, who is on maternity leave. Please go ahead.

現在，我想將會議交給今天的演講者 Corinne Franklin 和 Nectar Investor Relations，她將代替正在休產假的 Vivian Wu 發言。請繼續。

Thank you, Crystal, and good afternoon, everyone.

謝謝你，Crystal，大家下午好。

Thank you for joining us today.

感謝您今天加入我們。

With us on the call are Howard Robin, our President and Chief Executive Officer, Doctor Jonathan Zaleski, our Chief Research and Development officer, Doctor Brian Kotson, our Chief Medical Officer, and Sandra Gardiner our Chief Financial Officer.

與我們一起參加電話會議的有我們的總裁兼執行長 Howard Robin、我們的首席研發長 Jonathan Zaleski 博士、我們的首席醫療官 Brian Kotson 博士和我們的財務長 Sandra Gardiner。

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.

在今天的電話會議上，我們預計將對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發展計劃的陳述。

The timing of the initiation of clinical studies and the availability of clinical data for drug candidates.

候選藥物臨床研究的啟動時間和臨床數據的可用性。

The timing and plans for future clinical data presentations.

未來臨床數據展示的時間和計劃。

The formation, future development plans, or success of our collaboration agreements, financial guidance, and certain other certain statements regarding the future of our business.

我們的合作協議、財務指導以及有關我們業務未來的某些其他聲明的形成、未來發展計劃或成功。

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, or actual results may differ materially from these statements.

由於前瞻性陳述與未來有關，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，或者實際結果可能與這些陳述有重大差異。

Important risks and uncertainties are set forth in our Form 10k that was filed on March 14, 2025, which is available at SEC.gov.

我們於 2025 年 3 月 14 日提交的 10k 表中列出了重要的風險和不確定性，該表格可在 SEC.gov 上查閱。

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 Nectar's website at nectar.com. With that said, I would like to hand the call over to our President and CEO Howard Robin. Howard.

我們不承擔更新任何前瞻性陳述的義務，無論由於新資訊、未來發展或其他原因。本次電話會議的網路直播將在 Nectar 網站 nectar.com 的投資者關係頁面提供。現在，我將把電話會議交給我們的總裁兼執行長 Howard Robin。霍華德。

Thank you, Corinne, and thank you all for joining us today.

謝謝你，科琳，也謝謝大家今天加入我們。

During the first quarter of 2025 we've been concentrating on the successful development of our immunology pipeline with a focus on advancing ResPEGaldu leukin, also known as ResPEG, in three separate phase 2 studies and completing the IND enabling studies for our lead earlier stage program, Nectar 165 at TNFR2 ex agonist antibody.

在 2025 年第一季度，我們一直專注於成功開發我們的免疫學管道，重點是在三個獨立的 2 期研究中推進 ResPEGaldu 白細胞介素（也稱為 ResPEG），並完成我們領先的早期項目 Nectar 165 在 TNFR2 ex 激動劑抗體的 IND 支持研究。

ResPAG is a first in class regulatory cell biologic therapy with the broad potential in a number of immune disorders.

ResPAG 是一流的調節細胞生物療法，在多種免疫疾病方面具有廣泛的潛力。

As a novel immune modulator mechanism, ResPE is poised to help a significant number of patients battling chronic conditions.

作為一種新型的免疫調節機制，ResPE 有望幫助大量與慢性病奮鬥的患者。

In June we planned to share our first top line results from the 16 week induction period for the 400 patient phase 2b study known as resolve AD.

6 月份，我們計劃分享 400 名患者參與的 2b 期研究（即解決 AD）的 16 週誘導期的首批頂線結果。

Which is studying resPEG in biologic naive patients with moderate to severe ectopic dermatitis.

該研究正在對患有中度至重度異位皮膚炎的生物製劑初治患者進行 resPEG 治療。

I will let Jay-Z review the upcoming important data milestone and the study design in a moment.

我將讓 Jay-Z 稍後回顧即將到來的重要資料里程碑和研究設計。

Our objective in this study is to demonstrate efficacy and safety and establish a dose to take forward in phase 3 studies.

我們本研究的目標是證明其有效性和安全性，並確定在第三階段研究中採用的劑量。

The study also has a 36 week maintenance period where patients will receive the same dose from induction but at every 4 week or every 12 week dosing intervals. The data from this maintenance period will be available in early 2026.

研究還包含一個為期 36 週的維持期，在此期間，患者將接受與誘導期相同的劑量，但每 4 週或每 12 週給藥一次。此次維護期的數據將於 2026 年初提供。

Ectopic dermatitis is a significant opportunity as there's a high unmet need for new mechanisms to treat these patients. There are currently $30 million adult patients with ectopic dermatitis in the US and $220 million adult patients globally. About half of these patients have moderate to severe disease, and this means their eczema covers a significant portion of their body and can severely affect their overall quality of life. According to the National Eczema Association, adults with ectopic dermatitis are 3 times more likely to experience anxiety and depression, which increases with the severity of the disease. Eczema could also cause severe itching and inflammation, impact a patient's sleep, and lead to body shame.

異位性皮膚炎是一個重大機遇，因為對於治療這些患者的新機制存在著很大的未滿足需求。目前，美國有 3,000 萬名成年異位性皮膚炎患者，全球有 2.2 億成年患者。其中約一半的患者病情嚴重至重度，這意味著他們的濕疹覆蓋了身體的很大一部分，並可能嚴重影響他們的整體生活品質。根據國家濕疹協會的數據，患有異位皮膚炎的成年人出現焦慮和憂鬱的可能性高出 3 倍，並且隨著病情的嚴重程度而增加。濕疹也會引起嚴重的搔癢和炎症，影響患者的睡眠，並導致身體不適。

Currently, approximately 8% of the patients with moderate to severe disease are treated with a biologic, most frequentlydexin, and yet we know that about half of those patients ultimately either don't benefit from treatment or become refractory, and once treatment is stopped, their ectopic dermatitis returns.

目前，約有 8% 的中度至重度疾病患者接受生物製劑治療，最常見的是地辛，但我們知道，這些患者中約有一半最終要么無法從治療中受益，要么變得難以治愈，一旦停止治療，他們的異位皮膚炎就會復發。

We believe this is because the approved biologics are effective at controlling the signs and symptoms of the disease, but they do not therapeutically target the underlying disease pathology to restore and heal the skin.

我們認為這是因為已核准的生物製劑能夠有效控制疾病的徵兆和症狀，但它們並不能從治療上針對潛在的疾病病理來恢復和治癒皮膚。

As a regulatory cell therapy, ResPeg instead regulates multiple immune pathways to address the overall disorder, and so we believe it could provide a much needed alternative to the IL-13 and IL 31 based therapies currently approved for these patients.

作為一種調節細胞療法，ResPeg 可以調節多種免疫途徑來解決整體疾病，因此我們相信它可以為目前為這些患者批准的基於 IL-13 和 IL 31 的療法提供急需的替代方案。

For our ResPEG AA phase 2B study in alopecia areata, we will report topline results in December of this year.

對於我們的斑禿 ResPEG AA 2B 期研究，我們將在今年 12 月報告頂線結果。

The patients enrolled in this study have severe to very severe alopecia areata.

參與此項研究的患者患有嚴重至非常嚴重的斑禿。

These are patients who have lost at least 50% of the hair on their scalp. In addition, this disease can impact the patient's eyebrows, eyelashes, and facial hair. Nearly$ 7 million people in the US have alopecia areata and $160 million people worldwide. Many of these patients also have other autoimmune diseases.

這些患者的頭皮上至少有 50% 的頭髮脫落。此外，這種疾病也會影響患者的眉毛、睫毛和臉部毛髮。美國有近 700 萬人患有斑禿，全球有 1.6 億人患有斑禿。其中許多患者還患有其他自體免疫疾病。

Our 90 patients study.

我們對 90 名患者進行了研究。

Is evaluating a 36 week treatment period for patients with alopecia areata as compared compared to placebo.

正在評估斑禿患者 36 週的治療期並與安慰劑進行比較。

We will then evaluate patients once they are off therapy to understand the long-term remittive potential for ResPEG.

我們將在患者停止治療後對他們進行評估，以了解 ResPEG 的長期緩解潛力。

Today DAC inhibitors are used to treat alopecia, and we know that when therapy is removed, patients lose their hair again very quickly.

如今，DAC 抑制劑被用於治療脫髮，我們知道，當停止治療時，患者的頭髮會很快再次脫落。

Our hope is that Resay can provide a new treatment paradigm and a long-term solution for patients battling this chronic condition.

