Neurogene Inc (NGNE) 2022 Q2 法說會逐字稿

Good afternoon, and thank you for joining us today for the Neoleukin Therapeutics, conference call. (Operator Instructions) As a reminder, today's conference is being recorded.

下午好，感謝您今天參加我們的 Neoleukin Therapeutics 電話會議。 （操作員指示）提醒一下，今天的會議正在錄製中。

I would now like to turn the call over to Julie Rathbun, (sic) [Rathbun] Communications for Neoleukin Therapeutics. Julie, please go ahead.

我現在想將電話轉給朱莉·拉斯本 (Julie Rathbun)，（原文如此）[Rathbun] Neoleukin Therapeutics 通訊部。朱莉，請繼續。

Thank you. Good afternoon, and welcome to Neoleukin Therapeutics Second Quarter 2022 Conference Call. Joining me on the call today from Neoleukin are Jonathan Drachman, CEO; and Priti Patel, Chief Medical Officer; and Sean Smith, Vice President, Finance.

謝謝。下午好，歡迎參加 Neoleukin Therapeutics 2022 年第二季度電話會議。今天與我一起參加 Neoleukin 電話會議的是首席執行官 Jonathan Drachman；和首席醫療官 Priti Patel；肖恩·史密斯，財務副總裁。

Today's call is being recorded. It will be available for replay on the Investor Relations section of the Neoleukin website approximately 2 hours after the call for at least 30 days.

今天的通話正在錄音。電話會議結束後大約 2 小時，可在 Neoleukin 網站的投資者關係部分重播，持續至少 30 天。

Before we start, I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgments, intentions, beliefs and expectations about future events, strategies, product candidates and operating plans.

在開始之前，我想提醒您，今天的電話會議將包括基於當前預期的前瞻性陳述。此類陳述代表管理層對未來事件、戰略、產品候選者和運營計劃的判斷、意圖、信念和期望。

All forward-looking statements included in this presentation are made as of today and involve assumptions, risks and uncertainties, and actual results could differ materially from those anticipated in the forward-looking statements. Neoleukin undertakes no obligation to update or revise any forward-looking statements. Please refer to the company's filings with the SEC, which are available from the SEC or on the Neoleukin website information concerning the risk factors that could affect the company.

本演示文稿中包含的所有前瞻性陳述均截至今日作出，涉及假設、風險和不確定性，實際結果可能與前瞻性陳述中的預期存在重大差異。 Neoleukin 不承擔更新或修改任何前瞻性陳述的義務。請參閱該公司向 SEC 提交的文件，這些文件可從 SEC 或 Neoleukin 網站上獲取有關可能影響該公司的風險因素的信息。

I'd now like to turn the call over to Jonathan Drachman.

我現在想把電話轉給喬納森·德拉赫曼。

Thank you, Julie, and good afternoon. Neoleukin was founded in 2018 based on the vision that de novo protein design will become an important way to design new biologic therapies with customized properties, making them more suited to be therapeutics than native proteins.

謝謝你，朱莉，下午好。 Neoleukin 成立於 2018 年，其願景是從頭蛋白質設計將成為設計具有定制特性的新生物療法的重要方式，使它們比天然蛋白質更適合作為治療藥物。

In the past 3.5 years, we have continued to push the boundaries of de novo protein design, learning how to extend pharmacodynamic half-life, fine tune the affinity of the ligand for its cognate receptor, target the cytokine mimetic to specific cells and how to design increasingly complex molecules.

在過去的 3.5 年裡，我們不斷突破從頭蛋白質設計的界限，學習如何延長藥效半衰期、微調配體與其同源受體的親和力、將細胞因子模擬物靶向特定細胞以及如何設計越來越複雜的分子。

NL-201 is the first molecule in this new class of potential therapeutics, and we believe it is the first fully de novo protein to enter clinical testing. Through the ongoing Phase I clinical trial, we expect to learn a tremendous amount about the biological effects of de novo proteins in patients and how to continue expanding the capabilities of our technology.

NL-201 是此類新型潛在療法中的第一個分子，我們相信它是第一個進入臨床測試的完全從頭開始的蛋白質。通過正在進行的一期臨床試驗，我們希望了解大量有關從頭蛋白對患者的生物效應以及如何繼續擴展我們技術的能力的信息。

In addition to NL-201, we have other examples of our de novo protein design capabilities. In 2020, we announced the de novo protein that could prevent SARS-CoV-2 from entering human cells. In 2021, we presented data on an IL-2, IL-15 antagonist that could inhibit IL-2-induced proliferation and protect mice from graft versus host disease. And we have more recently announced that we are working on a T regulatory cell agonist with the goal of treating patients with autoimmune or inflammatory diseases.

