Kiniksa Pharmaceuticals International PLC (KNSA) 2024 Q1 法說會逐字稿

Good day and thank you for standing by. And welcome to Kiniksa Pharmaceuticals first quarter 2024 earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Rachel Frank, Head of Investor Relations. Please go ahead.

美好的一天，感謝您的支持。歡迎參加 Kiniksa Pharmaceuticals 2024 年第一季財報電話會議。（操作員指示）請注意，今天的會議正在錄製中。現在，我想將會議交給今天的發言人、投資者關係主管雷切爾·弗蘭克 (Rachel Frank)。請繼續。

Thank you, operator. Good morning, everyone. And thank you for joining Kiniksa's call to discuss our first quarter 2024 financial results and recent portfolio execution. A press release highlighting these results can be found on our website under the Investors section.

謝謝你，接線生。大家，早安。感謝您參加 Kiniksa 的電話會議，討論我們 2024 年第一季的財務表現和最近的投資組合執行情況。您可以在我們網站的「投資者」部分找到強調這些結果的新聞稿。

As for the agenda. Our Chief Executive Officer, Sanj K. Patel, will start with an introduction. Ross Moat, our Chief Commercial Officer, will provide an update on our ARCALYST commercial execution. John Paolini, our Chief Medical Officer, will provide an Abiprubart program review. And Mark Ragosa, our Chief Financial Officer, will review our first quarter 2024 financial results. And finally, Sanj will return for closing remarks and to kick off the Q&A session for which Eben Tessari, our Chief Operating Officer, will also be on the line.

至於議程。我們的執行長 Sanj K. Patel 將首先進行介紹。我們的商務長 Ross Moat 將提供 ARCALYST 商業執行的最新資訊。我們的首席醫療官 John Paolini 將提供 Abiprubart 計劃審查。我們的財務長 Mark Ragosa 將審查我們 2024 年第一季的財務表現。最後，Sanj 將返回進行閉幕致辭並開始問答環節，我們的首席營運長 Eben Tessari 也將參與其中。

Before getting started, please note that we will be making forward-looking statements today that are subject to risks and uncertainties and may cause actual results to differ materially from these statements. Our review of such statements and risk factors can be found on this slide as well as under the caption Risk Factors contained in our SEC filings. These statements speak only as of the date of this presentation. And we undertake no obligation to update such statements except as required by law.

在開始之前，請注意，我們今天將做出前瞻性聲明，這些聲明存在風險和不確定性，可能導致實際結果與這些聲明有重大差異。我們對此類聲明和風險因素的審查可以在這張投影片以及我們向 SEC 文件中包含的風險因素標題下找到。這些陳述僅代表本簡報發布之日的情況。除法律要求外，我們不承擔更新此類聲明的義務。

And with that, I will turn it over to Sanj.

有了這個，我會把它交給 Sanj。

Thanks, Rachel. And good morning, everyone. We are very encouraged with the ARCALYST commercial progress we continued to build upon the ARCALYST performance this quarter, marked by reaching an increasing number of recurrent pericarditis patients and growing to a net product revenue of $78.9 million.

謝謝，雷切爾。大家早安。我們對 ARCALYST 商業進展感到非常鼓舞，本季我們繼續在 ARCALYST 業績的基礎上取得進展，其特點是覆蓋越來越多的複發性心包膜炎患者，產品淨收入增長到 7890 萬美元。

We continue to see strength across key commercial drivers including growing prescriber adoption and high physician and patient satisfaction, which is been supported by our focus on frequent engagement with the existing and potential prescribers.

我們繼續看到關鍵商業驅動因素的優勢，包括處方者採用率的不斷提高以及醫生和患者的高滿意度，這得益於我們注重與現有和潛在處方者的頻繁接觸。

Importantly, we're also seeing an expanding utilization of ARCALYST as a steroid-sparing therapy for patients suffering from recurrent pericarditis. Looking to the year ahead, we now expect ARCALYST full year sales to be between $370 million to $390 million and this would represent 63% year-over-year growth at the midpoint.

重要的是，我們也看到 ARCALYST 越來越多地被用作復發性心包膜炎患者的類固醇節約療法。展望未來一年，我們現在預計 ARCALYST 全年銷售額將在 3.7 億美元至 3.9 億美元之間，這意味著中位數年增 63%。

In terms of our pipeline, we recently announced plans to initiate a Phase 2b trial with Abiprubart in Sjögren’s Disease. This is a debilitating disorder with no current FDA approved therapies and we believe Abiprubart has the potential to provide meaningful benefit to patients. Dr. John Paolini, our Chief Medical Officer will provide additional details about our planned Phase 2b trial, which is expected to initiate in the second half of this year.

就我們的產品線而言，我們最近宣布計劃啟動 Abiprubart 治療乾燥症的 2b 期試驗。這是一種使人衰弱的疾病，目前 FDA 尚未獲得批准的治療方法，我們相信 Abiprubart 有潛力為患者提供有意義的益處。我們的首席醫療官 John Paolini 博士將提供有關我們計劃的 2b 期試驗的更多詳細信息，該試驗預計將於今年下半年啟動。

And with that, I'll now turn it over to Ross to review our commercial execution.

現在，我將把它交給羅斯來審查我們的商業執行。

Thank you, Sanj. I want to start by highlighting that the end of Q1 marks the third anniversary of the approval of ARCALYST in recurrent pericarditis and we continue to deliver robust growth and be excited by the future of this franchise.

謝謝你，桑吉。首先，我想強調，第一季末標誌著 ARCALYST 治療復發性心包膜炎獲批三週年，我們將繼續實現強勁成長，並對該系列產品的未來感到興奮。

In Q1, ARCALYST net revenue was $78.9 million, which is an 85% growth versus Q1 of 2023. This revenue growth also represents strong quarter-on-quarter growth especially against the backdrop of Q1 specialty industry headwinds and a gross to net of 13.5%, which was predominantly due to co-pay resets. The net revenue growth was in part due to an acceleration in the number of prescribers.

