Protagonist Therapeutics, Inc. (PTGX) 2020 Q4 法說會逐字稿

Good afternoon, and welcome to Protagonist Therapeutics Fourth Quarter and Full Year 2020 Earnings Conference Call and Audio Webcast. (Operator Instructions) Please be advised that today's webcast is being recorded. (Operator Instructions)

下午好，歡迎參加 Protagonist Therapeutics 2020 年第四季和全年財報電話會議和音訊網路廣播。 （操作員指示）請注意，今天的網路廣播正在錄製。 （操作員指令）

With that, I would like to hand the conference over to our first speaker, Don Kalkofen, Chief Financial Adviser -- Chief Financial Officer. Thank you, and please go ahead.

現在，我想將會議交給我們的第一位發言人，財務顧問兼財務長唐‧卡爾科芬 (Don Kalkofen)。謝謝您，請繼續。

Thank you for joining us today. As a reminder, certain matters discussed in today's conference call and/or the answers we may be giving to questions asked may include forward-looking statements that are subject to risks and uncertainties related to the future events and/or financial performance of the company. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors sections of our annual report on Form 10-K for the year ended December 31, 2020, on file with the SEC.

感謝您今天加入我們。提醒一下，今天的電話會議中討論的某些事項和/或我們可能對所提問題給出的答案可能包括前瞻性陳述，這些陳述受與公司未來事件和/或財務業績相關的風險和不確定性的影響。由於各種重要因素，包括我們向美國證券交易委員會提交的截至 2020 年 12 月 31 日的 10-K 表年度報告中「風險因素」部分中討論的因素，實際結果可能與這些前瞻性陳述所示的結果存在重大差異。

A question-and-answer session will follow the formal presentation. And just as a reminder, the call is being recorded.

正式演講結束後將進行問答環節。提醒一下，通話正在錄音。

I'd now like to turn the call over to Dinesh Patel, President and CEO of Protagonist to provide a company update.

現在，我想將電話轉給 Protagonist 總裁兼執行長 Dinesh Patel，以提供公司的最新進展。

Thank you, Don. Good afternoon, everyone, and thank you all for joining our conference call to discuss Protagonist Therapeutics' Financial Results and Corporate Highlights for the Fourth Quarter and Full Year 2020. Don and I are joined on today's call by Samuel Saks, our Chief Medical Officer; David Liu, our Chief Scientific Officer; and Suneel Gupta, Chief Development Officer.

謝謝你，唐。大家下午好，感謝大家參加我們的電話會議，討論 Protagonist Therapeutics 2020 年第四季度和全年的財務業績和公司亮點。我們的首席科學官 David Liu；以及首席開發長 Suneel Gupta。

2020 was an exceptional and transformative year for Protagonist during which we expanded our clinical pipeline, and we now have 5 different new chemical entities or NCEs that are being advanced in 6 different clinical studies. And all of these studies are expected to be completed over the next 2 years.

2020 年對 Protagonist 來說是特殊而變革的一年，在這一年中，我們擴展了臨床產品線，現在我們擁有 5 種不同的新化學實體或 NCE，正在 6 個不同的臨床研究中推進。所有這些研究預計將在未來兩年內完成。

As many of you know, each of our clinical asset has been developed through our proprietary technology platform. And currently, we are developing novel therapeutic options across 3 distinct disease categories: one, various blood disorders influenced by excessive red blood cell production that is excessive erythrocytosis or by excessive iron overload conditions; two, inflammatory bowel disease or IBD, such as Crohn's disease and ulcerative colitis; and three, various inflammatory and autoimmune diseases that have already been clinically validated by the Interleukin-23 or IL-23 pathway.

眾所周知，我們的每項臨床資產都是透過我們的專有技術平台開發的。目前，我們正在針對 3 種不同疾病類別開發新的治療方案：一、因紅血球生成過多（即紅血球增多症過多或鐵超負荷）而導致的各種血液疾病；二、發炎性腸道疾病或IBD，例如克隆氏症和潰瘍性結腸炎；三、已經透過白血球介素-23或IL-23路徑進行臨床驗證的各種發炎和自體免疫疾病。

I would like to start today's call by reviewing rusfertide, previously known as PTG-300. As a reminder, rusfertide is a peptide mimetic of the natural hormone hepcidin, which is the key regulator of iron homeostasis, as it controls the absorption, storage and distribution of iron in the body. Rusfertide was developed to have superior drug-like properties, including its potency, half-life solubility, stability and ease of synthesis in comparison to the natural hormone.

