Lyra Therapeutics Inc (LYRA) 2021 Q3 法說會逐字稿

Good day and thank you for standing by. Welcome to the Lyra Therapeutics third quarter financial review and operational highlights conference call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. (Operator Instructions) Now I'll turn the call over to Stephanie Marks with Argot Partners.

美好的一天，感謝您的支持。歡迎參加 Lyra Therapeutics 第三季財務回顧與營運亮點電話會議。此時，所有參與者都處於只聽模式。演講者演講結束後，將進行問答環節。 （操作員說明）現在我將把電話轉給 Argot Partners 的 Stephanie Marks。

Thank you, operator. And welcome, everyone, to today's call. With me today are Dr. Maria Palasis, Lyra's President and Chief Executive Officer; Jason Cavalier, Chief Financial Officer; Dr. Robert Kern, Chief Medical Officer; and Corrine Noyes, SVP of Commercial Strategy and Market Development.

謝謝你，接線生。歡迎大家參加今天的電話會議。今天與我在一起的有 Lyra 總裁兼執行長 Maria Palasis 博士； Jason Cavalier，財務長； Robert Kern 博士，首席醫療官；以及商業策略和市場開發資深副總裁 Corrine Noyes。

This afternoon, Lyra issued a press release announcing its third quarter 2021 Financial Results and Business Update. A copy of the announcement can be found in the Investor Relations tab of the company's website, lyratherapeutics.com. During the conference call, management will make forward-looking statements, including statements related to the clinical development of the company's product candidates, business strategy and planned operations. These forward-looking statements are based on the company's current expectations and inherently involve risks and uncertainties.

今天下午，Lyra 發布新聞稿，宣布其 2021 年第三季財務業績和業務更新。該公告的副本可以在該公司網站 lyratherrapeutics.com 的投資者關係標籤中找到。在電話會議期間，管理階層將做出前瞻性陳述，包括與公司候選產品的臨床開發、業務策略和計畫營運相關的陳述。這些前瞻性陳述是基於公司目前的預期，本質上涉及風險和不確定性。

Lyra's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Factors that could cause results to be different from these statements include factors that the company describes in the section titled Risk Factors in the company's current report on Form 10-Q filed today on November 9, 2021. Lyra cautions you not to place undue reliance on forward-looking statements and undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations.

由於這些風險和不確定性，Lyra 的實際結果和事件發生的時間可能與此類前瞻性陳述中的預期有重大差異。可能導致結果與這些陳述不同的因素包括公司在 2021 年 11 月 9 日提交的 10-Q 表格當前報告中標題為「風險因素」的部分中描述的因素。並且不承擔因新資訊、未來事件或預期變更而更新任何前瞻性陳述的責任或義務。

And with that, I'll turn the call over to Maria.

這樣，我就把電話轉給瑪麗亞。

Thank you, Stephanie. And thank you all for joining us this afternoon. This third quarter of 2021 was another quarter of significant progress at Lyra. On the clinical front, we continue to generate data that strengthens the profile of our lead candidate, LYR-210 for the treatment of chronic rhinosinusitis. We announced new positive data from the Phase 2 LANTERN post-treatment evaluation, which showed continued safety in all patients and a durable response six months post-removal of LYR-210 in roughly half the patients that we've treated. This durable response in some of the patients, even six months after removal was impressive and an important differentiator relative to other treatments in the field.

謝謝你，斯蒂芬妮。感謝大家今天下午加入我們。 2021 年第三季是 Lyra 取得重大進展的另一個季度。在臨床方面，我們不斷產生數據，以加強我們的主要候選藥物 LYR-210 用於治療慢性鼻竇炎的概況。我們公佈了2 期LANTERN 治療後評估的新陽性數據，該數據顯示所有患者均持續安全，並且在我們治療過的約一半患者中，約一半患者在移除LYR-210 後六個月內出現持久反應。有些患者的持久反應，甚至在切除後六個月，也令人印象深刻，與該領域的其他治療方法相比，這是一個重要的區別。

We also reported the full results from the 56-day pharmacokinetic clinical study, which demonstrated that mometasone furoate blood levels were low and constant over time, providing further evidence that LYR-210 delivers a steady daily dose of mometasone. We believe that it is these drug release kinetics of LYR-210 that underpin the rapid and prolonged symptom relief that we've observed in our clinical studies. This third study further strengthens our data, safety and efficacy database. Dr. Kern will review these data in more detail shortly.

我們也報告了為期56 天的藥物動力學臨床研究的完整結果，該研究表明糠酸莫米鬆的血液水平較低且隨著時間的推移保持恆定，進一步證明LYR-210 提供穩定的莫米松每日劑量。我們相信，正是 LYR-210 的這些藥物釋放動力學支撐了我們在臨床研究中觀察到的快速且持久的症狀緩解。第三項研究進一步加強了我們的資料、安全性和有效性資料庫。科恩博士很快將更詳細地審查這些數據。

Both clinical studies were presented at the 67th Annual Meeting of the American Rhinologic Society last month. At ARS, we presented the data in two oral presentations and also received additional recognition by the Society for clinical research. The PK study was selected as a top clinical abstract at the meeting and the LANTERN Phase 2 manuscript won the ARS 2021 Clinical Science Maurice Cottle Award. This recognition speaks to the quality of the science at Lyra. Our clinical programs are advancing into late-stage development with the start of the Phase 3 clinical program for LYR-210 and the Phase 2 clinical trial for LYR-220 in the coming months.