我們希望 Resay 能夠為與這種慢性病作鬥爭的患者提供新的治療模式和長期解決方案。

In type 1 diabetes, Respa has great potential as a key regulatory cell therapy to slow the progressive loss of insulin producing beta cells, which are the target of the patient's overactive immune cells in this disease.

在第 1 型糖尿病中，Respa 具有巨大的潛力，可以作為關鍵的調節細胞療法，減緩產生胰島素的 β 細胞的逐漸喪失，而 β 細胞是這種疾病中患者過度活躍的免疫細胞的目標。

We're looking forward to the start later this year for the important proof of concept study in new onset type 1 diabetes, which is being sponsored and funded by Trials.

我們期待今年稍後開始對新發 1 型糖尿病進行重要的概念驗證研究，該研究由 Trials 贊助和資助。

Finally, with respect to our early stage immunology pipeline, we're advancing nectar 165, our TNFR2 agonist antibody program through IND enabling studies this year, and we've made great progress on this front.

最後，關於我們的早期免疫學管線，我們今年正在透過 IND 支持研究推進我們的 TNFR2 激動劑抗體計畫 Nectar 165，而我們在這方面取得了很大進展。

We're on track to complete these studies in 2025 and we'll be prepared to submit an IND filing. In addition, the by specific program Nectar 166, which incorporates a TNFR2 epitope with a validated antibody target. Is also on track and we're advancing this new program into preclinical studies.

我們預計在 2025 年完成這些研究，並準備提交 IND 文件。此外，透過特定的程序 Nectar 166，它將 TNFR2 抗原決定基與經過驗證的抗體標靶結合。一切進展順利，我們正在推動這個新計畫進入臨床前研究階段。

Lastly, we remain in a strong financial position with a runway into the 4th quarter of 2026.

最後，我們的財務狀況依然強勁，預計在 2026 年第四季實現成長。

And with that, I'll hand the call over to Zaleski, for a review of the upcoming data milestones. Zaleski,

說完這些，我將把電話交給札萊斯基，讓他審查即將到來的資料里程碑。札萊斯基，

Thanks, Howard, and thanks to everyone on today's call.

謝謝，霍華德，也感謝今天電話會議中的每個人。

To begin, I'd like to share with you some of the trial design details for our ResPEC studies, which will be providing nectar with numerous data catalysts over the next 9 months.

首先，我想與大家分享我們的 ResPEC 研究的一些試驗設計細節，這些研究將在未來 9 個月內為花蜜提供大量數據催化劑。

First, in atopic dermatitis, resolve AD enrolled approximately 400 biologic naive patients from October 2023 to January 2025 across multiple geographic regions globally.

首先，在異位性皮膚炎方面，Resolve AD 從 2023 年 10 月到 2025 年 1 月在全球多個地理區域招募了約 400 名未接受過生物製劑治療的患者。

The 52 week study is designed in two distinct phases, the induction phase and the maintenance phase.

這項為期 52 週的研究分為兩個不同的階段：誘導階段和維持階段。

As you'll recall, we only had the induction phase, which was 12 weeks of treatment in the prior ResPA phase 1b study.

您可能還記得，我們​​只有誘導階段，即先前 ResPA 1b 期研究中的 12 週治療期。

The goal of our phase 2b study is to identify a proper dose for an initial 16 week induction period, which can be our phase 3 dose, and also to identify a maintenance dose regimen that would be used for an additional 36 weeks after induction to maintain or potentially even improve effect for patients.

我們的 2b 期研究的目標是確定最初 16 週誘導期的適當劑量（可作為我們的 3 期劑量），並確定誘導後額外 36 週使用的維持劑量方案，以維持甚至可能改善患者的療效。

For the induction, we are evaluating 3 dose regimens as compared to placebo with a 3 to 3 to 3 to 2 design.

對於誘導治療，我們正在評估 3 種劑量方案，並與安慰劑進行比較，採用 3 比 3 比 3 比 2 的設計。

A high dose of 24 mcg per kilogram twice monthly, a mid-dose of 18 mcg per kilogram twice monthly, and a lower exposure dose of 24 mcg per kilogram once monthly with the goal, as I just stated, to establish a dose for induction treatment to advance into phase 3 studies.

高劑量為每月兩次每公斤 24 微克，中劑量為每月兩次每公斤 18 微克，較低暴露劑量為每月一次每公斤 24 微克，正如我剛才所說，目標是確定誘導治療的劑量，以進入第 3 階段研究。

As you will recall, the 24 mcg per kilogram dose given every two weeks was carried over from the phase 1B study of resin ectopic dermatitis, and this dose arm achieved statistical significance as compared to placebo following only a 12-week induction treatment period in that study.

您可能還記得，每兩週給予 24 微克/公斤的劑量是從樹脂異位性皮膚炎的 1B 期研究中延續下來的，並且在該研究中，僅在 12 週的誘導治療期後，該劑量組與安慰劑相比就達到了統計學意義。

ResPA resulted in an 83% decline in E scores as compared to 47% in placebo.

ResPA 導致 E 評分下降了 83%，而安慰劑則導致 E 評分下降了 47%。

After withdrawing the treatment in the phase 1B, we observed a strong signal of a remittive effect, with patients maintaining their reduced Escores for 36 weeks once the 24 mcg per kilogram twice a month dose was stopped at week 12.

在 1B 期停止治療後，我們觀察到了強烈的緩解效應訊號，在第 12 週停止每月兩次 24 微克/公斤的劑量後，患者維持降低的 E 評分達 36 週。

The mid dose of 18 mcg per kilogram given twice a month is a dose that is in between the 12 mcg per kilogram level that was studied in the phase 1b and the highest dose study of 24.

每月兩次給予的中等劑量為每公斤 18 微克，介於 1b 期研究的每公斤 12 微克水平和最高劑量研究的每公斤 24 微克水平之間。

And finally, in order to approximate the PK exposure for the low dose of 12 mcg per kilogram from the phase 1B study, we also gave the 24 mcg per kilogram dose once a month.

最後，為了接近 1B 期研究中每公斤 12 微克低劑量的 PK 暴露量，我們也每月給予一次每公斤 24 微克的劑量。

Importantly, because respeg is an agonist, we maintained weight-based dosing in our phase 2B study in atopic dermatitis, as well as in the alopecia study.

重要的是，由於 respeg 是一種激動劑，我們在異位性皮膚炎的 2B 期研究以及脫髮研究中維持了基於體重的劑量。

And our primary endpoint is the mean change and E score from baseline, and we are also measuring a secondary endpoints E 75, EZ 90, BSA, itch, and VIGA scores.

我們的主要終點是相對於基線的平均變化和 E 評分，同時我們也測量次要終點 E 75、EZ 90、BSA、搔癢和 VIGA 評分。

As you will recall in the stage 1B study for rape and ectopic dermatitis, all patients were enrolled in the US.

您可能還記得，在強姦和異位皮膚炎的 1B 期研究中，所有患者均在美國入組。

Because we observed an increased placebo effect in the US in our phase 1 study, and other investigators have experienced the same challenge, we targeted a lower enrollment number in the US for the phase 2 study.

由於我們在第 1 階段研究中觀察到美國安慰劑效應增強，其他研究人員也遇到了同樣的挑戰，因此我們針對第 2 階段研究在美國設定了較低的招募人數。

As a result, we enrolled only 17% of patients in the US with 67% in Europe, primarily in Poland, and the remainder in Australia and Canada.

因此，我們僅招募了美國 17% 的患者，歐洲 67% 的患者（主要在波蘭），其餘患者在澳洲和加拿大。

We took other important measures to address the high placebo rates observed in other atopic dermatitis studies. First, prior to randomization and resolve AD, baseline scores for patients were collected at screening and again at randomization. Patients with high variability in their baseline scores were screen failed, and this was done to eliminate patients with unstable disease.

我們採取了其他重要措施來解決其他異位性皮膚炎研究中觀察到的高安慰劑率問題。首先，在隨機分組和解決 AD 之前，在篩選時和隨機分組時收集患者的基線評分。基線評分變異性大的患者篩檢失敗，這樣做是為了排除病情不穩定的患者。

Another key objective in the phase 2 study was to utilize primarily sites that were led by board certified dermatologists who had specific prior experience in successful atopic dermat sites.

階段 2 研究的另一個關鍵目標是主要利用由委員會認證的皮膚科醫生領導的站點，這些醫生在成功的特應性皮膚病站點方面具有特定的經驗。

This ensured higher quality sites were participating in the study. We enrolled patients across 110 global sites, and the sites were carefully chosen and trained as part of our study operations.

