Cartesian Therapeutics Inc (RNAC) 2022 Q4 法說會逐字稿

Good morning, and welcome to the Selecta Bio Fourth Quarter 2022 Earnings Release Conference Call. (Operator Instructions) Please note this event is being recorded. I would now like to turn the conference over to Blaine Davis, Chief Financial Officer. Please go ahead.

早上好，歡迎來到 Selecta Bio 2022年第四季度收益發布電話會議。 （操作員說明）請注意正在記錄此事件。我現在想將會議轉交給首席財務官 Blaine Davis。請繼續。

Thank you, and good morning, everyone. Welcome to our fourth quarter and full year 2022 Financial Results and Business Update Conference Call. The press release reporting our financial results is available in the Investors and Media section of Selecta's website at www.selectabio.com in our Annual Report on Form 10-K for the year ended December 31, 2022, which was filed earlier this morning with the Securities and Exchange Commission or the SEC.

謝謝大家，早上好。歡迎來到我們的 2022 年第四季度和全年財務業績和業務更新電話會議。報告我們財務業績的新聞稿可在 Selecta 網站 www.selectabio.com 的投資者和媒體部分找到，在我們截至 2022 年 12 月 31 日的 10-K 表格年度報告中，該報告於今天上午早些時候提交給證券交易委員會或 SEC。

Joining me on today's call are Carsten Brunn, President and Chief Executive Officer; Kei Kishimoto, Chief Scientific Officer; and Peter Traber, our Chief Medical Officer. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy and regulatory and clinical progress of our product candidates, our financial projections and our future expectations, plans, partnerships and prospects.

與我一起參加今天電話會議的還有總裁兼首席執行官 Carsten Brunn； Kei Kishimoto，首席科學官；和我們的首席醫療官 Peter Traber。在今天的電話會議中，我們將做出某些前瞻性陳述，包括但不限於關於我們候選產品的潛在安全性、有效性以及監管和臨床進展、我們的財務預測以及我們未來的預期、計劃、合作夥伴關係和前景的陳述。

These statements are subject to various risks that are described in the filings made with the SEC, including our most recent Annual Report on Form 10-K and subsequent quarterly reports on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, March 2, 2023, and Selecta disclaims any obligation to update such statements, except as required by law, even if management's views change.

這些報表受向美國證券交易委員會提交的文件中描述的各種風險的影響，包括我們最近的 10-K 表格年度報告和隨後的 10-Q 表格季度報告。請注意不要過分依賴這些前瞻性陳述，這些陳述僅在今天，即 2023 年 3 月 2 日生效，Selecta 不承擔任何更新此類陳述的義務，除非法律要求，即使管理層的觀點發生變化。

With that, I'd now like to turn the call over to Carsten.

有了這個，我現在想把電話轉給 Carsten。

Thank you, Blaine. Good morning. I appreciate everyone taking the time to join us today. In the fourth quarter of 2022 and in the first months of 2023, we continue to make steady progress across our pipeline, and we believe we're well-positioned to execute on our key priorities and reach multi milestones throughout this year. In collaboration with our partner, Sobi, we expect to announce top line data from the Phase III DISSOLVE I and II clinical trials of SEL-212 later this quarter. [We remain blinded] to the data based on the results from previous trials in which we observed SEL-212's differentiated profile and convenient once-monthly dosing regimen, we remain confident in its potential to improve the lives of patients suffering from chronic refractory gout.

謝謝你，布萊恩。早上好。我感謝大家今天抽出時間加入我們。在 2022 年第四季度和 2023 年的頭幾個月，我們繼續在整個管道中取得穩步進展，我們相信我們已做好充分準備來執行我們的關鍵優先事項並在今年全年實現多個里程碑。通過與我們的合作夥伴 Sobi 合作，我們預計將在本季度晚些時候公佈 SEL-212 III 期 DISSOLVE I 和 II 臨床試驗的頂級數據。 [我們仍然對]基於我們觀察到 SEL-212 的差異化特徵和方便的每月一次給藥方案的試驗結果的數據，我們仍然相信它有可能改善慢性難治性痛風患者的生活。

Further, we plan to continue to leverage our growing safety database to advance our ImmTOR clinical development programs for our ongoing ReiMMAgine Phase I/II clinical trial of SEL-302 for the treatment of methylmalonic acidemia, or MMA, and propel our next-generation programs forward. Notably, we recently identified an Interleukin-2 or IL-2 candidate to be started in combination with ImmTOR in a broad set of potential autoimmune indications as well as an IgA protease candidate for the treatment of IgA Nephropathy. We also continue to accelerate our IgG Protease called Xork following a deal we signed with Astellas in early January, which involves the study of Xork in combination with AT845 an investigational adeno-associated virus or AAV-based treatment for Late-Onset Pompe Disease.

此外，我們計劃繼續利用我們不斷增長的安全數據庫來推進我們正在進行的用於治療甲基丙二酸血症或 MMA 的 SEL-302 ReiMMAgine I / II 期臨床試驗的 ImmTOR 臨床開發計劃，並推動我們的下一代計劃向前。值得注意的是，我們最近確定了一種 Interleukin-2 或 IL-2 候選藥物將與 ImmTOR 聯合用於廣泛的潛在自身免疫適應症，以及一種用於治療 IgA 腎病的 IgA 蛋白酶候選藥物。在我們於 1 月初與 Astellas 簽署協議後，我們還繼續加速我們名為 Xork 的 IgG 蛋白酶，該協議涉及 Xork 與 AT845 的研究，AT845 是一種研究性腺相關病毒或基於 AAV 的遲發性龐貝病治療方法。

As we look ahead, we intend to continue to advance our pipeline in autoimmune disease and explore additional collaborations to maximize the value of our ImmTOR platform and pipeline. On the cusp of this pivotal moment in the company's growth trajectory, we'd like to provide an update on recent activities and share details on how these programs align with our mission to solve the toughest challenges associated with unwanted immunogenicity. The current standards of care for autoimmune disease utilize immunosuppressive drugs or symptom-masking treatment. Unfortunately, these treatments often leave patients vulnerable to serious infections, malignancies and fail to adequately address the underlying cause of the disease, which is an imbalance of regulatory T-cells versus effective T-cells.

展望未來，我們打算繼續推進我們在自身免疫性疾病方面的管道，並探索更多的合作，以最大限度地發揮我們的 ImmTOR 平台和管道的價值。在公司發展軌蹟的這一關鍵時刻，我們想提供近期活動的最新情況，並分享這些計劃如何與我們的使命保持一致的細節，以解決與不良免疫原性相關的最嚴峻挑戰。當前的自身免疫性疾病護理標準使用免疫抑製藥物或症狀掩蔽治療。不幸的是，這些治療常常使患者容易受到嚴重感染、惡性腫瘤的影響，並且無法充分解決疾病的根本原因，即調節性 T 細胞與有效 T 細胞的失衡。

At Selecta, we're reimagining immunotherapy. There are over 24 million Americans still suffering from autoimmune diseases. We believe ImmTOR has the potential to transform the treatment landscape by restoring natural immune system balance through induction and expansion of regulatory T-cells in vivo. The combination of ImmTOR and IL-2, which we call ImmTOR-IL represents an evolution of Selecta's precision immune tolerance platform that has the potential to further enhance the magnitude and duration of immune tolerance in patients treated for autoimmune diseases.

在 Selecta，我們正在重新構想免疫療法。仍有超過 2400 萬美國人患有自身免疫性疾病。我們相信 ImmTOR 有可能通過在體內誘導和擴增調節性 T 細胞來恢復自然免疫系統平衡，從而改變治療格局。 ImmTOR 和 IL-2 的組合，我們稱之為 ImmTOR-IL，代表了 Selecta 精確免疫耐受平台的進化，它有可能進一步增強接受自身免疫性疾病治療的患者的免疫耐受程度和持續時間。

We have chosen IL-2 development candidate that will be started in combination with ImmTOR to potentially further advance and expand our pipeline in autoimmune disease. We plan to initiate IND enabling studies in 2023 while also exploring multiple autoimmune indications that may be suitable for study with ImmTOR-IL with an initial focus on diseases of the liver. We believe ImmTOR-IL has the potential to be a truly differentiated first-in-class treatment for those suffering from autoimmune diseases. We plan to initiate multiple preclinical studies this year with this exciting combination.

