Omeros Corp (OMER) 2022 Q4 法說會逐字稿

Good afternoon, and welcome to today's earnings call from Omeros Corporation. (Operator Instructions)

下午好，歡迎來到今天來自 Omeros Corporation 的財報電話會議。 （操作員說明）

Please be advised that this call is being recorded at the company's request, and a replay will be available on the company's website from 1 week from today. I'll turn the call over to Jennifer Williams, Investor Relations. Jennifer, you may begin.

請注意，根據公司的要求，此次通話正在錄音，從今天起 1 週後，公司網站將提供重播。我會把電話轉給投資者關係部的 Jennifer Williams。詹妮弗，你可以開始了。

Good afternoon, and thank you for joining the call today. I'd like to remind you that some of the statements that will be made on the call today will be forward-looking. These statements are based on management's beliefs and expectations as of today only and are subject to change. All forward-looking statements involve risks and uncertainties that could cause the company's actual results to differ materially. Please refer to the special note regarding forward-looking statements in the company's annual report on Form 10-K, which was filed today with the SEC, including the Risk Factors section for a discussion of these risks and uncertainties.

下午好，感謝您今天加入電話會議。我想提醒您，今天電話會議上的一些陳述將是前瞻性的。這些陳述僅基於截至今天的管理層的信念和期望，並且可能會發生變化。所有前瞻性陳述都包含可能導致公司實際結果出現重大差異的風險和不確定性。請參閱公司今天向美國證券交易委員會提交的 10-K 表格年度報告中有關前瞻性陳述的特別說明，其中包括風險因素部分，以討論這些風險和不確定性。

Now I would like to turn the call over to Dr. Greg Demopulos, Chairman and CEO of Omeros.

現在我想把電話轉給 Omeros 董事長兼首席執行官 Greg Demopulos 博士。

Thank you, Jennifer, and good afternoon, everyone. We'll start with the corporate update and an overview of our fourth quarter and full year 2022 financial results followed by a more detailed financial summary. Joining me on the call today are Mike Jacobsen, Nadia Dac, Cathy Melfi and Steve Whitaker, our respective heads of finance, commercial, regulatory and clinical.

謝謝你，詹妮弗，大家下午好。我們將從公司更新和我們第四季度和 2022 年全年財務業績的概述開始，然後是更詳細的財務摘要。今天和我一起參加電話會議的有 Mike Jacobsen、Nadia Dac、Cathy Melfi 和 Steve Whitaker，他們分別是我們的財務、商業、監管和臨床主管。

Before diving into the details of our specific program updates and coming events, I'd like to spend just a few minutes on our financial strength that we expect will enable those events without the need for near-term shareholder dilution, continuing to position Omeros for success.

在深入了解我們的具體計劃更新和即將舉行的活動的細節之前，我想花幾分鐘談談我們的財務實力，我們預計這將在不需要近期股東稀釋的情況下實現這些活動，繼續將 Omeros 定位為成功。

To provide some background, in December 2021, we completed the strategic sale of the cataract surgery product that we developed and commercialized, OMIDRIA to Rayner Surgical for an upfront payment of $125 million, $31 million of retained receivables, substantial ongoing royalties on Rayner's net sales of OMIDRIA and the potential to receive a $200 million milestone payment by securing for OMIDRIA continuous separate payment of at least 4 years. The initial royalty rate on U.S. net sales of OMIDRIA was 50%, which represented nearly 80% of the total operating profit.

為了提供一些背景信息，我們於 2021 年 12 月完成了將我們開發和商業化的白內障手術產品 OMIDRIA 戰略銷售給 Rayner Surgical，預付款為 1.25 億美元，保留應收賬款為 3100 萬美元，Rayner 淨銷售額的大量持續特許權使用費OMIDRIA，並有可能通過確保 OMIDRIA 連續單獨支付至少 4 年而獲得 2 億美元的里程碑付款。 OMIDRIA 在美國淨銷售額的初始特許權使用費率為 50%，佔總營業利潤的近 80%。

Last September, we sold a portion of our future OMIDRIA royalty stream to DRI Healthcare and received $125 million in cash. Because DRI's annual royalties are capped and as a result, Omeros received any financial upside in the OMIDRIA royalty stream, the royalty sale was recorded as debt on our balance sheet and no income was recognized related to the sale. Then 3 months later, in December 2022, Omeros achieved the Rayner milestone, receiving $200 million plus interest in early February. Under our agreement with Rayner Surgical after achieving the milestone, the royalty rate that we now receive on Rayner's U.S. net sales decreased to 30%, which represents approximately 40% of total OMIDRIA operating profits.

去年 9 月，我們將未來 OMIDRIA 專利流的一部分出售給了 DRI Healthcare，並獲得了 1.25 億美元的現金。由於 DRI 的年度特許權使用費是有上限的，因此，Omeros 在 OMIDRIA 特許權使用費流中獲得了任何財務收益，特許權使用費銷售在我們的資產負債表上被記錄為債務，並且沒有確認與銷售相關的收入。然後 3 個月後，即 2022 年 12 月，Omeros 實現了 Rayner 的里程碑，在 2 月初獲得了 2 億美元外加利息。根據我們在實現里程碑後與 Rayner Surgical 達成的協議，我們現在從 Rayner 美國淨銷售額中獲得的特許權使用費率降至 30%，約佔 OMIDRIA 總營業利潤的 40%。

Nearly half of all cataract procedures in the U.S. are performed on Medicare Part B patients with surgical and facility fee payments administered by the Centers for Medicare and Medicaid Services, or CMS. Since OMIDRIA's market launch in the second quarter of 2015 through multiple CMS awarded and congressionally mandated pass-through periods and then qualifying under the non-opioid pain management exclusion from packaging, OMIDRIA has received continuous separate payment from CMS interrupted over those 8 years for a total of only 11 months, 9 months in 2018, following successful legislation extending pass-through and 2 months in 2020 after qualifying for CMS' non-opioid packaging exclusion. But separate payment repeatedly needed to be one. So we, together with physicians and surgical facilities could never rely on CMS providing separate payment for OMIDRIA long term.

在美國，近一半的白內障手術是在醫療保險 B 部分患者身上進行的，手術和設施費用由醫療保險和醫療補助服務中心 (CMS) 管理。自 OMIDRIA 於 2015 年第二季度通過多個 CMS 授予和國會授權的傳遞期上市，然後根據非阿片類藥物疼痛管理排除在包裝之外的資格，OMIDRIA 已從 CMS 連續收到單獨付款，在這 8 年中中斷了總共只有 11 個月，2018 年是 9 個月，在成功立法延長通過期後，2020 年是 2 個月，在符合 CMS 的非阿片類藥物包裝排除資格後。但單獨支付多次需要一次。因此，我們與醫生和外科設施永遠不能依賴 CMS 為 OMIDRIA 長期單獨付款。

Despite this uncertainty, the drug to date has infused Omeros with effectively $1 billion in non-dilutive funding, fueling the development of our pipeline, while minimizing both outstanding share count and shareholder dilution. Now let's look at our financial results for both the fourth quarter and the year. Our net income for the fourth quarter was $128.7 million or $2.05 per share compared to $280.6 million or $4.49 per share for the fourth quarter of 2021. Both the current and the prior year quarters were significantly affected by OMIDRIA transactions that I just recounted, namely the December 2021 strategic sale of OMIDRIA and the December '22 achievement of the Rayner milestone. Looking only at continuing operations, our net loss for the fourth quarter of 2022 was $0.73 per share compared to $0.76 per share for the same quarter in 2021.

儘管存在這種不確定性，但迄今為止，該藥物已為 Omeros 注入了有效的 10 億美元非稀釋性資金，推動了我們管道的發展，同時最大限度地減少了流通股數量和股東稀釋。現在讓我們看看我們第四季度和全年的財務業績。我們第四季度的淨收入為 1.287 億美元或每股 2.05 美元，而 2021 年第四季度為 2.806 億美元或每股 4.49 美元。本季度和上一年季度都受到我剛剛敘述的 OMIDRIA 交易的重大影響，即2021 年 12 月 OMIDRIA 的戰略銷售和 22 年 12 月實現 Rayner 里程碑。僅看持續經營業務，我們 2022 年第四季度的淨虧損為每股 0.73 美元，而 2021 年同期為每股 0.76 美元。

Our cash burn for the fourth quarter of 2022 was $26 million. Omeros received $17.9 million in royalties from Rayner's OMIDRIA fourth quarter net sales of $35.8 million, a new quarterly record. Our net income for the full year 2022 was $47.4 million or $0.76 per share compared to $194.2 million or $3.12 per share in 2021. Our full year loss from continuing operations in 2022 was $182 million or $2.90 per share compared to a loss of $191.5 million or $3.07 per share in 2021. As of December 31, 2022, we had $195 million of cash and investments and $213 million in receivables, inclusive of the $200 million milestone payment. All of those receivables have now been collected. So in total, we had $408 million in cash, investments and receivables at December 31, 2022, to support ongoing operations and debt service.

