Akebia Therapeutics Inc (AKBA) 2020 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to Akebia Therapeutics Fourth Quarter 2020 Financial Results 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, Kristen Sheppard, Senior Vice President of Investor Relations. Thank you. Please go ahead.

女士們，先生們，感謝你們的支持，歡迎來到 Akebia Therapeutics 2020年第四季度財務業績電話會議。（操作員說明）請注意，今天的會議正在錄製中。我現在想把會議交給今天的演講者，投資者關係高級副總裁 Kristen Sheppard。謝謝。請繼續。

Thank you, and welcome to Akebia's Fourth Quarter and Fiscal Year 2020 Financial Results and Business Update Conference Call. Please note that the press release detailing our results for the fourth quarter and fiscal year 2020 was issued earlier this morning and is available on our Investor Relations website. For your convenience, a replay of today's call will also be available on our website shortly after we conclude today's event. Joining me for today's event is John Butler, our Chief Executive Officer; and David Spellman, our Chief Financial Officer.

謝謝，歡迎來到 Akebia 的第四季度和 2020 財年財務業績和業務更新電話會議。請注意，詳述我們第四季度和 2020 財年業績的新聞稿已於今天上午早些時候發布，可在我們的投資者關係網站上查閱。為了您的方便，今天的會議結束後不久，我們的網站上也將提供今天電話會議的重播。和我一起參加今天活動的是我們的首席執行官 John Butler；和我們的首席財務官 David Spellman。

Before we begin, I'd like to remind everyone that this call includes forward-looking statements. Each forward-looking statement contained in this call is subject to risks and uncertainties that could cause actual results to differ materially from those described in these statements. Additional information regarding these factors is described in the forward-looking statements section of the press release we issued earlier today, as well as in the risk factors in management's discussion and analysis sections of our most recent quarterly and annual reports filed with the SEC. The forward-looking statements on this call speak only as of the original date of this call, and except as required by law, we do not undertake any obligation to update or revise any of these statements.

在開始之前，我想提醒大家，本次電話會議包含前瞻性陳述。本次電話會議中包含的每項前瞻性陳述都存在風險和不確定性，這些風險和不確定性可能導致實際結果與這些陳述中描述的結果存在重大差異。有關這些因素的更多信息在我們今天早些時候發布的新聞稿的前瞻性聲明部分以及我們向美國證券交易委員會提交的最新季度和年度報告的管理層討論和分析部分的風險因素中進行了描述。本次電話會議的前瞻性陳述僅在本次電話會議的原始日期發表，除法律要求外，我們不承擔任何更新或修改這些陳述的義務。

With that, I'd now like to introduce our CEO, John Butler. John?

有了這個，我現在想介紹我們的首席執行官約翰巴特勒。約翰？

Thank you, Kristen, and thank you all for joining us today. 2020 was a year of focused execution for Akebia. We set out to accomplish a lot in 2020, and we did what we said we would do: advancing vadadustat, our lead product candidate, and laying the groundwork for a number of catalysts in 2021. More specifically, we achieved key clinical and regulatory milestones, including completing our global Phase III clinical development program for vadadustat and completing our pre-NDA meeting with the FDA. We also executed well against our commercial priorities. After securing the first regulatory approval of vadadustat with our partner, MTPC, earlier in the year, we began supporting the commercialization of vadadustat in Japan under the trade name Vafseo in Q3.

謝謝你，克里斯汀，感謝大家今天加入我們。2020 年是木通專注執行的一年。我們計劃在 2020 年完成很多工作，我們做了我們說過要做的事情：推進我們的主要候選產品 vadadustat，並為 2021 年的許多催化劑奠定基礎。更具體地說，我們實現了關鍵的臨床和監管里程碑，包括完成我們針對 vadadustat 的全球 III 期臨床開發計劃，以及完成我們與 FDA 的 NDA 前會議。我們還很好地執行了我們的商業優先事項。在今年早些時候與我們的合作夥伴 MTPC 一起獲得 vadadustat 的首次監管批准後，我們在第三季度開始支持 vadadustat 在日本以商品名 Vafseo 商業化。

As a company whose purpose is to better the lives of people impacted by kidney disease, I've been saddened to watch the disproportionate impact COVID-19 has had on patients on dialysis. Our team did a tremendous job of helping ensure that these patients, who continue to be at the highest risk, have access to our therapies despite the pandemic. As a result of these and other efforts, we grew Auryxia revenue over 2019. I'm incredibly proud of our entire team for all their work across 2020 and their continued commitment to both our purpose and our patients. Importantly, we achieved all this and more while keeping true to our goal of maintaining a strong balance sheet. With forward momentum from 2020, we have line of sight to significant milestones this year that we believe will further position Akebia to deliver on our strategy and build long-term value for our shareholders.

作為一家旨在改善受腎臟疾病影響的人們的生活的公司，我一直很難過看到 COVID-19 對透析患者產生的不成比例的影響。我們的團隊做了巨大的工作，幫助確保這些仍然處於最高風險的患者在大流行期間能夠獲得我們的治療。由於這些和其他努力，我們在 2019 年增加了 Auryxia 的收入。我為我們整個團隊在 2020 年所做的所有工作以及他們對我們的目標和患者的持續承諾感到無比自豪。重要的是，我們實現了所有這些以及更多，同時忠於我們保持強大資產負債表的目標。憑藉 2020 年的前進勢頭，我們有望實現今年的重要里程碑，我們相信這將進一步推動 Akebia 實現我們的戰略並為我們的股東創造長期價值。

Our highest priority is submitting our NDA for vadadustat for the treatment of anemia due to CKD with the FDA. Since completing our pre-NDA meeting in late October, our team has been hard at work putting together a very detailed and comprehensive data package in support of vadadustat's NDA submission. We remain firmly on track to achieve this milestone by the middle of the second quarter of this year. We also expect to follow this with vadadustat's MAA submission to the EMA in collaboration with Otsuka this year.

我們的首要任務是向 FDA 提交用於治療 CKD 引起的貧血的 vadadustat 的 NDA。自 10 月下旬完成 NDA 前會議以來，我們的團隊一直在努力整理非常詳細和全面的數據包，以支持 vadadustat 的 NDA 提交。我們仍然堅定地按計劃在今年第二季度中期實現這一里程碑。我們還希望今年與 Otsuka 合作向 EMA 提交 vadadustat 的 MAA。

As we advance vadadustat towards commercialization, subject to approval, we continue to execute on key commercial, development and financial priorities across our business. As dialysis is a primary focus, I'll start there. Data from INNO2VATE, our global Phase III program that evaluated the efficacy and safety of vadadustat in patients on dialysis, were clear, consistent and compelling. The data showed that vadadustat achieved non-inferiority to darbepoetin alfa on both the primary and key secondary hematologic efficacy endpoints as well as the primary and key secondary safety endpoints that included MACE, expanded MACE, cardiovascular MACE, cardiovascular mortality and all-cause mortality. Going a little deeper, our clinical data also demonstrated that vadadustat maintained EPO within a physiologic range, increased hemoglobin in a predictable and controlled manner and minimized hemoglobin excursions above that target range.

隨著我們將 vadadustat 推進商業化，在獲得批准的情況下，我們將繼續在我們的業務中執行關鍵的商業、開發和財務優先事項。由於透析是主要焦點，我將從這裡開始。我們的全球 III 期項目 INNO2VATE 的數據清晰、一致且令人信服，該項目評估了 vadadustat 在透析患者中的療效和安全性。數據顯示，vadadustat 在主要和關鍵的次要血液學療效終點以及主要和關鍵的次要安全性終點（包括 MACE 、擴大的 MACE 、心血管 MACE 、心血管死亡率和全因死亡率）方面均實現了對 darbepoetin alfa 的非劣效性。更深入一點，我們的臨床數據還表明，vadadustat 將 EPO 維持在生理範圍內，以可預測和可控的方式增加血紅蛋白，並最大限度地減少超過該目標範圍的血紅蛋白偏移。

We believe dialysis represents a potential $2 billion market opportunity in the U.S. alone. We're confident that upon approval, we have the potential to address the unmet needs of the over 500,000 adult patients on dialysis in the U.S. and rapidly establish vadadustat as the new oral standard of care for the treatment of anemia due to CKD. We anticipate that the strength of our data, which is clear and consistent across both prevalent and incident dialysis patients, will play a meaningful role in helping develop treatment protocols within dialysis providers, which are critical to driving adoption in the dialysis market, subject of course to regulatory approval.