我們選擇了將與 ImmTOR 聯合啟動的 IL-2 開發候選藥物，以進一步推進和擴大我們在自身免疫性疾病方面的產品線。我們計劃在 2023 年啟動 IND 支持研究，同時探索可能適合使用 ImmTOR-IL 進行研究的多種自身免疫適應症，最初的重點是肝臟疾病。我們相信 ImmTOR-IL 有潛力成為針對自身免疫性疾病患者的真正差異化的一流治療方法。我們計劃今年通過這種令人興奮的組合啟動多項臨床前研究。

Moving on to our gene therapy vertical, which we believe has the potential to enhance the efficacy and safety of AAV gene therapy and broaden the (inaudible) patient population for such therapy. ImmTOR is designed to enable patients to receive multiple lower doses of AAV gene therapy, titrate up to a therapeutic benefit and mitigate side effects associated with higher vector doses, thereby transforming the dosing paradigm from one-and-done to a low-and-slow. In December '22, we initiated ReiMMAgine, the Phase I/II clinical trial of SEL-302, an AAV gene therapy combined with ImmTOR for the treatment of MMA.

繼續我們的垂直基因治療，我們認為它有可能提高 AAV 基因治療的有效性和安全性，並擴大（聽不清）此類治療的患者群體。 ImmTOR 旨在使患者能夠接受多次較低劑量的 AAV 基因治療，滴定至治療益處並減輕與較高載體劑量相關的副作用，從而將劑量範式從一次完成轉變為低劑量和緩慢. 22 年 12 月，我們啟動了 ReiMMAgine，這是 SEL-302 的 I/II 期臨床試驗，SEL-302 是一種 AAV 基因療法，與 ImmTOR 聯合治療 MMA。

The ReiMMAgine trial is now enrolling patients and aims to evaluate the safety, tolerability and efficacy of SEL-302. ReiMMAgine builds on our human proof-of-concept study in healthy volunteers, where we observed that with a single dose of ImmTOR at 0.3 mg/kg, all subjects maintained utilizing antibodies or NAb titers below 1:25 at Day 30 and two-thirds of the subjects at this dose of ImmTOR maintained NAb titers below 1:5 at Day 30. We believe our preclinical data in nonhuman primates and mice indicate that two additional monthly doses of ImmTOR have the potential to provide durable inhibition of anti-AAV NAbs.

ReiMMAgine 試驗目前正在招募患者，旨在評估 SEL-302 的安全性、耐受性和有效性。 ReiMMAgine 建立在我們對健康志願者進行的人類概念驗證研究的基礎上，我們在其中觀察到，使用單劑量 0.3 mg/kg 的 ImmTOR，所有受試者在第 30 天和三分之二時保持使用抗體或 NAb 滴度低於 1:25接受此劑量 ImmTOR 的受試者在第 30 天時將 NAb 滴度維持在 1:5 以下。我們相信我們在非人類靈長類動物和小鼠中的臨床前數據表明，每月兩次額外劑量的 ImmTOR 有可能持久抑制抗 AAV NAb。

We've incorporated this dosing regimen in the ReiMMAgine trial. By advancing SEL-302 into the clinic, we believe we can help our current and future gene therapy partners accelerate the use of ImmTOR in their gene therapy programs by providing a clinical and regulatory blueprint to follow. In January 2023, we announced an exclusive licensing and development agreement for Xork to be developed for the use with AT845, Astellas investigational AAV-based treatment for Late-Onset Pompe Disease in adults. Xork a next-generation IgG protease. Most other IgG protease in development are derived from common human pathogens and as a result there is a high prevalence of pre-existing antibodies against these proteases that can restrict their utility.

我們已將此給藥方案納入 ReiMMAgine 試驗。通過將 SEL-302 推進臨床，我們相信我們可以通過提供可供遵循的臨床和監管藍圖，幫助我們當前和未來的基因治療合作夥伴加速 ImmTOR 在其基因治療計劃中的使用。 2023 年 1 月，我們宣布了 Xork 的獨家許可和開發協議，該協議將與 AT845 一起開發，AT845 是安斯泰來基於 AAV 的研究性治療成人遲發性龐貝病的藥物。 Xork 是一種下一代 IgG 蛋白酶。大多數其他正在開發的 IgG 蛋白酶都來自常見的人類病原體，因此，針對這些蛋白酶的預先存在的抗體非常普遍，這會限制它們的實用性。

Xork is differentiated by its low cross reactivity to pre-existing antibodies in human serum, and we believe it has the potential to deliver transformative gene therapy treatments to a broader range of patients living with debilitating diseases. Many patients are currently ineligible for clinical trials with investigational AAV gene therapies due to the presence of naturally occurring antibodies against AAV capsids. Due to its selective protease activity against anti-AAV NAbs, we believe Xork has the potential to expand access to life-changing gene therapies by addressing preexisting immunity to AAV.

Xork 的不同之處在於它與人血清中預先存在的抗體的交叉反應性較低，我們相信它有可能為更廣泛的患有衰弱性疾病的患者提供轉化基因治療。由於存在針對 AAV 衣殼的天然抗體，許多患者目前不符合 AAV 基因療法臨床試驗的資格。由於其針對抗 AAV NAbs 的選擇性蛋白酶活性，我們相信 Xork 有潛力通過解決對 AAV 的預先存在的免疫力來擴大獲得改變生命的基因療法的機會。

The objective of our gene therapy vertical is to bring hope to patients who may not have many other treatment options, enable companies to maximize the commercial potential of their gene therapy candidates and help to make otherwise uneconomic gene therapy candidates viable targets for commercial development. We plan to continue to pursue business development and out-licensing opportunities to maximize the value of our platform.

我們垂直基因治療的目標是為可能沒有太多其他治療選擇的患者帶來希望，使公司能夠最大限度地發揮其基因治療候選藥物的商業潛力，並幫助使原本不經濟的基因治療候選藥物成為商業開發的可行目標。我們計劃繼續尋求業務發展和對外許可機會，以最大限度地發揮我們平台的價值。

Now turning to our biologics pipeline; many biologics can be highly immunogenic, resulting in suboptimal responses due to the development of antidrug antibodies after treatment. Patients who develop an immune response may be forced to discontinue treatment or experience adverse reactions to continuous therapies. We believe the use of ImmTOR as an adjunct to biologics offers a promising approach to reduce the unwanted immune responses and improved patient outcomes. We believe our most advanced program, SEL-212, has served as clinical proof-of-concept for our ImmTOR platform with over 500 patients dosed to-date.

現在轉向我們的生物製劑管道；許多生物製劑可能具有高度免疫原性，由於治療後抗藥抗體的產生而導致反應不佳。產生免疫反應的患者可能被迫停止治療或對持續治療產生不良反應。我們相信使用 ImmTOR 作為生物製劑的輔助手段提供了一種有前途的方法來減少不需要的免疫反應並改善患者的預後。我們相信，我們最先進的項目 SEL-212 已作為我們 ImmTOR 平台的臨床概念驗證，迄今為止已有超過 500 名患者接受了給藥。

As a reminder, SEL-212 is comprised of ImmTOR co-administered with a proprietary uricase, pegadricase for the treatment of chronic refractory gout and was licensed to Sobi in 2020. Our Phase III DISSOLVE clinical program kicked off in the third quarter of 2020 and consists of two double-blind, placebo-controlled trials of SEL-212. In both trials, SEL-212 is being evaluated at two dose levels of ImmTOR, 0.1 mg/kg and 0.15 mg/kg with a single dose level of pegadricase at 0.2 mg/kg. We continue to work closely with our partner, Sobi, our clinical trial providers and regulatory authorities to advance towards the successful completion of the Phase III program, and we are on track to announce top line data for DISSOLVE I and II later this quarter.