我們 2022 年第四季度的現金消耗為 2600 萬美元。 Omeros 從 Rayner 的 OMIDRIA 第四季度淨銷售額 3580 萬美元中獲得了 1790 萬美元的特許權使用費，創下了新的季度記錄。我們 2022 年全年的淨收入為 4740 萬美元或每股 0.76 美元，而 2021 年為 1.942 億美元或每股 3.12 美元。我們在 2022 年的全年持續經營虧損為 1.82 億美元或每股 2.90 美元，而虧損為 1.915 億美元或每股2021 年每股 3.07 美元。截至 2022 年 12 月 31 日，我們擁有 1.95 億美元的現金和投資以及 2.13 億美元的應收賬款，包括 2 億美元的里程碑付款。所有這些應收款現已收回。因此，截至 2022 年 12 月 31 日，我們總共擁有 4.08 億美元的現金、投資和應收賬款，以支持持續運營和償債。

A good number of shareholders contacted us last week asking whether our corporate cash and investments were in any way exposed to Silicon Valley Bank, but to be clear, we do not have any assets on deposit with Silicon Valley Bank, nor do we have any other financial relationship with SVB or its affiliates. The $408 million now in hand provides Omeros the flexibility simply to pay off any or all of the $95 million of convertible debt that matures this November, while continuing to fund operations and advancing our multiple development programs well into 2025. Moreover, the recent (inaudible) the Consolidated Appropriations Act of 2023 also known as the 2023 Omnibus Bill mandates that CMS continue to pay separately for non-opioid pain management drugs like OMIDRIA in ambulatory surgery centers or ASCs until at least 2028.

許多股東上週聯繫我們，詢問我們的公司現金和投資是否以任何方式暴露於矽谷銀行，但需要明確的是，我們沒有任何資產存放在矽谷銀行，我們也沒有任何其他資產與 SVB 或其附屬公司的財務關係。現在手頭的 4.08 億美元使 Omeros 可以靈活地償還今年 11 月到期的 9500 萬美元可轉換債務中的任何或全部，同時繼續為運營提供資金並將我們的多個開發計劃推進到 2025 年。此外，最近（聽不清) 2023 年聯合撥款法案（也稱為 2023 年綜合法案）要求 CMS 至少在 2028 年之前繼續為門診手術中心或 ASC 中的 OMIDRIA 等非阿片類鎮痛藥物單獨支付費用。

While the majority of cataract surgery is performed in ASCs, approximately 20% of those procedures occur in hospital outpatient departments or HOPDs (inaudible) address this as well, directing CMS to pay separately for drugs like OMIDRIA not only in ASCs, but also in the HOPD setting, beginning no later than January 2025. The assurance of long-term separate payment in both the ASC and HOPD settings now provides physicians and surgical facility administrators, the confidence that they can incorporate OMIDRIA into their practices and plan on being adequately reimbursed for delivering best care to their patients.

雖然大多數白內障手術是在 ASC 中進行的，但其中大約 20% 的手術發生在醫院門診部或 HOPD（聽不清）也解決了這個問題，指示 CMS 單獨支付 OMIDRIA 等藥物的費用，不僅在 ASC 中，而且在HOPD 設置，不遲於 2025 年 1 月開始。ASC 和 HOPD 設置中的長期單獨付款保證現在為醫生和外科設施管理員提供了信心，他們可以將 OMIDRIA 納入他們的實踐併計劃獲得充分報銷為患者提供最好的護理。

We expect this increased certainty in CMS payment to result in meaningful OMIDRIA sales growth. Congressionally mandated long-term separate payment by CMS could also have a direct and positive effect on the other 2 major coverage systems for cataract surgery, Medicare Advantage and commercial insurance plans, driving expansion of separate payment across both of them, which would be good for ophthalmic surgeons and their patients.

我們預計 CMS 支付的這種增加的確定性將導致有意義的 OMIDRIA 銷售增長。國會要求 CMS 的長期單獨支付也可能對白內障手術、Medicare Advantage 和商業保險計劃的其他 2 個主要覆蓋系統產生直接和積極的影響，推動兩者單獨支付的擴展，這將有利於眼科醫生和他們的病人。

The fact that many Med Advantage and commercial plans are administered by the same payers, should accelerate this expansion. There are well over 4 million cataract procedures performed annually in the U.S. alone. As U.S. sales of OMIDRIA continue to grow, Omeros will continue to receive 30% of those revenues as royalties. Potentially further adding to our royalty stream, Rayner is planning to begin selling OMIDRIA outside of the U.S. later this year, resulting in 15% of any of those revenues also enuring to Omeros. Both the U.S. and international royalty rates paid to Omeros should remain (inaudible) until the expiration of OMIDRIA patents, which are slated to be no sooner than 2033.

許多 Med Advantage 和商業計劃由相同的付款人管理，這一事實應該會加速這種擴張。僅在美國，每年就有超過 400 萬例白內障手術。隨著 OMIDRIA 在美國的銷售額持續增長，Omeros 將繼續獲得這些收入的 30% 作為特許權使用費。 Rayner 計劃在今年晚些時候開始在美國以外的地區銷售 OMIDRIA，這可能會進一步增加我們的特許權使用費流，因此這些收入中的 15% 也將留給 Omeros。支付給 Omeros 的美國和國際特許權使用費率應保持（聽不清），直到 OMIDRIA 專利到期，預計不早於 2033 年。

So having laid out the current strength of our financial position, let's now turn to updates on Omeros' programs, beginning with narsoplimab in stem-cell transplant associated thrombotic microangiopathy, or TA-TMA. Following our appeal of FDA's complete response letter on our biologic license application or BLA, for narsoplimab in TA-TMA, in late 2022, we received guidance from FDA's Office of New Drugs, proposing a path forward to resubmit our BLA with additional analyses comparing response from our completed pivotal trial to a threshold derived from an independent literature analysis. Also requested was evidence of increased survival in our completed trial compared to an appropriate historical control group. We have identified and now can access robust sources of independent and historical response rates and survival in TA-TMA patients not treated with narsoplimab.

因此，在闡述了我們目前的財務狀況之後，現在讓我們來看看 Omeros 項目的更新，首先是乾細胞移植相關血栓性微血管病 (TA-TMA) 中的 narsoplimab。在我們於 2022 年底針對 TA-TMA 中的 narsoplimab 對 FDA 關於我們的生物許可申請或 BLA 的完整回复函提出上訴後，我們收到了 FDA 新藥辦公室的指導，提出了重新提交我們的 BLA 以及比較反應的其他分析的途徑從我們完成的關鍵試驗到來自獨立文獻分析的閾值。還要求提供與適當的歷史對照組相比，我們完成的試驗中存活率增加的證據。我們已經確定並且現在可以獲得獨立和歷史反應率和未接受 narsoplimab 治療的 TA-TMA 患者存活率的可靠來源。

Working with our regulatory and legal advisers led by (inaudible) toward a rapid resubmission of our BLA, we have requested a meeting with the FDA's Division of Non-Malignant Hematology to discuss the details of our proposed analyses and to confirm the information required by FDA to support narsoplimab's approval. This will be a Type B meeting, so we expect it to occur in the first half of the second quarter. For European approval, we have initiated clinical trials assessing narsoplimab in pediatric patients with TA-TMA to fulfill our pediatric investigation plan agreed with the European Medicines Agency or EMA. We expect to complete the submission of our marketing authorization application to EMA after resubmission of our BLA.

我們與由（聽不清）領導的監管和法律顧問合作，以快速重新提交我們的 BLA，我們已要求與 FDA 的非惡性血液學部門會面，討論我們提議的分析的細節並確認 FDA 要求的信息支持 narsoplimab 的批准。這將是 B 類會議，因此我們預計它會在第二季度的前半段舉行。為了獲得歐洲的批准，我們已經啟動了在 TA-TMA 兒科患者中評估 narsoplimab 的臨床試驗，以實現我們與歐洲藥品管理局或 EMA 商定的兒科調查計劃。我們希望在重新提交 BLA 後完成向 EMA 提交營銷授權申請。

Since our last earnings call, we've seen continued and substantial activity in peer-reviewed publications and presentations directed to TA-TMA the lectin pathway and narsoplimab. An international group of leading transplanters recently published a systemic review of signs and symptoms of TA-TMA in transplantation and cellular therapy. And a second manuscript on TA-TMA diagnosis and treatment has been accepted for publication by the journal, Bone Marrow Transplantation.