這兩項臨床研究均於上個月在美國鼻學會第 67 屆年會上發表。在 ARS，我們透過兩次口頭報告展示了這些數據，並獲得了該協會臨床研究的額外認可。此PK研究在會議上被選為頂級臨床摘要，LANTERN 2期手稿榮獲ARS 2021臨床科學Maurice Cottle獎。這項認可證明了天琴座科學的品質。隨著未來幾個月 LYR-210 的 3 期臨床計畫和 LYR-220 的 2 期臨床試驗的啟動，我們的臨床計畫正在進入後期開發。

On the corporate front, Jason Cavalier was appointed as our new Chief Financial Officer in September. He brings over two decades of experience as an investment banker and has an extensive track record in advising companies on financing and strategic alternatives. Most recently, he was Managing Director, Head of Life Sciences Mergers & Acquisitions at Cantor Fitzgerald, where he led numerous transactions across medical technology, diagnostics and biopharma sectors. He also held other investment banking positions at RBC Capital Markets, Barclays Capital, Bear Stearns and Lehman Brothers. Jason leads our financial and capital markets strategy and will support our investor, public relations and business development activities.

在公司方面，Jason Cavalier 於 9 月被任命為我們新任財務長。他擁有二十多年的投資銀行家經驗，並在為公司提供融資和策略替代方案方面擁有豐富的經驗。最近，他擔任 Cantor Fitzgerald 董事總經理兼生命科學併購主管，領導了醫療技術、診斷和生物製藥領域的許多交易。他也曾在加拿大皇家銀行資本市場、巴克萊資本、貝爾斯登和雷曼兄弟擔任其他投資銀行職位。 Jason 領導我們的金融和資本市場策略，並將支持我們的投資者、公共關係和業務發展活動。

He takes the reins from Don Elsey who guided the company through our IPO. As you know, Don's retiring, he'll remain an adviser through year end. On behalf of the entire Lyra team, I'd like to thank Don for his tremendous dedication, commitment and contributions to the Company.

他從唐·埃爾西 (Don Elsey) 手中接過領導權，後者指導公司完成了首次公開募股。如您所知，唐即將退休，他將在年底前繼續擔任顧問。我謹代表整個 Lyra 團隊感謝 Don 對公司的巨大奉獻、承諾和貢獻。

Now I'd like to take a few minutes to remind you why we have initially focused our development on a treatment for patients with chronic rhinosinusitis. CRS is a debilitating disease that has been largely ignored. The disease is highly prevalent in the world with about 14 million people just in the United States. Patients are currently treated with off-label medications that have not been approved to treat CRS. Consequently, about half of these patients fail medical treatment and continue to suffer with their disease. In the United States alone, there are 4 million patients that fail medical management each year. Their next option is invasive surgery. Currently marketed products have only been developed to treat polyps, which only represent 10% of the CRS patients. Lyra's mission is to provide the very first treatment for these millions of CRS patients who have been underserved by current treatment options by developing an effective drug that directly targets inflammation at the epicenter of the disease.

現在我想花幾分鐘時間提醒您為什麼我們最初將開發重點放在慢性鼻竇炎患者的治療上。 CRS 是一種使人衰弱的疾病，但在很大程度上被忽視了。這種疾病在世界各地非常流行，光在美國就有約 1400 萬人。患者目前正在接受尚未被批准用於治療 CRS 的超說明書藥物治療。因此，大約一半的患者未能接受治療並繼續遭受疾病折磨。光是在美國，每年就有 400 萬名患者未能接受醫療管理。他們的下一個選擇是侵入性手術。目前上市的產品僅開發用於治療息肉，僅佔 CRS 患者的 10%。 Lyra 的使命是透過開發一種直接針對疾病中心發炎的有效藥物，為數以百萬計的慢性鼻竇炎患者提供第一種治療方法，這些患者目前的治療方案尚未得到充分服務。

Our proprietary XTreo platform technology enables delivery of a targeted and consistent therapeutic dosing directly to the diseased submucosa for six months with one application. No one else has been able to achieve this to date. Lyra is developing two product candidates to fully address patients with CRS, LYR-210 and LYR-220. Both are small shape memory implants that are placed deep in the nasal passage using a small diameter applicator in an ENT's office during a routine endoscopy. LYR-210 is designed to be used early in the treatment paradigm in surgically naive patients after topical steroid sprays have failed. We estimate this population to represent about 2.4 million patients in the United States each year.

我們專有的 XTreo 平台技術能夠透過一次應用，直接向患病黏膜下層提供有針對性的、一致的治療劑量，持續六個月。迄今為止，還沒有其他人能夠實現這一目標。 Lyra 正在開發兩種候選產品，以全面解決 CRS 患者的問題：LYR-210 和 LYR-220。兩者都是小型形狀記憶植入物，在常規內視鏡檢查過程中，在耳鼻喉科辦公室使用小直徑施藥器將其植入鼻道深處。 LYR-210 設計用於在局部類固醇噴劑失敗後早期用於未接受過手術的患者的治療模式。我們估計美國每年約有 240 萬名患者。

The postsurgical market opportunity is also significant at about 1.6 million patients each year. To address this market, we're developing LYR-220, which is designed for the postsurgical anatomy in patients who continue to require therapy despite having had prior endoscopic sinus surgery. Our growing body of scientific evidence continues to support the safety and efficacy of LYR-210 and highlights the benefits of our proprietary XTreo platform technology. We have strong validation of our technology in CRS, our first targeted indication, and we intend to leverage the platform in new indications over the next year.