除了 NL-201 之外，我們還有其他從頭蛋白質設計能力的例子。 2020 年，我們宣布了可以阻止 SARS-CoV-2 進入人體細胞的 de novo 蛋白質。 2021 年，我們提供了有關 IL-2、IL-15 拮抗劑的數據，該拮抗劑可以抑制 IL-2 誘導的增殖並保護小鼠免受移植物抗宿主疾病。我們最近還宣布，我們正在開發一種 T 調節細胞激動劑，旨在治療患有自身免疫性疾病或炎症性疾病的患者。

Now we're entering the next phase of de novo protein design technology, which involves adding machine learning and neural networks to computational methods in order to develop new molecules. We have a team of scientists who have been working on this, and we believe it offers advantages for the development of de novo protein therapeutics.

現在我們正在進入從頭蛋白質設計技術的下一階段，其中涉及將機器學習和神經網絡添加到計算方法中以開發新分子。我們有一個科學家團隊一直致力於此研究，我們相信它為從頭蛋白質療法的開發提供了優勢。

Design methods leveraging machine learning can go faster, require less computational power, create designs for more complex proteins and don't require high-resolution crystal structures as a starting point. Over the last 6 months, we have used this technology to develop prototypes for 2 additional de novo cytokine mimetics. These proteins have established mechanisms of action that we believe could make them promising antitumor candidates, and the native proteins have more complex structures than those we have previously designed mimetics for.

利用機器學習的設計方法可以更快，需要更少的計算能力，為更複雜的蛋白質創建設計，並且不需要高分辨率晶體結構作為起點。在過去的 6 個月裡，我們使用這項技術開發了另外 2 種從頭細胞因子模擬物的原型。這些蛋白質已經建立了作用機制，我們相信這些機制可以使它們成為有希望的抗腫瘤候選者，並且天然蛋白質具有比我們之前設計的模擬物更複雜的結構。

We believe this is the future of de novo protein design, and we're very excited about entering into this next phase with our growing research pipeline.

我們相信這是從頭蛋白質設計的未來，我們對隨著我們不斷增長的研究管道進入下一階段感到非常興奮。

I'd now like to turn the call over to Priti Patel, our Chief Medical Officer, for an update on NL-201. Priti?

我現在想將電話轉給我們的首席醫療官 Priti Patel，了解 NL-201 的最新情況。普里蒂？

Thank you, Jonathan. I'm pleased to share an update on our clinical development program. As a reminder, NL-201 is a de novo protein that stimulates both the IL-2 and IL-15 receptors. It is more potent than native IL-2 and preferentially stimulates naive CD8 T cells and NK cells versus immunosuppressive key regulatory cells at low concentration.

謝謝你，喬納森。我很高興分享我們臨床開發計劃的最新情況。提醒一下，NL-201 是一種從頭蛋白，可刺激 IL-2 和 IL-15 受體。它比天然 IL-2 更有效，並且在低濃度下優先刺激初始 CD8 T 細胞和 NK 細胞，而不是免疫抑制關鍵調節細胞。

The first-in-human clinical trial of NL-201 is being conducted in patients with; relapsed or refractory solid tumors. The open-label Phase I trial of NL-201 is currently active at 12 sites in the United States, Australia and Canada.

NL-201 的首次人體臨床試驗正在以下患者中進行：復發或難治性實體瘤。 NL-201 的開放標籤 I 期試驗目前在美國、澳大利亞和加拿大的 12 個中心進行。

Our NL-201 clinical trial is progressing well with strong investigator engagement across our clinical sites and active enrollment. We're currently in the dose escalation phase and are exploring 2 dose schedules in order to assess safety, pharmacokinetics, pharmacodynamics and antitumor activity.

我們的 NL-201 臨床試驗進展順利，臨床中心的研究者積極參與，並且積極入組。我們目前正處於劑量遞增階段，正在探索 2 個劑量方案，以評估安全性、藥代動力學、藥效學和抗腫瘤活性。

The trial is evaluating 2 different schedules and multiple dose levels in order to determine a recommended Phase II dosing schedule. We have added intermediate dose levels to the clinical plan as we have progressed through dose escalation, which has extended the time line to reach a recommended Phase II dose and schedule. Due to the addition of these intermediate doses, we now expect to release our interim data on this clinical trial in 2023.