自上次財報電話會議以來，我們在同行評審的出版物和演示中看到了針對 TA-TMA 凝集素途徑和 narsoplimab 的持續和實質性活動。一個由領先的移植者組成的國際小組最近發表了對移植和細胞治療中 TA-TMA 體徵和症狀的系統評價。關於 TA-TMA 診斷和治療的第二篇手稿已被 Bone Marrow Transplantation 雜誌接受發表。

Presentation at the recent Annual Meeting of the American Society of Hematology detailed our clinical trial of narsoplimab in pediatric patients with TA-TMA and 2 additional abstracts on use of narsoplimab in TA-TMA have been accepted for presentation at the upcoming European Society for Blood and Marrow Transplantation.

在最近的美國血液學會年會上發表的演講詳細介紹了我們在 TA-TMA 兒科患者中進行的 narsoplimab 臨床試驗，另外 2 份關於在 TA-TMA 中使用 narsoplimab 的摘要已被接受在即將召開的歐洲血液和血液學會上發表骨髓移植。

Stem-cell transplanters internationally are increasingly identifying TA-TMA in their transplant patients and recognizing it as an urgent and unmet medical need. National diagnostic and procedural billing codes now officially recognize TA-TMA as a discrete complication of stem-cell transplantation. This means that once there is an approved treatment for TA-TMA off-label use, which occurs now with C5 inhibitors, should be rightly curtailed, further driving use of any approved treatment. We believe that narsoplimab deserves FDA approval for the treatment of TA-TMA and we are committed to continuing to work with FDA to make that a reality.

國際上的干細胞移植者越來越多地在他們的移植患者中識別出 TA-TMA，並將其視為一種緊迫且未得到滿足的醫療需求。國家診斷和程序計費代碼現在正式承認 TA-TMA 是乾細胞移植的一種獨立並發症。這意味著一旦 TA-TMA 標籤外使用的治療獲得批准（現在使用 C5 抑製劑），就應該正確地減少，進一步推動任何批准治療的使用。我們相信 narsoplimab 值得 FDA 批准用於治療 TA-TMA，我們致力於繼續與 FDA 合作以實現這一目標。

Also in our narsoplimab portfolio, our Phase III clinical trial in patients with IgA nephropathy remains on track to read out 9-month proteinuria data in the third quarter of this year. This is expected to form the basis for our BLA to be submitted to FDA, and we expect for our submission to European Regulators. Adding to a list of existing publications, a manuscript authored by a group of international experts on the role of the lectin pathway and the pathophysiology of IgA nephropathy, has been submitted to a leading peer-reviewed journey.

同樣在我們的 narsoplimab 產品組合中，我們對 IgA 腎病患者的 III 期臨床試驗仍在按計劃在今年第三季度公佈 9 個月的蛋白尿數據。預計這將構成我們的 BLA 提交給 FDA 的基礎，我們預計我們將提交給歐洲監管機構。除了現有的出版物清單之外，由一組國際專家撰寫的關於凝集素途徑的作用和 IgA 腎病病理生理學的手稿已提交給領先的同行評審之旅。

IgA nephropathy represents a multibillion-dollar market opportunity. While FDA has recently approved for IgA patients in both a steroid and a representative of a new class of agents that target blood pressure, clinical experts do not see these as competitors, but rather as complementary to inhibitors of the complement system. There currently is no complement inhibitor approved for IgA nephropathy, and we aim to make narsoplimab the first. As we've discussed in previous calls, our Phase III program in atypical hemolytic uremic syndrome, or aHUS, remains a low priority.

IgA 腎病代表著數十億美元的市場機會。雖然 FDA 最近批准了針對 IgA 患者的類固醇和靶向血壓的新型藥物的代表，但臨床專家並不認為這些是競爭對手，而是補體系統抑製劑的補充。目前還沒有批准用於 IgA 腎病的補體抑製劑，我們的目標是讓 narsoplimab 成為第一個。正如我們在之前的電話會議中所討論的那樣，我們在非典型溶血性尿毒症綜合徵 (aHUS) 中的 III 期項目仍然處於低優先級。

Enrollment has been challenging and due to what we and others see as a contracting commercial market for aHUS because of the increasing number of C5 biosimilars, we've diverted resources to other clinical programs within our complement franchise. At our labs in the University of Cambridge, collaborative work with multiple U.K. consortia in acute severe and long COVID is advancing. Dialogue is ongoing with relative branches of the U.S. government and with the resurgence of COVID and related diseases. There is continued interest from these agencies in accessing narsoplimab and funding narsoplimab-related activities. A manuscript directed the lectin pathway inhibition and well-established in vitro in animal models of both COVID and influenza-related acute respiratory distress syndrome, or ARDS, is being prepared for submission.

由於 C5 生物仿製藥數量的增加，我們和其他人認為 aHUS 的商業市場正在收縮，因此註冊一直具有挑戰性，我們已將資源轉移到我們補充特許經營權內的其他臨床項目。在我們劍橋大學的實驗室，與多個英國聯盟在急性嚴重和長期 COVID 方面的合作正在推進。正在與美國政府的相關部門進行對話，並應對 COVID 和相關疾病的捲土重來。這些機構一直有興趣獲得 narsoplimab 並資助與 narsoplimab 相關的活動。一份針對凝集素途徑抑製作用的手稿正在準備提交，該手稿在 COVID 和流感相關急性呼吸窘迫綜合徵 (ARDS) 的動物模型中得到了很好的體外驗證。

The evidence supporting the central role of the lectin pathway and the utility of narsoplimab in these diseases is only increasing. This is being further highlighted within government agencies as the utility of vaccines under increasing scrutiny becomes more questionable, and the need for therapeutics that directly target the central pathophysiology of COVID and other causes of ARDS moves to the forefront. Now let's look at OMS1029, our long-acting next-generation antibody targeting MASP-2 and the lectin pathway.

支持凝集素途徑的核心作用和 narsoplimab 在這些疾病中的效用的證據只會越來越多。隨著疫苗的實用性受到越來越多的審查，這在政府機構內得到了進一步強調，並且對直接針對 COVID 和 ARDS 其他原因的核心病理生理學的治療方法的需求已成為最前沿。現在讓我們看看 OMS1029，這是我們針對 MASP-2 和凝集素途徑的長效下一代抗體。

OMS1029 is complementary to narsoplimab, whereas narsoplimab is generally administered intravenously once weekly, ideal for acute or episodic treatment. Long-acting OMS1029 is designed for chronic use. Our strategy of developing OMS1029 is a long-acting follow-on to narsoplimab is to enable Omeros to control first-line therapies for the large majority of lectin pathway-related disorders.

OMS1029 是 narsoplimab 的補充，而 narsoplimab 通常每週一次靜脈內給藥，非常適合急性或間歇性治療。長效 OMS1029 專為長期使用而設計。我們開發 OMS1029 的策略是 narsoplimab 的長效後續藥物，旨在使 Omeros 能夠控制大多數凝集素通路相關疾病的一線治療。

In January of this year, we completed dosing of all cohorts in the OMS1029 single ascending dose Phase I clinical trial. As predicted, given our experience with narsoplimab, OMS1029 was well tolerated with no safety concerns identified. The trial did deliver excitement though in that the pharmacokinetic and pharmacodynamic data demonstrate that OMS1029 effectively ablates lectin pathway activity and should do so even with markedly protracted dosing intervals of once-quarterly administration. Detailed results from the single ascending dose study of OMS1029 are planned for presentation at an upcoming scientific congress. Dosing in the OMS1029 multiple ascending dose study in healthy subjects is scheduled to start this summer.

今年 1 月，我們完成了 OMS1029 單次遞增劑量 I 期臨床試驗中所有隊列的給藥。正如預測的那樣，鑑於我們使用 narsoplimab 的經驗，OMS1029 的耐受性良好，未發現安全問題。儘管藥代動力學和藥效學數據表明 OMS1029 可有效消除凝集素通路活性，但該試驗確實令人興奮，即使每季度一次給藥的給藥間隔顯著延長，也應如此。 OMS1029 單次遞增劑量研究的詳細結果計劃在即將舉行的科學大會上公佈。 OMS1029 在健康受試者中的多次遞增劑量研究定於今年夏天開始。

Wrapping up, our lectin pathway portfolio, we believe that we are very close to selecting a lead drug development candidate from our small molecule orally active, MASP-2 inhibitor program. Recent pharmacokinetic and pharmacodynamic data are compelling and safety data generated to date are clean. Together with our external advisers, including former heads of chemistry, pharmacokinetics and drug metabolism with GlaxoSmithKline and Merck, we are enthusiastic about these molecules and hope to select a lead compound next quarter. A successful orally dosed small molecule inhibitor of MASP-2 together with narsoplimab and OMS1029 should enable Omeros to control the gamut of diseases and disorders caused by dysregulation of the lectin pathway.