提醒一下，SEL-212由 ImmTOR 與專有尿酸酶 pegadricase 聯合給藥組成，用於治療慢性難治性痛風，並於 2020 年獲得 Sobi 的許可。我們的 III 期 DISSOLVE 臨床項目於 2020 年第三季度啟動，由 SEL-212 的兩項雙盲、安慰劑對照試驗組成。在這兩項試驗中，SEL-212 在 ImmTOR 的兩個劑量水平，0.1 mg/kg 和 0.15 mg/kg 以及單劑量水平的 pegadricase 0.2 mg/kg 下進行評估。我們將繼續與我們的合作夥伴 Sobi、我們的臨床試驗提供商和監管機構密切合作，以推進 III 期計劃的成功完成，我們有望在本季度晚些時候公佈 DISSOLVE I 和 II 的一線數據。

Based on the results from previous trials in which we've observed SEL-212's differentiated profile and convenient once-monthly dosing regimen, we believe SEL-212 is well-positioned against the current standard of care and other drugs in the class that target this patient segment. In our Phase II trial, we observed a high percentage of responders in patients with both visible uric acid crystal tissue deposits, or tophi and without tophi as well as statistically significant and clinically relevant reductions in serum uric levels in treatment periods 3 and 6.

根據我們觀察到 SEL-212 的差異化特徵和方便的每月一次給藥方案的先前試驗的結果，我們認為 SEL-212 相對於當前的護理標準和針對該類別的其他藥物處於有利地位患者部分。在我們的 II 期試驗中，我們觀察到在第 3 期和第 6 期治療期間，具有可見尿酸結晶組織沉積物或痛風石和無痛風石的患者中有很高比例的反應者以及血清尿酸水平在統計學上顯著和臨床相關的降低。

These responses were achieved with a favorable tolerability profile, simplified dosing and avoidance of immune suppression. With the promising clinical data generated to-date and SEL-212 currently in Phase III, we believe we're well-positioned to leverage these learnings into our second biologics indication in IgA nephropathy or IgAN, a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1, or IgA1, accumulates in the kidneys. In December 2022, we selected a next-generation IgA protease from IGAN Biosciences for the treatment of IgAN and plan to initiate IND-enabling studies in 2023.

這些反應是通過良好的耐受性、簡化的劑量和避免免疫抑制來實現的。憑藉迄今為止產生的有希望的臨床數據和目前處於 III 期的 SEL-212，我們相信我們已經做好了充分的準備，可以將這些知識用於我們在 IgA 腎病或 IgAN 中的第二個生物製劑適應症，這是一種腎臟疾病，當免疫複合物一種稱為免疫球蛋白 A1 或 IgA1 的抗體會在腎臟中積聚。 2022 年 12 月，我們選擇了 IGAN Biosciences 的下一代 IgA 蛋白酶用於治療 IgAN，併計劃在 2023 年啟動 IND 授權研究。

By combining ImmTOR with an IgA protease, we believe our novel approach has the potential to address the underlying pathophysiology of the disease by removing injurious IgA from the kidneys and improve markers of renal dysfunction. We're extremely excited about the advancements across our pipeline and the growing body of clinical data showcasing the promise of our ImmTOR platform in a number of applications. We look forward to continuing our momentum in the coming year.

通過將 ImmTOR 與 IgA 蛋白酶相結合，我們相信我們的新方法有可能通過從腎臟中去除有害的 IgA 並改善腎功能障礙的標誌物來解決該疾病的潛在病理生理學。我們對整個管道的進步和不斷增長的臨床數據體感到非常興奮，這些數據展示了我們的 ImmTOR 平台在許多應用程序中的前景。我們期待在來年繼續我們的勢頭。

With that, I'll turn the call over to our newly appointed Chief Financial Officer, Blaine Davis, to run through our financial results for the fourth quarter and full year. Blaine brings more than 25 years of experience in Investor Relations, Business Development, Corporate Affairs and Sales and Marketing at life science companies with a particular focus on rare diseases. Blaine's impressive track record makes him an ideal fit for Selecta at this critical inflection point, and we're truly delighted to have him on board.

有了這個，我將把電話轉給我們新任命的首席財務官布萊恩戴維斯，以了解我們第四季度和全年的財務業績。 Blaine 在生命科學公司的投資者關係、業務發展、公司事務以及銷售和營銷方面擁有超過 25 年的經驗，尤其關注罕見疾病。 Blaine 令人印象深刻的往績使他非常適合在這個關鍵的轉折點加入 Selecta，我們真的很高興他能加入。

Blaine?

布萊恩？

Thank you, Carsten. I'm thrilled to join the Selecta team and look forward to working closely with everyone as we deliver our mission to improve the lives of our patients. Now I would like to briefly run through our financial results for the fourth quarter and full year 2022. Revenue for the fourth quarter and full year 2022 was 16.8 and $110.8 million, respectively, as compared to 29.9 and $85.1 million for the same periods in 2021. Revenue was primarily driven by the license agreement with Sobi, resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase III DISSOLVE clinical program.

謝謝你，卡斯滕。我很高興加入 Selecta 團隊，並期待在我們履行改善患者生活的使命時與大家密切合作。現在我想簡要介紹一下我們 2022 年第四季度和全年的財務業績。2022 年第四季度和全年的收入分別為 16.8 和 1.108 億美元，而 2021 年同期為 29.9 和 8510 萬美元.收入主要由與 Sobi 的許可協議推動，來自臨床供應的裝運和 III 期 DISSOLVE 臨床計劃產生的費用的報銷。

Research and development expenses for the fourth quarter and full year 2022 were 19 and $72.4 million, respectively, as compared to 20.3 and $68.7 million for the same periods in 2021. The quarterly decrease was primarily driven by a decrease in expenses incurred for the SEL-212 clinical program. The annual increase was primarily driven by expenses incurred for preclinical programs, increased personnel expense and stock compensation expense. General and administrative expenses for the fourth quarter and full year 2022 were 6.3 and $23.9 million, respectively, as compared to 5.5 and $20.9 million for the same periods in 2021.

2022 年第四季度和全年的研發費用分別為 19 美元和 7240 萬美元，而 2021 年同期為 20.3 美元和 6870 萬美元。季度下降的主要原因是 SEL- 212臨床計劃。年度增長主要是由臨床前項目產生的費用、增加的人員費用和股票補償費用推動的。 2022 年第四季度和全年的一般和行政費用分別為 6.3 和 2,390 萬美元，而 2021 年同期分別為 5.5 和 2,090 萬美元。

The quarterly and annual increases were primarily driven by increases in stock compensation and personnel-related expenses. For the fourth quarter and full year 2022, Selecta reported net income of $5.9 million or basic net income per share of $0.04 and net income of $35.4 million or basic net income per share of $0.24, respectively.

季度和年度增長主要是由股票薪酬和人事相關費用的增長推動的。在第四季度和 2022 年全年，Selecta 報告的淨收入分別為 590 萬美元或每股基本淨收入 0.04 美元，淨收入為 3540 萬美元或每股基本淨收入 0.24 美元。

For the fourth quarter and full year 2021, Selecta reported net income of $12.2 million or $0.10 per share and a net loss of $25.7 million or $0.22 per share, respectively. Selecta had $136.2 million in cash, cash equivalents, marketable securities and restricted cash as of December 31, 2022 as compared to $129.4 million as of December 31, 2021. We believe our available cash, cash equivalents, restricted cash and marketable securities will be sufficient to meet our operating requirements into mid-2024.