第一季度，ARCALYST 淨收入為 7,890 萬美元，與 2023 年第一季相比成長 85%。這一收入成長也代表了強勁的季度環比增長，尤其是在第一季專業行業逆風和毛淨值增長 13.5%（主要是由於自付費用重置）的背景下。淨收入成長的部分原因是處方藥人數的增加。

Total prescribers of ARCALYST since launch grew to approximately 2,000 at the end of Q1 making it the largest quarter-on-quarter growth since launch. Additionally, we continued to observe robust underlying fundamentals across our commercialization including greater than 90% payer approval of completed cases, a total average duration of therapy of 23 months and high physician and patient satisfaction with ARCALYST.

自推出以來，ARCALYST 的處方者總數在第一季末增至約 2,000 名，這是自推出以來最大的季度環比增長。此外，我們在整個商業化過程中繼續觀察到穩健的基本面，包括超過90% 的付款人對已完成病例的批准、總平均治療持續時間為23 個月以及醫生和患者對ARCALYST 的高度滿意度。

Recurrent pericarditis is a debilitating rare flaring disease where patients are widely dispersed across the country. Since ARCALYST approval as the first and only FDA approved drug for the disease, we've been making robust inroads through our field teams and our marketing strategy to educate both physicians and patients on the disease.

復發性心包膜炎是一種使人衰弱的罕見突發疾病，患者廣泛分佈在全國各地。自從ARCALYST 成為FDA 批准的第一個也是唯一一個批准用於治療該疾病的藥物以來，我們一直在透過我們的現場團隊和行銷策略取得強有力的進展，以向醫生和患者提供有關該疾病的教育。

We've seen increasing acknowledgement that interleukin-1 Alpha and Beta are the underlying drivers of the disease. And once patients become recurrent, they require a targeted treatment to address the disease directly. As a result, the total prescriber base has continued to grow every quarter since launch and as physicians gain positive prescribing experience, and witness the impact ARCALYST can have on their patients, more and more physicians are becoming repeat prescribers.

我們越來越多地認識到白細胞介素 1 Alpha 和 Beta 是該疾病的根本驅動因素。一旦患者復發，他們就需要有針對性的治療來直接解決疾病。因此，自推出以來，處方者總數每季都在持續成長，隨著醫生獲得積極的處方經驗，並見證 ARCALYST 對患者的影響，越來越多的醫生正在成為重複處方者。

In fact, in Q1, greater than 40% of all new prescriptions were written by healthcare professionals who are repeat prescribers. We are making solid progress towards our ambition of ARCALYST becoming the standard of care in recurrent pericarditis.

事實上，在第一季度，超過 40% 的新處方是由重複開處方的醫療保健專業人員開立的。我們正在朝著 ARCALYST 成為復發性心包膜炎護理標準的目標取得堅實進展。

For the next slide, I’ll hand the call over to Dr. John Paolini, our Chief Medical Officer, to share some of the latest information coming from our RESONANCE Registry, describing the evolution in recurrent pericarditis management since launch. John?

在下一張幻燈片中，我將把電話轉給我們的首席醫療官 John Paolini 博士，分享來自我們 RESONANCE 註冊中心的一些最新信息，描述自推出以來復發性心包炎治療的進展。約翰？

Thanks, Ross. We're very excited to share some insights we’ve gained from our RESONANCE Registry and that we've recently shared at the American College of Cardiology. The data show a paradigm shift in RP management amongst cardiologists at the 21 participating centers in the US, away from the steroid-based 2015 European Society of Cardiology guidelines and towards a steroid-sparing approach using IL-1 pathway inhibition.

謝謝，羅斯。我們非常高興能夠分享我們從 RESONANCE 登記處獲得的以及我們最近在美國心臟病學會分享的一些見解。數據顯示，美國 21 個參與中心的心臟科醫生在 RP 管理方面發生了範式轉變，遠離基於類固醇的 2015 年歐洲心臟病學會指南，轉向使用 IL-1 通路抑制的類固醇節約方法。

Amongst these registry patients with a median three-year RP disease duration, IL-1 pathway inhibition use increased to 25% of medication patient years in 2023 with ARCALYST use driving this pattern. Also, amongst patients who had failed Aspirin NSAIDs and Colchicine and intensified treatment, the proportion of patients who transitioned to rilonacept has increased year-on-year with commensurately fewer patients transitioning to corticosteroids such that by 2023, 65% of transitions were made to ARCALYST with a two to one preference over corticosteroids. These data affirm the evidence-based adoption and growth of the steroid-sparing paradigm by RP-focused cardiologists.

在這些中位 RP 病程為三年的登記患者中，IL-1 通路抑制藥物的使用量到 2023 年將增加至藥物患者年數的 25%，ARCALYST 的使用推動了這種模式。此外，在阿斯匹靈非類固醇抗發炎藥和秋水仙鹼以及強化治療失敗的患者中，轉用利洛西普的患者比例逐年增加，轉用皮質類固醇的患者相應減少，因此到2023 年，65%的患者轉用ARCALYST與皮質類固醇有二比一的偏好。這些數據證實了以 RP 為重點的心臟科醫師基於證據的採用和發展類固醇節約範例。

Back to you, Ross.

回到你身上，羅斯。

Thanks, John. These compelling new data from pericarditis-focused cardiologists mirror our promotional messaging that recurrent pericarditis is an Interleukin-1 Alpha and Beta-driven disease. ARCALYST addresses the root cause of the disease and should be utilized prior to corticosteroids.

謝謝，約翰。這些來自專注於心包膜炎的心臟病專家的令人信服的新數據反映了我們的宣傳訊息，即復發性心包炎是一種白細胞介素 1 Alpha 和 Beta 驅動的疾病。ARCALYST 解決了疾病的根本原因，應在皮質類固醇之前使用。

Our Q1 net revenue growth signifies strong underlying business fundamentals and with only 9% of the target population addressed as of the end of 2023 we have a significant opportunity ahead.