該試驗正在評估 2 種不同的給藥方案和多種劑量水平，以確定推薦的 II 期給藥方案。隨著劑量遞增的進展，我們在臨床計劃中增加了中間劑量水平，這延長了達到推薦的 II 期劑量和時間表的時間線。由於增加了這些中間劑量，我們現在預計將在 2023 年發布該臨床試驗的中期數據。

After a recommended Phase II dosing schedule is identified through our dose escalation study, we plan to initiate enrollment of indication-specific expansion cohorts, including patients with renal cell carcinoma and melanoma.

通過我們的劑量遞增研究確定推薦的 II 期給藥方案後，我們計劃開始招募特定適應症的擴展隊列，包括腎細胞癌和黑色素瘤患者。

Earlier this year, we started the combination portion of our Phase I clinical trial with the addition of pembrolizumab to NL-201 in specific cohorts. Patients with relapsed or refractory solid tumors in these combination cohorts received a standard dose of pembrolizumab combined with ascending doses of NL-201 in order to define a recommended dosing schedule for the combination regimen. The NL-201 pembrolizumab combination will be tested as a separate arm of the ongoing Phase I trial.

今年早些時候，我們開始了 I 期臨床試驗的聯合部分，在特定隊列中將派姆單抗添加到 NL-201 中。這些聯合隊列中的複發或難治性實體瘤患者接受標準劑量的派姆單抗聯合遞增劑量的 NL-201，以確定聯合方案的推薦給藥方案。 NL-201 pembrolizumab 組合將作為正在進行的 I 期試驗的單獨部分進行測試。

With that, I'd now like to turn the call over to Sean Smith, VP of Finance, to discuss our second quarter 2022 financials. Sean?

現在，我想將電話轉給財務副總裁 Sean Smith，討論我們 2022 年第二季度的財務狀況。肖恩？

Thanks, Priti, and good afternoon, everyone. I'm pleased to present you with our second quarter financial results.

謝謝，普里蒂，大家下午好。我很高興向您介紹我們第二季度的財務業績。

Cash, cash equivalents and short-term investments totaled $116.5 million as of June 30, 2022, compared to $142.5 million as of December 31, 2021. Research and development expenses for the second quarter of 2022 increased to $11 million from $9.8 million for the second quarter of 2021. The increase was primarily due to increased clinical trial expense related to NL-201.

截至2022 年6 月30 日，現金、現金等價物和短期投資總額為1.165 億美元，而截至2021 年12 月31 日為1.425 億美元。2022 年第二季度的研發費用從第二季度的980 萬美元增加到1,100 萬美元。 2021 年第四季度。這一增長主要是由於與 NL-201 相關的臨床試驗費用增加。

General and administrative expenses for the second quarter of 2022 decreased to $4.9 million from $5.3 million for the second quarter of 2021. The decrease was primarily attributable to decreases in personnel-related and facility-related costs.

2022 年第二季度的一般及行政費用從 2021 年第二季度的 530 萬美元減少至 490 萬美元。減少的主要原因是人員相關和設施相關成本的減少。

Net loss for the second quarter of 2022 was $15.7 million compared to a net loss of $15.1 million in the second quarter of 2021. Based upon current internal infrastructure and pipeline initiatives, we believe our cash and short-term investments will be sufficient to fund operations through 2023.

2022 年第二季度的淨虧損為1570 萬美元，而2021 年第二季度的淨虧損為1510 萬美元。根據當前的內部基礎設施和管道計劃，我們相信我們的現金和短期投資將足以為運營提供資金到 2023 年。

Importantly, we are also evaluating opportunities to extend our runway by gaining certain activities and have slowed down growth due to the challenging capital markets. We remain focused on our core value-driving activities and feel confident that the amount of cash we have will enable important milestones over the next 1.5 years.

重要的是，我們還在評估通過開展某些活動來擴展我們跑道的機會，並由於資本市場的挑戰而放慢了增長速度。我們仍然專注於我們的核心價值驅動活動，並相信我們擁有的現金數額將在未來 1.5 年內實現重要的里程碑。

And with that, I'll turn the call back over to Jonathan for some concluding comments.

然後，我會將電話轉回給喬納森，以獲得一些結論性意見。

Thanks, Sean. We are looking forward to the coming months as we progress NL-201 through dose escalation and gather information to help guide optimal dosing and schedule based on tolerability, pharmacokinetics and pharmacodynamics. We look forward to learning more about our lead molecule, while also continuing our efforts to expand the potential offered by de novo protein design.