總結一下我們的凝集素途徑產品組合，我們相信我們非常接近從我們的小分子口服活性 MASP-2 抑製劑項目中選擇領先的藥物開發候選者。最近的藥代動力學和藥效學數據令人信服，迄今為止產生的安全數據是乾淨的。連同我們的外部顧問，包括葛蘭素史克和默克化學、藥代動力學和藥物代謝的前負責人，我們對這些分子充滿熱情，並希望在下個季度選擇先導化合物。一種成功的口服 MASP-2 小分子抑製劑連同 narsoplimab 和 OMS1029 應該能夠使 Omeros 控制由凝集素通路失調引起的各種疾病和病症。

We'll now complete the updates on our complement franchise with OMS906, our antibody targeting MASP-3. MASP-3 is the key activator of the alternative pathway of complement. As previously announced, we successfully completed a single ascending dose Phase I study of OMS906, evaluating both intravenous and subcutaneous administration in healthy subjects. The drug was well tolerated, and there were no safety signals of concern. Detailed clinical data from that study were presented in December at the Annual Meeting of the American Society of Hematology. Based on clinical data to date, we expect that we will be able to achieve once-quarterly dosing with OMS906, either intravenously or subcutaneously. This along with the other potential differentiating benefits of OMS906, should serve us very well in the competitive marketplace of alternative pathway inhibitors.

現在，我們將完成對 OMS906 補充專營權的更新，OMS906 是我們針對 MASP-3 的抗體。 MASP-3 是補體替代途徑的關鍵激活劑。正如之前宣布的那樣，我們成功完成了 OMS906 的單次遞增劑量 I 期研究，評估了健康受試者的靜脈內和皮下給藥。該藥物耐受性良好，沒有安全問題。該研究的詳細臨床數據於 12 月在美國血液學會年會上公佈。根據迄今為止的臨床數據，我們預計我們將能夠實現每季度一次的 OMS906 靜脈內或皮下給藥。這與 OMS906 的其他潛在差異化優勢一起，應該在競爭激烈的替代途徑抑製劑市場中為我們提供很好的服務。

Our clinical development strategy is to obtain rapid proof of concept data on the efficacy of OMS906 in multiple validated alternative pathway-related disorders, including paroxysmal nocturnal hemoglobinuria, or PNH, and complement 3 glomerulopathy, or C3G. On schedule, last December, we began enrolling treatment-naive PNH patients in one of our Phase Ib clinical trials evaluating OMS906, and dosing began early this year. Our second Phase Ib clinical trial, this one in PNH patients who have had an unsatisfactory response to the C5 inhibitor, ravulizumab, is also enrolling. We're scheduled to begin the first dosing of OMS906 in this study later this month once the ravulizumab monotherapy period has ended.

我們的臨床開發策略是快速獲得關於 OMS906 在多種經過驗證的替代途徑相關疾病（包括陣發性睡眠性血紅蛋白尿症或 PNH 和補體 3 腎小球病或 C3G）中療效的概念數據證明。按照計劃，去年 12 月，我們開始在我們的一項評估 OMS906 的 Ib 期臨床試驗中招募初治 PNH 患者，並於今年年初開始給藥。我們的第二個 Ib 期臨床試驗也在招募中，該試驗針對的是對 C5 抑製劑 ravulizumab 反應不佳的 PNH 患者。一旦 ravulizumab 單藥治療期結束，我們計劃於本月晚些時候在本研究中開始首次給藥 OMS906。

The current development plan for OMS906 and PNH involves a pivotal program consisting of 2 trials, one in treatment-naive patients and one in patients who don't respond well to improve PNH therapy, both with relatively small numbers of patients similar to the numbers enrolled for Novartis' iptacopan and Apellis' pegcetacoplan programs. We've also initiated a Phase Ib clinical trial evaluating OMS906 in patients with C3G. Enrollment here is expected to commence next month with data available in the third quarter of this year.

目前針對 OMS906 和 PNH 的開發計劃涉及一項關鍵計劃，包括 2 項試驗，一項針對初治患者，另一項針對改善 PNH 治療反應不佳的患者，這兩項試驗的患者人數相對較少，與入組人數相似用於諾華公司的 iptacopan 和 Apellis 的 pegcetacoplan 項目。我們還啟動了 Ib 期臨床試驗，在 C3G 患者中評估 OMS906。預計這裡的註冊將於下個月開始，數據將在今年第三季度公佈。

Here again, we're planning for relatively small study population similar to the number of C3G patients being enrolled by Novartis for iptacopan. Regulatory interactions in the U.S. and Europe are ongoing for OMS906 in both PNH and C3G. As discussed earlier, there is good evidence that MASP-3 and 906 could prove to be the premier target and drug, respectively, in the alternative pathway.

在這裡，我們再次計劃使用相對較小的研究人群，類似於諾華公司為 iptacopan 招募的 C3G 患者數量。 PNH 和 C3G 中的 OMS906 正在美國和歐洲進行監管互動。如前所述，有充分證據表明 MASP-3 和 906 可能分別被證明是替代途徑中的主要靶標和藥物。

The potential advantages of OMS906 over other alternative pathway inhibitors on the market or in development include safety, through a meaningfully decreased infection risk by not blocking the adaptive immune response, compliance and convenience with significantly better dosing profile and once-quarterly intravenous or subcutaneous administration and efficacy through greatly decreased risk and breakthrough of the underlying disease given that MASP-3 first is not an acute-phase reactant and that OMS906 has a long half-life, allowing MASP-3 to be blocked consistently and effectively.

OMS906 相對於市場上或正在開發的其他替代途徑抑製劑的潛在優勢包括安全性，通過不阻斷適應性免疫反應顯著降低感染風險，依從性和便利性，顯著更好的劑量曲線和每季度一次靜脈內或皮下給藥和考慮到 MASP-3 首先不是急性期反應物，並且 OMS906 具有較長的半衰期，從而使 MASP-3 能夠持續有效地被阻斷，因此通過大大降低潛在疾病的風險和突破來提高療效。

These advantages are well recognized by scientific and clinical experts across both academia and industry. The question that remains is whether MASP-3 inhibition and specifically OMS906 can demonstrate efficacy in any alternative pathway disorder. If it does, then the widely held expectation is that OMS906 will be efficacious across the full scale of alternative pathway-associated diseases and disorders. This is particularly true if we demonstrate efficacy in PNH, which because of the severity of the disease, sets a very high bar for alternative pathway inhibition. But efficacy in any alternative pathway disorder should readily allow a value calculation of the OMS906 program based on predicate alternative pathway drugs in programs such as C3, Factor B and even C5 inhibitors.

這些優勢得到了學術界和工業界科學和臨床專家的充分認可。剩下的問題是 MASP-3 抑制，特別是 OMS906 是否可以證明對任何旁路通路障礙有效。如果確實如此，那麼人們普遍認為 OMS906 將對所有替代途徑相關疾病和病症有效。如果我們證明對 PNH 有效，則尤其如此，因為疾病的嚴重性，為替代途徑抑制設置了非常高的標準。但在任何替代途徑障礙中的療效應該很容易允許根據 C3、B 因子甚至 C5 抑製劑等程序中的謂詞替代途徑藥物計算 OMS906 程序的值。

Should OMS906 demonstrate efficacy, we're confident that the safety, compliance and convenience and efficacy advantages that I described just a minute ago, would significantly differentiate OMS906 from those predicate alternative pathway inhibitors and others in development. Again, based on the science and evidence to date, we believe that MASP-3 is the premier target. And by extension and because of its attributes, OMS906 has the potential to be the premier drug in the alternative pathway market. So we look forward to sharing publicly clinical data from our OMS906 program.

如果 OMS906 證明有效，我們相信我剛才描述的安全性、依從性和便利性和有效性優勢將顯著區分 OMS906 與那些謂詞替代途徑抑製劑和其他正在開發的抑製劑。同樣，根據迄今為止的科學和證據，我們認為 MASP-3 是首要目標。此外，由於其屬性，OMS906 有潛力成為替代途徑市場的首選藥物。因此，我們期待公開分享我們 OMS906 計劃的臨床數據。

Turning now to OMS527, our PDE7 inhibitor program. Discussions continue regarding third-party funding for continued development of OMS527 as a treatment for addictive disorders. As has been widely and frequently broadcast, addiction is an enormous and worsening problem in the U.S. and worldwide. In the U.S. alone, in 2019, tangible measured cost of substance abuse were $0.5 trillion. With intangible costs such as loss of life, injury, reduced quality of life, all of those estimated at a staggering $3.2 trillion annually. With the Centers for Disease Control and Prevention, reporting that 1 in 7 Americans, 12 years of age or older have experienced a substance use disorder.