我們認為透析僅在美國就代表著潛在的 20 億美元的市場機會。我們相信，一旦獲得批准，我們有可能解決美國超過 500,000 名成年透析患者未滿足的需求，並迅速將 vadadustat 確立為治療 CKD 引起的貧血的新口服護理標準。我們預計，我們的數據在流行和事件透析患者中清晰且一致，這將在幫助透析提供者制定治療方案方面發揮有意義的作用，這對於推動透析市場的採用至關重要，當然是主題到監管部門的批准。

To further strengthen vadadustat's potential profile for in-center dialysis patients, we're working to demonstrate that vadadustat can also be dosed 3 times a week and plan to have that data available at launch, which will allow us to submit an sNDA for this regimen post approval.

為了進一步加強 vadadustat 對中心透析患者的潛在影響，我們正在努力證明 vadadustat 也可以每週給藥 3 次，併計劃在發佈時提供該數據，這將使我們能夠提交該方案的 sNDA後批准。

Although the significant majority of dialysis patients are cared for in-center, recently, several factors including the COVID-19 pandemic, changing patient preferences, government initiatives and reimbursement changes are supporting a shift towards home dialysis. We believe that as a convenient, once-daily oral therapeutic, vadadustat has the potential to offer an important value proposition both to the growing number of home dialysis patients and to dialysis providers looking to better support these patients and grow their home programs.

儘管絕大多數透析患者都在中心接受治療，但最近，包括 COVID-19 大流行、不斷變化的患者偏好、政府舉措和報銷變化在內的幾個因素正在支持向家庭透析的轉變。我們相信，作為一種方便的、每日一次的口服治療藥物，vadadustat 有可能為越來越多的家庭透析患者和希望更好地支持這些患者並發展他們的家庭計劃的透析提供者提供重要的價值主張。

We believe we are well positioned to support a strong vadadustat launch in dialysis in the U.S. upon approval. Our go-to-market strategy includes leveraging our existing nephrology-focused commercial organization with our partner, Otsuka, sharing in the launch costs and responsibilities. As well, we have an exclusive distribution relationship with Vifor Pharma that positions vadadustat for potential rapid adoption in up to 60% of the U.S. dialysis market. Adding to this is a unique reimbursement model in the U.S. dialysis market with TDAPA, an add-on payment to the bundle that's intended to encourage adoption of innovative therapies by clinicians and dialysis providers. To maximize our market potential and ensure commercial readiness upon U.S. approval, we're executing across many different workstreams within medical affairs, scientific communications, disease state education, patient services and manufacturing.

我們相信，在獲得批准後，我們有能力支持在美國透析領域推出強大的 vadadustat。我們的上市戰略包括與我們的合作夥伴 Otsuka 一起利用我們現有的以腎髒病學為中心的商業組織，分擔啟動成本和責任。此外，我們與 Vifor Pharma 建立了獨家經銷關係，使 vadadustat 有可能在高達 60% 的美國透析市場中迅速採用。此外，美國透析市場採用 TDAPA 的獨特報銷模式，這是捆綁的附加付款，旨在鼓勵臨床醫生和透析提供者採用創新療法。為了最大限度地發揮我們的市場潛力並確保在獲得美國批准後做好商業準備，我們正在醫療事務、科學傳播、疾病狀態教育、患者服務和製造等多個不同的工作流程中執行。

We also recently added LeAnne Zumwalt to our Board of Directors. Many of you may know LeAnne as she spent over 20 years serving in key leadership roles with DaVita, most recently as Group Vice President of Government Affairs before her retirement earlier this year. LeAnne's prospective and extensive operating experience with one of the largest dialysis providers in the U.S. will help ensure that our market and commercial strategies are well aligned with the needs of dialysis providers and their patients.

我們最近還讓 LeAnne Zumwalt 加入了我們的董事會。你們中的許多人可能都知道 LeAnne，因為她在 DaVita 擔任了 20 多年的重要領導職務，最近擔任政府事務集團副總裁，今年早些時候退休。LeAnne 在美國最大的透析供應商之一的前瞻性和廣泛運營經驗將有助於確保我們的市場和商業戰略與透析供應商及其患者的需求保持一致。

We, along with the executive steering committee who has overseen our Phase III development program, believe it is critical to publish our data. And collectively, we continue to execute on our robust publication plan. To date, this has included the presentation of our Phase III data at ASN and publication of both our INNO2VATE and PRO2TECT methods papers in peer-reviewed journals during the fourth quarter. Looking ahead, we plan to present additional data at the upcoming NKF Spring Clinical Meetings in April, and we have line of sight to publication of our INNO2VATE program in a prestigious peer-reviewed publication expected in the near term. PRO2TECT has been submitted earlier this year for publication as well. Again, there is a significant unmet need among patients with anemia due to CKD, and we see a promising opportunity in vadadustat to advance the care of patients on dialysis.

我們和監督我們 III 期開發計劃的執行指導委員會認為，發布我們的數據至關重要。我們將共同繼續執行我們強大的出版計劃。迄今為止，這包括在 ASN 上展示我們的 III 期數據，以及在第四季度在同行評審期刊上發表我們的 INNO2VATE 和 PRO2TECT 方法論文。展望未來，我們計劃在即將於 4 月舉行的 NKF 春季臨床會議上展示更多數據，並且我們有望在近期內在著名的同行評審出版物中發布我們的 INNO2VATE 計劃。PRO2TECT 也已於今年早些時候提交出版。同樣，由於 CKD 導致貧血的患者存在顯著未滿足的需求，我們在 vadadustat 中看到了一個有希望的機會來促進透析患者的護理。

Turning to non-dialysis. As we discussed last quarter, we plan to submit data from PRO2TECT, together with additional analyses, and pursue a broad label for adult patients not on dialysis as part of our vadadustat NDA submission. However, as PRO2TECT missed the primary MACE endpoint, we are remaining cautious on potential approval in non-dialysis.

轉向非透析。正如我們上個季度討論的那樣，我們計劃提交來自 PRO2TECT 的數據以及其他分析，並在我們提交的 vadadustat NDA 中為未接受透析的成年患者尋求廣泛的標籤。然而，由於 PRO2TECT 錯過了主要 MACE 終點，我們對非透析的潛在批准保持謹慎。

Now in compiling the NDA, we've been able to take a deeper dive into the data to better understand PRO2TECT's MACE result. The cardiovascular outcomes reported in PRO2TECT contrast with those reported in the INNO2VATE program as well as with the safety data from other clinical and preclinical studies of vadadustat in both dialysis and non-dialysis adult patients. Additional in-depth analyses conducted by our team continue to demonstrate that the greater number of MACE events observed among vadadustat patients not on dialysis as compared with those on darbepoetin alfa in the PRO2TECT program was primarily related to an excess of non-cardiovascular deaths and deaths of unknown cause in regions outside of the United States, where significant differences in treatment patterns for patients not on dialysis were observed. As we've previously discussed, we believe these and other analyses inform the cardiovascular safety profile of vadadustat in U.S. patients not on dialysis. We continue to believe that pursuing approval in non-dialysis is the right thing to do for patients, and we look forward to working with the FDA in their review.