術後市場機會也很大，每年約有 160 萬名患者。為了滿足這個市場的需求，我們正在開發 LYR-220，它專為那些儘管之前接受過內視鏡鼻竇手術但仍需要治療的患者進行術後解剖學設計。我們不斷增長的科學證據繼續支持 LYR-210 的安全性和有效性，並強調了我們專有的 XTreo 平台技術的優勢。我們在 CRS（我們的第一個目標適應症）方面對我們的技術進行了強有力的驗證，我們打算在明年在新的適應症中利用該平台。

In addition to our own research, we have also been hearing from key opinion leaders about their enthusiasm for the potential of LYR-210 to be a new treatment alternative for their CRS patients. Over the past few months, we hosted two events with leading ENTs who all shared their experiences in treating CRS patients, the shortcomings of current therapies and the need for new effective treatments. We urge you to listen to the webcasts, which are found in the IR section of our corporate website. I'm sure that you will find their perspectives informative.

除了我們自己的研究之外，我們還聽到了關鍵意見領袖的意見，他們對 LYR-210 成為 CRS 患者新治療替代方案的潛力充滿熱情。在過去的幾個月裡，我們與領先的耳鼻喉科專家舉辦了兩次活動，他們都分享了治療慢性鼻竇炎患者的經驗、當前療法的缺點以及對新的有效療法的需求。我們強烈建議您收聽網路廣播，這些網路廣播可以在我們公司網站的 IR 部分找到。我相信您會發現他們的觀點內容豐富。

With the upcoming initiations of our two clinical programs, our Phase 3 ENLIGHTEN program for LYR-210 and the Phase 2 BEACON program for LYR-220, we're one step closer to potentially changing the treatment paradigm for the millions of underserved CRS patients. I'll now turn the call over to Dr. Robert Kern, who will review the new data as well as the clinical trial designs for LYR-210 and LYR-220, which are both anticipated to initiate around year end. Rob?

隨著我們的兩個臨床項目即將啟動，即LYR-210 的3 期ENLIGHTEN 項目和LYR-220 的2 期BEACON 項目，我們距離改變數百萬得不到充分服務的CRS 患者的治療模式又近了一步。我現在將把電話轉給 Robert Kern 博士，他將審查新數據以及 LYR-210 和 LYR-220 的臨床試驗設計，預計這兩項試驗將在年底左右啟動。搶？

Thank you, Maria. As Maria mentioned, new positive data on LYR-210 was the subject of two presentations at the 67th Annual ARS, that's the American Rhinologic Society. Before I review these data, I wanted to remark on the award that the LANTERN manuscript received at that meeting. In my 30 years as a rhinologist and a member of that society, I have not seen that award given to industry-sponsored research. So it's quite an accomplishment for Lyra and a validation of our rigorous clinical program. The LANTERN posttreatment evaluation assessed the safety and efficacy over six months following matrix removal. During the posttreatment period, there was no increased incidence of treatment-related adverse events.

謝謝你，瑪麗亞。正如 Maria 所提到的，LYR-210 的新陽性數據是第 67 屆美國鼻科學會年度 ARS 上兩場演講的主題。在我回顧這些數據之前，我想談談 LANTERN 手稿在那次會議上獲得的獎項。在我擔任鼻科醫生和該協會成員的 30 年裡，我還沒有看到該獎項授予業界資助的研究。因此，這對 Lyra 來說是一項相當大的成就，也是對我們嚴格的臨床計劃的驗證。 LANTERN 治療後評估評估了基質去除後六個月內的安全性和有效性。在治療後期間，與治療相關的不良事件的發生率並沒有增加。

Also, approximately half of these CRS patients experienced a durable response six months after the removal of LYR-210, while roughly 90% of the patients in the control arm showed worsened CRS symptoms from weeks 24 to 48. The durable symptom relief observed in some patients after removal of LYR-210 offers potential long-term benefit as a meaningful differentiator relative to other treatments.

此外，大約一半的 CRS 患者在移除 LYR-210 後六個月出現持久反應，而對照組中約 90% 的患者在第 24 至 48 週期間出現了惡化的 CRS 症狀。移除LYR-210 後的患者俱有潛在的長期益處，這是一個有意義的差異化因素。

We also reported results from the 56 day pharmacokinetic study which showed that LYR-210 delivered a constant daily dose of mometasone furoate over the study period without a drug burst. The PK study enrolled 24 patients across four US sites to receive LYR-210, 2,500 and 7,500 picogram doses -- or 7,500 picogram doses. The study showed LYR-210 to be safe and effective in patients with less severe disease as patients in the PK study had baseline SNOT-22 scores of around 38 (sic - see Press Release, "36") compared to 68 in the LANTERN Phase 2 trial. Impressively, 63% of patients achieved a score below 20, the common standard threshold for surgery, and 38% of patients achieved a normal score, meaning below nine, by day 56.

我們也報告了 56 天藥物動力學研究的結果，該研究表明 LYR-210 在研究期間每天提供恆定劑量的糠酸莫米松，而沒有藥物爆發。這項 PK 研究招募了美國四個地點的 24 名患者，接受 LYR-210、2,500 和 7,500 皮克劑量，或 7,500 皮克劑量。研究顯示LYR-210 對於病情較輕的患者是安全有效的，因為PK 研究中患者的基線SNOT-22 評分約為38（原文如此- 參見新聞稿，「36」），而LANTERN 階段的患者為68 2 審判。令人印象深刻的是，到第 56 天，63% 的患者得分低於 20 分（手術的通用標準閾值），38% 的患者得分正常，低於 9 分。

These results further demonstrate our belief that LYR-210 has the potential to provide an effective treatment for mild all the way to severe CRS disease. We've now shown in three separate trials, both safety and efficacy for our lead product, LYR-210. We believe these impressive results validate the six-month treatment duration provided with a single administration and the potential for a more durable effect post-removal. As a practicing physician and otolaryngologist, I believe that LYR-210 offers a significant advantage over existing therapies and has the potential to establish a new standard of care for chronic rhinosinusitis.