現在轉向 OMS527，我們的 PDE7 抑製劑項目。關於繼續開發 OMS527 作為成癮性疾病治療的第三方資助的討論仍在繼續。正如廣泛和頻繁廣播的那樣，成癮在美國和世界範圍內是一個巨大且日益惡化的問題。僅在美國，2019 年藥物濫用的有形衡量成本就達到 0.5 萬億美元。加上生命損失、受傷、生活質量下降等無形成本，所有這些估計每年的損失高達 3.2 萬億美元。根據疾病控制和預防中心的報告，每 7 名 12 歲或以上的美國人中就有 1 人患有物質使用障礙。

A therapeutic that could treat the cause of abuse could change the lives of tens of millions of patients just in the U.S. We look forward to securing external funding and moving ahead with further clinical development of OMS527. In addition to the wide field of addiction and compulsion disorders, Omeros also controls broad intellectual property directed to PDE7 inhibition for the treatment of movement disorders.

一種可以治療濫用原因的療法可能會改變美國數千萬患者的生活。我們期待獲得外部資金並繼續推進 OMS527 的進一步臨床開發。除了成癮和強迫症的廣泛領域外，Omeros 還控制著針對 PDE7 抑制治療運動障礙的廣泛知識產權。

With collaborators at Emory University, we're evaluating OMS527 as potential treatment for L-DOPA-induced dyskinesias, or LID. These dyskinesias are crippling, involuntary movements in Parkinson's patient in part and ironically by prolonged treatment with L-DOPA, the most prescribed and the most effective therapy for Parkinson's. More than 10 million patients are living with Parkinson's worldwide and reportedly 50% or more of those treated with L-DOPA suffer from LID. Only one drug, extended-release amantadine is approved for the treatment of LID and it has limited efficacy with multiple significant adverse side effects. Here again, LID represents a large unmet patient need and a substantial market opportunity.

我們正在與埃默里大學的合作者一起評估 OMS527 作為左旋多巴誘發的運動障礙或 LID 的潛在治療方法。具有諷刺意味的是，這些運動障礙在帕金森患者中是嚴重的、無意識的運動，部分原因是長期使用 L-DOPA 治療，L-DOPA 是治療帕金森病最常用和最有效的療法。全世界有超過 1000 萬患者患有帕金森病，據報導，接受左旋多巴治療的患者中有 50% 或更多患有 LID。只有一種藥物，即緩釋金剛烷胺被批准用於治療 LID，它的療效有限且有多種顯著的不良副作用。在這裡，LID 代表著大量未滿足的患者需求和巨大的市場機會。

Data to date in a clinically predictive primate model of LID have been encouraging. We await data from one additional primate, which took longer to develop LID than anticipated by our Emory collaborators. Treatment with our PDE7 inhibitor is underway and data are expected next month. We'll close the update today with our immuno-oncology programs. These are platform programs for both cellular and molecular therapies for cancer, all are derivatives of our work on GPR174, our proprietary target in cancer immunity.

迄今為止，LID 臨床預測靈長類動物模型的數據令人鼓舞。我們等待來自另一隻靈長類動物的數據，這比我們的埃默里合作者預期的要花費更長的時間來開發 LID。我們的 PDE7 抑製劑治療正在進行中，預計下個月會有數據。我們將在今天結束我們的免疫腫瘤學計劃的更新。這些是癌症細胞和分子療法的平台程序，都是我們在 GPR174 上工作的衍生產品，GPR174 是我們在癌症免疫方面的專有目標。

For cellular therapies, we've developed and are evaluating novel approaches for both CAR T and adoptive T-cell therapy. We've identified specific T-cell signaling pathways, which once inhibited, significantly and preferentially enhance the expansion of memory T cells that distinctively recognize and efficiently kill tumor cells.

對於細胞療法，我們已經開發並正在評估 CAR T 和過繼性 T 細胞療法的新方法。我們已經確定了特定的 T 細胞信號通路，這些通路一旦被抑制，就會顯著並優先增強記憶 T 細胞的擴增，這些記憶 T 細胞能夠識別並有效殺死腫瘤細胞。

Our team is validating these novel approaches and establishing a broad (inaudible). We believe that the proprietary cellular technologies could markedly improve response rates for cancer patients, receiving either engineered or native T cell therapies for both liquid and solid tumors. On the molecular front, we have developed novel biologic platforms to target specifically and kill cancer cells. We expect that some of these biologics will function as therapeutic vaccines against a broad range of tumors.

我們的團隊正在驗證這些新穎的方法並建立廣泛的（聽不清）。我們相信專有的細胞技術可以顯著提高癌症患者的反應率，接受針對液體和實體腫瘤的工程或天然 T 細胞療法。在分子方面，我們開發了新的生物平台來特異性靶向並殺死癌細胞。我們預計其中一些生物製劑將作為針對多種腫瘤的治療性疫苗發揮作用。

Successful development of therapeutic cancer vaccines are widely pursued, have proven difficult to achieve with the current industry approaches, inducing only transient and ineffective immune responses. We believe that we've overcome this challenge.

治療性癌症疫苗的成功開發受到廣泛追求，但事實證明，目前的行業方法難以實現，只能誘導短暫且無效的免疫反應。我們相信我們已經克服了這一挑戰。

Having now engineered novel molecules that combine tumor antigens with a potent adjuvant, these combinations show high levels of killing in cancer cells and demonstrate the potential to transform the treatment of both solid tumors and hematological cancers. Here again, we're constructing a broad intellectual property (inaudible) around these multiple immunotherapy platforms.

現在已經設計出將腫瘤抗原與強效佐劑結合的新型分子，這些組合在癌細胞中顯示出高水平的殺傷力，並證明有可能改變實體瘤和血液癌症的治療方法。同樣，我們正在圍繞這些多種免疫治療平台構建廣泛的知識產權（聽不清）。

With that, I'll turn the call over now to Mike Jacobsen, our Chief Accounting Officer, who will go through a more detailed discussion of the financial results for the fourth quarter of the year. Mike?

有了這個，我現在將電話轉給我們的首席會計官 Mike Jacobsen，他將對今年第四季度的財務業績進行更詳細的討論。麥克風？

Thanks, Greg. As Greg discussed, in December of last year, Rayner acquired OMIDRIA and associated business operations. The sale required us to restate our financial statements for all periods into continuing operations and discontinued operations. Our net income for the fourth quarter was $128.7 million or net income of $2.05 share compared to a loss of $17.5 million or $0.28 per share in the third quarter of '22. The fourth quarter includes the $200 million milestone we earned from Rayner in December, which is included in discontinued operations. If we look at just continuing operations, our net loss for the fourth quarter was $0.73 per share compared to a net loss of $0.87 per share in the third quarter, a $14 improvement.

謝謝，格雷格。正如 Greg 所討論的那樣，去年 12 月，Rayner 收購了 OMIDRIA 和相關業務運營。出售要求我們將所有期間的財務報表重述為持續經營和終止經營。我們第四季度的淨收入為 1.287 億美元或每股淨收入 2.05 美元，而 2022 年第三季度虧損 1750 萬美元或每股 0.28 美元。第四季度包括我們在 12 月從 Rayner 獲得的 2 億美元的里程碑，這包括在已終止的業務中。如果我們只看持續經營業務，我們第四季度的淨虧損為每股 0.73 美元，而第三季度的每股淨虧損為 0.87 美元，減少了 14 美元。

At year-end, we had $195 million of cash and investments on hand and $213 million in receivables, all of which we have collected. The $213 million year-end receivable balance includes the $200 milestone payment as well as the OMIDRIA royalties for November and December, which are due 60 days after respective month ends. We, therefore, have approximately $408 million in cash available for operations and debt service when you add the cash and investments together with the receivables.

年底時，我們手頭有 1.95 億美元的現金和投資以及 2.13 億美元的應收賬款，我們已全部收回。 2.13 億美元的年終應收賬款餘額包括 200 美元的里程碑付款以及 11 月和 12 月的 OMIDRIA 特許權使用費，它們將在各自月底後 60 天到期。因此，當您將現金和投資與應收賬款相加時，我們有大約 4.08 億美元的現金可用於運營和償債。

Cost and expenses from continuing operations for the fourth quarter were $40 million, which is a decrease of $10.6 million from the third quarter. The decrease was primarily due to manufacturing commercial narsoplimab drug substance in the third quarter, which we expected given that we do not have FDA approval. As we finalize our path forward for TA-TMA, we continue to gauge our narsoplimab's marketing spend until the timing of FDA approval is clear.