這確保了更高品質的站點參與研究。我們在全球 110 個地點招募了患者，這些地點都是經過精心挑選和培訓的，這是我們研究操作的一部分。

As I just stated earlier, we saw a strong signal of remittive effect after the 12-week induction period in our phase 1B, even after removal of two twice monthly dose regimens after week 12. For the phase 2B, we are exploring what continued treatment with breast will look like after the induction period for a 36 week maintenance period.

正如我之前所說，我們在 1B 階段的 12 週誘導期後看到了強烈的緩解效應訊號，即使在第 12 週後取消了兩個每月兩次的給藥方案後也是如此。對於 2B 期，我們正在探索誘導期後 36 週維持期的持續乳房治療。

At the end of the 16 week induction period, patients who achieved at least an easy 50 score were re-randomized to receive one of two maintenance regimens at their original dose level for a 36 week treatment period on either a once a month or once every 3 month regimen.

在 16 週誘導期結束時，達到至少 50 分的患者將重新隨機分配接受兩種維持方案之一，以原始劑量水平進行 36 週的治療，治療方案為每月一次或每 3 個月一次。

We're excited to see the effect of continuing to treat after induction for Respa, which, as Howard said earlier, will be a future data readout in early 2026.

我們很高興看到 Respa 誘導後繼續治療的效果，正如霍華德之前所說，這將是 2026 年初的未來數據讀數。

Patients that did not need an easy 50 or better efficacy threshold at week 16 were permitted to go into an escape arm, which is the 24 mcg per kilogram dose given every 2 weeks.

在第 16 週時不需要達到簡單的 50 或更高療效閾值的患者可以進入逃避組，即每 2 週給予 24 微克/公斤的劑量。

Because RESPEC has an immune modulating mechanism, we are also following participants for one year after the conclusion of the 52 week treatment period, enabling us to evaluate RESPEC's potential for a long term remittive effect in patients.

由於 RESPEC 具有免疫調節機制，我們還會在 52 週治療期結束後對參與者進行一年的跟踪，以便我們評估 RESPEC 對患者產生長期緩解作用的潛力。

We want to understand how RESPEC differentiates from the IL-13 based mechanisms and DAC inhibitors where disease recurs in a substantial fraction of patients after discontinuing treatment.

我們想了解 RESPEC 與基於 IL-13 的機制和 DAC 抑制劑的區別，在這些機制和 DAC 抑制劑中，相當一部分患者在停止治療後會出現疾病復發。

Now moving on to alopecia areata, as Hower stated, we expect top line results from the 90 patient alopecia study in December of this year.

現在談談斑禿，正如豪爾所說，我們期待今年 12 月對 90 名患者進行的脫髮研究得出最重要的結果。

This study was started in March of 2024 and we completed enrollment in February of this year across 30 sites globally.

這項研究於 2024 年 3 月啟動，並於今年 2 月在全球 30 個地點完成了招募。

62% of patients were enrolled in Poland, 24% in Canada, and the rest in the US.

62% 的患者來自波蘭，24% 來自加拿大，其餘來自美國。

The study has a 36 week treatment period and is a similar design compared to the phase two study of baritin and alopecia.

研究的治療期為 36 週，與巴利汀和脫髮症的第二階段研究設計類似。

Alopecia areata is a dermal disease in which the patient's immune system mistakenly attacks the hair follicle and disrupts the body's normal ability to keep and grow hair, leading to severe hair loss and lack of hair regrowth.

斑禿是一種皮膚疾病，患者的免疫系統錯誤地攻擊毛囊，破壞身體正常的保持和生長毛髮的能力，導致嚴重脫髮和毛髮無法再生。

There is strong rationale for RESPEC in this indication based on the role of T. Rex to either prevent or downregulate the underlying pathology of the disease.

基於霸王龍在預防或調節該疾病潛在病理方面所起的作用，RESPEC 在該適應症中的應用具有充分的理由。

Patients had to present with severe to very severe disease to find the severity of alopecia tool score, or SALT 50 to salt 100, for at least 6 months in order to be eligible for inclusion.

患者必須患有嚴重至非常嚴重的疾病才能達到脫髮嚴重程度工具評分，或 SALT 50 至 SALT 100，持續至少 6 個月才有資格納入。

We are evaluating two doses, the 24 mcg per kilogram and the 18 mcg per kilogram given every two weeks as compared to placebo.

我們正在評估兩種劑量，即每兩週給予 24 微克/公斤和 18 微克/公斤，並與安慰劑進行比較。

Placebo rates tend to be quite low, under 10%.

安慰劑率往往很低，低於 10%。

Our primary endpoint for this study is mean% improvement in salt at week 36.

我們這項研究的主要終點是第 36 週時鹽含量的平均改善百分比。

We will also be looking at a number of other secondary endpoints, including the proportion of patients that had certain levels of improvement in SAT score, including the regulatory approval endpoint for a phase 3 study, the SALT 20 responder health.

我們還將研究其他一些次要終點，包括 SAT 分數有一定程度改善的患者比例，包括第 3 階段研究的監管批准終點、SALT 20 應答者健康狀況。

As Howard stated, we are also excited about the start of the phase 2 trial sponsored study, type 1 diabetes for breast.

正如霍華德所說，我們也對乳癌 1 型糖尿病第二階段試驗的開始感到興奮。

The 66 patient placebo-controlled study will enroll stage 3 new onset type 1 diabetes patients, and we look forward to providing the respi drug for this important indication.

這項由 66 名患者參與的安慰劑對照研究將招募第 3 階段新發 1 型糖尿病患者，我們期待為這項重要適應症提供呼吸藥物。

Finally, we are making great progress in the ID enabling studies for our novel TNFR2 agonist antibody program, Nectar 0165.

最後，我們在新型 TNFR2 激動劑抗體計畫 Nectar 0165 的 ID 支持研究中取得了巨大進展。

TNFR2 agonism potentiates Treg function as well as maintenance of T. Reg lineage stability, especially in the non-lymphoid tissue compartment.

TNFR2 激動劑增強了 Treg 功能以及 T. Reg 譜系穩定性的維持，尤其是在非淋巴組織區室中。

The first preclinical data from this program presented last year at UULAR demonstrated the nectar 0165 has a very high specificity for signaling through TNFR2 on Trex and enhancing their immuno regulatory phenotype.

該計畫去年在 UULAR 上展示的首批臨床前數據表明，nectar 0165 對透過 Trex 上的 TNFR2 發出信號並增強其免疫調節表型具有非常高的特異性。

It also showed that the agonist we discovered is able to signal to the TNFR2 multimeric receptor as a single-arm monovalent antibody.

它還表明我們發現的激動劑能夠作為單臂單價抗體向 TNFR2 多聚體受體發出訊號。

We believe this is the only antibody in this class being developed that has this attribute.

我們相信這是正在開發的此類抗體中唯一具有此屬性的抗體。

We are very excited with the unique and differentiated profile of this antibody, and we believe it has potential to become a first in class treatment for various autoimmune diseases, including multiple sclerosis, ulcerative colitis, and vitiliga.

我們對這種抗體的獨特和差異化特性感到非常興奮，我們相信它有潛力成為治療各種自體免疫疾病（包括多發性硬化症、潰瘍性結腸炎和白斑症）的一流藥物。

We're also designing a pipeline of by specific molecules that pair TNFR to agonism with other antibody targets, and we've identified the first by-specific antibody, nectar 016 in this program.

我們也正在設計一個由特異性分子組成的管道，將 TNFR 與其他抗體標靶配對以產生激動劑，我們在該專案中確定了第一個特異性抗體，即 nectar 016。

This first by specific antibody incorporates the TNFR2 epitope with another validated antibody target, and we are initiating our preclinical studies now.

這種首創的特異性抗體將 TNFR2 抗原決定基與另一種經過驗證的抗體標靶結合在一起，我們現在正在啟動臨床前研究。

We look forward to providing more details on this antibody as the studies progress.

我們期待隨著研究的進展提供有關該抗體的更多細節。

For NA 255, our IL-15 based oncology program, I am excited to share the data from our collaborators at the Fred Hutchinson Cancer Center in Seattle. We accepted for an oral presentation at this year's European Hematology Association congress being held in Milan.

對於 NA 255（我們的基於 IL-15 的腫瘤學計畫），我很高興與大家分享來自西雅圖弗雷德哈欽森癌症中心的合作者的數據。我們接受了在今年米蘭舉行的歐洲血液學會大會上進行口頭報告的邀請。

This will be the first data presented from their investigator sponsored study of nectar 255 following CD19 directed CAR T cells, brianzi in the 2nd and 3rd line, large B cell lymphoma patients.