我們第一季的淨收入成長顯示了強勁的業務基本面，截至 2023 年底，只有 9% 的目標人群得到滿足，我們面臨著巨大的機會。

In Q1, we delivered robust growth that broke through the typical Q1 industry headwinds. As such, we're pleased to increase our revenue guidance for 2024 from $360 million to $380 million to $370 million to $390 million.

在第一季度，我們實現了強勁的成長，突破了第一季典型的產業阻力。因此，我們很高興將 2024 年的營收指引從 3.6 億美元至 3.8 億美元提高到 3.7 億美元至 3.9 億美元。

And with that, I hand it back to John to discuss Abiprubart. John?

說完，我把它交還給約翰討論阿比魯巴特。約翰？

Thanks, Ross. As Sanj mentioned, and as we outlined in our previous announcement, several factors contributed to our decision to move forward with Abiprubart in Sjögren’s Disease. Importantly, Sjögren’s Disease is a debilitating disease currently with no FDA approved therapies.

謝謝，羅斯。正如 Sanj 所提到的，以及我們在先前的公告中概述的，有幾個因素促使我們決定繼續使用 Abiprubart 治療乾燥症。重要的是，乾燥症是一種使人衰弱的疾病，目前尚無 FDA 批准的治療方法。

Second, there are substantial external proof-of-concepts that inhibition of the CD40-CD154 co-stimulatory interaction could be an efficacious therapeutic approach for Sjögren’s Disease.

其次，有大量的外部概念證明，抑制 CD40-CD154 共刺激交互作用可能是乾燥症的有效治療方法。

Additionally, the totality of the Phase 2 Abiprubart data we've generated including highly statistically significant reductions in rheumatoid factor of approximately 40% across all three dose regimens demonstrate clear biological activity of the molecule and thus bolster our confidence in the potential efficacy in Sjögren’s Disease in Phase 2b the with either biweekly or monthly subcutaneous dosing.

此外，我們產生的第2 期Abiprubart 數據的整體，包括所有三種劑量方案中類風濕因子約40% 的高度統計顯著性降低，證明了該分子的明顯生物活性，從而增強了我們對Sjö¶潛在功效的信心格林氏症處於 2b 期，每兩週或每月皮下給藥。

Understanding that there are other assets in development for Sjögren’s Disease, we believe Abiprubart has the potential to demonstrate comparable efficacy, but with a more convenient route of administration, a profile which could potentially represent a compelling and differentiated option for patients.

了解乾燥症的其他資產正在開發中，我們相信 Abiprubart 有潛力表現出可比較的療效，但具有更方便的給藥途徑，這一特徵可能為患者提供令人信服的差異化選擇。

With that in mind, we are planning to initiate in the second half of 2024, a randomized double-blind placebo-controlled Phase 2b trial designed to evaluate the treatment response of chronic subcutaneous administration of Abiprubart in patients with Sjögren’s Disease. The intended trial design begins with a placebo-controlled portion that will randomize approximately 201 patients in a one-to-one-to-one ratio to receive Abiprubart 400 milligrams subcutaneously biweekly, 400 milligrams subcutaneously monthly, or placebo over a period of 24 weeks. The primary efficacy endpoint will be changed from baseline versus placebo in EULAR Disease Activity Index called ESSDAI at week 24.

考慮到這一點，我們計劃在 2024 年下半年啟動一項隨機雙盲安慰劑對照 2b 期試驗，旨在評估乾燥症患者長期皮下注射 Abiprubart 的治療反應。預期的試驗設計從安慰劑對照部分開始，將約 201 名患者以一對一的比例隨機分組，在 24 週內每兩週皮下注射 400 毫克、每月皮下注射 400 毫克或安慰劑。與安慰劑相比，第 24 週時 EULAR 疾病活動指數（稱為 ESSDAI）的主要療效終點將會改變。

Subsequently, we plan for patients to enter a long-term extension in which all participants will receive active treatment for an additional 24 weeks.

隨後，我們計劃讓患者進入長期延長期，所有參與者都將接受額外 24 週的積極治療。

I will now turn the call over to Mark to discuss the first quarter financials. Mark?

我現在將把電話轉給馬克，討論第一季的財務狀況。標記？

Thanks, John. Our detailed first quarter 2024 financial results can be found in the press release we issued earlier this morning. Over the next couple of minutes, I'd like to call your attention to a few items on this slide.

謝謝，約翰。我們詳細的 2024 年第一季財務業績可以在我們今天早上發布的新聞稿中找到。在接下來的幾分鐘內，我想提請您注意這張投影片上的一些項目。

First, total revenue in the first quarter of 2024 was $79.9 million, driven by ARCALYST net product revenue, which grew 85% year-over-year to $78.9 million.

首先，在 ARCALYST 淨產品收入的推動下，2024 年第一季的總營收為 7,990 萬美元，年增 85% 至 7,890 萬美元。

Second, ARCALYST collaboration operating profit in the first quarter grew 142% year-over-year to $40.2 million and primarily drove collaboration expenses of $20.8 million.

其次，第一季 ARCALYST 協作營運利潤年增 142% 至 4,020 萬美元，主要推動了協作支出 2,080 萬美元。

Third, higher cost of goods sold and collaboration expenses, both of which are largely driven by ARCALYST revenue growth, as well as the advancement of Abiprubart development and investment related to ARCALYST commercialization drove year-over-year operating expense growth in the first quarter.

第三，較高的銷售成本和合作費用，這兩者主要是由 ARCALYST 收入增長推動的，以及與 ARCALYST 商業化相關的 Abiprubart 開發和投資的推進推動了第一季度營運費用的同比增長。

Fourth, net loss in the first quarter was $17.7 million, compared to $12.3 million in the first quarter of last year. And lastly, our cash balance at the end of the first quarter was $213.6 million. This balance reflects net cash flow of $7.2 million, inclusive of the $10 million development milestone received from Genentech in the first quarter that was previously recognized as revenue in the fourth quarter of 2023.