2021 年第四季度和全年，Selecta 報告的淨收入分別為 1220 萬美元或每股 0.10 美元，淨虧損為 2570 萬美元或每股 0.22 美元。截至 2022 年 12 月 31 日，Selecta 擁有 1.362 億美元現金、現金等價物、有價證券和受限制現金，而截至 2021 年 12 月 31 日為 1.294 億美元。我們認為我們的可用現金、現金等價物、受限制現金和有價證券將足夠以滿足我們到 2024 年年中的運營要求。

With that, I'd now like to turn the call back to Carsten for closing remarks.

有了這個，我現在想把電話轉回卡斯滕，讓他發表結束語。

Thank you, Blaine. In 2022, we delivered on key milestones that we believe further validated the value and breadth of our innovative ImmTOR platform. We continue to advance our diversified clinical pipeline, and we established strategic collaborations that we believe can propel our next-generation programs toward multiple IND filings. We look forward to building on the momentum of our recently announced deal with Astellas for Xork and Pompe disease, the initiation of the Phase I/II trial in MMA, identification of an IL-2 candidate and selection of an IgA Protease candidate, and we remain on track to report top line data from the Phase III DISSOLVE I and II clinical trials, investigating SEL-212 in chronic refractory gout later this quarter.

謝謝你，布萊恩。 2022 年，我們實現了關鍵里程碑，我們認為這些里程碑進一步驗證了我們創新的 ImmTOR 平台的價值和廣度。我們繼續推進我們多元化的臨床管道，我們建立了戰略合作，我們相信這可以推動我們的下一代項目走向多個 IND 申請。我們期待在最近宣布的與 Astellas 就 Xork 和 Pompe 病達成的協議、MMA I/II 期試驗的啟動、IL-2 候選物的鑑定和 IgA 蛋白酶候選物的選擇的基礎上再接再厲，我們繼續按計劃報告來自 III 期 DISSOLVE I 和 II 臨床試驗的一線數據，本季度晚些時候調查慢性難治性痛風中的 SEL-212。

We remain blind to the data, but as previously stated, are confident in SEL-212's competitive profile and potential to treat chronic refractory gout based on the positive results from previous trials. We look forward to providing further updates in the coming weeks. Looking ahead, we remain deeply committed to solving the hardest challenges in autoimmune disease and helping patients overcome autoimmunity and unwanted immunogenicity.

我們對數據仍然視而不見，但如前所述，基於先前試驗的積極結果，我們對 SEL-212 的競爭優勢和治療慢性難治性痛風的潛力充滿信心。我們期待在未來幾週內提供進一步的更新。展望未來，我們仍然堅定地致力於解決自身免疫性疾病中最嚴峻的挑戰，幫助患者克服自身免疫和不需要的免疫原性。

In parallel, we intend to continue to seek opportunities to strategically partner in our gene therapy vertical to maximize the value of our platform. Before we conclude today's call, I would once again like to thank the entire Selecta team, our investors and the many people who have been supportive along the way, including our patients and their families.

與此同時，我們打算繼續尋求機會在我們的基因治療垂直領域進行戰略合作，以最大限度地發揮我們平台的價值。在我們結束今天的電話會議之前，我要再次感謝整個 Selecta 團隊、我們的投資者以及一路上給予支持的許多人，包括我們的患者及其家人。

With that, we're happy to take questions.

有了這個，我們很樂意回答問題。

(Operator Instructions) And our first question will come from Joseph Schwartz of SVB Securities.

（操作員說明）我們的第一個問題將來自 SVB 證券公司的 Joseph Schwartz。

I was wondering, first of all, SEL-302, if you could provide us with any more clarity on what we might expect to see from the first data readout from the study that you're commencing? I know you've previously said that you expect to release data on a patient-by-patient basis. But since the first patient, I think, is being dosed without ImmTOR. I was wondering if you expect to wait until you have the first ImmTOR dosed patient as well to present this initial data set?

我想知道，首先，SEL-302，您是否可以讓我們更清楚地了解我們可能期望從您開始的研究中讀取的第一個數據中看到什麼？我知道您之前曾說過，您希望逐個患者發布數據。但我認為，自從第一位患者在沒有使用 ImmTOR 的情況下接受給藥。我想知道您是否希望等到第一個接受 ImmTOR 給藥的患者時再展示這個初始數據集？

Yeah, that's a great question. Yeah, as we've previously guided, we will report interim data, so it's three months data, looking -- obviously, this is primarily a safety study, but also biomarker of the disease. And then specifically, we are interested in ImmTOR and the Nab response. So we expect to release data towards the end of this year, as you rightly said, the first patient only receives the gene therapy, the second patient then will receive ImmTOR. So we'll likely release data towards the end of the year.

是的，這是一個很好的問題。是的，正如我們之前的指導，我們將報告中期數據，所以這是三個月的數據，看起來——顯然，這主要是一項安全性研究，也是該疾病的生物標誌物。然後具體來說，我們對 ImmTOR 和 Nab 響應感興趣。所以我們預計將在今年年底發布數據，正如你所說的那樣，第一個患者只接受基因治療，第二個患者將接受 ImmTOR。因此，我們可能會在年底前發布數據。

Okay. And then on ImmTOR-IL, I was wondering if we could get your thoughts on the recent IL-2 trial failure in [SLE]? And why do you think your PBC program is perhaps better suited for success? And do you plan to report any new preclinical data across your early-stage pipeline this year?

好的。然後關於 ImmTOR-IL，我想知道我們是否可以了解您對最近 [SLE] 中 IL-2 試驗失敗的看法？為什麼您認為您的 PBC 計劃可能更適合成功？您是否計劃在今年報告您早期管道中的任何新的臨床前數據？

Yeah, that's another great question. Obviously, we haven't looked at the data in a lot of detail. But obviously, where we think we are highly differentiated is the combination of ImmTOR with an engineered IL-2. We actually are really a first-in-class by inducing and expanding Treg-selective sales. So I think that approach -- the end -- specific approach is really unique and you have a much better chance of addressing the underlying disease. We are going into autoimmune diseases of the liver. And we think it's really low-hanging fruit also because of ImmTOR accumulates in the liver. And actually, we've shown in a couple of models that ImmTOR alone actually already is hepatoprotective. So we're pretty confident in the liver approach. And yes, we will release after everybody has the eyes on DISSOLVE this quarter but after DISSOLVE readout, we'll throughout the year, we'll also provide more data from various animal models that Kei and his team have been working on, which are very encouraging.

是的，這是另一個很好的問題。顯然，我們還沒有非常詳細地查看數據。但顯然，我們認為我們高度差異化的地方是 ImmTOR 與工程 IL-2 的組合。通過誘導和擴大 Treg 選擇性銷售，我們實際上是一流的。所以我認為這種方法——最終——特定的方法確實是獨一無二的，你有更好的機會解決潛在的疾病。我們正在研究肝臟的自身免疫性疾病。而且我們認為它真的很容易實現，因為 ImmTOR 會在肝臟中積聚。實際上，我們已經在幾個模型中表明，單獨使用 ImmTOR 實際上已經具有保肝作用。所以我們對肝臟方法非常有信心。是的，我們將在本季度每個人都關注 DISSOLVE 之後發布，但在 DISSOLVE 讀數之後，我們將全年提供更多來自 Kei 和他的團隊一直在研究的各種動物模型的數據，這些數據是非常鼓舞人心。

The next question comes from Kristen Kluska of Cantor Fitzgerald.

下一個問題來自 Cantor Fitzgerald 的 Kristen Kluska。

The first one to two quarter on gene therapy. So given that your partners were willing to sign deals with you ahead of MMA reading out and in some cases, even before the empty capsid data, I wanted to know how you believe that some of the MMA data and of course, your discussions with the respective regulatory agencies could further help with your conversations with current partners, but then also how it could potentially open the door for others that are interested?