這將是他們由研究人員贊助的研究中展示的第一批數據，該研究針對的是 nectar 255 繼 CD19 導向的 CAR T 細胞之後，用於治療二線和三線大 B 細胞淋巴瘤患者。

We believe these data reinforce the potential for nectar 2.5 to improve upon existing cell therapies for patients.

我們相信這些數據增強了 Nectar 2.5 改善現有患者細胞療法的潛力。

We continue to explore opportunities for continued development of this drug candidate in partnership with collaborators.

我們將繼續與合作夥伴共同探索繼續開發該候選藥物的機會。

And now I'd like to turn the call over to Sandy for a review of our financials.

現在我想把電話轉給桑迪來審查我們的財務狀況。

Thank you, Jay-Z, and good afternoon, everyone. We ended the first quarter of 2025 with $220.7 million in cash and investments and with no debt on our balance sheet.

謝謝你，Jay-Z，大家下午好。截至 2025 年第一季度，我們的現金和投資為 2.207 億美元，資產負債表上沒有債務。

We remain in a strong financial position and still expect our cash runway to extend into the 4th quarter of 2026 and to end 2025 with approximately $100 million in cash and investments.

我們的財務狀況依然強勁，預計現金流將延續到 2026 年第四季度，到 2025 年底，現金和投資將達到約 1 億美元。

Turning to the income statement, our first quarter 2025 revenue of $10.5 million was within our guidance range and comprised of non-cash loyalty revenue.

談到損益表，我們 2025 年第一季的營收為 1,050 萬美元，在我們的指導範圍內，並由非現金忠誠度收入組成。

We currently expect our quarterly revenue to remain at a similar level to Q1 for the remainder of 2025, totaling approximately $40 million for the full year.

我們目前預計，2025 年剩餘時間的季度營收將保持與第一季相似的水平，全年總計約 4,000 萬美元。

Our R&D expenses were $30.5 million for the first quarter of 2025, and we still anticipate full year R&D expense to range between $110 and $120 million including approximately $5 to $10 million of non-cash depreciation and stock-based compensation expense.

2025 年第一季度，我們的研發費用為 3,050 萬美元，我們仍預計全年研發費用將在 1.1 億美元至 1.2 億美元之間，其中包括約 500 萬至 1,000 萬美元的非現金折舊和股票薪資費用。

Our GNA expenses were $24.3 million for the first quarter. We still continue to expect GNA expense for the full year of 2025 to be between $60 and $65 million, including approximately $5 to $10 million of non-cash depreciation and stock-based compensation expense.

我們第一季的 GNA 支出為 2430 萬美元。我們仍預期 2025 年全年的 GNA 支出將在 6,000 萬至 6,500 萬美元之間，其中包括約 500 萬至 1,000 萬美元的非現金折舊和股票薪資支出。

Note that our operating expenses are not ridable throughout the year and will vary based on the level and type of activities each quarter. For example, our R&D expenses are higher in the first half of the year with greater study operational activities in our ResPEG Phase 2 atopic dermatitis study.

請注意，我們的營運費用不是全年都可以負擔的，並且會根據每個季度的活動水平和類型而有所不同。例如，由於 ResPEG 第 2 階段異位性皮膚炎研究中的研究營運活動增加，我們上半年的研發費用較高。

Non-cash interest expense for the first quarter was $5 million and is expected to remain at a similar level for the remaining three quarters, totaling approximately $20 million for 2025.

第一季的非現金利息支出為 500 萬美元，預計剩餘三個季度將保持在類似水平，2025 年總計約為 2000 萬美元。

This quarter we have included a new non-operating line item on our income statement titled Gain or Loss from equity Method Investment.

本季度，我們在損益表中增加了一項新的非營業項目，名為「權益法投資損益」。

As a reminder, on December 2, 2024, we completed the sale of our Huntsville manufacturing facility for consideration of $64.7 million in cash, net of transaction costs, and approximately 20% ownership in the new portfolio company Gannet Biochem or Gannet.

提醒一下，2024 年 12 月 2 日，我們完成了亨茨維爾製造工廠的出售，對價為 6,470 萬美元現金（扣除交易成本）以及新投資組合公司 Gannet Biochem 或 Gannet 約 20% 的所有權。

Under the required equity method of accounting, our investment in Gannet was recorded at fair value.

根據所需的權益法會計，我們對 Gannet 的投資以公允價值記錄。

At each subsequent period and date, our share of Gannet's gains or losses are recorded using the hypothetical liquidation at book value or HLDV method.

在每個後續期間和日期，我們所佔 Gannet 的收益或損失份額均採用帳面價值假設清算或 HLDV 方法記錄。

The HLBV method calculates the change in the hypothetical amount we would be entitled to receive if Gannet were liquidated at book value at the end of each period. This is a non-cash charge recorded outside of nectar's operating expenses and from period to period could fluctuate from a loss to a gain.

HLBV 方法計算如果 Gannet 在每個期間末以帳面價值清算，我們有權獲得的假設金額的變動。這是在花蜜公司營運費用之外記錄的非現金費用，並且各個時期可能會從虧損變為盈利。

In the first quarter, due to this accounting methodology, we recorded a non-cash loss from equity method investment of $4.5 million and we currently expect a loss of approximately $10 million for the full year 2025.

第一季度，由於這種會計方法，我們記錄了 450 萬美元的權益法投資非現金損失，目前我們預計 2025 年全年損失約為 1000 萬美元。

And importantly, as I just said, this is non-cash. We have no commitments to contribute cash to Gannet as an equity investor. We are simply providing this information as a housekeeping item so that you can forecast the rest of 2025 for this new non-cash line item.

而且重要的是，正如我剛才所說，這是非現金的。我們沒有承諾作為股權投資者向 Gannet 注入現金。我們只是將此資訊作為日常事務提供，以便您可以預測 2025 年剩餘時間的這一新的非現金項目。

Our net loss for the first quarter was $50.9 million or $0.24 basic and diluted net loss per share.

我們第一季的淨虧損為 5,090 萬美元，即每股基本淨虧損和稀釋淨虧損 0.24 美元。

Net loss before the equity method investment totaled $46.4 million equating to a non-gap basic and diluted net loss per share of $0.22.

權益法投資前的淨虧損總計 4,640 萬美元，相當於每股非差距基本和稀釋淨虧損 0.22 美元。

And as I stated earlier, we still expect the year to end the year with approximately $100 million in cash and investments with our cash friendly extending into the 4th quarter of 2026.

正如我之前所說，我們仍然預計今年年底將有大約 1 億美元的現金和投資，並且我們的現金狀況將延續到 2026 年第四季。

Finally, as we head into our June data reporting, we intend to enter into a quiet period for the month of June until we report the top line results for the ResPEG atopic dermatitis study.

最後，在我們進入 6 月數據報告之際，我們打算在 6 月進入靜默期，直到我們報告 ResPEG 異位性皮膚炎研究的頂線結果。

And with that we'll now open the call for questions operator.

現在我們將開始提問環節。

(operator instruction)

（操作員指令）

Yasmin Rahimi from Piper Sandler.

派珀·桑德勒 (Piper Sandler) 樂隊的 Yasmin Rahimi。

Hi, this is Dominic ontrias.

你好，我是 Dominic ontrias。

Thank you for taking our questions and congrats on the quarter. Could you, I have a couple of questions. One, could you remind us kindly what you hope to see in Resolve AD to move forward into a phase 3? And is your plan to move forward with one or two doses for that? And then also, what is your expectation for the placebo response in Resolve AD?

感謝您回答我們的問題，並祝賀本季取得的成績。你能嗎，我有幾個問題。首先，您能否提醒我們，您希望在 Resolve AD 中看到什麼，以進入第 3 階段？您打算注射一劑還是兩劑呢？那麼，您對 Resolve AD 中的安慰劑反應有何期望？

Thank you.

謝謝。

Jay-Z, would you like to answer that?

Jay-Z，你願意回答這個問題嗎？

Certainly, thank you for the question. So firstly, one of our objectives is that we, of course, had phase one data already. And have demonstrated proof of concept in atopic dermatitis. So one of the things we'd like to see is a replication of that data. So that's one of the of the components of efficacy that we'd like to see. And then we'd also compare the results against the other key benchmarks. And of course Dupikin is a very important benchmark. It is the leading standard of care in this space, so we'd like to be, minimum in the range of the efficacy that you see with Dupikin.