第四季度持續經營成本和費用為 4000 萬美元，比第三季度減少 1060 萬美元。減少主要是由於第三季度生產商業 narsoplimab 原料藥，鑑於我們沒有獲得 FDA 批准，我們預計會出現這種情況。在我們最終確定 TA-TMA 的前進道路時，我們將繼續評估我們的 narsoplimab 的營銷支出，直到 FDA 批准的時間明確為止。

Interest expense for the fourth quarter was $7.9 million compared to $4.9 million in the third quarter. The $3 million increase is due to interest on the DRI agreement, which we entered on September 30 of this year. Now let's look at OMIDRIA royalties. As I've mentioned previously, royalties earned are recorded as a reduction in the OMIDRIA contract royalty asset on our balance sheet. Since the sale of OMIDRIA in December of 2021, we have been receiving royalties of 50% of U.S. net sales of OMIDRIA. Upon the achievement of the $200 million milestone on December 29, 2022, OMIDRIA royalties decreased to 30% of U.S. net sales. The 30% royalty equates to approximately 40% of U.S. OMIDRIA operating profit, considering the OMIDRIA operating expenses we no longer have to pay.

第四季度的利息支出為 790 萬美元，而第三季度為 490 萬美元。 300 萬美元的增加是由於我們在今年 9 月 30 日簽訂的 DRI 協議產生的利息。現在讓我們看看 OMIDRIA 的版稅。正如我之前提到的，所賺取的特許權使用費在我們的資產負債表上記錄為 OMIDRIA 合同特許權使用費資產的減少。自 2021 年 12 月出售 OMIDRIA 以來，我們一直在收取 OMIDRIA 美國淨銷售額的 50% 的特許權使用費。在 2022 年 12 月 29 日達到 2 億美元的里程碑後，OMIDRIA 特許權使用費降至美國淨銷售額的 30%。考慮到我們不再需要支付的 OMIDRIA 運營費用，30% 的特許權使用費相當於美國 OMIDRIA 運營利潤的約 40%。

The 30% royalty rate extends for the duration of the relevant patent terms, which we expect to be at least through 2033. For the fourth quarter, our 50% royalty on Rayner net sales was $17.9 million, on sales of $35.8 million. The $35.8 million is a (inaudible) million increase in net sales over Q3 and establishes a new all-time high for a OMIDRIA quarterly sales. Income from discontinued operations in the fourth quarter includes 4 key components.

30% 的特許權使用費率在相關專利期限內延長，我們預計至少會持續到 2033 年。第四季度，我們對 Rayner 淨銷售額的 50% 特許權使用費為 1790 萬美元，銷售額為 3580 萬美元。 3580 萬美元是第三季度淨銷售額（聽不清）百萬美元的增長，並創下了 OMIDRIA 季度銷售額的歷史新高。第四季度終止經營業務收入包括4個關鍵組成部分。

The $200 million milestone payment, $4.9 million of interest earned on the OMIDRIA contract royalty asset, $26.2 million of expense due to the remeasurement adjustments to the OMIDRIA contract royalty asset, and state income tax expense of $4 million. We do not owe any federal income tax due to the utilization of a portion of our outstanding net operating losses. The remeasurement of the contract royalty asset is primarily due to the reduction of future OMIDRIA royalties when the rate was reduced from 50% to 30% of net sales.

2 億美元的里程碑付款、490 萬美元的 OMIDRIA 合同特許權使用費資產利息、2620 萬美元的 OMIDRIA 合同特許權使用費資產重新計量調整費用，以及 400 萬美元的州所得稅費用。由於使用了我們未清淨經營虧損的一部分，我們不欠任何联邦所得稅。合同特許權使用費資產的重新計量主要是由於當費率從淨銷售額的 50%降至 30%時，未來的 OMIDRIA 特許權使用費減少。

Now let's take a quick look at our first quarter expected results. We expect overall operating costs from continuing operations in the first quarter to remain relatively consistent with the fourth quarter. Interest income should be nearly $3 million, and interest expense for the first quarter should be consistent with the fourth quarter at approximately $8 million. Income from discontinued operations should be in the $7 million to $8 million range.

現在讓我們快速看一下我們第一季度的預期結果。我們預計第一季度持續經營業務的總體運營成本與第四季度保持相對一致。第一季度的利息收入應接近 300 萬美元，利息支出應與第四季度保持一致，約為 800 萬美元。已終止業務的收入應在 700 萬至 800 萬美元之間。

With that, I'll turn the call back over to Greg. Greg?

有了這個，我會把電話轉回給格雷格。格雷格？

Thanks, Mike. Operator, why don't we open the call to questions.

謝謝，邁克。接線員，我們為什麼不打開問題電話。

(Operator Instructions) And our first question comes from Colin Bristow from UBS.

（操作員說明）我們的第一個問題來自瑞銀的 Colin Bristow。

Congrats on all the progress. So on the TMA filing and the regulatory path, I know you anticipate a meeting with the FDA in 2Q. Have you had any additional conversations with the agency or any additional feedback since the last update you provided, which I think was in November? And then with regards to this upcoming FDA meeting, what are the primary questions or points of discussion you're looking to cover? Is it -- since it felt that in last feedback from FDA, there was a sort of fairly prescriptive kind of path to what is required from you to restart the process?

祝賀所有的進步。因此，關於 TMA 備案和監管路徑，我知道您預計在第二季度與 FDA 會面。自從您提供的上次更新（我認為是在 11 月）以來，您是否與該機構進行過任何其他對話或任何其他反饋？然後關於即將召開的 FDA 會議，您希望討論的主要問題或討論要點是什麼？是嗎——因為它覺得在 FDA 的上次反饋中，有一種相當規範的途徑來說明你需要什麼來重啟這個過程？

Colin, thanks for the question. First, we don't discuss specific timing of discussions or details of discussions with FDA. But with respect to your second question, the purpose of the meeting, I think, as we said, is to just confirm and make sure we're all clear on whether what we are proposing as analyses will be acceptable. So this is really to reach agreement with FDA as to what needs to be done, what will suffice with respect to those analyses so that we can deliver to FDA specifically what they need so that we can get this drug approved. I mean, Cathy, do you want to add anything to that?

科林，謝謝你的提問。首先，我們不討論具體的討論時間或與 FDA 討論的細節。但關於你的第二個問題，正如我們所說，我認為會議的目的只是確認並確保我們都清楚我們提出的分析建議是否可以接受。因此，這實際上是為了與 FDA 就需要做什麼達成協議，這些分析足以滿足我們的需求，以便我們可以向 FDA 提供他們具體需要的東西，以便我們可以批准這種藥物。我的意思是，凱茜，你想補充什麼嗎？

No, I think that pretty much covers that. As Greg said, we will be working with FDA to go over our proposal based on the feedback that we've received to date. And we want to make sure that what's in our resubmission is what's needed to approve the drug.

不，我認為這幾乎涵蓋了這一點。正如 Greg 所說，我們將與 FDA 合作，根據我們迄今為止收到的反饋來審查我們的提案。我們希望確保我們重新提交的內容是批准該藥物所需的內容。

And our next question comes from Steve Brozak from WBB Securities.

我們的下一個問題來自 WBB Securities 的 Steve Brozak。

Just one quick one. Can you go into and give us much detail on your diagnostic collaboration with Cambridge and what can you tell us about what kind of data you're seeing there? And what are the ramifications from that? And I'll jump back in the queue.

只是一個快速的。您能否詳細介紹一下您與劍橋的診斷合作以及您能告訴我們您在那裡看到的數據類型？這會產生什麼後果？我會跳回到隊列中。

Yes. We'll be publishing more data, Steve, coming out of Cambridge, so I don't want to preempt that. But with respect to the diagnostics specifically, what we have identified is a pattern of complement factor changes that occur with severe acute COVID and even moderate COVID but hospitalized COVID patients that specifically link to the lectin pathway. And we are in discussions with government agencies around. That panel of assets that we are working through. This may also have applicability to long COVID (inaudible), but it is, I think, currently premature to make any definitive statements about that.

是的。我們將發布更多來自劍橋的數據，史蒂夫，所以我不想搶占先機。但就具體的診斷而言，我們已經確定了一種補體因子變化模式，這種模式發生在重症急性 COVID 甚至中度 COVID 但住院的 COVID 患者身上，這些患者與凝集素途徑特別相關。我們正在與各地的政府機構進行討論。我們正在處理的資產面板。這可能也適用於長 COVID（聽不清），但我認為，目前就此做出任何明確聲明還為時過早。

And our next question comes from Greg Harrison from Bank of America.

我們的下一個問題來自美國銀行的 Greg Harrison。

It's Mary Kate on for Greg. Congrats with the milestone payment. I guess looking at the narsoplimab program here in IgAN and given the Phase III data expected, what are your commercial expectations for narsoplimab, if approved in this indication?