第四，第一季淨虧損為1,770萬美元，去年第一季淨虧損為1,230萬美元。最後，第一季末我們的現金餘額為 2.136 億美元。這一餘額反映了 720 萬美元的淨現金流，包括第一季從基因泰克收到的 1000 萬美元的開發里程碑，該里程碑之前被確認為 2023 年第四季度的收入。

We continue to expect cash reserves, as well as strong commercial execution and financial discipline to support our current operating plan, which we expect to remain cash flow positive on an annual basis.

我們仍然期望現金儲備以及強大的商業執行力和財務紀律來支持我們當前的營運計劃，我們預計每年將保持正現金流。

And with that, I'll turn the call back to Sanj for closing remarks.

接下來，我將把電話轉回 Sanj，讓其結束語。

Thanks, Mark. As you’ve heard, we remain committed to advancing all areas of our business in the year ahead. Importantly, we expect our robust commercial performance to meaningfully contribute to our strong financial position and our ability to drive growth across the business.

謝謝，馬克。正如您所聽說的，我們仍然致力於在未來的一年裡推進我們業務的所有領域。重要的是，我們預計強勁的商業業績將為我們強勁的財務狀況和推動整個業務成長的能力做出有意義的貢獻。

Based on the current operating plan, which includes advancing Abiprubart through Phase 2 development in Sjögren’s Disease, we expect to remain cash flow positive on an annual basis. We're excited by the opportunity to continue to provide life-changing medicines for patients and we believe we are in a strong position to deliver on our goals.

根據目前的營運計畫（包括推進 Abiprubart 乾燥症的第二階段開發），我們預計每年將保持正現金流。我們很高興有機會繼續為患者提供改變生活的藥物，我們相信我們有能力實現我們的目標。

I do want to thank all of you for your time today and I'll now hand it back to the operator for any questions.

我確實要感謝大家今天抽出寶貴的時間，如果有任何問題，我現在會將其交還給接線員。

(Operator Instructions) Anupam Rama, JP Morgan.

（操作員指令）Anupam Rama，摩根大通。

Hi guys. Thanks so much for taking the question and congrats on the quarter. For ARCALYST, it seems like the physician prescribers continue to grow here. How much do you attribute this to the expanded sales force and getting to those kind of next tier of physicians versus deeper penetration into some of your top centers and existing academic center relationships? Thanks so much.

嗨，大家好。非常感謝您提出問題並祝賀本季。對 ARCALYST 來說，醫生開處方的人數似乎持續增加。您將這在多大程度上歸因於擴大的銷售團隊和接觸到的下一級醫生，而不是更深入地滲透到一些頂級中心和現有的學術中心關係？非常感謝。

Yes, thanks Anupam, this is Ross. Thank you very much for the question. So certainly we did go into 2024 with around 85 representatives, which gave us a boost in the coverage than we could achieve across the US. So we went from covering around 6,000 physicians up to 11,000. And so certainly some of it is done through the larger field team that we have been able to see certainly increase the breadth of how confessions we could reach, but also within those top tier high docile doctors that we really focus on have the highest group of recurrent pericarditis patients.

是的，謝謝 Anupam，我是羅斯。非常感謝你的提問。因此，進入 2024 年時，我們確實有大約 85 名代表，這使我們的覆蓋範圍比我們在全美範圍內所能達到的要高。因此，我們的覆蓋範圍從約 6,000 名醫生增加到 11,000 名。因此，當然，其中一些工作是透過更大的現場團隊完成的，我們已經看到，這無疑增加了我們可以達到的坦白的廣度，而且在我們真正關注的那些頂級、溫順的醫生中，擁有最高的團隊復發性心包膜炎患者。

And we are also increasing the frequency within those. So, we do think that’s an important element along with just continued execution that we've always been focused on and the message that we've got to deliver and the number of patients we've got to help out there and we still believe that there's a huge opportunity ahead of us.

我們也增加了這些內容的頻率。因此，我們確實認為這是一個重要因素，與我們一直關注的持續執行、我們必須傳遞的訊息以及我們必須幫助的患者數量一樣，我們仍然相信我們面前有一個巨大的機會。

So, you see from the 11,000 doctors that we target. We’ve now got around 2,000 prescribers in total since launch. So that alone tells you we've got a huge headroom ahead and certainly out of those 2,000 prescribers not all of them are within that target population of the 11,000 to 12,000. So we've got a long way to go to continue to grow the breadth of prescribers of the total prescriber base, as well as the repeat prescribing, which you can see has remained at 24% of an ever significantly increasing base of total prescribers.

所以，你可以從我們針對的 11,000 名醫生中看到。自推出以來，我們現在共有約 2,000 名處方者。因此，僅憑這一點就可以告訴您，我們還有巨大的發展空間，當然，在這 2,000 名處方者中，並非所有人都在 11,000 至 12,000 名目標人群之內。因此，要繼續擴大處方者總數以及重複處方的範圍，我們還有很長的路要走，您可以看到，在不斷顯著增加的處方者總數中，重複處方率仍保持在 24%。

So, and that the fact that they contributed around 40% of all the new enrollments that we had within Q1 also tells you that that the repeat prescribers is growing nicely and contributing significantly to the business as well. So thanks for the question. We're very pleased with where we are and then the opportunity we have ahead.

因此，他們佔第一季所有新註冊人數的 40% 左右這一事實也告訴您，重複處方者增長良好​​，並對業務做出了重大貢獻。謝謝你的提問。我們對我們所處的位置以及未來的機會感到非常滿意。

Thanks so much for taking our question.

非常感謝您提出我們的問題。

Paul Choi, Goldman Sachs.