我想透過回顧 rusfertide（以前稱為 PTG-300）來開始今天的電話會議。提醒一下，rusfertide 是天然荷爾蒙鐵調素的勝肽類似物，它是鐵穩態的關鍵調節劑，因為它控制著體內鐵的吸收、儲存和分佈。與天然激素相比，Rusfertide 具有更優異的類藥物特性，包括效力、半衰期溶解度、穩定性和易於合成。

Our most-advanced clinical program with this candidate is in patients with polycythemia vera, also known as PV, a rare and progressive blood disorder affecting about 160,000 patients in the United States alone. In May of 2020, we presented a very small but robust data set for 7 patients from our ongoing Phase II PV trial, and that proved to be a turning point for Protagonist. In December last year, in an oral presentation at the ASH Conference, we shared the data for 18 patients from the same study, and we're pleased to see the continuation of the robust clinical responses observed earlier in May.

我們針對該候選藥物最先進的臨床項目是針對真性紅血球增多症（也稱為 PV）患者，這是一種罕見的進行性血液疾病，僅在美國就影響了約 16 萬名患者。 2020 年 5 月，我們展示了正在進行的 II 期 PV 試驗中 7 名患者的非常小但可靠的數據集，事實證明這是 Protagonist 的轉折點。去年 12 月，在 ASH 大會的口頭報告中，我們分享了同一項研究中 18 名患者的數據，我們很高興看到 5 月初觀察到的強勁臨床反應得以延續。

To quickly recap the data, rusfertide appears to be safe, well tolerated and very effective in managing hematocrit control below 45% across the 18 adult patients evaluated. This tight hematocrit control also led to a dramatic decrease in the need for therapeutic phlebotomy, the most common treatment modality for this condition. Furthermore, we also observed a reversal of iron deficiency in these patients. Iron deficiency is a typical undesired outcome of therapeutic phlebotomy in these patients.

快速回顧一下數據，在接受評估的 18 名成年患者中，rusfertide 似乎是安全的、耐受性良好的，並且在將血球容積比控制在 45% 以下方面非常有效。嚴格的血球容積比控制也導致治療性放血療法（此症最常見的治療方式）的需求急劇減少。此外，我們也觀察到這些患者的缺鐵症狀有逆轉。對這些患者來說，缺鐵是治療性放血的典型不良後果。

While phlebotomy is the current mainstay of PV treatment, many patients are unable to maintain hematocrit levels below 45% as per the NCCN Guidelines. And this is unfortunately true even for those patients receiving frequent phlebotomies and receiving treatment with cytoreductive agents.

儘管靜脈切開術是目前 PV 治療的主要方法，但許多患者無法按照 NCCN 指南將血球比容維持在 45% 以下。不幸的是，即使對於那些接受頻繁放血和接受細胞減滅劑治療的患者來說，情況也是如此。

So to develop a clear understanding of the current treatment regimen and evaluate it through effectiveness, last year, we took a large-scale retrospective analysis of real-world patient data of over 28,000 patients, and we also obtained hematocrit measurements from blood test results for a subgroup of over 4,000 patients. Our findings were an eye-opener, and it showed that hematocrit levels were poorly managed for a majority of patients. In fact, only 22% of the patients on current treatment had consistent adherence to NCCN Guidelines of keeping hematocrit below 45%. This is concerning at many levels, including the fact that with high hematocrit levels, PV patients may be exposed to higher risk of life-threatening thrombotic events. This analysis further confirms our belief that there is a large and glaring need for better treatment options for these PV patients.

因此，為了清楚了解目前的治療方案並透過有效性進行評估，去年我們對超過 28,000 名患者的真實患者數據進行了大規模回顧性分析，並且還從超過 4,000 名患者的亞組血液測試結果中獲得了血細胞比容測量值。我們的發現令人大開眼界，它顯示大多數患者的血球容積比水平管理不佳。事實上，目前接受治療的患者中只有 22% 始終遵循 NCCN 指南，將血球容積比保持在 45% 以下。這在許多層面上都令人擔憂，其中包括，由於血細胞比容水平高，真性紅血球增多症患者可能面臨更高的危及生命的血栓事件風險。這項分析進一步證實了我們的信念：這些 PV 患者迫切需要更好的治療選擇。

Based on our promising Phase II results, we believe that a natural hormone mimetic like rusfertide can potentially provide PV patients with a safe, noncytoreductive and effective therapy that improves upon the standard of care options, not only for patients receiving frequent phlebotomy, but also for patients who continue to receive phlebotomies in combination with other pharmaceutical treatments. Our ongoing Phase II rusfertide PV study is progressing on track. Recruitment has, in fact, recently accelerated, and we expect to complete the enrollment of 50 patients by mid-2021.