這些結果進一步證明了我們的信念，LYR-210 有潛力為輕度至重度 CRS 疾病提供有效的治療。我們現在已經在三個獨立的試驗中證明了我們的主導產品 LYR-210 的安全性和有效性。我們相信這些令人印象深刻的結果驗證了單次給藥提供的六個月治療持續時間以及去除後更持久效果的潛力。作為一名執業醫師和耳鼻喉科醫生，我相信 LYR-210 比現有療法具有顯著優勢，並有可能為慢性鼻竇炎建立新的護理標準。

Looking ahead, the global Phase 3 ENLIGHTEN program for LYR-210 is expected to initiate around year end. We anticipate enrollment in each trial of about 180 adult patients with CRS who have failed medical management and are surgically naive. The two studies will be randomized two to one to LYR-210 versus control. Primary endpoint will be the three cardinal symptom scores at 24 weeks with secondary endpoints to include SNOT-22, rescue treatments, sinus CT scans, quality of life, and pharmaco-economic evaluations.

展望未來，LYR-210 的全球第 3 階段 ENLIGHTEN 計畫預計將於年底左右啟動。我們預計每項試驗都會招募約 180 名患有 CRS 的成年患者，這些患者醫療管理失敗且未接受過手術。這兩項研究將隨機分為 2 比 1 進行，分別分配給 LYR-210 與對照組。主要終點將是 24 週時的三個主要症狀評分，次要終點包括 SNOT-22、救援治療、鼻竇 CT 掃描、生活品質和藥物經濟學評估。

The design is largely similar to the Phase 2 LANTERN study, which was highly statistically significant in the three cardinal symptoms at 24 weeks. ENLIGHTEN-1 will include a six-month extension study where placebo patients will cross over to LYR-210 treatment and 50% of the treated patients will receive a repeat dose. It is important to note that the extension study will not delay top line readout on the primary endpoint at 24 weeks. We believe that ENLIGHTEN is a robust clinical development program, the first of its kind in this field.

該設計在很大程度上類似於 2 期 LANTERN 研究，該研究在 24 週時的三個主要症狀方面具有高度統計顯著性。 ENLIGHTEN-1將包括一項為期六個月的擴展研究，其中安慰劑患者將過渡到LYR-210治療，並且50%的治療患者將接受重複劑量。值得注意的是，擴展研究不會延遲 24 週時主要終點的頂線讀數。我們相信，ENLIGHTEN 是一個強大的臨床開發項目，也是該領域的首個此類項目。

Later this month, we will also start the Phase 2 BEACON study for LYR-220. We plan to enroll approximately 65 postsurgical patients across sites in the United States and Australia randomized one to one to one to receive one of two different matrix designs, each at a dose of 7,500 picograms or control. Primary endpoint will be safety and feasibility over 24 weeks with secondary endpoints including PK, SNOT-22, three cardinal symptoms, rescue treatment, sinus CT, nasal biomarkers and quality of life.

本月晚些時候，我們也將開始 LYR-220 的 2 期 BEACON 研究。我們計劃在美國和澳洲各地招募約 65 名術後患者，以一對一的方式隨機分配，接受兩種不同基質設計中的一種，每種劑量為 7,500 皮克或對照組。主要終點將是 24 週內的安全性和可行性，次要終點包括 PK、SNOT-22、三個主要症狀、搶救治療、鼻竇 CT、鼻生物標記和生活品質。

Let me now turn the call over to Jason, who will review the quarter's financials. Jason?

現在讓我將電話轉給傑森，他將審查本季的財務狀況。傑森？

Thank you, Dr. Kern. Before I review the quarter's financials, I would like to take this opportunity to express my enthusiasm for the opportunity at Lyra. Over the course of my investment banking career, I have worked with numerous companies across the healthcare sector, and I believe that Lyra is uniquely positioned with tremendous potential to change the treatment paradigm for CRS patients. I'm honored to be working with a stellar team here and support our mission to be a leader in CRS treatments.

謝謝你，克恩醫生。在回顧本季的財務狀況之前，我想藉此機會表達我對 Lyra 的機會的熱情。在我的投資銀行職業生涯中，我曾與醫療保健行業的眾多公司合作過，我相信 Lyra 具有獨特的地位，具有改變 CRS 患者治療模式的巨大潛力。我很榮幸能在這裡與一支優秀的團隊合作，並支持我們成為 CRS 治療領域領導者的使命。

Turning to the quarter's financial results, a press release was just issued, but let me review select highlights. Lyra ended the third quarter with cash and cash equivalents of $58.1 million compared to $69.0 million as of June 30, 2021. We believe that Lyra has sufficient cash to fund the company's planned operations through 2022.

談到本季的財務業績，我們剛剛發布了一份新聞稿，但讓我回顧一下精選的亮點。 Lyra 截至第三季末的現金和現金等價物為 5,810 萬美元，而截至 2021 年 6 月 30 日為 6,900 萬美元。

Research and development expenses for the quarter ended September 30, 2021, were $7.1 million compared to $3.7 million for the same period in 2020 primarily attributable to an increase in product development and manufacturing expenses related to the tech transfer to our contract manufacturer, as well as an increase in research and development headcount and consulting expenses as we ramp up for our later-stage clinical programs. G&A expenses for the third quarter 2021 were $4.0 million compared to $2.7 million for the same period in 2020, primarily attributable to an increase in professional and consulting expenses, stock-based compensation, and general and administrative headcount.