這是瑪麗凱特為格雷格。祝賀里程碑付款。我想看看 IgAN 中的 narsoplimab 項目，並考慮到預期的 III 期數據，如果在該適應症中獲得批准，您對 narsoplimab 的商業期望是什麼？

Well, we think the opportunities for narsoplimab is a lot. As I said, the IgAN market is a large market. It's a multibillion-dollar opportunity as you know. And what's been approved as been in orally -- orally available steroid, one that works primarily within the gut. And an agent that is another approach to blood pressure control. But what we're talking about with narsoplimab specifically, is an anti-complement agent. And we think the utility of that could be substantial, particularly in patients with high proteinuria or patients with high levels of protein spillage in the urine. And when I say that, I mean those patients somewhat arbitrarily, but those patients who have 24-hour urine proteins of 2 grams or more per day.

嗯，我們認為 narsoplimab 的機會很多。正如我所說，IgAN 市場是一個很大的市場。如您所知，這是一個價值數十億美元的機會。什麼被批准為口服 - 口服類固醇，一種主要在腸道內起作用的類固醇。還有一種藥物是另一種控制血壓的方法。但我們具體談論的是 narsoplimab，是一種抗補體藥物。我們認為它的效用可能是巨大的，特別是對於高蛋白尿患者或尿液中蛋白質溢出水平高的患者。當我這麼說時，我指的是那些病人，但那些病人每天 24 小時尿蛋白為 2 克或更多。

We think that there is a very large opportunity for the treatment of those patients as well as those with lesser degrees of proteinuria, and we think that certainly, there's a need for complement inhibition and specifically lectin pathway inhibition. As I think we've discussed before, lectin pathway inhibition is important, not only at the glomerulus but also in the tubular endothelium. And as you know, that is where all end-stage proteinuric renal diseases pass. So really, if you can affect the tubular interstitial, you are effectively treating or potentially treating all proteinuric renal diseases. So we think the opportunity is very large.

我們認為這些患者以及蛋白尿程度較輕的患者有很大的治療機會，我們認為當然需要補體抑制，特別是凝集素途徑抑制。正如我認為我們之前討論過的那樣，凝集素通路抑制很重要，不僅在腎小球中而且在腎小管內皮中也是如此。如您所知，那是所有終末期蛋白尿性腎病都會過去的地方。所以真的，如果你能影響腎小管間質，你就能有效治療或潛在治療所有蛋白尿性腎病。所以我們認為機會非常大。

And one moment for our next question. And our next question comes from Brandon Folkes from Cantor.

請稍等一下我們的下一個問題。我們的下一個問題來自 Cantor 的 Brandon Folkes。

I just want to come back to that first question around narsoplimab and the TA-TMA meeting with the FDA. Is there a way to contextualize sort of the level of work you've done ahead of this meeting? And what I mean by that is if you do have a meeting (inaudible) the approach to sort of addressing the CRL, is this something we should expect a submission relatively shortly thereafter? Or is it more just going to agree on an approach and then it could be a couple of months or quarters of work behind that?

我只想回到關於 narsoplimab 和與 FDA 的 TA-TMA 會議的第一個問題。有沒有一種方法可以將您在這次會議之前所做的工作水平進行背景化？我的意思是，如果您確實召開了會議（聽不清）來解決 CRL，那麼我們是否應該期望此後相對較短的時間提交？還是只是就一種方法達成一致，然後可能需要幾個月或幾個季度的工作？

Yes. Let me first say that in the prepared comments, I think I made it clear that we've identified and now can access the sources of information that we need or we believe we need them to address FDA's concerns. So I think it would be premature though on the front-end of that FDA meeting to talk about how long it will take us to satisfy FDA. Let's get through the meeting first, and then I think we can speak more definitively about that. Otherwise, it's pure speculation. But I think part of your question is what have we been doing. And certainly, in the meantime, since our last public statement around this, there's been a tremendous amount of work being done.

是的。我首先要說的是，在準備好的評論中，我想我已經明確表示我們已經確定並且現在可以訪問我們需要的信息來源，或者我們認為我們需要它們來解決 FDA 的擔憂。因此，我認為在 FDA 會議的前端討論我們需要多長時間才能讓 FDA 滿意還為時過早。讓我們先完成會議，然後我想我們可以更明確地討論這個問題。否則，這純粹是猜測。但我認為你的部分問題是我們一直在做什麼。當然，與此同時，自從我們上次就此發表公開聲明以來，已經開展了大量工作。

One, in identifying those sources of information; two, obtaining access to those. Certainly, we aren't running analyses upfront because we want to make sure that we with FDA agree on one analysis we're going to run. But then I think, running them. If we're all in agreement on what we're doing, should not be a lengthy process. But let me see, again, I'll ask Cathy and/or Steve, if you have any other comments on this.

第一，確定那些信息來源；二，獲得訪問權限。當然，我們不會預先進行分析，因為我們想確保我們與 FDA 就我們將要進行的一項分析達成一致。但後來我想，運行它們。如果我們都同意我們正在做的事情，那應該不會是一個漫長的過程。但是讓我再想想，如果你們對此有任何其他意見，我會問 Cathy 和/或 Steve。

Thanks, Greg. Yes, we have been working quite a bit since the last update. And also, as Greg mentioned earlier, we're working with our real regulatory consultants and working closely with them to make sure that we're providing the best information that we can and trying to set ourselves up for success.

謝謝，格雷格。是的，自上次更新以來我們一直在努力。而且，正如 Greg 之前提到的，我們正在與我們真正的監管顧問合作，並與他們密切合作，以確保我們提供我們所能提供的最佳信息，並努力為成功做好準備。

Great. That's very helpful. One more, if I may. You've done a tremendous job shoring up the balance sheet. And I think the commentary in the press release was sort of funded through at least 2025. Can you just give us a sense of which programs you include in that runway? Is that your sort of the whole breadth of the pipeline? Or just how you're thinking about kind of maybe focusing on some? Anything you can do to speed up these trials just given your strong balance sheet?

偉大的。這很有幫助。如果可以的話，再來一張。你在支撐資產負債表方面做得非常出色。而且我認為新聞稿中的評論至少在 2025 年得到了資助。你能告訴我們你在跑道上包括了哪些項目嗎？這是你的整個管道嗎？或者你是如何考慮可能專注於某些方面的？鑑於您強大的資產負債表，您可以做些什麼來加快這些試驗？

Yes. Sure. Thanks again, Brandon. Well, certainly, our focus on narsoplimab is a high priority. Similarly, our focus on 906, I think as we made clear, we began enrolling last December, we began dosing in January. We are pushing hard on that program. We think that that's going to be a very important program not only for us, but for patients with alternative pathway disorders. So that's a priority. When we kind of march down, you look at OMS1029, which is our backup to narsoplimab, that program is sailing through. Everything looks good there. Similarly, the small molecule program, let's see if we select. If we select a development candidate next quarter, we'll be looking at advancing that.

是的。當然。再次感謝，布蘭登。嗯，當然，我們對 narsoplimab 的關注是重中之重。同樣，我們對 906 的關注，我認為正如我們明確指出的那樣，我們去年 12 月開始註冊，我們在 1 月開始給藥。我們正在大力推進該計劃。我們認為這將是一個非常重要的計劃，不僅對我們，而且對患有替代途徑障礙的患者。所以這是一個優先事項。當我們走下坡路時，您會看到 OMS1029，這是我們對 narsoplimab 的備份，該程序正在順利通過。那裡的一切看起來都很好。同樣的，小分子程序，看我們選不選。如果我們在下個季度選擇開發候選人，我們將考慮推進它。

But as you know, that's really a lot of pre-IND work, and that's pretty contained with respect to costs. 527, we're looking for external funding. And once we have that, assuming we get it, we expect that to fund clinical work and further development. If we turn over a positive card on the levodopa-induced dyskinesias, that's another area that we would consider a clinical trial. But again, that would be limited in size first. It would be proof of concept, so costs would be pretty contained.

但正如你所知，這確實是很多 IND 前的工作，而且在成本方面非常有限。 527，我們正在尋找外部資金。一旦我們有了它，假設我們得到它，我們希望它能為臨床工作和進一步發展提供資金。如果我們在左旋多巴引起的運動障礙方面取得了積極的成績，那將是我們考慮進行臨床試驗的另一個領域。但同樣，這將首先限制大小。這將是概念驗證，因此成本將得到很好的控制。

Then when you look at our immuno-oncology programs, those are preclinical, but we hope to, over the coming months, be able to start to move one or more of them into IND-enabling work, which, again, those costs are pretty contained. So I think I've answered your question, but let me be very specific about it.