保羅‧崔，高盛。

Hi, thanks. Good morning and congratulations on the good start to the year. My first question is for Ross and just with regards to ARCALYST patient behavior. Can you just maybe comment on if you are seeing any trends in terms of patients who discontinued therapy coming back maybe a little faster versus prior quarters?

你好謝謝。早上好，恭喜新年的好開始。我的第一個問題是問 Ross 的，並且涉及 ARCALYST 患者的行為。您能否評論一下您是否發現停止治療的患者恢復速度可能比前幾季更快一些的趨勢？

And just what the messaging on restarting and maintenance of therapy has been like and how that has resonated? And then I had a Abiprubart question for John afterwards as a follow-up.

關於重新開始和維持治療的訊息到底是什麼樣的？然後我向約翰提出了一個阿比魯巴特問題作為後續行動。

Okay, Choi, I'll maybe start from the ARCALYST one and then hand back to Paolini for the Abiprubart’s question. So, thank you for that. I think we haven't seen any significant changes in patient behavior from different cohorts that we're aware of different types of patients around either the ways in which they stopped therapy or indeed with the restart and the restart rate interestingly has remained consistent for quite some time now of about 45% of all those patients who stopped therapy come back on to restart.

好的，Choi，我可能會從 ARCALYST 開始，然後交回 Paolini 回答 Abiprubart 的問題。非常感謝你的幫忙。我認為我們還沒有看到不同隊列的患者行為有任何顯著變化，我們知道不同類型的患者無論是停止治療的方式還是重新啟動的方式，有趣的是，重新啟動率在相當長的一段時間內保持一致。

And generally patients are able to restart if they suffer from ongoing symptomology or the symptomology returns. And very often they have pills left on their prescription. They have the title approval in place. Sometimes they have stock on hand still from where they want it previously. So it's often very simple for patients to restart therapy if they do suffer from the disease continuously just acknowledging that this is a chronic disease for the most patients it's multiple years.

一般來說，如果患者出現持續症狀或症狀復發，他們能夠重新開始。他們的處方上常常還留有藥物。他們已獲得產權批准。有時他們手頭上的庫存仍然來自他們之前想要的地方。因此，如果患者確實持續患有這種疾病，那麼他們通常很容易重新開始治療，只需承認這對大多數患者來說是一種慢性疾病，而且會持續多年。

So, for these patients they stopped too early it's likely the symptomology will indeed come back. We just continue to focus on our education with healthcare professionals about the natural history of the disease and thus the patients who suffer for two or more recurrences, they generally have three years’ worth of median duration of therapy. One-third of the patients still suffer from the disease five years out. And you may remember from our clinical experience recently from our long-term extension portion of our study, the median was two years’ worth of oculus treatments up to three years.

因此，對於這些過早停止治療的患者來說，症狀很可能確實會回來。我們只是繼續專注於對醫療保健專業人員進行有關疾病自然史的教育，因此對於兩次或兩次以上復發的患者，他們通常有三年的中位治療時間。三分之一的患者五年後仍患有這種疾病。您可能還記得我們最近的長期擴展研究部分的臨床經驗，中位數是兩年——最長三年的治療。

So, we've seen the total duration of therapy grow over time in the commercial setting most recently around 23 months. But we really continue to focus on the natural history and just want patients to stay on therapy, as well the expected course of their disease is that they often multiple years.

因此，我們看到商業環境中的治療總持續時間隨著時間的推移而增長，最近約為 23 個月。但我們確實繼續關注自然史，只是希望患者繼續接受治療，而且他們的預期病程通常是多年。

Okay. Great. Thanks for that Ross. And then for John, as you look at the prior RA data and the available preclinical data for Abiprubart, can you maybe just comment on as you think about your Phase 2 plan for Sjögren’s, just what areas do you think Abiprubart might be able to be show evidence of differentiation or what, I guess, gives you the confidence for potential success here relative to some of the other assets in the class that may be further along in the clinic? Thank you.

好的。偉大的。謝謝你的羅斯。然後，約翰，當您查看先前的 RA 數據和 Abiprubart 的可用臨床前數據時，您能否在考慮 Sjögren 的第二階段計劃時發表評論，您認為 Abiprubart 的領域是什麼？證據，或者我想，相對於該類別中可能在臨床上進一步發展的一些其他資產，什麼能讓您對這裡的潛在成功充滿信心？謝謝。

Sure. Thank you, Paul and appreciate the question. Yes, we have confidence in the data that we've generated so far with Abiprubart. The data from Phase 1 show of course, important suppression of the mechanism as evidenced by suppression of antibody formation. And then we carry that forward into the Phase 2 program where we saw with all three dosing regimens, so with weekly, biweekly and even monthly dosing.

當然。謝謝你，保羅，謝謝你提出這個問題。是的，我們對迄今為止透過 Abiprubart 產生的數據充滿信心。當然，第一階段的數據顯示了對該機制的重要抑制，如抗體形成的抑制所證明的那樣。然後我們將其推進到第二階段計劃，我們看到了所有三種給藥方案，即每週、每兩週甚至每月給藥。

Suppression of rheumatoid factor to around 40% that was highly statistically significant. And then that translated into clinical outcomes using the DASH 1 to 8 CRP score. So that’s showing us that in a clinical setting, we have strong target engagement and that's with any of the three dosing regimens.

將類風濕因子抑制至 40% 左右，具有高度統計意義。然後使用 DASH 1 至 8 CRP 評分將其轉化為臨床結果。因此，這向我們表明，在臨床環境中，我們具有很強的目標參與度，並且這三種給藥方案中的任何一種都是如此。

What that means then translated forward is in terms of let’s say differentiation is that we've worked hard on making sure that we have a high concentration liquid formulation that's supports chronic subcutaneous dosing.