根據我們令人鼓舞的 II 期結果，我們相信像 rusfertide 這樣的天然荷爾蒙模擬物可以為 PV 患者提供安全、非細胞減滅性和有效的治療方法，從而改善護理選擇的標準，不僅適用於頻繁接受靜脈穿刺的患者，也適用於繼續接受靜脈穿刺與其他藥物治療相結合的患者。我們正在進行的第二階段 rusfertide PV 研究正在順利進行中。事實上，招募工作最近已經加快，我們預計到 2021 年中期將完成 50 名患者的招募。

With the compelling clinical trial data in hand, we are consulting with U.S. regulatory authorities in the first half of 2021 to discuss and finalize our registrational study plan. I would also add that rusfertide has received Fast Track designation for PV from the U.S. FDA, and orphan drug designation from both the U.S. and European regulatory agencies. The advancement of rusfertide to a pivotal trial in this indication will be a key turning point for Protagonist in 2021. In the future, if approved, it's possible that rusfertide could reshape the treatment paradigm in PV and become the main long-term noncytoreductive therapy of choice for many patients living with this challenging condition.

憑藉手頭上令人信服的臨床試驗數據，我們將在 2021 年上半年與美國監管機構進行磋商，討論並最終確定我們的註冊研究計劃。我還要補充一點，rusfertide 已獲得美國 FDA 頒發的 PV 快速通道資格，以及美國和歐洲監管機構頒發的孤兒藥資格。拉菲替肽推進至此適應症的關鍵試驗將成為 Protagonist 在 2021 年的關鍵轉折點。

Now, rusfertide's clinical momentum does not stop at PV. We are also evaluating this candidate for hereditary hemochromatosis, or HH, in an open-label Phase II proof-of-concept study. HH is a disease characterized by iron overload where persistent iron overload can lead to heart and liver damage that could ultimately lead to more life-threatening situations. Today, HH impacts approximately 1 million patients in the U.S. and Canada, and phlebotomy is the only therapeutic option for these patients. There are no FDA-approved drugs for this indication. Efforts are also underway by us to better understand which subpopulations of this 1 million HH patients may derive maximal benefit from a drug like rusfertide in comparison to phlebotomy.

現在，rusfertide 的臨床發展勢頭不止於 PV。我們也在一項開放標籤 II 期概念驗證研究中評估此遺傳性血色素沉著症（HH）候選藥物。 HH 是一種以鐵超載為特徵的疾病，持續的鐵超載會導致心臟和肝臟損害，最終可能導致更危及生命的情況。如今，HH 影響著美國和加拿大約 100 萬名患者，而放血療法是這些患者唯一的治療選擇。目前尚無 FDA 核准用於治療該症狀的藥物。我們也正在努力更了解這 100 萬 HH 患者中的哪些亞群可以從像 Rusfertide 這樣的藥物（與靜脈放血相比）中獲得最大益處。

We are pleased with the progress of the current Phase II study, and we should be able to share preliminary results in the second half of the year. Based on these results, we will determine next steps and the path forward for rusfertide in the indication of hereditary hemochromatosis.

我們對目前第二階段研究的進展感到滿意，我們應該能夠在今年下半年分享初步結果。基於這些結果，我們將確定魯斯菲特在治療遺傳性血色素沉著症方面的下一步和發展方向。

Beyond PV and HH, we are actively evaluating additional indications for rusfertide and plan to select one new therapeutic program for rusfertide in 2021. The core idea is to capitalize on the excellent clinical attributes of this natural hormone mimetic and expand its utility to multiple diseases influenced by excessive iron accumulation or erythrocytosis in patients. Finally, we are also working on an oral hepcidin mimetic, which may ultimately bring more convenience and preferred options to patients with certain conditions.

除了 PV 和 HH，我們正在積極評估 rusfertide 的其他適應症，併計劃在 2021 年為 rusfertide 選擇一種新的治療方案。最後，我們也正在研究口服鐵調素類似物，這最終可能會為患有某些疾病的患者帶來更多便利和優先選擇。

Now I would like to turn the conversation towards inflammatory bowel disease, or IBD program. First, let us talk about our fully-owned asset, PN-943 in the IBD space. PN-943 is a first-in-class orally delivered, gut-restricted antagonist of alpha-4-beta-7 integrin, a validated biological target for IBD. We believe the gut-restricted alpha-4-beta-7 integrin blockade is unique and potentially groundbreaking in treating IBD as it allows us to achieve receptor target engagement directly and locally in the GI tissue compartment.