第一個到第二個季度是關於基因治療的。因此，鑑於你的合作夥伴願意在 MMA 讀取之前與你簽署協議，在某些情況下，甚至在空衣殼數據之前，我想知道你如何相信一些 MMA 數據，當然還有你與各個監管機構可以進一步幫助您與當前合作夥伴進行對話，但它又如何可能為其他感興趣的人打開大門？

Yes, Kristen, that's a great question. I think the fact that we signed two deals with Takeda and Sarepta, ahead of the empty capsid just shows the unmet medical need in this field. I mean there's tremendous unmet need to prevent the formation of NAbs and give patients a chance to receive a second dose. We definitely believe that just the fact that we have empty capsid data available is an important data point. And most importantly, we have a clear regulatory path. I think that's really important. That's the reason we're actually running the MMA program, and we can give clear guidance to our partners on how to develop ImmTOR and in this case, with three monthly doses of ImmTOR. And obviously, we believe that the data from the MMA study will also be helpful along the way as well.

是的，克里斯汀，這是一個很好的問題。我認為我們在空衣殼之前與 Takeda 和 Sarepta 簽署了兩項協議這一事實恰恰表明了該領域未滿足的醫療需求。我的意思是，在防止 NAb 的形成並讓患者有機會接受第二劑治療方面，存在巨大的未滿足需求。我們絕對相信，我們擁有可用的空衣殼數據這一事實就是一個重要的數據點。最重要的是，我們有明確的監管路徑。我認為這非常重要。這就是我們實際運行 MMA 計劃的原因，我們可以就如何開發 ImmTOR 以及在這種情況下每月三個月劑量的 ImmTOR 向我們的合作夥伴提供明確的指導。顯然，我們相信 MMA 研究的數據也將在此過程中有所幫助。

Then the second part on gene therapy is, how would you say that general awareness of the platform potential here has increased given you've had more data over time, there have been safety and durability hiccups from others in this space as well as, of course, you're seeing the number of deals you've been able to execute as well.

然後關於基因治療的第二部分是，你怎麼說這裡的平台潛力的普遍認識已經提高，因為隨著時間的推移你有更多的數據，這個領域的其他人已經出現了安全性和耐用性問題，以及，當然，您也會看到您能夠執行的交易數量。

Can you just repeat the question, you were breaking up here on my end, sorry.

你能再重複一遍這個問題嗎，對不起，你在我這邊分手了。

Yeah. Sorry about that. The question was just on understanding the awareness of the platform potential. Given you've had more data, there have been some safety and durability hiccups in this space as well as just seeing the execution you've had through striking deals with others.

是的。對於那個很抱歉。問題只是關於了解平台潛力的意識。鑑於您擁有更多數據，在這個領域存在一些安全性和耐用性問題，以及通過與其他人達成交易而獲得的執行力。

Got it. Yeah, sorry about that. Yeah, I mean there's -- obviously, there is increased awareness and there have been a number of setbacks the last two years in the gene therapy field with toxicities associated with AAV. So I think there's acute awareness around ImmTOR and the potential of ImmTOR, but also, we really position ourselves as a solution provider, addressing some of the key challenges in gene therapy, which, number one, is the ability to potentially redose with ImmTOR but also secondly, with our IgG Protease Xork to increase the number of patients eligible to genotherapy as well. And I think our deal with Astellas is testament to that. There's a lot of awareness and interest in the platform in gene therapy. And we've been pretty outspoken. This is really a vertical we want to pursue from a partnering perspective.

知道了。是的，對此感到抱歉。是的，我的意思是 - 顯然，人們的意識有所提高，並且在過去兩年中基因治療領域出現了一些與 AAV 相關的毒性的挫折。因此，我認為人們對 ImmTOR 和 ImmTOR 的潛力有著敏銳的認識，而且，我們確實將自己定位為解決方案提供商，解決了基因治療中的一些關鍵挑戰，其中第一，是潛在地重新使用 ImmTOR 的能力，但其次，我們的 IgG 蛋白酶 Xork 也可以增加有資格接受基因治療的患者數量。我認為我們與 Astellas 的交易證明了這一點。基因治療平台引起了很多關注和興趣。我們一直非常直言不諱。從合作的角度來看，這確實是我們想要追求的垂直領域。

Great. And then the last question I have for you is just how many roughly liver diseases do you believe more ImmTOR-IL could be evaluated in? And then what are some of the criteria on your wish list essentially when choosing which indication you might start with?

偉大的。然後我要問你的最後一個問題是，你認為有多少肝病可以評估更多的 ImmTOR-IL？那麼在選擇您可能開始的適應症時，您的願望清單上的一些標準是什麼？

Yeah, that's a great question. And I'll actually throw this question to our resident hepatologist, Peter, and maybe talk about PBC, but also other indications we're interested in and why we're interested in that. Peter?

是的，這是一個很好的問題。實際上，我會將這個問題拋給我們的常駐肝病學家 Peter，也許還會談談 PBC，還有我們感興趣的其他跡像以及我們為什麼對此感興趣。彼得？

Yeah. Thanks, Carsten. And thanks for the question, Kristen. I think that we're going to be giving once the DISSOLVE data comes out and so forth, we're going to be really giving a lot more information on how we've chosen, how we will choose diseases for ImmTOR-IL. But to your specific question about liver diseases, there are a number of clearly autoimmune liver diseases which are T-cell mediated and affect the liver. PBC is a quintessential one, but there are others that are even more clinically important and have more unmet medical needs, such as autoimmune hepatitis. There are a couple of types of that disorder, primary biliary cholangitis, which is associated with inflammatory bowel diseases and clearly has an autoimmune underlying mediology.

是的。謝謝，卡斯滕。謝謝你的問題，克里斯汀。我認為一旦 DISSOLVE 數據出來等等，我們將提供更多關於我們如何選擇的信息，我們將如何為 ImmTOR-IL 選擇疾病。但是對於你關於肝病的具體問題，有許多明顯的自身免疫性肝病是 T 細胞介導的並影響肝臟。 PBC 是典型的一種，但還有其他一些在臨床上更為重要並且有更多未滿足的醫療需求，例如自身免疫性肝炎。這種疾病有幾種類型，原發性膽汁性膽管炎，它與炎症性腸病有關，並且顯然具有自身免疫性基礎病學。

And then there are overlap syndromes with parts of each -- PBC with autoimmune hepatitis and so forth. But those -- collectively, those autoimmune liver diseases represent a significant number of affected individuals and significant unmet medical need. While there's therapy in PBC available, as you know, there's only a single approach to AI autoimmune hepatitis and no successful therapies in primary sclerosing cholangitis, PSC. So we think that there's an area there to make an impact, which will be one of our focuses. Not the only focus we'll have in autoimmune disease, but a key one.

然後有部分重疊綜合徵——PBC 與自身免疫性肝炎等。但是那些 - 總的來說，那些自身免疫性肝病代表了大量受影響的個體和未滿足的重大醫療需求。如您所知，雖然 PBC 有可用的治療方法，但 AI 自身免疫性肝炎只有一種方法，原發性硬化性膽管炎 PSC 沒有成功的治療方法。所以我們認為有一個領域可以產生影響，這將是我們的重點之一。自身免疫性疾病不是我們關注的唯一焦點，而是一個關鍵焦點。

The next question comes from John Newman of Canaccord Genuity.

下一個問題來自 Canaccord Genuity 的 John Newman。

Regarding the top line data for SEL-212, I'm just curious as to how much information you might be able to share regarding the safety, specifically the gout flares. I know that some of the early developments suggested that in addition to good efficacy, you may actually be able to improve the incidence of gout flares maybe lower that a bit. Just curious if you'll be able to talk about that at all, excuse me, on the top line readout?