這意味著，我們可以說，差異化是指我們一直在努力確保我們擁有支持長期皮下給藥的高濃度液體製劑。

And so that ability to do Abiprubart as a subcutaneous drug rather than intravenous drug in these rheumatologic diseases and then to be able to spread out the dosing in the whole, so you test not only biweekly dosing, which is pretty standard, but even to stretch it out to potentially monthly dosing, which would be relatively unique in this space to have monthly subcutaneous dosing to us gives us a lot of confidence as we go forward into the Sjögren’s study that Abiprubart has the opportunity, we have the potential opportunity to show differentiation across other assets.

因此，在這些風濕病中，阿比魯巴特可以作為皮下藥物而不是靜脈注射藥物，然後能夠分散整個劑量，因此您不僅可以測試每兩週一次的劑量（這是相當標準的），甚至可以延長劑量它可能是每月一次的給藥，這在這個領域是相對獨特的，每月一次的皮下給藥給我們帶來了很大的信心，因為我們繼續進行Sjögren 的研究，阿比魯巴特有機會，我們有展示其他資產差異化的潛在機會。

Great. Thank you.

偉大的。謝謝。

David Nierengarten, Wedbush Securities.

大衛‧尼倫加滕 (David Nierengarten)，韋德布希證券公司 (Wedbush Securities)。

Okay. Thanks for taking our question. I had two. So, maybe following up on the Sjögren’s kind of competitive landscape is. I was curious who you considered your main competitor and if as a sub part of that how predictive do you think the rheumatoid factor is reduction for symptom relief in Sjögren’s?

好的。感謝您提出我們的問題。我有兩個。所以，也許是對乾燥型競爭格局的追蹤。我很好奇您認為誰是您的主要競爭對手，如果作為其中的一部分，您認為類風濕因子的減少對乾燥症症狀緩解的預測作用有多大？

And then a quick question on ARCALYST. I mean, it seems obvious, but just checking that that the physician kind of paradigm seems to be shifting to Aspirin maybe Colchicine in the frontline kind of recurrent pericarditis setting for the majority of patients and then ARCALYST, is that, is that a fair characterization of the market shift? Thanks.

然後是關於 ARCALYST 的一個簡短問題。我的意思是，這似乎是顯而易見的，但只要檢查一下，醫生的範式似乎正在轉向阿斯匹靈，也許是秋水仙鹼，用於大多數患者的複發性心包炎前線治療，然後是ARCALYST，這是一個公平的表徵市場的轉變？謝謝。

Yeah, hi, David, this is Ross. Maybe I’ll start with the ARCALYST one and then I could hand over to Eben on COA for the Abiprubart question. So, yeah, I - just to summarize, I think that's a fair characteristic. I think you said for patients that first of all suffer from pericarditis are generally treated with NSAIDs and not the Colchicine as well often when they come back and then recurrent patients, it's often the same treatment regimen, but with for the longer duration.

是的，嗨，大衛，我是羅斯。也許我會從 ARCALYST 開始，然後我可以將 COA 交給 Eben 來解決 Abiprubart 問題。所以，是的，我 - 只是總結一下，我認為這是一個公平的特徵。我想你說過，對於患有心包膜炎的患者，通常在他們回來時通常用非類固醇抗發炎藥物而不是秋水仙鹼治療，然後復發的患者，通常是相同的治療方案，但持續時間更長。

And then obviously we are focused on patients go on their second recurrence or more and making sure that ARCALYST is really the standard of care of choice for those patients. At that time, they are clearly being the current patients and suffered from the disease and going to break it through the usual early therapy options and really requiring something that targets the recurrence of the disease.

顯然，我們關注的是第二次或多次復發的患者，並確保 ARCALYST 確實成為這些患者選擇的護理標準。那時，他們顯然是目前的患者，患有這種疾病，並且要突破通常的早期治療方案，並且真正需要針對疾病復發的治療方法。

So, yes, we think that’s the way we're seeing it and as John shared with the RESONANCE Registry, we are certainly starting to see those key physicians focused on recurrences of the disease utilizing ARCALYST ahead of corticosteroids, which again is addressing the physicians that we are aiming for. Eben?

所以，是的，我們認為這就是我們所看到的方式，正如John 與RESONANCE 登記處分享的那樣，我們肯定開始看到那些主要醫生在使用皮質類固醇之前先使用ARCALYST 來關注疾病的複發，這又是向我們的目標醫師發表演說。埃本？

Yeah, hey David (inaudible) Thanks for the question. So we often look at the better landscape with a broad lens and follow all of the programs currently in clinical studies and producing data. Maybe to narrowly answer your question looking at the CD40-CD154 antagonist class alone, there are three others that have either produced results or are studying their asset ratio versus these those are the horizon now Amgen molecule (inaudible) which is currently rolling in a Phase 3 study with a IV formulation.

是的，嘿大衛（聽不清楚）謝謝你的提問。因此，我們經常以更廣闊的視角看待更好的前景，並追蹤目前正在進行臨床研究和產生數據的所有項目。也許為了狹隘地回答你的問題，只看CD40-CD154 拮抗劑類別，還有其他三個藥物要么已經產生了結果，要么正在研究它們的資產比率，這些是現在的安進分子（聽不清） ，目前正在階段滾動3 研究採用靜脈注射製劑。

There is Iscalimab from Novartis which has finished the Phase 2 program with five weekly subcu dosing. Both of those programs have demonstrated specifically significant efficacy in this population, which give us a lot of confidence going into this study that we're in the right patient population to potentially demonstrate an efficacy.

諾華公司的 Iscalimab 已經完成了 2 期計劃，每週 5 次 subcu 給藥。這兩個項目都在該族群中表現出了特別顯著的療效，這讓我們對這項研究充滿信心，並相信我們在合適的患者族群中可能會表現出療效。

And then the third program is a safety program called for Iscalimab which has been studied in Sjögren’s suppressing (inaudible) with no results reported as of yet. And I think where - given the data we generate today with 404, we're pretty excited about our study and the ability to test not only exclusively a subcutaneous formulation, but also testing at biweekly and also monthly.