謝謝，肖恩。我們期待著未來幾個月，我們將通過劑量遞增來推進 NL-201 的進展，並收集信息以幫助指導基於耐受性、藥代動力學和藥效學的最佳劑量和時間表。我們期待更多地了解我們的先導分子，同時繼續努力擴大從頭蛋白質設計提供的潛力。

We are thankful for our dedicated team at Neoleukin that remains diligently focused on our goal to advance new therapeutics to improve outcomes for patients with serious diseases.

我們感謝 Neoleukin 的專業團隊，他們始終致力於推進新療法以改善嚴重疾病患者的治療效果。

Operator, we can now open the call up for questions.

接線員，我們現在可以發起提問。

(Operator Instructions) And we'll first go to Greg Harrison of Bank of America.

（操作員指示）我們首先請美國銀行的格雷格·哈里森 (Greg Harrison)。

This is Mary filling in for Greg. Maybe could you add some additional color to your expectations for the NL-201 update? Maybe what should we expect to see in the initial data update? And how has this changed at all with the addition of the intermediate doses?

這是瑪麗代替格雷格。也許您可以為 NL-201 更新的期望添加一些額外的色彩嗎？也許我們應該在初始數據更新中看到什麼？添加中間劑量後，情況發生了怎樣的變化？

Sure. I'll start, and then I'll ask Priti to elaborate. We -- I don't believe that the addition of intermediate doses will change anything in terms of what we will be presenting next year, and you should expect to see a data set that will include safety, tolerability, biomarker data, pharmacokinetics and any anecdotal antitumor activity that comes from the clinical trial. Priti, anything you'd like to add to that? .

當然。我先開始，然後我會請 Priti 詳細說明。我們——我不相信中間劑量的添加會改變我們明年將展示的內容，您應該期望看到一個數據集，其中包括安全性、耐受性、生物標誌物數據、藥代動力學和任何來自臨床試驗的軼事抗腫瘤活性。 Priti，您還有什麼要補充的嗎？ 。

No. I think that covers it.

不，我認為這涵蓋了它。

Our next question will come from Charles Zhu of Guggenheim Securities.

我們的下一個問題將來自古根海姆證券公司的查爾斯·朱。

I had another question on the intermediate dose cohorts that you've announced. I'm kind of wondering if you could provide some additional color as to what exactly that means. For example, have you dosed escalated up to a certain level and then now you're coming back down? Or are these additional intermediate doses kind of like further steps up as you continue to upwards in escalation? And then how should we think about the additional number of doses that you may evaluate?

我對您宣布的中間劑量組還有另一個問題。我想知道您是否可以提供一些額外的顏色來說明這到底意味著什麼。例如，您的劑量是否增加到一定水平，然後現在又下降了？或者這些額外的中間劑量是否有點像隨著你繼續向上升級而進一步增加？那麼我們應該如何考慮您可能評估的額外劑量？

Thanks for the question, Charles. So with any clinical trial, there are adjustments that are made during the course of it. And during the trial, we felt that in order to best and fully evaluate both safety and activity, it was best to add intermediate dose levels to our planned dose levels, and we continue dose escalation. So there's no deescalation going on.

謝謝你的提問，查爾斯。因此，任何臨床試驗都會在過程中進行調整。在試驗過程中，我們認為，為了最好、全面地評估安全性和活性，最好在我們計劃的劑量水平上添加中間劑量水平，並且我們繼續劑量遞增。所以沒有降級的情況發生。

Got it. Okay. And then how are you thinking about -- are you able to, for example, refine timing within 2023? Or we should still think about some time within that full year of 2022 for your initial data?

知道了。好的。然後您如何考慮——例如，您是否能夠在 2023 年內完善時間安排？或者我們仍然應該考慮 2022 年全年的某個時間來獲取您的初始數據？

At this time, we're going to leave it at 2023, and we'll definitely update you as time goes on.

目前，我們將其保留在 2023 年，隨著時間的推移，我們一定會向您更新。

Will now move to a question from Ben Burnett of Stifel.

現在轉向 Stifel 的 Ben Burnett 提出的問題。

I wanted to also ask a question around just the dose scheduling and the new cohorts. But I guess , first, regarding the 2 schedules, schedules A and B, I guess, do you feel confident at this point that these are the right schedules? Or is there an appetite to maybe look at further additional schedules beyond that?

我還想問一個有關劑量安排和新隊列的問題。但我想，首先，關於兩個時間表，時間表A和B，我想，你現在有信心這些是正確的時間表嗎？或者是否有興趣考慮除此之外的更多額外時間表？

Well, whenever you're working with an agonist, I think that getting the interval right is a very important part of how you develop a drug because the pharmacodynamic activity is -- can often be much longer than the pharmacokinetic half-life. Based on extensive preclinical work that we did, we feel like these are the right schedules. And at this point, we continue with the original plans to look at day 1 and 8 schedule as well as the day 1 schedule for 3-week intervals.