關於 SEL-212 的頂級數據，我只是想知道您可以分享多少有關安全性的信息，特別是痛風發作。我知道一些早期的發展表明，除了良好的療效外，您實際上可能能夠降低痛風發作的發生率。只是想知道您是否能夠在頂行讀數上談論這個，對不起，？

Yes, that's a great question, John. And obviously, what's important to note that we've been completely blinded to the data, so we haven't seen the data, but I'll let Peter address what we expect in terms of showing the top line perspective.

是的，這是一個很好的問題，約翰。顯然，重要的是要注意我們對數據完全視而不見，所以我們沒有看到數據，但我會讓彼得在顯示頂線視角方面解決我們的期望。

Yeah, John, I'll tell you what we expect, but I'll just clarify a little bit kind of some of the historical data from our program. So first of all, it's well established that gout flares increase with uricase therapy. That's been established by -- in all of the pegloticase trials that have been done. So you do get an increase in gout flares as you start to dissolve and reduce the urate deposits in the body. In Phase I and early Phase II, it did appear that there was some reduction in gout flares incidents with SEL-212.

是的，約翰，我會告訴你我們的期望，但我只是澄清一下我們計劃中的一些歷史數據。所以首先，眾所周知，尿酸酶治療會增加痛風發作。這是由——在所有已完成的 pegloticase 試驗中確定的。因此，當您開始溶解和減少體內的尿酸鹽沉積物時，痛風發作確實會增加。在 I 期和 II 期早期，SEL-212 似乎確實減少了痛風發作事件。

But in the COMPARE trial, which as you know, was a large comparison trial with 83 patients receiving SEL-212 we didn't see a real reduction in gout flares. Now in DISSOLVE, we'll be comparing -- we'll be doing the best comparison because we'll be comparing gout flares versus placebo. And we'll be able to look at the number of gout flares in different periods of time of the therapy versus placebo. So we will have those data, and we'll be able to report on that.

但在 COMPARE 試驗中，如您所知，這是一項大型比較試驗，有 83 名患者接受 SEL-212，我們沒有看到痛風發作真正減少。現在在 DISSOLVE 中，我們將進行比較——我們將進行最好的比較，因為我們將比較痛風發作與安慰劑。我們將能夠查看治療與安慰劑在不同時間段內痛風發作的次數。所以我們將擁有這些數據，並且我們將能夠就此進行報告。

The next question comes from Yun Zhong of BTIG.

下一個問題來自BTIG的雲中。

So the first one is kind of a follow-up question on the indication selection for ImmTOR-IL-2. I don't see the press release specifically mentioned PBC. I just wanted to confirm that PBC is still likely the first indication to choose or I do believe that you mentioned that multiple preclinical IND enabling studies will be initiated in 2022 -- sorry, 2023. So I assume those studies are for different indications.

所以第一個是關於 ImmTOR-IL-2 適應症選擇的後續問題。我沒有看到新聞稿特別提到 PBC。我只是想確認 PBC 仍然可能是第一個選擇的適應症，或者我相信你提到多項臨床前 IND 支持研究將在 2022 年啟動——抱歉，2023 年。所以我假設這些研究是針對不同的適應症。

Yeah. It's a great -- very observant and a great question. As Peter said, I mean, PBC definitely is still part of the mix. We want to open the funnel a little bit and look broader at autoimmune of the liver as there are multiple indications of high interest indications that are well suited for ImmTOR-IL like PBC, where we know the autoantigen impacting the disease, PBC-2, but also there's other indications with high united, as Peter mentioned, like autoimmune hepatitis. So definitely, PBC is still part of the mix, but we want to open up the funnel and we'll give more detailed guidance after the DISSOLVE readout.

是的。這是一個很好的——非常善於觀察，也是一個很好的問題。正如彼得所說，我的意思是，PBC 肯定仍然是其中的一部分。我們想稍微打開漏斗，更廣泛地了解肝臟自身免疫，因為有多種非常適合 ImmTOR-IL 的高興趣適應症，如 PBC，我們知道影響疾病的自身抗原 PBC-2，但正如 Peter 提到的，high united 還有其他跡象，例如自身免疫性肝炎。所以肯定地，PBC 仍然是組合的一部分，但我們想打開漏斗，我們將在 DISSOLVE 讀出後提供更詳細的指導。

Okay. Then second question on the collaboration with Astellas. It's a very exciting one. But I believe the gene therapy program uses AAV8 which happens to be the capsid used in the empty capsid study. So just curious, did Astellas show any interest in ImmTOR? And I just wanted to confirm also that ImmTOR and also Xork both of them are agnostic to the capsid used in the study. So the effect is not affected by which capsid to choose. Is that correct?

好的。然後是關於與 Astellas 合作的第二個問題。這是一個非常令人興奮的。但我相信基因治療程序使用的 AAV8 恰好是空衣殼研究中使用的衣殼。所以很好奇，Astellas 是否對 ImmTOR 表現出任何興趣？我只想確認 ImmTOR 和 Xork 都不知道研究中使用的衣殼。所以效果不受選擇哪個衣殼的影響。那是對的嗎？

Yeah, that's a good question. And yes, so Astellas exclusive licensees of Xork for the use in their Pompe program. And you're also right that both approaches as far as we know, are agnostic. We've shown with different AAV subtypes that ImmTOR prevents the formation of losing antibodies. And we assume the same for Xork as a pretreatment, the same that's agnostic actually to the AAV exposure that patients had.

是的，這是個好問題。是的，所以 Astellas 獨家許可 Xork 用於他們的 Pompe 程序。而且你也是對的，據我們所知，這兩種方法都是不可知論的。我們已經用不同的 AAV 亞型證明了 ImmTOR 可以防止丟失抗體的形成。我們假設 Xork 與預處理相同，與患者實際接觸的 AAV 無關。

The next question comes from Gil Blum of Needham & Company.

下一個問題來自 Needham & Company 的 Gil Blum。

Maybe a simple question here. So given the number of pretty large indications for autoimmunity, even in the liver, how much of this is going to be finding a partner?

也許這裡是一個簡單的問題。因此，考慮到自身免疫的大量適應症，即使是在肝臟中，其中有多少是為了尋找合作夥伴？

Yeah, Gil, that's a good question as well. It is indeed a large area, and we've spent a significant amount of time kind of prioritizing indications -- and we kind of landed on the liver as an interesting area. As Peter mentioned, it's -- we think its low-hanging fruit because into accumulation in the liver, there are indications that we can execute on as a company all the way through commercial actually. I mean these are all attractive, but still kind of orphan-type indications that we can execute on. At the same time, there are larger indications, which are of interest. We might potentially do an initial proof-of-concept study, but then you would look for partnerships to see this through for sure, given the complexity that this specific disease expertise, but also the cost of the programs.

是的，吉爾，這也是個好問題。這確實是一個很大的領域，我們花了很多時間來確定適應症的優先級——我們把肝臟作為一個有趣的領域。正如彼得所提到的，它是——我們認為它是唾手可得的果實，因為在肝臟中積累，有跡象表明我們可以作為一家公司在整個商業過程中一直執行下去。我的意思是這些都很有吸引力，但仍然是我們可以執行的孤兒類型的跡象。同時，還有更大的適應症，值得關注。我們可能會進行初步的概念驗證研究，但考慮到這種特定疾病專業知識的複雜性，以及項目的成本，你會尋找合作夥伴來確定這一點。

Excellent. And maybe just to organize things for us here. What sort of milestones are you expecting on a positive readout from the pivotal studies for Sobi here?

出色的。也許只是為了在這里為我們組織一些事情。您期望從這裡對 Sobi 的關鍵研究中獲得積極的讀數，會有什麼樣的里程碑？

Yeah. Good question as well. So -- and I think we've guided in the past. So just to remind you of the overall deal terms. So we licensed the asset to Sobi in 2020, received $100 million upfront. We also received $630 million in milestones. That's broken down $80 million in regulatory and development and $550 million in commercial. Out of the $80 million, we have received $15 million so far. So we were still eligible to receive $65 million. We haven't broken out to which event these are tied to. And then also, we are eligible to receive royalties in the double digits as well.