當然，謝謝你的提問。因此，首先，我們的目標之一是，我們當然已經擁有第一階段的數據。並已證明異位性皮膚炎的概念證明。因此，我們希望看到的事情之一就是複製這些資料。這是我們希望看到的功效要素之一。然後我們也會將結果與其他關鍵基準進行比較。當然，杜皮金是一個非常重要的基準。它是該領域的領先護理標準，因此我們希望其療效達到 Dupikin 的最低水平。

And then of course we'd like to even better improve on that and replicate our results of phase one. In terms of the number of dose levels that we would like to study, the purpose of the phase 2 study is that it's a classical dose range finding study. So ideally we would identify, a pretty clear dose and dose regimen that we would take forward. We'd have to obviously see what the results show us, but in the ideal case we would have one dose level that we would be taking forward into the phase 3 studies.

當然，我們希望在此基礎上進一步改進，並複製第一階段的成果。就我們想要研究的劑量水平數量而言，第二階段研究的目的是進行經典的劑量範圍探索研究。因此，理想情況下，我們會確定一個非常明確的劑量和劑量方案，並採取相應的措施。我們顯然必須觀察結果，但在理想情況下，我們會有一個劑量水平，並將其帶入第 3 階段的研究。

And can you remind me your third question, please?

您能提醒我您的第三個問題嗎？

Yeah.

是的。

It was what are the expectations for the placebo response in Resolve 8D?

對於 Resolve 8D 中的安慰劑反應有何期望？

Yeah, okay, thank you. Yeah, so as I mentioned in the call, in the phase one, we use sites that were 100% in the 13 sites, and we saw about a 47% placebo response, which was a little bit on the higher side, still in the range of modern studies, but on the higher end, and it's certainly reflective of a general trend that we're seeing, particularly in sites in the US. And so we took, proactive measures in order to TRY and control the placebo response rate by only enrolling a proportion of patients in the US, 17%, and enrolling in the rest of the world for the remainder of the patient population, as well as some of the other things that I mentioned, such as using board certified dermatologists and the majority of sites to have consistent and highest quality rating of the disease.

嗯，好的，謝謝。是的，正如我在電話中提到的，在第一階段，我們使用了 13 個站點中 100% 的站點，我們看到了大約 47% 的安慰劑反應，這個數字有點偏高，仍然在現代研究的範圍內，但處於較高水平，這肯定反映了我們所看到的總體趨勢，特別是在美國的站點。因此，我們採取了積極措施，試圖控制安慰劑反應率，具體方法是僅招募美國的一部分患者（17%），並在世界其他地區招募剩餘的患者群體，以及採取我提到的其他一些措施，例如使用委員會認證的皮膚科醫生和大多數站點對疾病進行一致且最高的品質評級。

So we'd like to see, a lower rate, for example, than what we saw in that might be and we'll look forward to reporting, the actual placebo response rate as we prepare and and report the top line next month.

因此，我們希望看到一個比我們所看到的更低的比率，並且我們期待在下個月準備和報告頂線時報告實際的安慰劑反應率。

Thank you.

謝謝。

Julian Harrison from BTIG.

BTIG 的 Julian Harrison。

I congrats on the progress and thank you for taking my questions.

我祝賀您取得的進展，並感謝您回答我的問題。

On the phase 2B atopicderm data we're expecting in June, or rather the trial, I have a specific question. I was wondering if you're able to tell us how many patients have progressed to the maintenance portion of the trial so far, and of those, how many have crossed over to the escape arm of the trial?

關於我們預計在 6 月公佈的 2B 期 Atopicderm 數據，或者更確切地說是試驗，我有一個具體的問題。我想知道您是否可以告訴我們，到目前為止，有多少患者已經進入試驗的維持部分，其中有多少人已經進入試驗的逃脫部分？

Are you blinded to that, or is that maybe something you could disclose now?

您對此視而不見嗎，或者您現在可以透露一些事情？

Jay, did you get that question Julian? Yeah, this is Jay-Z. Yeah, so it's a good question.

傑伊，朱利安，你明白這個問題嗎？是的，這是 Jay-Z。是的，這是個好問題。

We can't disclose that kind of information right now, but we will disclose that as well as more features of the data and the actual results, next month when we present the top line results.

我們現在無法披露此類信息，但我們將在下個月公佈最終結果時披露這些信息以及更多數據特徵和實際結果。

All right, thank you.

好的，謝謝。

Thank you.

謝謝。

Jay Olson - Oppenheimer & Co. Inc.

Jay Olson - Oppenheimer & Co. Inc.

Oh hey, congrats on the progress and thank you for taking our questions.

哦，嘿，祝賀您取得進展，感謝您回答我們的問題。

When you share the results from the Phase 2B results study, can you just talk about the scope of the data you're planning to share and of the secondary end points which are most important?

當您分享 2B 期結果研究的結果時，您能否談談您計劃分享的數據範圍以及最重要的次要終點？

Yeah, thanks, Jay.

是的，謝謝，傑伊。

So one of the kind of unique things about the dermatology conferences is that they're a little bit more lenient than say ASCO is in terms of embargo data, and I think that's a good thing, here.

因此，皮膚病學會議的獨特之處之一是，它們在禁運數據方面比 ASCO 稍微寬鬆一些，我認為這是一件好事。

So certainly when we present the topline data, the primary endpoint will be a key key element that we would present. And that's the percent change from baseline and score and compared to placebo, all of the cohorts one by one and then there are secondary end points and you ask which ones are, quite important. So definitely EZ 75, EZ 90, the IGA, those are quite important. Probably itch is also quite important. I mean, those are the ones that really firstly are used as registering end points in the case of EB 75 VIGA and also things like H are just key, for the kind of comparisons that we do and then we also give, the picture isn't efficacy it be the total tolerability, the total ability to understand the both risk and the benefit of the drug. So I hope that gives you a flavor of the kind of things we would present.

因此，當我們展示頂線資料時，主要終點肯定是我們要展示的關鍵要素。這是相對於基線和分數的百分比變化，並與安慰劑進行比較，所有隊列逐一比較，然後是次要終點，您要問哪些是相當重要的。所以 EZ 75、EZ 90、IGA 絕對非常重要。或許搔癢也很重要。我的意思是，這些是 EB 75 VIGA 案例中首先用作註冊終點的因素，而且像 H 這樣的因素也是關鍵，對於我們所做的比較，我們還給出，圖像不是功效，而是總體耐受性，是理解藥物風險和益處的總體能力。我希望這能讓您了解我們將要呈現的內容。

Yeah, absolutely super helpful and maybe if I could please ask one follow up, will you be taking weight-based dosing into phase 3, or will it be a fixed dose?

是的，絕對非常有幫助，如果我可以問一個後續問題，您是否會根據體重進入第 3 階段進行劑量控制，還是採用固定劑量？

Yeah, so one of the things that we've learned about this drug as an agonist, it's quite important. To dose it very precisely. And so weight-based dosing is what we've identified is critical.

是的，我們了解到的有關這種藥物作為激動劑的事情之一，是非常重要的。劑量要非常精確。因此，我們認為基於體重的劑量至關重要。

So our plan is to continue to use weight-based dosing and it's pretty common, there are many drugs that are dosed in what you call weight bands, so if a person is between weight A and weight B, they get this SKAU or SKU, for example, Orencia and other drugs, many other drugs that do that way. So we would be using weight-based dosing and then our long term goal would be also that we would launch, in an auto injector and maintain that kind of weight-based banding as our dose approach.

因此，我們的計劃是繼續使用基於體重的劑量，這很常見，許多藥物的劑量都是根據所謂的體重範圍確定的，所以如果一個人的體重在 A 和 B 之間，他們就會得到這個 SKAU 或 SKU，例如，Orencia 和其他藥物，許多其他藥物都是這樣給藥的。因此，我們將使用基於體重的劑量，然後我們的長期目標也是推出自動注射器，並保持這種基於體重的劑量帶作為我們的劑量方法。

Great thanks so much for taking the question.

非常感謝您回答這個問題。

Roger Song from Jeffrey's.

來自 Jeffrey's 的 Roger Song。

Great, thanks for the update and taking your question.

太好了，感謝您的更新和回答您的問題。

Can you remind us what is the dropout rate for your phase 1 B dermatitis trial, as I understand the small, but what is the expectation for your phase two? Anything you can tell us on the blind blinded fashion, what is the discontinuation you're seeing, would you report both ITT and Esimal for the efficacy endpoint?

您能否提醒我們，您的第 1 階段 B 皮膚炎試驗的退出率是多少，據我所知，退出率很小，但您對第 2 階段的期望是多少？您能否以盲法告訴我們任何訊息，您所看到的停藥情況如何，您是否會報告 ITT 和 Esimal 的療效終點？

Yeah, hey Roger, yeah, thanks for the question. So you know when we published The results from the phase 1B last year in our nature communication paper we showed that there was between a 30% and 20% dropout rate for placebo and the two dose levels of Respe, and it was actually higher for placebo, 30% for placebo, and in the low to mid-20s for the respeg arms for the low dose and the high dose. And so, we presented that data.