現在在編制 NDA 時，我們已經能夠更深入地研究數據，以更好地了解 PRO2TECT 的 MACE 結果。PRO2TECT 中報告的心血管結果與 INNO2VATE 計劃中報告的結果以及透析和非透析成年患者 vadadustat 的其他臨床和臨床前研究的安全性數據形成對比。我們的團隊進行的其他深入分析繼續表明，在 PRO2TECT 計劃中，與接受 darbepoetin alfa 治療的患者相比，在未接受透析的 vadadustat 患者中觀察到的 MACE 事件數量更多主要與非心血管死亡和死亡人數過多有關在美國以外的地區，原因不明，觀察到未接受透析的患者的治療模式存在顯著差異。正如我們之前所討論的那樣，我們相信這些和其他分析可以為未接受透析的美國患者提供 vadadustat 的心血管安全性概況。我們仍然相信，為患者尋求非透析批准是正確的做法，我們期待與 FDA 合作進行審查。

In addition, I want to share that as part of our NDA work, we undertook a review of hepatic safety across the vadadustat clinical program, which includes data from over 8,000 patients across 36 completed Phase I, II and III clinical studies conducted by Akebia and our partner, MTPC. The review of hepatic safety included a blinded assessment of all hepatic events in the studies by a panel of hepatic experts and analysis by an independent hepatic expert and our team. I'm very pleased to report that based on this review, we concluded that the data across the clinical program showed that the hepatic safety profiles of vadadustat and darbepoetin alfa, an injectable ESA and the current standard of care, appear to be similar, and that there were no Hy's law events identified across the entire vadadustat clinical development program.

此外，我想分享一下，作為我們 NDA 工作的一部分，我們對整個 vadadustat 臨床項目的肝臟安全性進行了審查，其中包括來自 Akebia 和我們的合作夥伴，MTPC。肝臟安全性審查包括由一組肝臟專家對研究中的所有肝臟事件進行盲法評估，並由一名獨立的肝臟專家和我們的團隊進行分析。我很高興地報告，基於這次審查，我們得出的結論是，整個臨床項目的數據表明，vadadustat 和 darbepoetin alfa、一種可注射的 ESA 和當前的護理標準似乎相似，並且在整個 vadadustat 臨床開發計劃中沒有發現 Hy 定律事件。

More specifically, we concluded that a 2014 case previously reported by us as meeting the biochemical criteria for Hy's law, while complicated, was in fact not a case of Hy's law. Our conclusion on this case will be reflected in our NDA for vadadustat. We wanted to share this report finding as we believe it reinforces what we expect will be a high-quality NDA submission for vadadustat. As well, this finding reinforces our confidence around the long-term strategic vision for vadadustat.

更具體地說，我們得出的結論是，我們之前報告的 2014 年案例符合 Hy 定律的生化標準，雖然複雜，但實際上不是 Hy 定律的案例。我們對這個案例的結論將反映在我們對 vadadustat 的 NDA 中。我們想分享這份報告的發現，因為我們相信它強化了我們對 vadadustat 高質量 NDA 提交的期望。同樣，這一發現增強了我們對 vadadustat 長期戰略願景的信心。

An important aspect of this strategy is focused on innovation, so let me shift a little bit and talk about our future development plans. Innovation is a core capability at Akebia that we have built over the past decade with robust research and clinical development resources. This engine has yielded significant scientific advancements, including vadadustat, which is based on Nobel Prize winning science. While the near-term and largest commercial opportunity for vadadustat is within anemia due to CKD, we believe there is the potential for additional opportunities for vadadustat.

這個戰略的一個重要方面就是注重創新，所以我稍微轉移一下，談談我們未來的發展計劃。創新是 Akebia 的核心能力，我們在過去十年中憑藉強大的研究和臨床開發資源建立起來。該引擎取得了重大的科學進步，包括基於諾貝爾獎獲獎科學的 vadadustat。雖然 vadadustat 近期和最大的商業機會在於 CKD 引起的貧血，但我們相信 vadadustat 有可能獲得更多機會。

We're encouraged that the current study evaluating the use of vadadustat as a potential therapy to prevent and lessen the severity of acute respiratory distress syndrome, or ARDS, in adult patients who've been hospitalized due to COVID-19 is progressing well. As a reminder, this is a clinical investigator-sponsored study led by UTHealth that we provided supportive funds for last year. UTHealth has shared that over 120 patients are enrolled and recently announced that they have been awarded $5.1 million in funding from the U.S. Department of Defense to expand this clinical trial at their facilities. If the results of this study are positive, we believe this COVID-related clinical experience could offer possibilities not only to move forward and help COVID patients, but also to explore vadadustat for a large and enduring opportunity as a treatment for ARDS beyond COVID. After being relatively quiet in 2020, we look to share more information on potential development opportunities for vadadustat later this year, and where possible, updates from UTHealth.

我們感到鼓舞的是，目前評估使用 vadadustat 作為預防和減輕因 COVID-19住院的成年患者急性呼吸窘迫綜合徵（ARDS）嚴重程度的潛在療法的研究進展順利。提醒一下，這是一項由 UTHealth 領導的臨床研究者贊助的研究，我們去年提供了支持資金。UTHealth 透露，有 120 多名患者入組，並且最近宣布他們已從美國國防部獲得 510 萬美元的資金，用於在他們的設施中擴大這項臨床試驗。如果這項研究的結果是積極的，我們相信這種與 COVID 相關的臨床經驗不僅可以提供向前發展和幫助 COVID 患者的可能性，而且還可以探索 vadadastat 作為 COVID 以外的 ARDS 治療的巨大而持久的機會。在 2020 年相對平靜之後，我們希望在今年晚些時候分享更多關於 vadadustat 潛在發展機會的信息，並在可能的情況下分享 UTHealth 的更新。

To sum up, as we transition to 2021, we plan to continue executing to prepare for the expected commercialization of vadadustat, while investing in potential opportunities to help position Akebia for the long term. We're pleased to be doing all this from a place of financial strength with a cash runway that extends beyond the expected U.S. launch of vadadustat, assuming timely regulatory approval and the receipt of associated regulatory milestones. And as Dave will discuss, we remain committed to both maintaining a strong balance sheet and improving our cost structure moving forward.

總而言之，隨著我們過渡到 2021 年，我們計劃繼續執行以準備 vadadustat 的預期商業化，同時投資於潛在機會以幫助長期定位 Akebia。我們很高興能夠從一個財務實力強大的地方做這一切，現金跑道延伸到美國預期推出的 vadadustat 之外，假設及時獲得監管批准並收到相關的監管里程碑。正如戴夫將要討論的那樣，我們仍然致力於保持強大的資產負債表並改善我們的成本結構。

In further evidence of these objectives, we recently announced a $60 million transaction with HealthCare Royalty Partners to monetize our Vafseo royalties and sales milestones under our collaboration agreement with MTPC. While Dave will provide more detail shortly, we believe this transaction is strong validation of the value that Vafseo can bring to patients in Japan. As well, we believe it underscores our commitment to preserving both our strategic and financial flexibility while investing for the successful launch of vadadustat upon approval.

為了進一步證明這些目標，我們最近宣布與 HealthCare Royalty Partners 達成一項 6000 萬美元的交易，根據我們與 MTPC 的合作協議，將我們的 Vafseo 版稅和銷售里程碑貨幣化。雖然 Dave 將很快提供更多細節，但我們相信這筆交易是對 Vafseo 可以為日本患者帶來的價值的有力驗證。同樣，我們相信它強調了我們致力於保持戰略和財務靈活性的承諾，同時投資於在獲得批准後成功推出 vadadustat。

As we head into the next chapter of Akebia, there's a lot of important work ahead of us in 2021. We remain confident that our hard work in 2020 has laid the foundation for the year ahead and the journey that we're on for the longer term. We're excited about the future. And together with our collaborator, Otsuka, we look forward to bringing vadadustat for the treatment of anemia due to CKD to patients globally upon approval.

當我們進入 Akebia 的下一章時，2021 年我們還有很多重要的工作要做。我們仍然相信，我們在 2020 年的辛勤工作為來年和我們的長期旅程奠定了基礎。我們對未來感到興奮。我們期待與我們的合作者 Otsuka 一起，在獲得批准後將 vadadustat 用於治療 CKD 引起的貧血，帶給全球患者。

I'll now turn the call over to Dave who will review our financial results. Dave?

我現在將電話轉給戴夫，他將審查我們的財務結果。戴夫？

Thank you, John, and good morning, everyone. As John discussed, we met key goals in 2020, including the headline, completing our Phase III development program for vadadustat. We also demonstrated the resiliency of our organization and business in response to challenges across the year. Despite these challenges, I'm pleased that we were able to continue supporting our patients and customers and accomplish all that we did while keeping with our objective to maintain a strong balance sheet. This progress underscores our focus on execution and our commitment to our patients.