好吧，每當您使用激動劑時，我認為正確的間隔時間是開發藥物的一個非常重要的部分，因為藥效活性通常比藥代動力學半衰期長得多。根據我們所做的大量臨床前工作，我們認為這些是正確的時間表。此時，我們繼續按照最初的計劃查看第 1 天和第 8 天的時間表以及每 3 週間隔的第 1 天的時間表。

Okay. Excellent. And is there anything you can comment on regarding safety? And have you seen any DLTs at this point?

好的。出色的。關於安全您有什麼可以評論的嗎？您目前看到過任何 DLT 嗎？

We really can't comment on that at this point, but we look forward to providing a full update next year.

目前我們確實無法對此發表評論，但我們期待明年提供完整的更新。

Okay. Understood. And maybe if I could just ask one more. Just regarding your comments around some of the T reg pursuits. I know it's early, but do you have a sense for which autoimmune disorders would maybe suffer from poor functioning T regs that might represent low-hanging fruit in this setting?

好的。明白了。也許我可以再問一個問題。只是關於您對一些 T reg 追求的評論。我知道現在還為時過早，但您是否知道哪些自身免疫性疾病可能會因功能不良的 T 調節細胞而受到影響，而這些調節性T細胞在這種情況下可能是唾手可得的成果？

We do have some ideas about areas that are interesting to pursue. But again, we're not prepared to discuss that at this time. I think there's a lot of opportunities, though, for expanded T regulatory cells to have an impact in both inflammatory and autoimmune conditions.

我們確實對感興趣的領域有一些想法。但同樣，我們現在不准備討論這個問題。不過，我認為擴增的 T 調節細胞有很多機會對炎症和自身免疫性疾病產生影響。

(Operator Instructions) We will now go to Mara Goldstein of Mizuho Securities.

（操作員指示）我們現在請瑞穗證券的瑪拉·戈德斯坦 (Mara Goldstein) 發言。

I just wanted to ask also about the intermediate dose if, a, that is being incorporated into the combination arm and as well as just trying to understand, there's no discussion of the hematology study and whether or not that is still in the works also at this dosing schedule.

我只是想問一下中間劑量是否被納入聯合治療組中，並且只是想了解一下，沒有討論血液學研究以及是否仍在進行中該給藥方案。

Yes. Thanks for the question, Mara. The -- what we learn from the solid tumor monotherapy dosing will be used to guide the dosing for other studies in the future as well as for the combination with pembrolizumab since that was started later and is earlier in dose escalation. .

是的。謝謝你的提問，瑪拉。我們從實體瘤單藥治療劑量中學到的知識將用於指導未來其他研究以及與派姆單抗聯合用藥的劑量，因為該藥物開始較晚且劑量遞增較早。 。

As far as the hematology study goes, as we announced last quarter, we have decided to wait on initiating that trial until we've learned more about the dosing schedule from the ongoing solid tumor trial. It's still something that we are interested in and have seen good activity preclinically across lymphoma and multiple myeloma, and we've presented those data previously. So that remains an interest.

就血液學研究而言，正如我們上季度宣布的那樣，我們決定等待啟動該試驗，直到我們從正在進行的實體瘤試驗中了解更多有關給藥方案的信息。它仍然是我們感興趣的東西，並且已經在淋巴瘤和多發性骨髓瘤的臨床前看到了良好的活性，並且我們之前已經提供了這些數據。所以這仍然是一個興趣。

But rather than doing the same thing in terms of dose escalation and dose finding across a second Phase I study, decided to wait until we learn more from this ongoing study.

但我們決定等到我們從這項正在進行的研究中了解更多信息，而不是在第二項 I 期研究中在劑量遞增和劑量發現方面做同樣的事情。

And as there are no further questions, I'd like to turn the call back to Jonathan Drachman for closing remarks.

由於沒有其他問題，我想將電話轉回給喬納森·德拉赫曼（Jonathan Drachman），讓其作結束語。

All right. Thanks, everyone, for joining our call today. We look forward to sharing our progress with you in the months ahead. Thank you.

好的。感謝大家今天加入我們的電話會議。我們期待在未來幾個月與您分享我們的進展。謝謝。

And with that, everyone, that does conclude today's conference call. We'd like to thank you again for your participation. And you may now disconnect.

各位，今天的電話會議到此結束。我們再次感謝您的參與。您現在可以斷開連接。