是的，嘿羅傑，是的，謝謝你的提問。因此，您知道，當我們去年在《自然通訊》論文中發表 1B 期研究結果時，我們發現安慰劑組和兩種劑量水平的 Respe 組的退出率在 30% 到 20% 之間，而安慰劑組的退出率實際上更高，為 30%，而低劑量和高劑量的 Respeg 組的退出率則在 20% 左右的退出率則在 20% 左右。因此，我們展示了這些數據。

For example, if you consider a study like the Lebrecizumab phase 2 trial there in that study when they looked at the overall pool analysis, I think they had about a 28% dropout rate.

例如，如果您考慮像 Lebrecizumab 第 2 階段試驗這樣的研究，當他們查看整體匯集分析時，我認為他們的退出率約為 28%。

It's just another benchmark. And for us, in the case of June, we'll report that, the dropout rates, and we'll report that, for example, patients that discontinued during the induction period as well as the earlier question, patients that completed the induction period that either went on to re-randomize into maintenance or that went into the escape.

這只是另一個基準。對我們來說，就六月而言，我們將報告退出率，例如，我們將報告在誘導期內停藥的患者以及先前的問題，完成誘導期的患者要么繼續重新隨機進入維持治療，要么進入逃脫治療。

So stay tuned and we'll report all of those results next month.

請繼續關注，我們將在下個月報告所有結果。

Got it. Okay. And then in terms of the next step, given the phase two is biologic 9 patient population, how would you consider to expand this into post biologics and then in the phase 3?

知道了。好的。然後就下一步而言，考慮到第二階段是生物製劑 9 名患者群體，您會如何考慮將其擴展到生物製劑後以及第三階段？

Thank you.

謝謝。

Yeah, so you know our data is really built upon what we've seen in our own proof of concept study, right? And that's why we ran that phase 1 in biologic naive patients and we ran the phase 2 biologic naive patients and we would expect to also run our phase 3 studies in the biologic naive patients.

是的，所以您知道我們的數據實際上是基於我們在概念驗證研究中看到的內容而建立的，對嗎？這就是為什麼我們在未接受過生物製劑治療的患者中開展了第 1 階段研究，並在未接受過生物製劑治療的患者中開展了第 2 階段研究，並且我們還希望在未接受過生物製劑治療的患者中開展第 3 階段研究。

However, during the phase 3 program, we would also study the drug. In biologic experience. And so that would be something that we would do as part of the phase 3 program. Different companies use different approaches, for example, Amgen with the oka program combined biologic naive and experience into the same study. Whereas lebbracizumab and amitumab did separate studies, for those populations, so we'll still be, deciding the best approach for us, but we'll definitely evaluate both naive and experience-based populations in the phase 3 program.

然而，在第 3 階段計劃期間，我們也會研究該藥物。在生物學經驗中。這將是我們作為第三階段計劃的一部分要做的事情。不同的公司使用不同的方法，例如，安進公司的 oka 計劃將生物製劑的初步研究和經驗研究結合到了同一項研究中。而 lebbracizumab 和 amitumab 針對這些人群進行了單獨的研究，因此我們仍然會決定最適合我們的方法，但我們肯定會在第三階段計劃中評估初治人群和基於經驗的人群。

Excellent. Just one last quick question in terms of the partnership, would you be considering, seeking partnership after phase two, or you will take this, red flag into phase phase 3 on your own.

出色的。關於合作關係，我只想問最後一個問題，您是否會考慮在第二階段之後尋求合作關係，或者您是否會獨自承擔這個危險信號進入第三階段。

Thank you.

謝謝。

Yeah, that's this Howard. That's a very good question, Roger. I think, look, if you look at Nectar's current financial position, we clearly aren't in a position to, execute on a full phase 3 program without a partner. So I think what we will be doing is looking at the quality and the strength of the data, and we will be talking to companies about collaborating now. That doesn't mean we'll be out licensing the drug. Way we will do that, but we will be talking to companies and come up with a collaboration that allows, the least amount of dilutive financing for our investors and at the same point allows us to retain, a significant portion of ownership of the drug and there's lots of lots of different ways to do that, but clearly, collaboration is likely the direction we go

是的，這就是霍華德。這是一個非常好的問題，羅傑。我認為，如果你看看 Nectar 目前的財務狀況，我們顯然無法在沒有合作夥伴的情況下執行完整的第三階段計劃。所以我認為我們將要做的是專注於數據的品質和強度，並且我們將與公司討論合作事宜。這並不意味著我們將取消該藥物的許可。我們會這樣做，但我們會與各公司進行溝通，並達成合作，讓我們的投資者獲得最少的稀釋性融資，同時讓我們保留該藥物的大部分所有權，有很多不同的方法可以做到這一點，但顯然，合作可能是我們的方向

Excellent. Thank you.

出色的。謝謝。

Mayank Mamtani - B. Riley Securities

Mayank Mamtani - B. Riley 證券

Yeah, yes, good afternoon. Thanks for taking our questions. JZ, are you able to provide any color on your where your baseline E could come out and how much is going from 12 to 16 weeks, in this phase 2B versus phase 1 be important for that separation from placebo and is there expectation for all those levels, including the 24 meg per gig. Once every monthly, everything sort of statistically, clearing the static bar and 24, the monthly dose being the lowest therapeutic effective dose.

是的，是的，下午好。感謝您回答我們的問題。JZ，您能否提供任何關於您的基線 E 值可能出現的位置以及從 12 到 16 週的變化量，在這個 2B 期與 1 期中，與安慰劑的區分很重要，並且對所有這些水平都有預期，包括每千兆 24 兆。每個月一次，一切都按統計方式進行，清除靜態條和 24，每月劑量是最低治療有效劑量。

Great, yeah, thanks, so.

太好了，是的，謝謝。

So, obviously, when we report the top line results, we'll get the detailed baseline easy, but I can tell you that with the kind of prospective actions that we took in the study, such as the geographic footprint, as well as focusing on, experienced dermatologists, board certified derms that have successfully participated sites, we'd like to see. Our baseline easy rate between 25 and 30, and we think that when you look across successful studies, whether they are phase two or phase three, this is a, that's a very good zone to be in. You'll note, of course, from our publications, we're a little bit lower than that in our phase one, we were in 22, 23 range. Again, that was all US sites, so we'd like to see a higher baseline using at this study.

因此，顯然，當我們報告頂線結果時，我們會很容易地得到詳細的基線，但我可以告訴你，透過我們在研究中採取的預期行動，例如地理足跡，以及關注經驗豐富的皮膚科醫生、成功參與站點的委員會認證的皮膚科醫生，我們希望看到。我們的基線輕鬆率在 25 到 30 之間，我們認為，當你回顧成功的研究時，無論是第二階段還是第三階段，這都是一個非常好的區域。當然，您會從我們的出版物中註意到，我們比第一階段的數字略低，在 22、23 的範圍內。再次強調，這些都是美國網站，因此我們希望在本研究中看到更高的基準。

And then you ask the other interesting question about the impact of increasing the time of dosing, the overall dose interval, and we do think that that's quite important. So the phase 1 B was really informative and it showed us that a 12-week, twice a month dosing regimen could definitely deliver quite a lot of efficacy and it could deliver a remittive effect.

然後您問了另一個有趣的問題，關於增加服藥時間、整體服藥間隔的影響，我們確實認為這非常重要。因此，第 1 B 期確實很有啟發性，它向我們展示了 12 週、每月兩次的給藥方案肯定可以產生相當多的療效，並且可以產生緩解效果。

I was seen in the majority of people, but it was also evident that there were people that could have done better with additional doses. And when you look at that week 12 to week 19 off drug period, we lost a few people at the different dose levels that really had an effect, but then that effectwed. So there were clearly people that could have done with additional dosing. So one of the first things that we'll be looking at in this study is the additional extension of the induction period from 12 to 16 weeks. That also gives more as you described space and the separation from placebo. But then also, beyond that is the fact that we keep dosing in the maintenance period, which is also something that that I mentioned we're very excited about because it's possible we haven't really mapped out the extent of efficacy. And that would continue treatment through 52 weeks. Patients could see even more benefits. So we're very excited to see the effect of that additional dosing. And then to your last question about the different dose levels. So we gave an additional caller in the call today, about our expectations about the PK exposure and the kind of you see that's matched across those dose levels. But also remember this is a very well powered study. And we enrolled 400 patients into the study in order, to fill the maintenance arms, and then the benefit of that is that the induction is very well powered. So that gives us a very good opportunity and, a very good chance to hit significance across multiple dose arms. So thanks for the questions.