謝謝約翰，大家早上好。正如 John 所討論的那樣，我們在 2020 年實現了關鍵目標，包括標題，完成了 vadadustat 的 III 期開發計劃。我們還展示了我們的組織和業務應對全年挑戰的彈性。儘管面臨這些挑戰，但我很高興我們能夠繼續支持我們的患者和客戶並完成我們所做的一切，同時保持我們保持強勁資產負債表的目標。這一進展強調了我們對執行的關注以及我們對患者的承諾。

Before reviewing our 2020 financial results, I'd like to provide some detail around our recent $60 million non-dilutive transaction with HealthCare Royalty Partners to monetize our Vafseo royalties and associated sales milestones under our collaboration agreement with MTPC, which for clarity is not included in our 2020 results.

在回顧我們 2020 年的財務業績之前，我想提供一些關於我們最近與 HealthCare Royalty Partners 進行的 6000 萬美元非稀釋性交易的一些細節，以便根據我們與 MTPC 的合作協議將我們的 Vafseo 版稅和相關銷售里程碑貨幣化，為清楚起見，不包括在內在我們 2020 年的業績中。

Under the terms of the agreement with HCRP, Akebia receives an upfront cash payment of $45 million and is eligible to receive an additional $15 million if certain sales milestones are achieved. In exchange, HCRP has the right to receive Vafseo royalties and sales milestones due to us under our collaboration agreement, subject to an annual cap of $13 million and an aggregate cap of $150 million. After the annual cap is met in any given calendar year, Akebia will recognize 85% of Vafseo royalties and sales milestones from MTPC for that year. After the aggregate cap is met, Akebia will recognize 100% of the Vafseo royalties and sales milestones until the revenue stream ends under the terms of the company's collaboration agreement with MTPC. The transaction does not include potential future regulatory milestones to be paid by MTPC.

根據與 HCRP 達成的協議條款，Akebia 收到 4500 萬美元的預付款，如果達到某些銷售里程碑，還有資格獲得額外的 1500 萬美元。作為交換，HCRP 有權根據我們的合作協議收取我們應得的 Vafseo 特許權使用費和銷售里程碑，但年度上限為 1300 萬美元，總上限為 1.5 億美元。在任何給定日曆年達到年度上限後， Akebia 將承認該年 MTPC 85%的 Vafseo 特許權使用費和銷售里程碑。在達到總上限後， Akebia 將確認 100% 的 Vafseo 特許權使用費和銷售里程碑，直到收入流根據公司與 MTPC 的合作協議的條款結束。該交易不包括 MTPC 支付的潛在未來監管里程碑。

We're very pleased with this transaction. As a reminder, the third quarter marked the first commercial availability of Vafseo in Japan. Since launching in late August, we recorded approximately $400,000 in royalty revenue related to the sale of Vafseo in Japan by Mitsubishi Tanabe.

我們對這筆交易非常滿意。提醒一下，第三季度標誌著 Vafseo 在日本的首次商業上市。自 8 月下旬推出以來，我們記錄了與 Mitsubishi Tanabe 在日本銷售 Vafseo 相關的特許權使用費收入約 400,000 美元。

Now turning to our financial results, starting with revenue. Total revenue was $56.7 million for the fourth quarter of 2020 compared to $69.6 million for the fourth quarter of 2019, and $295.3 million for the full year 2020 compared to $335.0 million for the full year of 2019. The decline in both periods was driven by lower collaboration revenue consistent with the company successfully completing our global Phase III clinical development program for vadadustat, which included the INNO2VATE and PRO2TECT studies. As you know, 80% of our Phase III vadadustat development costs are pre-funded by our collaborator, Otsuka, and these corresponding payments are recorded as collaboration revenue. So as these costs decline, so will the corresponding payments. Separately, I'll note that subject to the terms of our collaboration agreement with Otsuka, Akebia has the potential to receive both regulatory and commercial milestone payments from Otsuka upon the approval and commercialization of vadadustat in both the U.S. and Europe.

現在轉向我們的財務業績，從收入開始。2020 年第四季度總收入為 5670 萬美元，而 2019 年第四季度為 6960 萬美元；2020 年全年總收入為 2.953 億美元，而 2019 年全年為 3.350 億美元。這兩個時期的下降都是由於合作收入減少，這與公司成功完成我們的 vadadustat 全球 III 期臨床開發計劃一致，其中包括 INNO2VATE 和 PRO2TECT 研究。如您所知，我們 III 期 vadadustat 開發成本的 80% 由我們的合作者 Otsuka 預先資助，這些相應的付款記錄為合作收入。因此，隨著這些成本的下降，相應的付款也會減少。另外，我會注意到，根據我們與 Otsuka 的合作協議條款，Akebia 有可能在 vadadustat 在美國和歐洲獲得批准和商業化後從 Otsuka 獲得監管和商業里程碑付款。

Collaboration revenue was $22.1 million for the fourth quarter of 2020 compared to $40.6 million for the fourth quarter of 2019, and $166.4 million for the full year 2020 compared with $223.9 million for the full year 2019. As I just mentioned, the change in both periods is due to the timing in which vadadustat development expenses are incurred, and the associated revenue is recognized on a percentage-of-completion basis. Also, this includes approximately $400,000 in royalties from MTPC received in 2020.

2020 年第四季度的合作收入為 2210 萬美元，而 2019 年第四季度為 4060 萬美元；2020 年全年的合作收入為 1.664 億美元，而 2019 年全年為 2.239 億美元。正如我剛才提到的，兩個時期的變化是由於 vadadustat 開發費用發生的時間，相關收入是按完成百分比確認的。此外，這還包括 MTPC 在 2020 年收到的約 400,000 美元特許權使用費。

In terms of Akebia's commercial performance, net product revenue for Auryxia was $34.6 million for the fourth quarter of 2020 compared with $28.9 million for the fourth quarter of 2019, an increase of 20%, and $128.9 million for the full year 2020 compared to $111.1 million for the full year of 2019, an increase of 16%.

在 Akebia 的商業業績方面，Auryxia 2020 年第四季度的產品淨收入為 3460 萬美元，相比 2019 年第四季度的 2890 萬美元，增長 20%，2020 年全年為 1.289 億美元，相比之下為 1.111 億美元。 2019 年全年增長 16%。

We are very proud that our team continued to execute across 2020, getting our therapies to those in need. While we did not experience significant impact from COVID-19 on our revenues during the first 9 months of 2020, we believe there was an impact on our revenue growth in Q4, primarily as the kidney patient populations that we serve continue to experience both higher hospitalization and mortality rates due to COVID-19. As COVID-19 continues to adversely and disproportionately impact our patient population, we expect that COVID-19 will have a negative impact on future revenue growth.

我們感到非常自豪的是，我們的團隊在 2020 年繼續執行，將我們的療法提供給有需要的人。雖然我們在 2020 年前 9 個月沒有受到 COVID-19 對我們收入的重大影響，但我們認為這對我們第四季度的收入增長產生了影響，主要是因為我們服務的腎病患者群體繼續經歷更高的住院率以及 COVID-19 導致的死亡率。由於 COVID-19 繼續對我們的患者群體產生不利和不成比例的影響，我們預計 COVID-19 將對未來的收入增長產生負面影響。

Cost of goods sold was $63.2 million for the fourth quarter of 2020 compared to $38.1 million for the fourth quarter of 2019. Excluding non-cash purchase accounting adjustments as a result of the merger with Keryx, the increase in the fourth quarter of 2020 was primarily driven by a $14.8 million non-cash charge related to excess purchase commitments. Cost of goods sold was $295.9 million for the full year 2020 compared with $145.3 million for the full year 2019. Cost of goods sold for 2020 includes a $115.5 million non-cash charge related to the impairment of the Auryxia intangible asset in the second quarter of 2020, a $25.1 million non-cash charge related to excess purchase commitments and a $20.1 million non-cash charge for inventory write-downs largely related to a previously disclosed manufacturing quality issue related to Auryxia. We expect COGS to normalize in the second half of 2021 as we continue to focus on quality and work through remaining non-cash purchase accounting adjustments associated with inventory.