是的。好問題也是如此。所以 - 我認為我們過去已經指導過。所以只是提醒你整體交易條款。所以我們在 2020 年將資產授權給 Sobi，預付了 1 億美元。我們還收到了 6.3 億美元的里程碑。其中包括 8000 萬美元的監管和開發費用以及 5.5 億美元的商業費用。在這 8000 萬美元中，到目前為止我們已經收到了 1500 萬美元。所以我們仍然有資格獲得 6500 萬美元。我們還沒有弄清楚這些與哪個事件有關。然後，我們也有資格獲得兩位數的版稅。

The next question comes from Tiffany Marchell of William Blair.

下一個問題來自 William Blair 的 Tiffany Marchell。

This is Tiffany on for Raj. For the IgG Protease Xork, can you maybe discuss a bit how you and Astellas plan to use Xork prophylactically for preexisting antibodies? And do you imagine there's still a certain cutoff in the level of preexisting antibodies that it might be effective for or really just how much do you imagine Xork could expand the treatable population here?

這是 Raj 的 Tiffany。對於 IgG 蛋白酶 Xork，您能否討論一下您和 Astellas 計劃如何預防性地使用 Xork 來處理先前存在的抗體？你是否認為它可能有效的現有抗體水平仍然存在一定的界限，或者你真的認為 Xork 可以擴大這裡的可治療人群多少？

Yeah, that's a great question. And obviously, I can't comment how Astellas plans to develop this, but I can just comment on how we kind of view the approach. And so there's interesting data from IgG Protease that they basically cleave preexisting antibodies, which prevent dosing. And specifically, we're looking here patients had a natural AAV infection. So not necessarily patients that were exposed to an AAV gene therapy get very high titers in the thousands.

是的，這是一個很好的問題。顯然，我不能評論 Astellas 計劃如何開發這個，但我只能評論我們如何看待這種方法。因此，來自 IgG 蛋白酶的有趣數據表明，它們基本上會切割預先存在的抗體，從而阻止給藥。具體來說，我們正在尋找患有自然 AAV 感染的患者。因此，接受 AAV 基因治療的患者不一定會獲得數以千計的非常高的滴度。

We're looking to here more at natural AAV infections. And that inflicts between 30% to 70% of all patients had a natural AAV infection, not eligible to receive gene therapy. So we think that's very attractive, both from a patient perspective but also a commercial perspective, you potentially double the number of patients eligible and that definitely played a part of why Astellas license Xork.

我們更多地關注自然 AAV 感染。並且所有患者中有 30% 到 70% 患有自然 AAV 感染，不符合接受基因治療的條件。因此，我們認為這非常有吸引力，無論是從患者的角度還是從商業的角度來看，您都有可能使符合條件的患者數量增加一倍，這無疑是 Astellas 許可 Xork 的部分原因。

Great. That makes sense. And I guess for Xork, do you also plan to share any additional preclinical data this year on that?

偉大的。這就說得通了。我想對於 Xork，你是否還計劃在今年分享任何額外的臨床前數據？

So we haven't guided to that. I think we have shared some of the initial data. But I mean, at this point, we don't -- we have not guided specifically to share additional data.

所以我們沒有指導那個。我認為我們已經共享了一些初始數據。但我的意思是，在這一點上，我們沒有——我們沒有專門指導分享額外的數據。

The next question comes from Boobalan Pachaiyappan of H.C. Wainwright.

下一個問題來自 H.C. 的 Boobalan Pachaiyappan。溫賴特。

This is Boobalan. Can you hear me okay?

這是布巴蘭。你能聽到我說話嗎？

Yes. Boobalan, we can hear you. Thank you.

是的。 Boobalan，我們能聽到你的聲音。謝謝。

All right. Great. A few questions from our end. So firstly, with respect to IgA Nephropathy, obviously, you might have -- you are aware of FDA approval of Filspari, sparsentan. So I'm curious how this FDA approval might alter the dynamics of your IgAN program, especially in light of the fact that the agent that was approved may increase the risk of liver injury and birth defects.

好的。偉大的。我們這邊的幾個問題。所以首先，關於 IgA 腎病，很明顯，你可能知道 FDA 批准了 Filspari，sparsentan。所以我很好奇 FDA 的批准可能會如何改變你的 IgAN 計劃的動態，特別是考慮到被批准的藥物可能會增加肝損傷和先天缺陷的風險。

Yeah. So maybe I'll let Peter just talk a little bit about our approach here and why we think it's a truly novel approach and really see this complementary to some of the other products in development, Peter?

是的。所以也許我會讓彼得談談我們在這裡的方法，以及為什麼我們認為這是一種真正新穎的方法，並且真的看到它與其他一些正在開發的產品相輔相成，彼得？

Yeah, happy to answer that question. I think that what you're referring to is that there were some warnings on the latest approval based on age group. We don't anticipate age group issues, but of course, we will be starting our development program in adults. Now with regard to the specific approach, all the approaches that are -- have either been approved or are in development are either looking at a type of steroid, which affects the upstream production of IgA or downstream effects of the deposits in the kidney.

是的，很高興回答這個問題。我認為你指的是基於年齡組的最新批准有一些警告。我們預計不會出現年齡組問題，但當然，我們會在成人中啟動我們的開發計劃。現在關於具體方法，所有已經批准或正在開發的方法都在研究一種類固醇，它會影響 IgA 的上游生產或腎臟沉積物的下游影響。

We're the only approach, which is targeting the IgA immune complexes in the kidney to try to clear those to see whether that will improve the disease. So our approach is complementary to the two drugs that have been recently approved as well as all of those in the development pipeline. Now approval of additional drugs will certainly affect the development program from the standpoint of exclusions and inclusions and standard of care and so forth. But we'll have to wait to see how that evolves with the recent approvals. But by and large, ours is a novel approach that no one else at this point is utilizing.

我們是唯一的方法，它以腎臟中的 IgA 免疫複合物為目標，試圖清除它們，看看這是否會改善疾病。因此，我們的方法是對最近批准的兩種藥物以及所有正在開發中的藥物的補充。現在，從排除和納入以及護理標準等角度來看，額外藥物的批准肯定會影響開發計劃。但我們必須拭目以待，看看最近的批准會如何發展。但總的來說，我們的方法是一種新穎的方法，目前還沒有其他人在使用。

As you're thinking deeply about your IgAN program, just curious, are there specific biomarkers that you'll be paying close attention maybe in the next few quarters to gain confidence in the program in addition to say (inaudible)?

當你深入思考你的 IgAN 計劃時，只是好奇，除了說（聽不清）之外，是否有特定的生物標誌物你可能會在接下來的幾個季度中密切關注以獲得對該計劃的信心？

Yes. So biomarkers, you're talking about of effect in IgAN. Yes. Okay. Yeah. So the biomarkers that have been looked at, of course, and are most important is urinary protein excretion. That's number one. Number two is kind of the most important one is the effect on kidney function, which would be eGFR. But we're also exploring a variety of urinary markers and other markers that we might be able to utilize. But the two most important are urinary protein for albumin excretion and eGFR, if I understood your question properly.

是的。所以生物標誌物，你說的是對 IgAN 的影響。是的。好的。是的。因此，當然，最重要的生物標誌物是尿蛋白排泄。這是第一。第二個是最重要的一個是對腎功能的影響，即 eGFR。但我們也在探索各種我們可能能夠利用的尿液標記物和其他標記物。但最重要的兩個是用於白蛋白排泄的尿蛋白和 eGFR，如果我正確理解你的問題的話。

Got it. And then maybe a market opportunity question in IgAN. So roughly 30,000 to 50,000 patients. So is there a specific population that you're planning to target with your agent or is it for general or all IgAN patients?