現在我想討論一下發炎性腸道疾病（或稱為 IBD 計劃）。首先，讓我們來談談 IBD 領域的全資資產 PN-943。 PN-943 是同類首創的口服、腸道限制性 α-4-β-7 整合素拮抗劑，是 IBD 的經過驗證的生物學標靶。我們相信腸道限制的 α-4-β-7 整合素阻斷在治療 IBD 方面是獨一無二的並且具有突破性的意義，因為它使我們能夠在胃腸道組織區室直接局部實現受體標靶的結合。

More importantly, let me remind you that we have already established clinical proof-of-concept through a Phase IIa study in patients with moderate-to-severe ulcerative colitis with our first-generation drug, PTG-100. PN-943 is our second-generation drug that is at least threefold more potent across all in vitro, in vivo, preclinical and clinical measures of potency and efficacy that we have assembled to date. We continue to advance our 150-patient Phase II IDEAL study, evaluating the safety, tolerability and efficacy of PN-943 in ulcerative colitis. While we stop providing guidance in 2021 for this study because of COVID-19-related impact on enrollment, we are very pleased with the current enrollment rates and are forecasting the completion of this global study in 2022.

更重要的是，讓我提醒您，我們已經透過對中度至重度潰瘍性結腸炎患者進行的 IIa 期研究建立了第一代藥物 PTG-100 的臨床概念驗證。 PN-943 是我們的第二代藥物，根據我們迄今為止收集的所有體外、體內、臨床前和臨床效力和功效測量結果，其效力至少提高了三倍。我們繼續推進涉及 150 名患者的 II 期 IDEAL 研究，評估 PN-943 在潰瘍性結腸炎中的安全性、耐受性和有效性。雖然由於 COVID-19 對入學人數的影響，我們將於 2021 年停止為這項研究提供指導，但我們對目前的入學率非常滿意，並預測這項全球研究將於 2022 年完成。

Finally, I'll discuss the ongoing strategic collaboration with Janssen Pharmaceuticals. The partnership was initiated 3.5 years ago with a $50 million upfront and now an additional $30 million have been earned so far from achievement of various milestones. It is a very rewarding deal structure with more milestones in the future and up to double-digit royalties and U.S. co-detailing rights. It's also a very productive collaboration, with now a portfolio of 3 distant candidates in different stages of clinical development.

最後，我將討論與楊森製藥公司正在進行的策略合作。該合作關係於三年半前啟動，首期投入 5,000 萬美元，目前已透過實現各個里程碑額外賺取 3,000 萬美元。這是一個非常有益的交易結構，未來將有更多的里程碑以及高達兩位數的特許權使用費和美國共同詳述權。這也是一次非常有成效的合作，目前已有 3 位遠距候選人處於臨床開發的不同階段。

The Janssen-Protagonist partnership aims to discover and develop oral IL-23 receptor antagonist with application in various diseases that could be approached with the blockade of the IL-23 pathway. While the pathway is a validated therapeutic mechanism, orally delivered therapies for blocking this pathway have not yet been made available. With our collaboration with Janssen, we are working to change the treatment paradigm through differentiated assets that could facilitate transition from injectable to oral-targeted therapy.

楊森與 Protagonist 合作旨在發現和開發口服 IL-23 受體拮抗劑，以應用於可透過阻斷 IL-23 路徑治療的各種疾病。雖然該途徑是一種經過驗證的治療機制，但尚未出現用於阻斷該途徑的口服療法。透過與楊森的合作，我們致力於透過差異化資產改變治療模式，促進從注射治療到口服標靶治療的轉變。

In the past few months, we added 2 new entities, PN-235 and 232 to the clinical development program with Janssen, in addition to the first collaboration asset, PTG-200. A Phase I trial of 235 and a Phase I trial of 232 are expected to be completed in the second half of 2021. Additionally, for PTG-200, enrollment continues for patients in a Phase II proof-of-concept study for Crohn's disease. All 3 candidates were discovered through our peptide technology platform, which further demonstrates our versatility in finding therapies where there are no adequate treatment options. The multiple products should provide numerous strategic and clinical development options to Janssen and Protagonist.