2020 年第四季度的銷貨成本為 6320 萬美元，而 2019 年第四季度為 3810 萬美元。排除與 Keryx 合併導致的非現金采購會計調整，2020 年第四季度的增長主要是由與超額採購承諾相關的 1,480 萬美元非現金費用推動的。2020 年全年的銷售成本為 2.959 億美元，而 2019 年全年為 1.453 億美元。2020 年的銷售成本包括與 2020 年第二季度 Auryxia 無形資產減值相關的 1.155 億美元非現金費用、與超額採購承諾相關的 2510 萬美元非現金費用以及 2010 萬美元的非現金費用庫存減記主要與先前披露的與 Auryxia 相關的製造質量問題有關。我們預計 COGS 將在 2021 年下半年正常化，因為我們將繼續關注質量並通過與庫存相關的剩餘非現金采購會計調整來開展工作。

Research and development expenses were $37.6 million for the fourth quarter of 2020 compared to $80.4 million for the fourth quarter of 2019, and $218.5 million for the full year 2020 compared to $323.0 million for the full year 2019. Again, the decline in both periods was driven primarily by a decrease in the costs consistent with the company completing the INNO2VATE and PRO2TECT studies. We continue to expect that R&D expenses will remain significant as we continue to support ongoing planned clinical work as well as the cost of our supply chain and inventory build ahead of the expected approval of vadadustat.

2020 年第四季度的研發費用為 3760 萬美元，而 2019 年第四季度為 8040 萬美元；2020 年全年的研發費用為 2.185 億美元，而 2019 年全年為 3.23 億美元。同樣，這兩個時期的下降主要是由於公司完成 INNO2VATE 和 PRO2TECT 研究的成本下降所致。我們繼續預計，隨著我們繼續支持正在進行的計劃中的臨床工作以及我們的供應鏈成本和庫存建設成本，研發費用將仍然很高，因為我們會在預期批准 vadadustat 之前。

Selling, general and administrative expenses were $40.3 million for the fourth quarter of 2020 compared to $44.9 million for the fourth quarter of 2019, and $153.9 million for the full year of 2020 compared to $149.5 million for the full year of 2019. For 2021, we expect that SG&A expenses will increase modestly from 2020 as we invest in pre-commercial activities for vadadustat and continue to support Auryxia.

2020 年第四季度的銷售、一般和管理費用為 4030 萬美元，而 2019 年第四季度為 4490 萬美元；2020 年全年為 1.539 億美元，而 2019 年全年為 1.495 億美元。對於 2021 年，我們預計 SG&A 費用將從 2020 年開始適度增加，因為我們投資於 vadadustat 的商業前活動並繼續支持 Auryxia。

For our bottom line, the company reported a net loss of $87.0 million for the fourth quarter of 2020 compared to $94.5 million for the fourth quarter of 2019, and $383.5 million for the full year of 2020 compared to $279.7 million for the full year 2019. The increase in net loss for the full year of 2020 was primarily due to lower collaboration revenue and higher COGS, partially offset by lower operating expenses.

對於我們的底線，該公司報告 2020 年第四季度淨虧損 8700 萬美元，而 2019 年第四季度為 9450 萬美元；2020 年全年淨虧損為 3.835 億美元，而 2019 年全年為 2.797 億美元。2020 年全年淨虧損的增加主要是由於合作收入減少和銷貨成本增加，部分被運營費用減少所抵消。

Turning to our capital position. Cash, cash equivalents and available-for-sale securities were $268.7 million at December 31, 2020. This balance includes the remaining $20 million available under our loan agreement with Pharmakon that we drew down in the fourth quarter as well as $10.6 million in proceeds from the sales under our ATM in the fourth quarter. Additionally, we added approximately $15.9 million in proceeds from ATM sales subsequent to year end.

轉向我們的資本狀況。截至 2020 年 12 月 31 日，現金、現金等價物和可供出售證券為 2.687 億美元。這筆餘額包括根據我們與 Pharmakon 的貸款協議，我們在第四季度提取的剩餘 2000 萬美元，以及第四季度 ATM 下銷售的 1060 萬美元收益。此外，我們在年底之後增加了約 1590 萬美元的 ATM 銷售收入。

As COVID-19 continues to adversely and disproportionately impact our patient population with higher hospitalization and mortality rates, we expect this will have a negative impact on Auryxia revenue growth. While we are unable to fully quantify the impact of the COVID-19 pandemic on future revenues and revenue growth, we continue to work to position the company to navigate these challenges. As such, our financial priorities remain focused on improving our cost structure and maintaining a strong balance sheet as evidenced by our recent royalty transaction with HCRP that I mentioned earlier.

由於 COVID-19繼續對住院率和死亡率較高的患者群體產生不利和不成比例的影響，我們預計這將對 Auryxia 收入增長產生負面影響。雖然我們無法完全量化 COVID-19 大流行對未來收入和收入增長的影響，但我們將繼續努力使公司能夠應對這些挑戰。因此，我們的財務優先事項仍然集中在改善我們的成本結構和保持強勁的資產負債表上，正如我之前提到的我們最近與 HCRP 的特許權使用費交易所證明的那樣。

From a tactical perspective, in addition to being disciplined on the investments we make, we remain focused on quality, driving efficiencies and improvements in manufacturing and supply chain, managing costs and driving operating leverage from our existing commercial resources as we move toward an expected vadadustat launch in the U.S., subject to approval.

從戰術角度來看，除了對我們所做的投資進行紀律外，我們仍然專注於質量、提高製造和供應鏈的效率和改進、管理成本並在我們朝著預期的 vadadustat 邁進時從我們現有的商業資源中提高運營槓桿在美國推出，須經批准。

To wrap up, we expect our cash resources to fund our current operating plan beyond the expected U.S. launch of vadadustat, assuming timely regulatory approval and the receipt of associated regulatory milestones. With that, we'll open up the line for questions. Operator?

總而言之，我們預計我們的現金資源將為我們當前的運營計劃提供資金，超出預期的美國推出 vadadustat，前提是及時獲得監管批准並收到相關的監管里程碑。有了這個，我們將打開問題熱線。操作員？

(Operator Instructions) Our first question comes from Chris Raymond with Piper Sandler.

（操作員說明）我們的第一個問題來自 Chris Raymond 和 Piper Sandler。

Just a couple of questions here. Maybe first on your color on the impact to Auryxia, the renal business may be writ large from COVID. So first, John, renal of course is notoriously promotion sensitive as a specialty group. Is there also maybe any impact you're seeing from the fact that your reps can't access clinics like they used to? And then maybe, I know you guys talked sort of in generalities about how this COVID impact might spill over into 2021, but maybe can you give some color on how to think about this? I guess on one hand, case rates across the U.S. have been sort of coming down, but the first part of Q1 was still pretty high. So maybe is there any sort of -- any more color you can give on how that's -- you think that would play out this year?

這裡只有幾個問題。也許首先是你對 Auryxia 的影響的顏色，腎臟業務可能會因 COVID 而變得很大。所以首先，約翰，腎臟作為一個專業群體當然是出了名的推廣敏感。您的銷售代表無法像以前那樣訪問診所這一事實是否也可能對您造成任何影響？然後也許，我知道你們談到了這種 COVID 影響可能如何蔓延到 2021 年的籠統討論，但也許你能給出一些關於如何思考這個問題的顏色嗎？我想一方面，美國的病例率一直在下降，但第一季度的第一部分仍然很高。所以也許有什麼——你能給出更多的顏色——你認為這會在今年發揮作用嗎？

Sure, Chris. So, certainly -- it's an interesting question. It's hard to kind of parse it out. I've been pretty impressed by the kinds of access our reps have been able to get. It's really different parts of the country to parts of the country. Some are back in the field, some are still working on Zoom, but quite effective when they get there. If you look at the fourth quarter, for instance, the product grew, but just not as much as we had expected. And when you look at the overall prescriptions in the phosphate binder category, the overall prescriptions were dropping. Now the size of the prescription is a little higher. But it says that there's an impact from COVID, and it's not just an access. Particularly when you listen to Fresenius, DaVita on their calls earlier this quarter, they're talking about a clear impact to their patients. And there's data, I can't remember the source, that the mortality rate among dialysis patients is 20%. Way higher than the rest of the population. So exactly how that plays out is very hard, obviously, to say. First quarter always is a soft quarter for us because we have the prior auths that we have to kind of go through. The team knows how to do that. But how the excess mortality and hospitalization also plays into that is much harder to say. We've been pushing -- in my KCP role, we talked about prioritizing dialysis patients for vaccine. I think that's happening in different states, so exactly how long this plays out. But if we've lost patients, we've lost patients. And I do think that's going to have an impact. Exactly how much? To be determined.