知道了。然後可能是 IgAN 中的市場機會問題。所以大約有 30,000 到 50,000 名患者。那麼，您是否計劃使用您的藥物針對特定人群，還是針對一般或所有 IgAN 患者？

Well, I think that we are looking at that carefully. We haven't decided exactly which patient population or segment that we will focus our development program on. Obviously, there are different ways to segment the patients in terms of when they were diagnosed, whether they have failed other therapies, what their baseline renal function is, whether they have evidence of progressive -- rapidly progressive disease or slowly progressive disease. We'll be looking at all of that to take into account how to focus our program. And we haven't really made those decisions yet, but we do think that patient segmentation will be an important part of the program.

好吧，我認為我們正在仔細研究。我們還沒有確切地決定我們將把發展計劃的重點放在哪個患者群體或細分市場上。顯然，根據診斷時間、其他治療是否失敗、基線腎功能、是否有進展的證據（快速進展性疾病或緩慢進展性疾病），可以採用不同的方法對患者進行細分。我們將研究所有這些，以考慮如何集中我們的計劃。我們還沒有真正做出這些決定，但我們確實認為患者細分將是該計劃的重要組成部分。

Great. And maybe one final question with respect to your Astellas gene therapy collaboration. This is more a clarification. Is there a requirement that the agent or the gene therapy agent plus your Xork it should get to skeletal and cardiac muscles.

偉大的。最後一個問題可能是關於你們的 Astellas 基因治療合作。這更像是一個澄清。是否要求藥劑或基因治療劑加上你的 Xork 它應該到達骨骼肌和心肌。

If I understand the question correctly, is this around ImmTOR or Xork. Just ImmTOR works through the liver, but we have partnerships and all the data we have generated is in liver-directed vectors. But obviously, we do have a partnership with Sarepta and looking at neuromuscular disease, where we also believe that there's a good rationale why we could use ImmTOR as (inaudible) migrate, obviously, as well systemically that hopefully address the question?

如果我正確理解了這個問題，這是圍繞 ImmTOR 還是 Xork。 Just ImmTOR 通過肝臟工作，但我們有合作夥伴關係，我們生成的所有數據都在肝臟定向載體中。但顯然，我們確實與 Sarepta 建立了合作夥伴關係並研究神經肌肉疾病，我們也相信有一個很好的理由說明為什麼我們可以使用 ImmTOR 作為（聽不清）遷移，顯然，以及系統地希望解決這個問題？

So the question was not about ImmTOR, it was about Xork but yeah, thanks for the color there.

所以問題不是關於 ImmTOR，而是關於 Xork 但是，是的，感謝那裡的顏色。

I can comment on the Xork. So the Xork works through variance of systemic IgG so of the neutralizing antibodies included. So regardless of where the capsid target is, it's going -- as long it's systemically delivered, it's going to be intercepted by the neutralizing antibodies. So the Xork enzyme should be active in that situation.

我可以對 Xork 發表評論。因此，Xork 通過系統性 IgG 的變化以及所包含的中和抗體的變化來發揮作用。因此，無論衣殼目標在哪裡，它都會去——只要它被系統地遞送，它就會被中和抗體攔截。所以 Xork 酶在那種情況下應該是活躍的。

Next question comes from Uy Ear of Mizuho.

下一個問題來自瑞穗的Uy Ear。

So I guess the first question is on the MMA study that you guys are ongoing. Just curious to sort of get a better sense of what you're seeing in terms of patients' interest in the gene therapy? And I guess my second question is given the completion of the DISSOLVE 1 and DISSOLVE 2 studies, just curious to -- curious to see if you can help us understand how to think about R&D for 2023. It looks like the consensus is projecting kind of flat R&D versus 2022. And yeah, that's essentially it.

所以我想第一個問題是關於你們正在進行的 MMA 研究。只是想更好地了解您在患者對基因治療的興趣方面所看到的情況？我想我的第二個問題是 DISSOLVE 1 和 DISSOLVE 2 研究的完成，只是好奇——好奇你是否能幫助我們理解如何思考 2023 年的研發。看起來共識正在預測某種研發與 2022 年持平。是的，基本上就是這樣。

Great. Yes. I'll give the first question to Peter, who is obviously intimately involved in the ReMagine trial, which we're running at a single center at the NIH, Peter?

偉大的。是的。我會向彼得提出第一個問題，他顯然密切參與了 ReMagine 試驗，我們在 NIH 的一個中心進行，彼得？

Yeah, happy to answer that. In terms of the patient interest, we have done a good deal of promotion of the trial through the Organic Acidemia Society, the website for the trial and so forth. And we have gotten a lot of interest both in the U.S. and internationally. But of course, this is a trial where we are sequentially enrolling subjects over time.

是的，很高興回答這個問題。在患者利益方面，我們通過有機酸血症協會、試驗網站等對試驗進行了大量宣傳。我們在美國和國際上都引起了很多興趣。但當然，這是一項試驗，我們會隨著時間的推移依次招募受試者。

So it's not like the trial success is going to be dependent on a very large group of patients interested right at the beginning because we're going to enroll them sequentially over the course of two years. We have, as you know, the trial is active. It has been since the end of last year. We have enrolled a subject -- first subject, and that subject is going through the extensive screening process leading up to treatment. And we don't have a specific date or timing yet for that, but it's -- the program is moving along with screening and evaluating the first subject.

因此，試驗的成功並不取決於一開始就感興趣的大量患者，因為我們將在兩年內按順序招募他們。如您所知，我們已經開始試用。自去年年底以來一直如此。我們已經招募了一個受試者——第一個受試者，該受試者正在經歷導致治療的廣泛篩選過程。我們還沒有具體的日期或時間，但它是 - 該計劃正在與篩选和評估第一個主題一起進行。

Great. And Blaine, if you handle the second around R&D expenses.

偉大的。布萊恩，如果你處理第二個關於研發費用的問題。

Sure. Yes. So relative to R&D expenses, well, we don't kind of specifically guide to how to think about future expenses for the organization overall. Let me give a little bit of context. So as you could expect, we continue to have clinical trial expenses associated with the SEL-212 program that will be continuing in 2023. And then we'll also start to have obviously a decent amount of ramp-up activity associated with the earlier stage pipeline around preclinical activities as well as kind of a number of other sort of R&D-related expenses.

當然。是的。因此，相對於研發費用，我們並沒有具體指導如何考慮整個組織的未來費用。讓我給出一些背景信息。因此，正如您所預料的那樣，我們將繼續承擔與 SEL-212 計劃相關的臨床試驗費用，該計劃將在 2023 年繼續進行。然後我們也將開始明顯地有相當數量的與早期階段相關的加速活動圍繞臨床前活動的管道以及其他一些與研發相關的費用。

So there will start to be a shift in kind of where those R&D expenses are associated on a go-forward basis. We do have a number of kind of early-stage activities and programs as well as the ongoing MMA study that will start to have a shift overall. But I don't want to provide kind of specific guidance at this particular juncture on how to think about overall expenses. But hopefully, that gives a little bit of context in some of the moving parts as we think about 2023.

因此，這些研發費用在向前發展的基礎上的關聯方式將開始發生轉變。我們確實有一些早期的活動和項目，以及正在進行的 MMA 研究，這些研究將開始全面轉變。但我不想在這個特定時刻提供關於如何考慮總體支出的具體指導。但希望這能為我們考慮 2023 年的一些活動部分提供一些背景信息。

This concludes our question-and-answer session. I would like to turn the conference back over to Carsten Brunn for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給 Carsten Brunn，聽取任何閉幕詞。

Thank you, operator, and thank you to everyone who joined us this morning. Stay safe and healthy. This concludes today's call. Thanks.

謝謝接線員，也感謝今天早上加入我們的每一個人。保持安全和健康。今天的電話會議到此結束。謝謝。