在過去的幾個月裡，除了第一個合作資產 PTG-200 之外，我們還在與 Janssen 的臨床開發專案中增加了 2 個新實體，PN-235 和 232。 235 的 I 期試驗和 232 的 I 期試驗預計將於 2021 年下半年完成。所有 3 種候選藥物都是透過我們的勝肽技術平台發現的，這進一步證明了我們在沒有足夠治療選擇的情況下尋找治療方法的多功能性。這多種產品將為楊森和 Protagonist 提供眾多策略和臨床開發選擇。

So in summary, we are incredibly excited with simultaneous progress in 3 specific categories: one, the rusfertide program for polycythemia vera and hereditary hemochromatosis; two, advancement of the gut-restricted oral integrin blocker PN-943 in ulcerative colitis; and three, progression of 3 different oral IL-23 receptor antagonist in clinical development in partnership with Janssen to treat various inflammatory and autoimmune diseases.

總而言之，我們對 3 個特定類別同時取得的進展感到非常興奮：一是針對真性紅血球增多症和遺傳性血色素沉著症的 Rusfertide 計劃；二、腸道限制性口服整合素阻斷劑PN-943在潰瘍性結腸炎治療的進展；三、與楊森合作，在臨床開發中推進 3 種不同的口服 IL-23 受體拮抗劑用於治療各種發炎和自體免疫疾病。

With that, I would now like to turn the call over to our CFO, Don Kalkofen. Don?

說完這些，我現在想將電話轉給我們的財務長唐卡爾科芬 (Don Kalkofen)。大學教師？

Thank you, Dinesh. Once again, thank you all for joining us this afternoon. Today, we issued our earnings release for year-end 2020 and are filing our 10-K, where you can find further details on our most recent financials. On the call today, I'd like to review some of the key financial highlights for 2020.

謝謝你，Dinesh。再次感謝大家今天下午加入我們。今天，我們發布了 2020 年底的收益報告並提交了 10-K 報表，您可以在其中找到有關我們最新財務狀況的更多詳細資訊。在今天的電話會議上，我想回顧一下 2020 年的一些關鍵財務亮點。

So starting with our revenue. We reported license and collaboration revenue for the full year of 2020 of $28.6 million as compared to $0.2 million for the full year of 2019. As you may recall, last year, the company's 2019 revenue was offset by a onetime cumulative adjustment related to the application of revenue recognition principles, following the amendment of the Janssen Biotech agreement in May of '19. This had reduced the 2019 revenue recognition by $9.4 million. The 2020 revenue increase over prior year was also related to recognition of revenue from providing preclinical and clinical development activities under the collaboration agreement with Janssen for both new assets, PN-235 and PN-232 as well as an update to the forecast of the remaining services to be delivered under the collaboration. License and collaboration revenue for the fourth quarter of 2020 was $5.7 million compared to $2.7 million for the same period of 2019.

所以從我們的收入開始。我們報告稱，2020 年全年許可和合作收入為 2860 萬美元，而 2019 年全年為 20 萬美元。 您可能還記得，去年，在 19 年 5 月修訂 Janssen Biotech 協議後，該公司 2019 年的收入被與應用收入確認原則相關的一次性累計調整原則所抵消。這使得 2019 年的收入確認減少了 940 萬美元。 2020 年收入較上年增加也與根據與 Janssen 達成的合作協議為新資產 PN-235 和 PN-232 提供臨床前和臨床開發活動的收入確認以及對合作下將提供的剩餘服務的預測更新有關。 2020 年第四季的授權和合作收入為 570 萬美元，而 2019 年同期為 270 萬美元。

Moving on to our expenses. Our research and development expenses were $74.5 million for the full year of 2020, up from $65 million for the full year of 2019, and our fourth quarter R&D expenses were $19.5 million for the quarter ended 2020, up from $15.9 million for the fourth quarter of 2019. The increases in R&D expenses in 2020 were primarily due to the advancing of our clinical trials with our pipeline assets, rusfertide and PN-943 as well as all 3 of the IL-23 receptor antagonist assets under the Janssen Biotech collaboration.