當然，克里斯。所以，當然——這是一個有趣的問題。很難把它解析出來。我們的代表能夠獲得的各種訪問權限給我留下了深刻的印象。該國的不同地區與該國的部分地區確實不同。有些人回到了現場，有些人仍在研究 Zoom，但當他們到達那裡時非常有效。例如，如果你看一下第四季度，產品會增長，但沒有我們預期的那麼多。當您查看磷酸鹽結合劑類別的總體處方時，總體處方正在下降。現在處方量大了一點。但它說 COVID 有影響，而不僅僅是訪問。特別是當你在本季度早些時候聽 Fresenius 和 DaVita 的電話時，他們正在談論對患者的明顯影響。還有數據，我不記得來源了，透析患者的死亡率是 20%。遠遠高於其他人群。因此，很明顯，很難說到底是怎麼回事。第一季度對我們來說總是一個疲軟的季度，因為我們有我們必須經歷的事先授權。團隊知道如何做到這一點。但超額死亡率和住院率如何影響這一點就很難說了。我們一直在推動——在我的 KCP 角色中，我們談到優先考慮透析患者接種疫苗。我認為這在不同的州都在發生，所以這到底會持續多久。但如果我們失去了病人，我們就失去了病人。我確實認為這會產生影響。究竟是多少？待定。

Okay. Thanks. And maybe also a follow-up just on vadadustat. So I think you're guiding now I think a little bit more color on timing, so mid this year. Maybe just on use of that PRV, is there a point when you'll be able to give some indication as to whether you can actually use that?

好的。謝謝。也許還有關於 vadadustat 的後續行動。所以我認為你現在正在指導我認為時間上有更多的色彩，所以今年年中。也許只是在使用那個 PRV 時，你能給出一些關於你是否真的可以使用它的指示嗎？

So just to clarify, it's mid-second quarter is the guidance, which is a little earlier than mid-year.

所以澄清一下，第二季度中期是指導，比年中早一點。

Yes, sorry.

是的，對不起。

No problem. And the -- we still have the potential to access to PRV. And that's a decision we would make with Vifor and with Otsuka. So that -- we still have that, but beyond that, not ready to comment.

沒問題。而且 - 我們仍然有可能獲得 PRV。這是我們將與 Vifor 和 Otsuka 一起做出的決定。所以 - 我們仍然有，但除此之外，不准備發表評論。

We would issue a press release while we submit and [education] at that point in time.

我們會在那個時間點提交和[教育]時發布新聞稿。

Yes. Thanks, Kristen. Yes, we will issue a press release and then you'll know.

是的。謝謝，克里斯汀。是的，我們會發布新聞稿，然後你就會知道。

And our next question comes from Difei Yang with Mizuho. Would you check your mute button?

我們的下一個問題來自楊迪飛和瑞穗。你會檢查你的靜音按鈕嗎？

Difei Yang here.

楊迪飛來了。

Would you check your mute button? I'll go to the next line. Difei Yang, your line is open.

你會檢查你的靜音按鈕嗎？我將轉到下一行。楊迪飛，你的電話開通了。

Yes. I'm here. Can you hear me?

是的。我在這。你能聽到我嗎？

Yes.

是的。

Yes. Hey, Difei.

是的。餵，迪菲。

Just a couple quick ones. With regards to the Hy's law case, you were talking about eventually you were able to determine it was not a Hy's law case. Would you give us a little bit more color on what led to that decision? And then secondarily, with regards to the once-daily dosing versus the 3x weekly dosing, and how do you think it will be utilized in the field?

只是幾個快速的。關於 Hy 案，您談到最終您能夠確定這不是 Hy 案。你能給我們更多關於導致該決定的原因的顏色嗎？其次，關於每日一次給藥與每週 3 次給藥，您認為它將如何在該領域使用？

Sure. So first on the Hy's law case. We have -- this was a complicated case. That I can't stress enough. There was a patient with very elevated liver enzyme levels but never was hospitalized, never symptomatic. But we said at the time when we reported it that we were always looking at our data. Now post PRO2TECT and INNO2VATE, we're looking at 8,000 patients. And we were able to have an outside expert panel do a blinded assessment and look at all of the data with that lens and the lens of 8,000 more. And beyond just the Hy's law case, the fact that vadadustat versus darbepoetin, a product that's never been shown to have any kind of liver impact, we determined that there's really no difference between those. And so that's a very important finding and similarly with the single Hy's law case. Complicated case. Continued to look at it. Looking at that as part of this blinded review, we've made this determination. And at the time, I mentioned when we first reported it that this is how we had reported it to the FDA. Now, I also mentioned in our NDA we're saying that this wasn't a Hy's law case, and we wanted to make sure that we reported that to you as well. And then the second question was on 3x weekly versus daily. And the 3x weekly dosing is important for the in-center dialysis. We have those studies ongoing. We expect to have data at launch, and that will allow us to submit a supplemental NDA quickly. But one of the interesting kind of things that's happening in the dialysis treatment is that there's a really significant push towards home dialysis. And whether that's the COVID impact, which is clear, there are some reimbursement schemes that are pushing people to expand that program and the dialysis providers want to expand those programs. And that's less than 20% of the market today, but the fastest growing part of the market. And we think that having the once-a-day option for those patients is ideal, and we think that will be something that people will want to adopt quickly.

當然。所以首先是 Hy 的法律案例。我們有 - 這是一個複雜的案例。我怎麼強調都不過分。有一位患者的肝酶水平非常高，但從未住院，也從未出現過症狀。但我們在報告時表示，我們一直在查看我們的數據。現在發布 PRO2TECT 和 INNO2VATE，我們正在研究 8,000 名患者。我們能夠讓外部專家小組進行盲法評估，並使用該鏡頭和 8,000 多個鏡頭查看所有數據。除了 Hy 的法律案例之外，事實上 vadadustat 與 darbepoetin，一種從未被證明對肝臟有任何影響的產品，我們確定它們之間確實沒有區別。因此，這是一個非常重要的發現，與單一的 Hy 案類似。複雜的情況。繼續看下去。將其視為本次盲審的一部分，我們做出了這個決定。當時，我提到當我們第一次報告它時，我們就是這樣向 FDA 報告的。現在，我還在我們的 NDA 中提到，我們說這不是 Hy 的法律案件，我們想確保我們也向您報告了這一點。然後第二個問題是每週 3 次與每天 3 次。每週 3 次給藥對於中心透析很重要。我們正在進行這些研究。我們希望在發佈時獲得數據，這將使我們能夠快速提交補充 NDA。但在透析治療中發生的一件有趣的事情是，家庭透析得到了巨大的推動。很明顯，這是否是 COVID 的影響，有一些報銷計劃正在推動人們擴大該計劃，而透析提供者希望擴大這些計劃。這還不到今天市場的 20%，但卻是市場增長最快的部分。我們認為為這些患者提供每天一次的選擇是理想的，我們認為這將是人們希望迅速採用的東西。

Our next question comes from Ed Arce with H.C. Wainwright.

我們的下一個問題來自 Ed Arce 和 H.C.溫賴特。

Just a couple. I just wanted to ask, John, if you could discuss in a bit more detail your mention of the analysis of PRO2TECT and how it was found that the excess of deaths were primarily non-cardiovascular and in patients ex-U. S. If you could just give us a bit more detail around what you found. And also, is there any possibility, given -- does that -- I guess, does that give you increased confidence of a potential for the approval in non-dialysis?