第三個項目是名為 Iscalimab 的安全項目，該項目已在 Sjögren 抑制（聽不清楚）中進行了研究，但目前尚未報告任何結果。我認為，鑑於我們今天使用 404 產生的數據，我們對我們的研究以及不僅能夠專門測試皮下製劑，而且能夠每兩週和每月進行測試的能力感到非常興奮。

Geoff Meacham, Bank of America.

傑夫‧米查姆，美國銀行。

Morning guys. Thanks for the question and congrats on a good quarter. Ross, just on ARCALYST, you've had a successful launch so far, but obviously raising awareness I suspect will be key. So, are there plans to publish RESONANCE? And are there other studies that you guys were thinking about in terms of raising the profile?

早安各位。感謝您的提問，並祝賀您度過了一個美好的季度。Ross，就ARCALYST 而言，到目前為止您已經成功推出，但我認為提高意識顯然是關鍵。那麼，有計劃發布 RESONANCE 嗎？你們還考慮過其他研究來提高知名度嗎？

And then second question for Sanj, you'll obviously be investing in Abiprubart going forward, but you guess have committed to remaining cash flow positive. So I guess the question is how important is profitability or pipeline expansion from us on a strategic basis relative to your commercial investments in ARCALYST? Thanks guys.

然後問 Sanj 的第二個問題，你顯然會繼續投資 Abiprubart，但你猜你已經承諾保持正現金流。所以我想問題是，相對於您對 ARCALYST 的商業投資，我們在策略基礎上的獲利能力或管道擴張有多重要？多謝你們。

Thanks, Geoff. John, do you want to start?

謝謝，傑夫。約翰，你想開始嗎？

Absolutely. Thanks Geoff for the question. Yeah, we’re really excited about the RESONANCE Registry, because that's really an important tool by which we're learning about recurrent pericarditis epigenealogy and disease management. And importantly there are more than 20 centers across the US that are led by cardiologist investigators who have a focus on recurrent pericarditis and these are really the leading edge of managing the disease.

絕對地。感謝傑夫提出的問題。是的，我們對 RESONANCE 註冊表感到非常興奮，因為這確實是我們了解復發性心包膜炎表觀譜系和疾病管理的重要工具。重要的是，美國有 20 多個由心臟病專家領導的中心，重點關注復發性心包炎，這些中心確實是治療該疾病的前沿。

So in that sense, the data serves as an example for other clinicians around the country who are seeking to grow their knowledge base. So, this is what we're looking to do and as we've done in the past is this is a five-year registry and we're kind of right in the middle of it right now.

因此，從這個意義上說，這些數據可以為全國各地尋求擴大知識庫的其他臨床醫生提供參考。所以，這就是我們想要做的事情，正如我們過去所做的那樣，這是一個為期五年的註冊，我們現在正處於其中。

So about halfway enrolled, about halfway through the follow-up period adding patients all the time we’ve presented at prior scientific meetings and we just presented at the American College of Cardiology and there's a lot of information in this registry that we hope to harvest as we go forward and gaining a lot of insights about it.

因此，大約在入組的一半左右，大約在隨訪期的一半左右，我們一直在之前的科學會議上介紹過，並且剛剛在美國心臟病學會上介紹過，我們一直在增加患者，並且我們希望在這個註冊表中提供很多資訊在我們前進的過程中收穫並獲得很多感悟。

In this time around the fact that we learned about the penetration of IL-1 pathway inhibition as a concept and then importantly that these evidence-based cardiologists are adopting a steroid-sparing paradigm in the treatment of the disease meaning that other movements from the NSAIDs and Colchicine directly to IL-1 pathway inhibition and that's really been driven by ARCALYST and that's been a growing trend year-on-year.

在此期間，我們了解了 IL-1 通路抑製作為一個概念的滲透，重要的是，這些循證心臟病專家在治療該疾病時採用了類固醇節約範例，這意味著 NSAID 的其他作用和秋水仙鹼直接抑制IL-1 通路，這確實是由ARCALYST 推動的，並且呈現逐年增長的趨勢。

To us this is an important and exciting data that people are taking the evidence and really using that to drive management of their patients. So we look forward to harvesting other information from these centers and from these cardiologists as we go forward. So more to come. Thanks so much for the question.

對我們來說，這是一個重要且令人興奮的數據，人們正在獲取證據並真正利用它來推動患者的管理。因此，我們期待著從這些中心和心臟病專家那裡收集其他資訊。未來還會有更多。非常感謝你的提問。

And Geoff, to you had a second part of your question and as you said we did disclose in this quarter that we - based on our current operation plan we do expect to remain cash flow positive on annual basis. But that said, growth and creating value are certainly remain quite paramount and now while we're very excited about continuing the development that is through part as you've seen, we’ve shown this highly active molecule today with a compelling safety profile.

傑夫，你有問題的第二部分，正如你所說，我們確實在本季度披露了，根據我們當前的營運計劃，我們確實預計每年的現金流量將保持為正。但話雖如此，成長和創造價值肯定仍然非常重要，現在，雖然我們對繼續進行開發感到非常興奮，正如您所看到的，我們今天已經展示了這種高度活躍的分子，具有令人信服的安全性。

We are very pleased with the ongoing commercial execution with ARCALYST. We continue actually to look very hard at business development opportunities across the whole range of areas. So really all of that tells you that our first and primary goal is to create value. And certainly the current operating plan means that we expect to remain cash flow positive on an annual basis.

我們對與 ARCALYST 正在進行的商業執行感到非常滿意。實際上，我們繼續非常努力地尋找整個領域的業務發展機會。所以，所有這些確實告訴您，我們的首要目標是創造價值。當然，目前的營運計劃意味著我們預計每年將保持正現金流。

But ultimately, it's value creation that's important to us. So we're in a great position. Obviously, we are in a great financial position right now and obviously a lot of exciting development coming forward. So I think we are in a great spot.