然後，當您查看我們的免疫腫瘤學項目時，這些項目是臨床前的，但我們希望在未來幾個月內能夠開始將其中的一個或多個項目轉移到支持 IND 的工作中，同樣，這些成本非常高包含。所以我想我已經回答了你的問題，但讓我非常具體地說明一下。

All of the programs I've just mentioned are laid out there for the budget and fall within what we're doing all the way well into 2025. Again, based on where we see success, we can always push the hammer down even more on those specific programs. But we are looking for additional revenue beyond OMIDRIA coming in and continuing to drive further development of the pipeline.

我剛才提到的所有計劃都列在預算中，並且在我們一直到 2025 年所做的工作範圍內。同樣，根據我們看到的成功，我們總是可以進一步推動那些具體的程序。但我們正在尋找 OMIDRIA 以外的額外收入，並繼續推動管道的進一步發展。

And our next question comes from Serge Belanger from Needham & Company.

我們的下一個問題來自 Needham & Company 的 Serge Belanger。

A couple of questions for us. The first one on the ARTEMIS Phase III trial that I think is expected to read out in the third quarter of this year. Greg, I think you mentioned that you expect this trial to support the BLA filing. Just curious when you would expect the BLA filing, assuming that we get positive results in the third quarter? What kind of other data would you need to complete that filing?

我們有幾個問題。關於 ARTEMIS III 期試驗的第一個，我認為預計將在今年第三季度宣讀。 Greg，我想你提到過你希望這個試驗能夠支持 BLA 申請。只是好奇，假設我們在第三季度取得積極成果，您什麼時候會收到 BLA 申請？您需要什麼樣的其他數據來完成該備案？

Yes. Remember what we -- thanks, Serge. What we're going to be looking at as the primary endpoint is proteinuria data. So if those data are positive, and we hope and frankly, expect that they will be, but we need to see those data. When we see those, assuming they are positive, we would be moving quickly to put those data into the BLA. The safety data, all of the other components of the BLA are already being pulled together. So I think on timing, conservatively, I would look at a 4- to 6-month time frame from data to submission. But let me look to Steve and to Cathy to see if there are any other comments.

是的。記住我們——謝謝，Serge。作為主要終點，我們將要關注的是蛋白尿數據。因此，如果這些數據是積極的，我們希望並且坦率地說，期望它們會是積極的，但我們需要看到這些數據。當我們看到這些時，假設它們是積極的，我們將迅速採取行動將這些數據放入 BLA 中。安全數據以及 BLA 的所有其他組成部分都已經整合在一起。所以我認為在時間上，保守地說，我會考慮從數據到提交的 4 到 6 個月的時間框架。但是讓我看看史蒂夫和凱茜，看看是否還有其他意見。

No. I think we've identified everything that go in the BLA and have plans together at all. So try to put in quickly.

不，我認為我們已經確定了 BLA 中的所有內容，並製定了共同計劃。所以嘗試快速投入。

The top line data -- once we have the top line data, that kind of what triggers the pre-BLA meeting with FDA. And so OMIDRIA, I concur with the timing that Greg has proposed.

頂線數據——一旦我們有了頂線數據，就會觸發與 FDA 的 BLA 前會議。所以 OMIDRIA，我同意 Greg 提議的時間安排。

So there would be no issues in having 2 separate BLA filings, one for TA-TMA and another one for IgA nephropathy?

那麼，有 2 份單獨的 BLA 申請，一份針對 TA-TMA，另一份針對 IgA 腎病，不會有問題嗎？

Yes. You're talking about, I think, resource allocation and workload. We -- remember that we're looking for Q3 data on IgA. So we would expect that they would blend well. But Steve, this is partly your group as well. So why don't you address this?

是的。我認為你在談論資源分配和工作量。我們——請記住，我們正在尋找 IgA 的第三季度數據。所以我們希望它們能很好地融合。但是史蒂夫，這部分也是你的團隊。那你為什麼不解決這個問題？

We've identified resources we need so they can run in parallel, and there's overlap between the 2 as well. So I wouldn't see any one blocking the other.

我們已經確定了我們需要的資源，因此它們可以並行運行，並且兩者之間也有重疊。所以我不會看到任何人阻止另一個人。

And then a couple on OMIDRIA. Now that the you've gotten the milestone payment and the royalty rates knocked us down from 50% to 30%. Does that have any implication for the DRI royalty agreements?

然後是 OMIDRIA 上的一對夫婦。現在您已經獲得了里程碑式的付款，而且特許權使用費率將我們從 50% 降低到了 30%。這對 DRI 特許權使用費協議有任何影響嗎？

Yes. Let me just answer that first. No, I think our agreement with DRI, frankly anticipated. Our success in achieving a milestone and DRI was and is very aware of that 30%. But we also -- all of us, I think DRI included expect overall sales to continue to increase with the legislative successes that have been achieved for all non-opioid pain management drugs, and also as we start to focus on, I hope, Med Advantage as well.

是的。讓我先回答一下。不，我認為我們與 DRI 的協議坦率地預料到了。我們成功地實現了一個里程碑，DRI 曾經並且非常清楚這 30%。但我們也——我們所有人，我認為包括 DRI 在內的所有人都希望隨著所有非阿片類鎮痛藥物在立法上取得的成功，以及我們開始關注 Med 時，整體銷售額將繼續增長優勢也一樣。

And the last question, your partner Rayner now has a lot more visibility on the overall coverage of OMIDRIA. Do you expect they'll increase your commercial support for the product going forward?

最後一個問題，您的合作夥伴 Rayner 現在對 OMIDRIA 的整體覆蓋範圍有了更多的了解。您預計他們會增加您對未來產品的商業支持嗎？

That's a great question for Rayner. I would expect they would. You now have secure long-term separate payment in the ASC. You also have HOPD payment beginning in 2025, January 1, 2025. That's another 20% of the market. And so I would expect that they would be capitalizing on the broad support of the product and ramping up to do the same. But let me see, Mike, any comments on that?

這對雷納來說是一個很好的問題。我希望他們會。您現在可以在 ASC 中獲得安全的長期單獨付款。您還有從 2025 年開始的 HOPD 付款，即 2025 年 1 月 1 日。那是另外 20% 的市場。因此，我預計他們會利用該產品的廣泛支持並加大力度做同樣的事情。但是讓我看看，邁克，對此有何評論？

No. I think Rayner's obviously looking at it. They are very aware that we've gotten the milestone and preserve the long-term payment. And the HOPD side increases the potential there as well. So I think Rayner is really aware of the opportunities they have (inaudible).

不，我認為 Rayner 顯然在看它。他們非常清楚我們已經達到了里程碑並保留了長期付款。 HOPD 方面也增加了那裡的潛力。所以我認為雷納真的意識到他們擁有的機會（聽不清）。

There's a tremendous opportunity as well on the Med Advantage side. And I think I'm sure that Rayner realizes that and is focused as they should be on expanding Med Advantage payments, not just coverage, but payment. And there are ways, I think, that the congressional action can carry through, and we've looked at that as well, that, that can carry through to Med Advantage and help educate the Med Advantage payers, which often are the same payers as commercial as to why they should be separately paying for OMIDRIA in the same way that Congress has mandated CMS did.

Med Advantage 方面也有巨大的機會。而且我認為我確信 Rayner 意識到了這一點，並且他們應該專注於擴大 Med Advantage 支付，而不僅僅是覆蓋範圍，而是支付。我認為，國會的行動可以通過多種方式進行，我們也研究過，可以貫徹到 Med Advantage 並幫助教育 Med Advantage 付款人，這些付款人通常與為什麼他們應該像國會要求 CMS 那樣單獨支付 OMIDRIA 的商業費用。

And I am showing no further questions. I would now like to turn the call back over to Dr. Demopulos for closing remarks.

我不再提出更多問題。我現在想把電話轉回給 Demopulos 博士作結束語。

All right. Thank you very much, operator. Once again, thank you, everyone, for joining us today. As I think you can see, and as I think we were just discussing with some of the analysts, Omeros is well positioned financially to develop the deep pipeline of assets that we control. So with multiple and frequent near and midterm milestone events, the financial strength that Omeros now has really despite the tumultuous times globally and macroeconomically, will allow us to remain focused throughout 2023 and beyond on really bringing life-saving products to patients and value to our shareholders. And we'll continue to keep you updated on our progress. As always, we appreciate your continued support. Have a good evening.

好的。非常感謝你，接線員。再次感謝大家今天加入我們。正如我想你所看到的，正如我認為我們剛剛與一些分析師討論的那樣，Omeros 在財務上處於有利地位，可以開發我們控制的深層資產管道。因此，隨著近期和中期里程碑事件的頻繁發生，儘管全球和宏觀經濟處於動盪時期，但 Omeros 現在真正擁有的財務實力將使我們能夠在整個 2023 年及以後繼續專注於真正為患者提供挽救生命的產品並為我們創造價值股東。我們將繼續讓您了解我們的最新進展。一如既往，我們感謝您一直以來的支持。晚上好。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。