只是一對。我只是想問，約翰，你是否可以更詳細地討論你提到的 PRO2TECT 分析，以及如何發現過量死亡主要是非心血管疾病和前美國患者。S. 如果您能就您的發現向我們提供更多詳細信息。而且，是否有任何可能性，鑑於 - 我猜，這是否讓你對非透析批准的潛力更有信心？

Ed, thanks for the question. It's an important one. And I think I want to make sure I say upfront again that we did miss the overall primary safety endpoint. And that is -- with that, I think we should all be cautious. But at the end of the day the question is, what's the cardiovascular safety profile of the product? And as I mentioned, when you look at that ex-U. S. population, you did see the excess mortality was driven by non-cardiovascular and deaths of unknown cause. And very importantly, when you think about how non-dialysis patients are treated globally and you look at some of the markets here, they're just very different treatment paradigms for non-dialysis patients around when they start therapy, whether they're offered dialysis or not, et cetera. And there's no smoking gun here. But when you look at the overall picture and then you look at that U.S. data, which we know how patients are treated very consistently there, we think that that demonstrates that vadadustat does have an acceptable risk. And I think also when you think about dialysis treatment, dialysis treatment is much more homogeneous across the world once you start dialysis. And look at the INNO2VATE data. It was very consistent globally. So we still missed the primary safety endpoint. This will be a review issue. But we think it's the right thing for patients to file -- to submit an application for both the dialysis and non-dialysis indications.

埃德，謝謝你的問題。這是一個重要的。而且我想我想確保我再次預先聲明我們確實錯過了總體主要安全終點。那就是——有了這個，我認為我們都應該保持謹慎。但歸根結底，問題是該產品的心血管安全性如何？正如我提到的，當你看那個前 U 時。S. population，你確實看到過高的死亡率是由非心血管疾病和不明原因的死亡造成的。非常重要的是，當您考慮全球如何治療非透析患者並查看這裡的一些市場時，它們只是非透析患者開始治療時的非常不同的治療模式，無論是否提供透析與否，等等。而且這裡沒有確鑿的證據。但是，當您查看整體情況，然後查看美國數據時，我們知道那裡的患者是如何得到非常一致的治療的，我們認為這表明 vadadustat 確實具有可接受的風險。我還認為，當您考慮透析治療時，一旦您開始透析，透析治療在世界範圍內就會變得更加同質化。並查看 INNO2VATE 數據。它在全球範圍內非常一致。所以我們仍然錯過了主要的安全終點。這將是一個審查問題。但我們認為患者提交申請是正確的——同時提交透析和非透析適應症的申請。

Okay. Great. That's helpful. Then just one other question you had touched upon earlier with regards to the negative impacts of COVID-19 on future Auryxia growth. I was just curious as to why -- I think you said that the impacts really weren't felt until the fourth quarter and are expected to continue through at least the foreseeable future into this year. Just curious as to what specifically you think was missing in the second and third quarter that led to negligible impacts there.

好的。偉大的。這很有幫助。然後是您之前提到的另一個問題，即 COVID-19 對 Auryxia 未來增長的負面影響。我只是想知道為什麼 - 我想你說過直到第四季度才真正感受到影響，並且預計至少在可預見的未來會持續到今年。只是想知道您認為第二季度和第三季度具體缺少什麼導致那裡的影響可以忽略不計。

It's a great question, Ed. And I think when you look at how the pandemic impacted across the country, you saw more regional differences, whereas kind of post the summer you saw much more across the U.S. impact. And it all just kind of layers on top of each other. And as I mentioned, the Auryxia prescriptions grew across the year because I think that the messaging that we're delivering is having an impact, but the overall market is shrinking. So it may have been kind of muted a little bit in what we were seeing. But clearly, as we go into the fourth quarter, as I said, we still grew in the fourth quarter; just not to the extent that we had expected. And then when you look at the caution that we're hearing from the people who are treating these patients, I think it just behooves us to reflect that caution to you as well.

這是一個很好的問題，埃德。而且我認為，當您查看大流行如何影響全國時，您會看到更多的地區差異，而在夏季之後，您會看到更多的美國影響。這一切都只是一層一層地疊加在一起。正如我所提到的，Auryxia 處方藥全年都在增長，因為我認為我們傳遞的信息正在產生影響，但整體市場正在萎縮。因此，我們所看到的可能有點靜音。但很明顯，當我們進入第四季度時，正如我所說，我們在第四季度仍在增長；只是沒有達到我們預期的程度。然後當你看到我們從治療這些患者的人那裡聽到的警告時，我認為我們也應該向你反映這種警告。

And our next question comes from David Lebowitz with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 David Lebowitz。

When you think about Auryxia going into the first quarter, do you expect to see a similar disruption with respect to the IDA, I guess re-approval, so to speak.

當你想到 Auryxia 進入第一季度時，你是否期望看到與 IDA 相關的類似中斷，我想重新批准，可以這麼說。

Reauthorizations.

重新授權。

Reauthorization.

重新授權。

Yes. Yes, certainly. That's an annual event for us at this point to ensure that all of the patients who are on have a reauthorization. Team did a great job with that last year. I think similarly they're doing that this year. But it's still an impact. There's no question. I think when we look at 2020 versus 2019, you saw much less stark difference. But what's really the challenge here is to layer on what's COVID -- how is COVID going to impact this as well? Is it we're seeing softness because of the reauthorizations, we'll get those done and climb? Or is it we're actually losing patients from the market? And that's what we have to work on. And really it's just to say that Q1 is always soft, but be cautious about kind of how COVID's going to impact us.

是的。是的，當然了。在這一點上，這是我們的年度活動，以確保所有接受治療的患者都獲得重新授權。團隊去年在這方面做得很好。我認為他們今年也在這樣做。但還是有影響的。毫無疑問。我認為當我們比較 2020 年與 2019 年時，你會發現差異要小得多。但是，這裡真正的挑戰是對什麼是 COVID 進行分層——COVID 將如何影響這一點？我們是否因為重新授權而看到疲軟，我們會完成這些並攀升？還是我們實際上正在從市場上流失患者？這就是我們必須努力的。實際上，這只是說 Q1 總是疲軟，但要謹慎對待 COVID 將如何影響我們。

And on R&D, clearly the numbers are stepping down as the Phase III program is done. Should we look at 4Q as the run rate, or will it continue to step down as we move into next year?

而在研發方面，顯然隨著第三階段計劃的完成，數字正在下降。我們應該將第 4 季度的運行率視為運行率，還是會隨著我們進入明年而繼續下降？

Yes. So we're not providing specific guidance on the ramp. But I think what I would just give context is while the Phase IIIs do continue to wind down from an expense perspective, we are investing in the supply chain build for vadadustat globally before its approval. So we can't capitalize any of the inventory yet. It will run through the R&D expense line.

是的。所以我們沒有提供關於坡道的具體指導。但我想我只想提供背景信息，雖然從費用角度來看，第三階段確實繼續結束，但我們正在投資 vadadustat 在全球範圍內的供應鏈建設，然後再獲得批准。所以我們還不能將任何庫存資本化。它將貫穿研發費用線。

Okay.

好的。

And we do have the other studies like MODIFY and FOCUS, the 3x weekly study. So there's still a significant rate of R&D. Certainly not like we had with INNO2VATE and PRO2TECT.

我們確實有其他研究，例如 MODIFY 和 FOCUS，每週 3 次研究。因此，研發速度仍然很高。當然不像我們使用 INNO2VATE 和 PRO2TECT 那樣。

Sure. Makes sense. And then I guess my last question on milestones. I know originally we had anticipated milestones in 2021. Where -- how should we think about milestones payments relative to the submission and approval for vadadustat now in the context of how things have shifted?

當然。說得通。然後我想我最後一個關於里程碑的問題。我知道最初我們曾預計 2021 年的里程碑。在哪裡——在事情發生變化的背景下，我們現在應該如何考慮與 vadadustat 的提交和批准相關的里程碑付款？

Yes. So I would say I don't think anything has shifted. We're still on track. And we just provide the guidance on submitting the NDA by mid-second quarter. The milestones themselves are due to us upon approval in the U.S. and Europe and tied to the DD and NDD indications.