大多數人都出現了這種情況，但顯然有些人如果增加劑量可能會表現得更好。當您觀察第 12 週到第 19 週的停藥期時，我們發現，在不同劑量水平下，一些患者確實受到了影響，但這種影響隨後就消失了。因此顯然有些人需要額外劑量。因此，我們在本研究中要研究的第一件事就是將誘導期從 12 週延長至 16 週。正如您所描述的，這也提供了更多的空間以及與安慰劑的分離。但除此之外，事實上我們在維持期內仍繼續用藥，這也是我提到的讓我們非常興奮的事情，因為我們可能還沒有真正確定療效的程度。治療將持續 52 週。患者可以看到更多的好處。因此，我們非常高興看到額外劑量的效果。然後回答您關於不同劑量等級的最後一個問題。因此，我們在今天的電話會議中又聯繫了一位來電者，詢問他對 PK 暴露的預期，以及您所看到的與這些劑量水平相匹配的情況。但也請記住，這是一項非常有力的研究。我們招募了 400 名患者參與研究，以填補維持治療組，這樣做的好處是誘導治療效果非常好。因此，這為我們提供了一個非常好的機會，也是一個非常有可能在多個劑量組中實現顯著效果的機會。感謝您的提問。

Great.

偉大的。

Great. And if I may squeeze in a alopecia study question please, do you have a sense of what a proportion of patients between very severe versus severe subgroups and if you could comment on the kinetics of response, relative to a pretty fast onset, you get an AD, how, what would be your expectation be on the kinetics there and then I have just one last follow up after that.

偉大的。如果我可以插入一個脫髮研究問題，您是否知道非常嚴重和嚴重亞組之間的患者比例是多少，並且您是否可以評論一下反應動力學，相對於相當快速的發病，您會得到 AD，您對那裡的動力學的期望是什麼，然後我只需進行最後一次跟進。

Sure. So if you just look at the epidemiology, if you look at people that are salt 50 or higher, you'd find between, well, between a third and half are actually in the very severe, which are 95% and high, right? And those are also the people that tend to be the candidates for clinical trials as well. So that's just where the epidemiology breaks down in that from a third to a half are in that very severe category, which is defined as 95 to 100 on the SAT scale. And then your other question about onset, it's it's a very interesting question. The physiology in that disease is very different, like, in atopic dermatitis, you're dealing with effectively an organ that recovers quickly in the skin. Rashes can come and appear and clear quickly, as and so can other excoriation latification, other features of the disease as well.

當然。因此，如果您只看流行病學，如果您觀察鹽含量為 50 或更高的人，您會發現，三分之一到一半的人實際上處於非常嚴重的狀態，即 95％ 以上，對嗎？這些人也往往是臨床試驗的候選人。這就是流行病學的分類，三分之一到一半的患者屬於非常嚴重的類別，在 SAT 量表上定義為 95 到 100。然後您關於發病的另一個問題，這是一個非常有趣的問題。這種疾病的生理學非常不同，例如，在異位性皮膚炎中，您需要有效地處理皮膚中快速恢復的器官。皮疹可以很快出現並消退，其他擦傷、皮膚剝脫和疾病的其他特徵也是如此。

But hair is its own thing, right? There's different stages of hair growth. In patients with alopecia, they have an arrest, but the hair follicle, so there's inflammation that slows down and it really interrupts the stem cell, a portion of the disease. And so that's why we actually are doing a 36 week induction period in that study, and we see that even with DAC inhibitors, right, it can take time, to grow hair. So so we're doing a longer induction period and in December we look forward, to present the top line results of that study, and there we'll be able to characterize not just the magnitude but also the cadets of the response. So we'll stay tuned for until December for that.

但頭髮本身就是一個東西，對吧？頭髮生長有不同的階段。對於患有脫髮症的患者來說，他們的毛囊會停滯，因此發炎會減緩，並會真正阻斷幹細胞，這是疾病的一部分。這就是為什麼我們在該研究中實際上進行了 36 週的誘導期，我們發現即使使用 DAC 抑制劑，頭髮的生長也需要時間。因此，我們正在進行一個更長的入職培訓期，我們期待在 12 月展示這項研究的最終結果，屆時我們將能夠不僅描述回應的規模，還能描述學員的反應。因此，我們將持續關注直至十二月。

Great, and just one corporate question. Any anything you guys can comment on the, lili litigation, just update on what next steps are and, if it all respects progression, to they say development has any impact on potential damages, thanks again for taking our question.

太好了，只有一個公司問題。你們對莉莉訴訟有什麼評論嗎？只需更新下一步的進展，如果一切都進展順利，他們說發展會對潛在損害產生影響，再次感謝您回答我們的問題。

Yeah, look, I can't obviously can't go into detail on our litigation. I can only tell you that we strongly believe we've been damaged by Lilly. And we're active, we're clearly actively pursuing an aggressive strategy in this legal action, and I think whether whether Respe is successful or reseg is not successful, I don't think it has really much impact on the damage that they've done us. So let's watch and wait as we move towards a trial.

是的，看，我顯然不能詳細說明我們的訴訟。我只能告訴你，我們堅信我們受到了禮來的傷害。而且我們很積極，我們顯然在這次法律行動中積極推行積極的策略，我認為無論 Respe 成功還是 reseg 失敗，我都不認為這對他們給我們造成的損害有太大影響。因此，讓我們拭目以待，等待審判的到來。

Understood.

明白了。

Thank you.

謝謝。

Arthur He -HC Wainwright & Co.

Arthur He -HC Wainwright & Co.

Hey, good afternoon. How are your team. Thanks for taking my question. So JZ, you read my mind about the by disclosing the dose level for the AA study. And, so I'm just wondering, so assuming this phase to be starting in the A, can that meets your guys' expectation. How should we think about the design for when you guys evaluating the maintenance of the in the A patient? Would that follow similar design path as the AD study?

嘿，下午好。你的團隊怎麼樣？感謝您回答我的問題。所以 JZ，你透過披露 AA 研究的劑量水平讀懂了我的想法。所以我只是想知道，假設這個階段從 A 開始，這能否滿足你們的期望。當你們評估 A 患者的維持情況時，我們該如何考慮設計？這是否會遵循與 AD 研究類似的設計路徑？

Yeah, it's a it's a really great question, Arthur. Yeah, thank, thanks for that. So yeah, one of the things we're going to learn in this phase to the study is what happens when we stop treatment, right? So in the study design, there's a 9 month induction and then the 6 month, off treatment period, and our hope and desire in designing the study that way was that we could see, the same kind of remittive potential in alopecia that we saw in atopic dermatitis in that on drugg period there. That would be a complete transformational, change in this indication. So firstly, there is no biologic approved in this disease, and the DAC inhibitors, can be effective for people with alopecia. They're kind of difficult drugs to take because you have to take them for so long and this disease and you also have to step up a dose in patients. But then, as Howard and I described it, it's very difficult for patients because when you stop taking the Jack inhibitor.

是的，這是一個非常好的問題，亞瑟。是的，謝謝，謝謝。是的，我們在研究的這個階段要了解的一件事就是當我們停止治療時會發生什麼，對嗎？因此，在研究設計中，有一個 9 個月的誘導期和 6 個月的停藥期，我們以這種方式設計研究的希望和願望是，我們可以看到，在脫髮中我們看到了與我們在異位性皮膚炎用藥期間看到的相同的緩解潛力。這將是這一跡象的徹底轉變和改變。首先，目前還沒有針對這種疾病的生物製劑獲得批准，而 DAC 抑制劑對脫髮患者有效。這些藥物很難服用，因為你必須服用很長時間，而且對於這種疾病，你還必須增加患者的劑量。但是，正如霍華德和我所描述的，當你停止服用傑克抑制劑時，這對患者來說非常困難。

The rate of hair loss is quick and you don't have a regrowth or a maintenance of what you grew. So so we do think there's a really unique opportunity and again being having the potential of being in a very exciting position as a biologic. Tested in the potential for it to be so early into the space as a biologic therapy. The way we would approach a phase 3 study, we would of course have to see the results of the phase 2, where we'd have to learn about the dose ranging that we've done in the phase 2 study. And then as we look at the off drug period, we would think about what is the appropriate maintenance regimen. Most likely we would treat and approach alopecia the way we approach atopic dermatitis where there would be an induction period that would be a higher frequency of dosing. And then there would be a maintenance period that would be much lower in frequency.