但歸根究底，價值創造對我們來說很重要。所以我們處於有利地位。顯然，我們現在的財務狀況良好，而且顯然還有很多令人興奮的發展即將到來。所以我認為我們處於一個很好的位置。

Okay. Thanks guys.

好的。多謝你們。

Liisa Bayko, Evercore ISI.

莉莎·貝科，Evercore ISI。

Hi. And just congrats on the quarter and great to see you being able to be sustainably cash flow positive. Just to drill down a little bit more on Abiprubart, can you maybe talk through some of the characteristics that make you feel like you'd be competitive?

你好。恭喜本季度，很高興看到您能夠持續實現正現金流。為了更深入了解 Abiprubart，您能否談談一些讓您覺得自己有競爭力的特質？

Maybe specifically some of the pharmacokinetic dynamics in Phase 2 data that kind of lead you to believe that and just still kind of curious about any findings on kind of the treatments benefit over placebo in cohort 4 and kind of what that means from RAs as you think about transition to a different disease?

也許特別是第 2 期數據中的一些藥物動力學動力學會讓您相信這一點，並且仍然對第 4 組中治療優於安慰劑的任何發現感到好奇，以及您認為的 RA 意味著什麼關於轉變為另一種疾病？

And obviously there's kind of a bit more of a placebo response in the RA study kind of any implications to read through to what we might expect from the next phase of development. Thanks.

顯然，RA 研究中存在更多的安慰劑反應，可以通讀我們對下一階段開發的預期。謝謝。

Hi Liisa. Thank you so much for that question. Yes, so with regards to the pharmacokinetics of Abiprubart, as you might remember, what we have shown previously is that the threshold for a target engagement and suppression of antibody formation is that a plasma concentration of roughly two micrograms per mil.

嗨，莉莎。非常感謝你提出這個問題。是的，關於 Abiprubart 的藥物動力學，您可能還記得，我們​​之前已經表明，靶點參與和抑制抗體形成的閾值是大約每密耳 2 微克的血漿濃度。

And what we've shown in our pharmacokinetic curves and the modeling that comes from that is that even with the monthly dose of Abiprubart, so 400 milligrams given every four weeks, the trough plasma concentrations are roughly around 20 to 30 micrograms per mil. So roughly in order of magnitude greater than the plasma concentration which is required to suppress antibody formation.

我們在藥物動力學曲線和由此得出的模型中顯示，即使採用每月劑量的 Abiprubart，即每四周給藥 400 毫克，血漿濃度谷值也大約為每密耳 20 至 30 微克。因此大致比抑制抗體形成所需的血漿濃度大一個數量級。

And then the biweekly and the weekly dose levels are providing even higher plasma concentration. So in that sense, that's the reason why we have confidence in the rheumatoid factor data, which shows a 40% reduction across all three of those dosing regimens with highly statistically significant P values with two or three zeros demonstrating really the strength of that finding.

然後每兩週和每週的劑量水平提供更高的血漿濃度。因此，從這個意義上說，這就是我們對類風濕因子數據充滿信心的原因，該數據顯示所有三種給藥方案均減少了40%，具有高度統計顯著性的P 值，其中有兩個或三個零，真正證明了這項發現的強度。

So that's kind of the fundamentals and the fact that this is all being done with a subcutaneous formulation really provides a lot of flexibility going forward for chronic dosing. And then in terms of how that then translates forward into Sjögren’s Disease, as we mentioned that there's substantial external proof-of-concept that this mechanism has been implicated and it’s highly involved in the pathophysiology of the disease and that suppression of this mechanism could be an efficacious approach.

這就是基本原理，事實上，這一切都是透過皮下製劑完成的，這確實為長期給藥提供了極大的靈活性。然後就如何轉化為乾燥疾病而言，正如我們所提到的，有大量的外部概念證明表明這種機制與該疾病的病理生理學有關，並且它與該疾病的病理生理學密切相關抑制這種機制可能是一種有效的方法。

And so, by taking the biweekly and the monthly dose into Sjögren’s Disease we believe that we have a solid platform if you will for delivering enough drug to suppress the mechanism and to do that in a manner that would be convenient for patients. And the other part of that of course is that by following this out over a longer period of time we get more experience with the chronic use of the drug.

因此，透過每兩週一次和每月一次的劑量治療乾燥疾病，我們相信，如果您願意提供足夠的藥物來抑制該機制，並以一種方便的方式做到這一點，我們就有了一個堅實的平台。當然，另一部分是，透過長期跟踪，我們可以獲得更多長期使用該藥物的經驗。

So there's a placebo-controlled portion upfront and then that's followed by a longer term extension where all the patients remain on active therapy and so that we can understand the full magnitude of the effect of the drug over time. So thanks so much for the question.

因此，先有一個安慰劑對照部分，然後是長期延長，所有患者都繼續接受積極治療，這樣我們就可以了解藥物隨時間的影響的全部程度。非常感謝你的提問。

Thanks.

謝謝。

And thank you. And I am showing no further questions. I would now like to turn the call over to Sanj Patel, Chief Executive Officer, for closing remarks.

謝謝你。我沒有提出任何進一步的問題。現在我想將電話轉交給執行長桑吉·帕特爾 (Sanj Patel)，讓其致閉幕詞。

Thanks, operator. I appreciate all the questions and everyone joining the call today. Clearly got a very exciting year ahead of us and we're very much looking forward to continuing to execute and providing additional updates in the future.

謝謝，接線生。我感謝所有的問題以及今天加入電話會議的每個人。顯然，我們即將迎來非常激動人心的一年，我們非常期待在未來繼續執行並提供更多更新。

So with that, have a great day. Thank you.

就這樣，祝你有美好的一天。謝謝。

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。您現在可以斷開連線。