是的。所以我會說我認為沒有任何變化。我們仍在軌道上。我們只是提供了在第二季度中期提交 NDA 的指導。里程碑本身是由於我們在美國和歐洲獲得批准並與 DD 和 NDD 適應症相關聯。

So that would likely be 2022. Is it based on -- is the $250 million, is it half for each indication, so $125 million per indication? Or is it just $250 million collectively for an approval overall?

所以那可能是 2022 年。它是基於 - 是 2.5 億美元，是每個適應症的一半，所以每個適應症 1.25 億美元？或者總共只有 2.5 億美元才能獲得批准？

So we can -- we haven't really disclosed what each of the individual milestones are and what their breakouts are. But you can assume that there are various milestones that are attached to U.S DD, U.S. NDD, ex-U. S., et cetera.

所以我們可以——我們還沒有真正披露每個里程碑是什麼以及它們的突破是什麼。但是您可以假設有各種里程碑附加到美國 DD、美國 NDD、ex-U。S.等。

Right. For Otsuka.

正確的。為了大塚。

For Otsuka, yes. Sorry.

對於大塚來說，是的。對不起。

Our next question comes from Eric Joseph with JPMorgan.

我們的下一個問題來自摩根大通的埃里克約瑟夫。

First, would be curious to get your thoughts on how conducive the current COVID environment is for new product launches and hip uptake and whether COVID is a net positive or negative, in your view, for vadadustat, assuming it's first to market with its approval -- potential approval later this quarter. And then just following up on your comments on home dialysis, how high do you see -- do you ultimately see that trending as you report on those overall dialysis patients? And how should we be thinking about the splitting up with the commercial and detailing effort between you, Otsuka and Vifor in that patient population?

首先，很想知道您對當前 COVID 環境對新產品發布和臀部吸收有多大幫助的想法，以及在您看來，對於 vadadustat 而言，COVID 是淨正面還是負面，假設它是第一個獲得批准的市場 - - 本季度晚些時候可能獲得批准。然後就您對家庭透析的評論進行跟進，您認為有多高——您在報告所有透析患者時最終是否看到了這種趨勢？我們應該如何考慮您、Otsuka 和 Vifor 在該患者群體中分拆商業和細節工作？

Sure. So I won't comment on another product's launch. Obviously COVID has impacted everything about how we do, and Chris mentioned the more challenging access for our reps. As we think about it, that's something we're working to get around. I'm sure other companies in the space are all working to try to get to physicians. It is clear when we think about our access to physicians in dialysis, with the kind of impact you're having for COVID in dialysis patients, physicians are really focused on keeping their patients alive and getting them vaccinated. And as I think about Auryxia, I've been really pleased with the growth that we've seen, given that focus hasn't been on changing care or doing new things. It's been on just kind of keeping folks in the chair and healthy and alive. So I think that's just a backdrop that until our population is fully vaccinated, it is going to be a challenge for them. And as I mentioned on the home dialysis side, it's -- there were some very aggressive goals that were set out and during the Trump administration when they had this focus on -- American focus on kidney health, that we're kind of looking for at least 1/4 of new patients to be on home dialysis, I can't remember exactly when, within a few years. That was pretty aggressive. It does take more to get a patient on home dialysis than it does on in-center dialysis. But patients want it, the government wants it and dialysis providers want to provide it. And to be -- to remain competitive, they'll have to move in that direction. So they're all looking at how they can grow their home programs. Exactly where that lands, obviously I'm not sure. But it is -- as I said, it's sub-20% of the market today. That will grow significantly because it's growing quickly, and we'll see together. But that's going to be very important. And when we have conversations with physicians, this is -- that's the kind of market that they just get extremely excited about having a once-a-day oral product to deliver to patients, and not in a small way. That's also -- Auryxia is also an important product in the home market as well. So we've got a lot of traction there as well.

當然。所以我不會評論其他產品的發布。顯然 COVID 影響了我們工作方式的方方面面，Chris 提到了對我們的代表來說更具挑戰性的訪問。正如我們所考慮的那樣，這是我們正在努力解決的問題。我敢肯定，該領域的其他公司都在努力爭取醫生。很明顯，當我們考慮我們在透析中接觸醫生時，以及您對 COVID 對透析患者產生的影響，醫生真正關注的是讓他們的患者活著並讓他們接種疫苗。當我想到 Auryxia 時，我對我們所看到的增長感到非常高興，因為重點並沒有放在改變護理或做新事物上。它只是讓人們坐在椅子上，保持健康和活力。所以我認為這只是一個背景，在我們的人口完全接種疫苗之前，這對他們來說將是一個挑戰。正如我在家庭透析方面提到的那樣，它是 - 在特朗普政府期間制定了一些非常積極的目標，當時他們關注 - 美國人對腎臟健康的關注，我們正在尋找至少有 1/4 的新患者要在家接受透析，具體時間我記不清了，應該是幾年之內。那是相當激進的。與中心透析相比，讓患者進行家庭透析確實需要更多時間。但患者想要它，政府想要它，透析提供者想要提供它。為了保持競爭力，他們必須朝那個方向前進。所以他們都在研究如何發展他們的家庭項目。確切地落在哪裡，顯然我不確定。但它是——正如我所說，它在今天的市場中所佔比例不到 20%。這將顯著增長，因為它正在快速增長，我們將共同見證。但這將非常重要。當我們與醫生交談時，這就是他們對每天一次口服產品提供給患者的那種市場感到非常興奮，而且不是很小的方式。這也是——Auryxia 也是國內市場的重要產品。所以我們在那裡也有很大的吸引力。

Okay. Great. And maybe just a follow-up. You said on -- with respect to 3x weekly and having data on that administration profile at launch, can you just kind of clarify what the studies you are referring to there and whether we should anticipate results from the FO2RWARD-2 trial which completed? And it's a fairly decently sized trial ahead of a launch, approval and launch of vadadustat.

好的。偉大的。也許只是一個後續行動。你說——關於每週 3 次並在發佈時有關於該管理概況的數據，你能否澄清一下你在那裡指的是什麼研究，以及我們是否應該預期已完成的 FO2RWARD-2 試驗的結果？在 vadadustat 的發布、批准和發布之前，這是一個規模相當大的試驗。

Yes. FO2RWARD-2 was a small trial that was kind of really asking a lot of different questions. We have that data. We'll be presenting that at a scientific meeting. The studies that really are going to underpin the 3x weekly supplemental NDA are the MODIFY study, which our partner, Otsuka, is running in the U.S. and in Europe, and FOCUS, which we're running here in the U.S., and both of those studies are ongoing. And as I said, we do expect to have data from them both by the time we launch vadadustat in the U.S., and obviously, we'll report that data and then use it to quickly file a supplemental NDA for that dosing regimen.

是的。FO2RWARD-2 是一個小型試驗，實際上是在問很多不同的問題。我們有這些數據。我們將在科學會議上展示它。真正支持 3 倍每週補充 NDA 的研究是我們的合作夥伴 Otsuka 在美國和歐洲開展的 MODIFY 研究，以及我們在美國開展的 FOCUS 研究，以及這兩項研究研究正在進行中。正如我所說，我們確實希望在美國推出 vadadustat 時從他們那裡獲得數據，顯然，我們將報告該數據，然後使用它快速提交該劑量方案的補充 NDA。

Okay. Got it.

好的。知道了。

And currently, I'm showing no further questions. At this time, I'd like to turn the call back over to Mr. John Butler for closing comments.

目前，我沒有再提出任何問題。此時，我想將電話轉回給約翰·巴特勒先生以徵求意見。

Thank you, Norma, and thanks, everyone, for joining us this morning. We look forward to updating you on what will be an exciting 2021 for Akebia. Thank you all for joining.

謝謝 Norma，也謝謝大家今天早上加入我們。我們期待著向您介紹 Akebia 令人興奮的 2021 年。謝謝大家的加入。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.

女士們，先生們，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。每個人都有美好的一天。