掉髮速度很快，而且長出的頭髮無法再生，也無法維持原狀。因此，我們確實認為這是一個非常獨特的機會，並且再次有可能成為非常令人興奮的生物製劑。測試了其作為生物療法早期應用的潛力。我們進行第 3 階段研究的方式當然是必須看到第 2 階段的結果，我們必須了解我們在第 2 階段研究中所做的劑量範圍。然後，當我們觀察停藥期時，我們會思考什麼是適當的維持方案。我們很可能會像治療異位性皮膚炎一樣治療脫髮，即有一個誘導期，即更高的給藥頻率。然後維護期的頻率就會低很多。

That's the most likely what we would see, but of course, we have to see the final results of the study to make that final design.

這是我們最有可能看到的，但當然，我們必須看到研究的最終結果才能做出最終的設計。

Thanks, Jason.

謝謝，傑森。

So just a quick one, on the technical side for the study design for the alopecia study. So I noticed that, for those patients did not reach aAR score less than 20, they can get an additional 16 week treatment, right? So the, those patients will also be followed in an additional 24 weeks. So, is that right? Or I mean, for that thing, those patients' kind of the total study time period will be a little bit longer.

因此，我只想簡單介紹一下脫髮研究的設計技術方面。所以我注意到，對於那些 aAR 評分未達低於 20 的患者，他們可以得到額外的 16 週治療，對嗎？因此，這些患者也將接受額外 24 週的追蹤。那麼，是這樣嗎？或者我的意思是，就那件事而言，那些患者的總研究時間會更長一些。

It's the latter. So, for those people, everybody gets 24 weeks off drug. So even if some people had were were improving at the end of week 36 and had an extension, they would still be followed for 24 weeks at the end of do. You are correct.

是後者。因此，對於這些人來說，每個人都可以停藥 24 週。因此，即使有些人在第 36 週結束時病情有所好轉並獲得了延長，他們仍然會在最後 24 週接受跟踪。你是對的。

Okay, got it, yeah.

好的，明白了，是的。

Thanks for taking my question.

感謝您回答我的問題。

Jessica Fye from JPMorgan.

摩根大通的傑西卡費伊 (Jessica Fye)。

Hey guys, good afternoon. Thanks for taking my question. Is it fair to expect that you would wait for the 36 week AD data before pursuing an end phase two meeting with FDA and preparing to initiate a phase 3 trial, or is there potentially motivation to meet with the FDA sooner on the back of this upcoming data and get the ball rolling on phase 3 that much sooner?

大家好，下午好。感謝您回答我的問題。您是否應該等待 36 週 AD 數據，然後再與 FDA 進行第二階段會議並準備啟動第三階段試驗，或者是否有潛在的動力在即將獲得的數據的支持下儘早與 FDA 會面並儘早啟動第三階段試驗？

Thank you.

謝謝。

Yeah, thanks for the question, Jeff, and it's the latter, so we don't have to wait for the completion of the maintenance, which would come in the very early part of next year before we connect with that the induction regimen.

是的，謝謝傑夫的提問，是後者，所以我們不必等到維護工作完成，維護工作將在明年年初完成，然後我們再進行誘導治療。

And so in fact it is our plan that with the top line data when it comes next month, we would begin eyeing in end of phase two meeting.

因此，事實上，我們的計劃是，下個月獲得頂線數據後，我們將開始關注第二階段會議的結束。

With that 16 week induction data being the main substance and substrate as well as the driver of the phase 3 study design that we would take forward, so yeah, actually we would, we don't need to wait, and our goal would be to really to keep the momentum. On the program. So if the study gives us the kind of results, that we think it can, our intention would be to move quickly, maintain the momentum, and I phase 3, moving into that phase 3 program as quickly as we can.

由於 16 週的誘導數據是主要內容和底物，也是我們將要推進的 3 期研究設計的驅動力，所以，是的，實際上我們不需要等待，我們的目標是真正保持這種勢頭。在節目上。因此，如果研究能為我們帶來我們認為可以得到的結果，我們的目標是迅速採取行動，保持勢頭，盡快進入第三階段計劃。

Okay, thank you.

好的，謝謝。

Thank you.

謝謝。

Our next question comes from Andy Shea from William Blair. Your line is open.

下一個問題來自 William Blair 的 Andy Shea。您的線路已開通。

Oh, thanks for taking our questions. So, 22 for me, I, I'm just curious for the protocol for atopic dermatitis, do you allow patients to be off the drug but still on the trial? The reason I'm, why I'm asking this question is perhaps for the first look, you can potentially get a glimpse into potential remittive effects, like you said, Jay-Z for those patients who are off drug but still on trial. So that's question number one. Question number 2 is for the primary employee, I'm curious about which imputation method you're using. I think this is going back to Roger's question before, but I also have the same question.

哦，感謝您回答我們的問題。所以，對我來說 22，我只是好奇異位性皮膚炎的治療方案，您是否允許患者停藥但仍參加試驗？我之所以問這個問題，也許是為了乍一看，你可以了解到潛在的緩解效應，就像你說的，Jay-Z 為那些已經停藥但仍在接受試驗的患者提供了幫助。這是第一個問題。問題 2 是針對主要員工的，我很好奇您使用哪種估算方法。我認為這又回到了羅傑之前的問題，但我也有同樣的問題。

Thank you.

謝謝。

Okay, sure.

好的，當然。

Yeah, so in terms of your first question, so like any other protocol, right, there are rules for either stopping the study or stopping the treatment, right? And then there are, if you fall into one of those categories like any other protocol, you still keep the patients in the study. They continue to have follow-up visits, not just an end of study, but even after the end of treatment, they could continue to be followed. And so our protocol is no different than any others, and it does allow that.

是的，就您的第一個問題而言，就像任何其他協議一樣，停止研究或停止治療都有規則，對嗎？然後，如果您像任何其他協議一樣屬於其中一個類別，您仍然可以將患者留在研究中。他們會繼續接受隨訪，不僅是研究結束時，即使在治療結束後，他們仍可以繼續接受隨訪。因此我們的協議與其他協議沒有什麼不同，並且確實允許這樣做。

And again, like, so yeah, so that's something that is allowed in our protocol.

再說一次，是的，這是我們的協議允許的事情。

And then the second question that you asked was about imputation.

您提出的第二個問題是關於歸責。

And so yeah, the kind of imputation methods that are used are typical of phase two studies, right? So the FDA likes you to use an estim demand approach, right, when you report this kind of data.

是的，所使用的歸因方法是第二階段研究的典型方法，對嗎？因此，當您報告此類數據時，FDA 希望您使用估計需求方法。

So there are events called in current events, and again, they're well defined and the FDA gives this guidance to all sponsors when you have a study of phase two size.

因此，存在被稱為當前事件的事件，並且它們被明確定義，當您進行第二階段規模的研究時，FDA 會向所有贊助商提供此指導。

So we'd be using a primary estimate analysis. And again, the routine kind of imputation methods that are typical of other studies. When we present the results, we'll get into the details, the methodologies so you can see that before you see the protocol, for example, when we publish the study results, but that I hope that gives you the kind of flavor. It's a it's a standard imputation of a primary estimate analysis. Yeah, that's helpful.

所以我們將使用初步估計分析。再次強調，這是其他研究中典型的常規歸因方法。當我們展示結果時，我們會深入討論細節和方法，以便您在看到協議之前（例如，當我們發布研究結果時）能夠看到這些，但我希望這能為您帶來一些啟發。這是對初步估計分析的標準估算。是的，這很有幫助。

Thank you, Jay-Z.

謝謝你，Jay-Z。

Thank you.

謝謝。

And I am showing no further questions from our phone lines. I now like to pass it back to Howard Robin for any closing remarks.

我沒有從我們的電話線中提出其他問題。現在我想將其交還給霍華德羅賓 (Howard Robin)，請他做最後發言。

Well, thank you all for joining us today and we greatly appreciate your continued support, and I want to thank all of our employees for their hard work and diligence, and I look forward to sharing our RESPEC date in June. So please stay tuned.

好吧，感謝大家今天加入我們，我們非常感謝你們一直以來的支持，我要感謝我們所有員工的辛勤工作和勤奮，我期待著在六月分享我們的 RESPEC 日期。因此請繼續關注。

Thank you. This concludes today's conference call.

謝謝。今天的電話會議到此結束。

Thank you for your participation. You may now disconnect, everyone, have a wonderful day.

感謝您的參與。各位現在可以斷開連線了，祝大家有美好的一天。