截至 2021 年 9 月 30 日的季度研發費用為 710 萬美元，而 2020 年同期為 370 萬美元，主要歸因於與向合約製造商轉讓技術相關的產品開發和製造費用增加，以及隨著我們後期臨床項目的推進，研發人員數量和諮詢費用也會增加。 2021 年第三季的一般管理費用為 400 萬美元，而 2020 年同期為 270 萬美元，主要歸因於專業和諮詢費用、股票薪酬以及一般和行政人員人數的增加。

Total operating expenses for the third quarter were $11.1 million compared to $6.4 million for the same period in 2020. Net loss for the third quarter was $11.1 million compared to $6.3 million for the same period in 2020. And shares outstanding as of September 30, 2021 were approximately 13 million.

第三季的總營運費用為1,110 萬美元，而2020 年同期為640 萬美元。股票大約有1300萬。

With that, I'll turn the call back to Maria.

這樣，我會把電話轉回給瑪麗亞。

Thank you, Jason. Lyra is poised to be a dominant player in the CRS market. LYR-210 and LYR-220 are designed to be disease-modifying and best in class treatments for the millions of CRS patients who are underserved by current medical management. We're extremely excited to be advancing into late-stage development with the start of the Phase 3 clinical program for LYR-210 and a Phase 2 clinical trial for LYR-220 in the coming months. Now we're ready to take your questions. Operator?

謝謝你，傑森。 Lyra 有望成為 CRS 市場的主導者。 LYR-210 和 LYR-220 旨在為數百萬目前醫療管理服務不足的 CRS 患者提供疾病緩解和一流的治療方法。我們非常高興能夠在未來幾個月內啟動 LYR-210 的 3 期臨床計劃和 LYR-220 的 2 期臨床試驗，進入後期開發。現在我們準備好回答您的問題。操作員？

Thank you. (Operator Instructions) Tim Lugo, William Blair.

謝謝。 （操作員說明）蒂姆·盧戈，威廉·布萊爾。

Thanks for taking the question and congratulations on all the progress. I guess one quick housekeeping question. Can you give us an update on the manufacturing capacity at Lyra? And at what point in the future do you likely scale that capacity?

感謝您提出問題並祝賀所有進展。我想問一個快速的內務問題。您能為我們介紹一下 Lyra 製造能力的最新情況嗎？您可能在未來什麼時候擴展該容量？

Hi, Tim. Thank you for the question. As we have mentioned in the past, we have transferred the technology to an outside contractor in the past. We have also manufactured in-house, and we've used our SMEs here to transfer the process. The scale-up right now is geared towards our clinical studies and we're sufficient for those studies.

嗨，提姆。感謝你的提問。正如我們過去所提到的，我們過去已將技術轉移給外部承包商。我們也進行內部製造，並利用我們的中小企業來轉移流程。目前的擴大規模是針對我們的臨床研究，我們足以進行這些研究。

As you know, we have three trials. We have the ENLIGHTEN-1, the ENLIGHTEN-2 and also BEACON. And so we're in very good shape with our manufacturing. We're going to be spending time during the enrollment period and follow-up periods to be scaling up at our contract manufacturer. And as I think I mentioned in the past, we've very selective with who we have chosen. We've chosen a contract manufacturer that we believe is very well suited to be able to scale up the matrix for commercial.

如您所知，我們有三項試驗。我們有 ENLIGHTEN-1、ENLIGHTEN-2 和 BEACON。因此，我們的製造狀況非常好。我們將在註冊期和後續期花費時間來擴大我們的合約製造商的規模。正如我之前提到的，我們對選擇的人非常挑剔。我們選擇了一家合約製造商，我們認為該製造商非常適合擴大商業矩陣。

Okay. So there's no need for second sourcing or I guess you consider it second sourcing since you have manufactured in-house in the past?

好的。所以沒有必要進行第二次採購，或者我猜您認為這是第二次採購，因為您過去曾在內部製造過？

Well, at this point, we don't, but yes, we will absolutely have a backup. We'll continue to look at other backup in addition to Lyra. Certainly at this point, we can and we're well positioned between our contract manufacturer and Lyra, but certainly in the future, we will have additional source to manufacture the product.

好吧，目前我們還沒有，但是，是的，我們絕對會有備份。除了 Lyra 之外，我們將繼續關注其他備份。當然，在這一點上，我們可以而且我們在合約製造商和 Lyra 之間處於有利地位，但將來我們肯定會有更多的來源來製造該產品。

Okay, great. And I'm interested, I believe it was Dr. Kern that mentioned this in the past or maybe it was you, Maria, as well. In the fact that you won the Clinical Science Maurice Cottle Award and you are the first company from industry that has won this award. I guess what do you think the society saw in the Phase 2 data specifically, which stood out beyond the other biologics and the other kind of larger Phase 3s that have obviously been presented in the past?

好的，太好了。我很感興趣，我相信克恩博士過去提到過這一點，或者也許也是你，瑪麗亞。事實上，你們贏得了臨床科學莫里斯·科特爾獎，並且你們是第一家獲得該獎項的行業公司。我想您認為社會在第二階段數據中具體看到了什麼，這些數據比其他生物製品和過去明顯提出的其他類型的較大第三階段數據脫穎而出？

I should probably answer that. I think the magnitude of the response is -- with a single administration is very striking. That's the only thing that comes close to this in the change in the SNOT-22 would be either the biologics, which you have to give regularly and require -- and are extraordinarily expensive. And the other option is surgery. So to have that kind of outcome at six months is striking. The statistics were robust and the presentation was appropriately scaled, it wasn't -- it was measured, but it was exciting, I think, was probably the main reason and it was well done.

我或許應該回答這個問題。我認為，單一政府所做出的反應是非常驚人的。 SNOT-22 的變化中唯一接近這一點的是生物製劑，你必須定期給予和需要——而且非常昂貴。另一個選擇是手術。因此，在六個月內取得這樣的結果是令人震驚的。統計數據是可靠的，簡報的規模也適當，但它不是——它是經過測量的，但我認為這很令人興奮，這可能是主要原因，而且做得很好。

Yeah, maybe I can also -- thanks, Rob. I totally agree with everything. One thing -- I've been in this space for a long time doing drug delivery from implants and the fact that we had two doses and we did a dose response, I think really stood out. It's really a rare thing to see. Because you do have to create a whole new product and formulation and it just speaks to the strength of our development and scientific teams that we did that. We went into the study really not knowing whether we would see a dose response and the fact that we did see it was validating, certainly to Lyra and to the scientific community.

是的，也許我也可以──謝謝，羅布。我完全同意一切。有一件事——我已經在這個領域工作了很長時間，透過植入物進行藥物輸送，事實上我們有兩次劑量並且我們做了劑量反應，我認為這真的很突出。這確實是一件很難得的事。因為你確實必須創造一種全新的產品和配方，而這正好證明了我們的開發和科學團隊的實力，我們做到了這一點。當我們進入這項研究時，我們真的不知道我們是否會看到劑量反應，而我們確實看到了它的事實是有效的，當然對萊拉和科學界來說。

I'd agree. Congratulations on that milestone. And I guess one last question. Could you give us an update on the LianBio development plan, if that's kind of come together for your Asian partner?

我同意。祝賀這一里程碑。我想還有最後一個問題。如果您的亞洲合作夥伴有這樣的計劃，您能為我們介紹一下聯拓生物發展計劃的最新情況嗎？

Sure. This is Corinne Noyes. We're very pleased with how the LianBio collaboration is progressing and we are on track to -- and have them participate in our second of the two Phase 3 studies. And the goal with that participation is for them to submit and commercialize shortly after we do in the US.

當然。這是科琳·諾伊斯。我們對聯拓生物合作的進展感到非常滿意，我們正在努力讓他們參與我們兩項三期研究中的第二項。這種參與的目標是讓他們在我們在美國提交並商業化後不久。

Great. Congratulations on the progress.

偉大的。祝賀取得的進展。

Thank you, Tim.

謝謝你，提姆。

Thank you. Bert Hazlett, BTIG.

謝謝。伯特·哈茲利特，BTIG。

Yes, thanks -- just two for me. My congratulations on all the progress as well. Just with regard to the financial statements and looking forward, given that you're starting the two major efforts -- the three studies but two major efforts with LYR-210 and LYR-220, how should we think about the trajectory of R&D going forward? It's been $7 million plus over the past couple of quarters. Should that materially increase on a quarter-to-quarter basis? And if so, roughly what levels should we be thinking about in terms of models?

是的，謝謝——只給我兩個。我也祝賀所有的進展。就財務報表和展望而言，鑑於您正在開始兩項主要工作——三項研究，但兩項主要工作是 LYR-210 和 LYR-220，我們應該如何考慮未來研發的軌跡？過去幾季已經超過 700 萬美元。這個數字是否應該按季度大幅增加？如果是這樣，我們應該在模型方面大致考慮什麼程度？

Hi. This is Jason. So I think given that we've completed the tech transfer to our contract manufacturer, we expect that spending to obviously tail off, offset by increase in the manufacturing expense to supply the units for the clinical trials. So we would expect a slight uptick overall in our R&D which is the manufacturing as well as the -- obviously, the clinical expenses. So given that we're starting three trials, so I would expect a slight uptick. But again, we feel like with the cash on hand and expected milestones, we will have enough cash to run the business through the end of next year.

你好。這是傑森。因此，我認為鑑於我們已經完成了向合約製造商的技術轉讓，我們預計支出將顯著減少，並被為臨床試驗提供設備的製造費用的增加所抵消。因此，我們預計我們的研發（即製造以及臨床費用）總體上會略有上升。鑑於我們正在開始三項試驗，所以我預計會略有上升。但我們再次認為，憑藉手頭上的現金和預期的里程碑，我們將有足夠的現金來經營業務到明年年底。

Terrific. Thank you. And then just a question on the clinical data, the durability of effect scene is terrific data. How does that make you think about your kind of retreatment rates with LYR-210, either patients with polyps or non-polyps, does that make you think about the rate of re-treatment or is that pretty steady? And just your general thoughts there in terms of the numbers of procedures that you would expect a patient with CRS to undergo per year with either LYR-210 or LYR-220?

了不起。謝謝。然後只是關於臨床數據的問題，效果場景的持久性是很棒的數據。這如何讓您考慮 LYR-210 的再治療率，無論是息肉患者還是非息肉患者，這是否讓您考慮再治療率，或者是否相當穩定？您對 CRS 患者每年接受 LYR-210 或 LYR-220 手術的數量有何整體想法？

Yes. So maybe I can start and then turn it over to Corinne and we can get her perspective, too. We were excited to see that in about half the patients, we did see a durable response. I think it really speaks to the fact that these patients are getting a consistent and targeted dose of steroid, which is a broad anti-inflammatory, which then potentially results in some remodeling of the tissue. It's small numbers, clearly. So we do have to evaluate this further in Phase 3. And as you heard from Rob, we do plan to do that in the Phase 3 extension study. Corinne?

是的。所以也許我可以開始，然後將其交給科琳，我們也可以了解她的觀點。我們很高興地看到，在大約一半的患者中，我們確實看到了持久的反應。我認為這確實說明了這樣一個事實：這些患者正在接受一致且有針對性的劑量的類固醇，這是一種廣泛的抗發炎藥，然後可能會導致組織的一些重塑。顯然，這個數字很小。因此，我們確實必須在第三階段進一步評估這一點。科琳娜？

Yeah. And I think we've shared in the past that, with our modeling internally, we always assume about one and a half -- 1.5 uses per year so that 50% of patients get a re-treatment. And interestingly enough, this early data that emerged from the LANTERN study directly aligns with that assumption, that around 50% of patients would get another one and 50% wouldn't need one in the first year, but might need another one at some point. So I think we'll see a mix of repeat use and some patients that have a durable response and we [monitor that currently].

是的。我認為我們過去已經分享過，透過我們的內部建模，我們總是假設每年大約使用一次半——1.5 次，以便 50% 的患者得到重新治療。有趣的是，LANTERN 研究中出現的早期數據直接符合這一假設，即大約50% 的患者會在第一年接受另一種治療，50% 的患者在第一年不需要另一種治療，但在某個時候可能需要另一種治療。所以我認為我們會看到重複使用和一些具有持久反應的患者的混合，我們[目前正在監測]。

Terrific. That's very helpful. Just one more question then for me. A brief one. You've had some very intriguing additional data releases, presentations. We had nice publications based on LANTERN and other data for LYR-210. Should we expect additional publications or presentations upcoming in the not-too-distant future?

了不起。這非常有幫助。那麼還有一個問題想問我。簡短的一則。你們發布了一些非常有趣的附加數據、簡報。我們基於 LANTERN 和 LYR-210 的其他數據發表了很好的出版物。我們是否應該期待在不久的將來會有更多的出版品或簡報？

Our next conference is at COSM, which is --

我們的下一次會議將在 COSM 舉行，這是—

Yeah. So we've submitted some data at COSM in April, and we've submitted abstracts there. We'll find out if they are -- hope to find out soon if they're accepted, but we will be presenting some new data if all goes well at that conference. And as soon as we hear about that we will make that available.

是的。所以我們四月在 COSM 上提交了一些數據，並在那裡提交了摘要。我們會知道它們是否被接受，希望很快就能知道它們是否被接受，但如果會議一切順利，我們將提供一些新數據。一旦我們聽到這個消息，我們就會立即提供。

Outstanding. Thanks so much.

傑出的。非常感謝。

Thank you. Chris Howerton, Jefferies.

謝謝。克里斯·豪爾頓，杰弗里斯。

Great. Thank you so much for taking the questions. Two from me. One would be -- what would be the expected enrollment cadence or timeline for the Phase 3 programs for LYR-210? And if you're unwilling or unable to kind of provide clear estimates there, maybe you could remind us what the timelines were for the LANTERN study.

偉大的。非常感謝您提出問題。我的兩個。其中之一是 LYR-210 第 3 階段專案的預期註冊節奏或時間表是什麼？如果您不願意或無法提供明確的估計，也許您可以提醒我們 LANTERN 研究的時間表。

And then the second question would be you know, just as I think we actually discussed this recently, but I'd be curious to see if Dr. Kern or anyone else on the team had additional thoughts here about why is it that you're seeing a durable effect six months after the removal of the device. Is there something about tissue remodeling or something else that could be going on to explain some of those durable effects? Thank you.

然後第二個問題是你知道的，正如我認為我們最近實際上討論過這個問題一樣，但我很想知道克恩博士或團隊中的其他任何人是否有更多關於為什麼你是這樣的想法移除裝置六個月後即可看到持久效果。是否有組織重塑或其他因素可以解釋其中一些持久的影響？謝謝。

Thank you, Chris. I'll go ahead and take the first question and then Rob can address the second one. We expect that enrollment for both ENLIGHTEN-1 and ENLIGHTEN-2 will take approximately 12 months. We think we'll be enrolling patients through 2022. Clearly, we'll be trying to enroll patients as quickly as we can where we're thinking a lot about the sites that we pick to ensure that happens. We intend to not only have sites in the US but also in Europe so we feel good about those estimates and we're hoping that we'll be able to accelerate as possible. Rob?

謝謝你，克里斯。我將繼續回答第一個問題，然後羅布可以解決第二個問題。我們預計 ENLIGHTEN-1 和 ENLIGHTEN-2 的註冊將需要大約 12 個月的時間。我們認為我們將在 2022 年之前招募患者。我們不僅打算在美國設立站點，而且還打算在歐洲設立站點，因此我們對這些估計感到滿意，並希望能夠盡可能加速。搶？

Sure. Yes. I mean, obviously, it's a very intriguing and encouraging finding that half of the patients really sustain the improvement, but it's a small study. And we need to keep in mind that this is improvement. It's not cure. Cure is a dangerous word to use with a chronic disease. You can [get] a couple of colds and can spin the whole thing out of control.

當然。是的。我的意思是，顯然，這是一個非常有趣和令人鼓舞的發現，一半的患者確實維持了這種改善，但這是一項小型研究。我們需要記住，這是一種進步。這不是治癒方法。治癒對於慢性病來說是一個危險的詞。你可能會感冒幾次，然後整件事情就會失控。

So while it's encouraging, we're not getting carried away. I think if you want me to put my basic science immunologist hat on, I could say that the -- what we don't see -- before I get to that, what we don't see is a rebound effect. The biologics, despite they're power, as soon as you take the drug away, they start to revert back.

因此，雖然這令人鼓舞，但我們並沒有得意忘形。我想，如果你想讓我戴上基礎科學免疫學家的帽子，我可以說，在我講到這一點之前，我們沒有看到的是反彈效應。生物製劑儘管很有效，但一旦你把藥物拿走，它們就會開始恢復。

Now the difference and again, I've got my speculative hat on, my immunology speculation hat on -- the steroids are much broader. They basically squelch almost the entire inflammatory cascade. The biologics punch little holes in it. They are like little targets. So my sense is that what we are doing and we are so broadly suppressing it that there is some element of remodeling that we are kind of turning back -- takes years to get this disease. We are suppressing all aspects of the inflammatory response so we are, perhaps, walking back the clock. If that answers your question.

現在的區別是，我再次戴上了我的推測帽子，我的免疫學推測帽子 - 類固醇的範圍要廣泛得多。它們基本上抑制了幾乎整個發炎級聯反應。生物製劑在上面打了一些小洞。他們就像小目標。所以我的感覺是，我們正在做的事情以及我們如此廣泛地壓制它，以至於我們正在逆轉一些重塑的因素——需要數年時間才能患上這種疾病。我們正在抑制發炎反應的各個方面，所以我們也許正在倒退。如果這回答了你的問題。

No, I appreciate it, Dr. Kern, I really do. Thank you. And actually, Maria, if I might sneak in just another follow-up, could you give us maybe similar expectations for the Phase 2 LYR-220 study as well?

不，我很感激，科恩博士，我真的很感激。謝謝。事實上，Maria，如果我可以偷偷地進行另一次後續行動，您能否給我們對 2 期 LYR-220 研究提出類似的期望？

So the Phase 2 study is going to initiate this month and there are two -- the two parts to that study there is the open label part where we're going to be assessing the feasibility. We're going to be optimizing the procedure of delivery, and then after that, we're going to be going into the randomized portion of the study. And so we'll be starting in Australia and then we're going to be clearly with the US is focused on LYR-210, but we expect, then, we'll get started in the US, too. So in terms of enrollment, again, it would be through 2022 that that we'll be enrolling that study.

因此，第二階段研究將於本月啟動，有兩個部分——研究的兩個部分是開放標籤部分，我們將在其中評估可行性。我們將優化分娩程序，然後，我們將進入研究的隨機部分。因此，我們將從澳洲開始，然後我們將明確與美國合作，並專注於 LYR-210，但我們預計，我們也會在美國開始。因此，就註冊而言，我們將在 2022 年之前註冊該研究。

Okay, all right. Thank you very much, and congratulations on the progress.

好吧，好吧。非常感謝，並祝賀取得的進展。

Thank you, Chris.

謝謝你，克里斯。

Thank you. (Operator Instructions) Ashwani Verma, Bank of America.

謝謝。 （操作員指令）Ashwani Verma，美國銀行。

Thanks for taking our question. Congrats on the progress. Two from me. So this LianBio collaboration -- just wanted to make sure I heard it right. I think you're assuming that they will launch in the geographies one year after you can in the US and how much of the milestone payments can we assume in the next one year and out of that 135 and how much would be around the approval and launch? That's my first question.

感謝您提出我們的問題。祝賀取得的進展。我的兩個。所以這次聯拓生物合作——只是想確保我沒聽錯。我認為你假設他們將在美國推出一年後在其他地區推出，我們可以在接下來的一年中承擔多少里程碑付款，在這 135 個地區中，有多少是在批准和發射？這是我的第一個問題。

And just on the Phase 2 design that you just discussed. So like when you conduct the open-label part of the study, just like optimizing the procedure, is that something that you are going to share with us just around -- I'm assuming that you want to identify whether the retention is good enough or not, or for bigger metrics. So just curious if you will share that with us.

就您剛才討論的第二階段設計而言。因此，就像當您進行研究的開放標籤部分時，就像優化程序一樣，您將與我們分享一些東西 - 我假設您想確定保留是否足夠好或不，或更大的指標。所以只是好奇你是否願意與我們分享。

Hi, Ash. Thank you for your questions. We'll start with Corinne and Jason can address the first one.

嗨，阿什。謝謝您的提問。我們將從 Corinne 開始，Jason 可以解決第一個問題。

So to answer your question about the timing of launch in China, our current development plans have China launching shortly after the US, so sooner than a year.

因此，回答你關於在中國推出時間的問題，我們目前的發展計劃是中國在美國之後不久推出，所以不到一年。

And on the milestones, we haven't disclosed the specifics around the milestones and timing of the LianBio collaboration. I would say that, you know, the structure, the overall structure of it is not dissimilar from similar agreements, but we haven't released specifics around the milestone payments.

至於里程碑，我們尚未透露聯拓生物合作的里程碑和時間安排的具體細節。我想說的是，它的結構、整體結構與類似協議沒有什麼不同，但我們還沒有發布有關里程碑付款的具體細節。

So Ash, on your second question about the Phase 2 design and whether we'll be able to share data from the open label, certainly, we would report out when we have that data on hand. And I would expect it in the second half of 2022. And really what we're going to be assessing there is the feasibility of placement. And so whatever data we have from that and the safety we'll be certainly reporting out.

Ash，關於第二階段設計以及我們是否能夠共享開放標籤資料的第二個問題，當然，我們會在手頭上有這些資料時報告。我預計在 2022 年下半年實現。因此，無論我們從中獲得什麼數據以及安全性，我們都一定會報告出來。

Yeah. Okay. Got it. Thanks.

是的。好的。知道了。謝謝。

Thank you.

謝謝。

Ladies and gentlemen, that concludes our Q&A session for today. I'll hand it back over to Maria Palasis, the CEO, for any closing remarks.

女士們先生們，今天的問答環節到此結束。我將把它交還給執行長瑪麗亞·帕拉西斯 (Maria Palasis)，讓其發表結束語。

Thank you, operator. And thank you all for joining us today. We look forward to updating you on our progress. You may now disconnect. Enjoy your day.

謝謝你，接線生。感謝大家今天加入我們。我們期待向您通報我們的最新進展。您現在可以斷開連線。祝您愉快。