繼續討論我們的開支。 2020 年全年我們的研發費用為 7,450 萬美元，高於 2019 年全年的 6,500 萬美元，2020 年第四季度我們的研發費用為 1,950 萬美元，高於 2019 年第四季的 1,590 萬美元。種 IL-23 受體拮抗劑資產的臨床試驗的推進。

Our general and administration expenses for the full year of 2020 were $18.6 million, up from $15.7 million for the full year of 2019, and our G&A expenses were $5 million for the fourth quarter of 2020 compared to $4.1 million for the fourth quarter of 2019. The increases in our G&A expenses were primarily related to higher professional fees, insurance costs and employee compensation-related expenses in support of the growth of our operations.

我們 2020 年全年的一般及行政開支為 1,860 萬美元，高於 2019 年全年的 1,570 萬美元，2020 年第四季度的一般及行政開支為 500 萬美元，而 2019 年第四季度為 410 萬美元。

In summary, we reported a net loss of $66.2 million or a net loss of $1.92 per share for the year ended 2020 compared to $77.2 million net loss or a net loss of $2.98 per share for the year ended 2019. And for the fourth quarter of 2020, we reported a net loss of $18.9 million or a net loss of $0.48 per share compared to a net loss of $17.5 million or a net loss of $0.63 per share for the fourth quarter of 2019.

綜上所述，我們報告稱，2020 年度淨虧損為 6,620 萬美元，即每股淨虧損 1.92 美元，而 2019 年度淨虧損為 7,720 萬美元，即每股淨虧損 2.98 美元。為 1,750 萬美元，即每股淨虧損 0.63 美元。

Moving over to our cash position. Protagonist ended 2020 with $307.8 million in cash, cash equivalents and marketable securities. Also of note, through our successful capital raise activity during the year, including our 2 public offerings and our ATM program, we raised $255 million in 2020 for the company. We forecast the company's cash, cash equivalents and marketable securities, along with access to our debt facility, will fund our planned operating and capital expenditures through mid-2024, allowing us to complete the current ongoing trials as well as fund our key clinical, regulatory and operational activities through mid-2024.

轉到我們的現金狀況。截至 2020 年底，Protagonist 的現金、現金等價物和有價證券總額為 3.078 億美元。另外值得注意的是，透過我們今年成功的融資活動，包括我們的兩場公開發行和 ATM 計劃，我們在 2020 年為公司籌集了 2.55 億美元。我們預測，公司的現金、現金等價物和有價證券以及我們的債務融資將為我們到 2024 年中期計劃的運營和資本支出提供資金，使我們能夠完成目前正在進行的試驗，並為我們到 2024 年中期的關鍵臨床、監管和運營活動提供資金。

This concludes my summary of the fourth quarter and full year of 2020 financial overview. Now I'd like to turn the meeting back to Dinesh.

這是我對 2020 年第四季和全年財務概況的總結。現在我想將會議轉回給 Dinesh。

Thank you, Don. We are very pleased with our progress to date, and we look forward to continue our strong momentum as we move to 2021. We thank our shareholders for their support and the confidence in our work. We thank the investigators who advance our clinical studies and the patients who participate in these studies.

謝謝你，唐。我們對迄今為止的進展感到非常滿意，並期待在邁向 2021 年時繼續保持強勁勢頭。我們感謝推進我們臨床研究的研究人員和參與這些研究的患者。

Finally, I want to personally thank the Protagonist team. Amid the challenges that 2020 imposed on the world at large, our employees not only stayed the course but instead excelled in several functions. Their unwavering focus and dedication is what has made the progress possible that we are describing today. Collectively, as a team, we look forward to even more exciting progress in the months and years ahead.

最後，我要親自感謝Protagonist團隊。面對 2020 年給全世界帶來的挑戰，我們的員工不僅堅持了下來，而且在多個職能領域表現出色。他們堅定不移的專注和奉獻精神使得我們今天所描述的進步成為可能。作為一個團隊，我們共同期待在未來的歲月中取得更令人興奮的進展。

With that, I would now like to open the call to questions. Operator?

現在，我想開始提問。操作員？

(Operator Instructions) Your first question comes from the line of Yasmeen Rahimi with Piper Sandler.

(操作員指示)您的第一個問題來自 Piper Sandler 的 Yasmeen Rahimi。

This is Rachel on for Yasmeen. So our first question is, can you help us understand how the regulatory pathway could differ between development in low-risk versus high-risk PV patients who fail on current treatment options? In other words, can you help us understand what part of the Phase III design is set in stone and which factors remain to be discussed?

這是 Rachel 為 Yasmeen 表演的。因此，我們的第一個問題是，您能否幫助我們了解對於目前治療方案失敗的低風險 PV 患者和高風險 PV 患者，其發展中的調控途徑有何不同？換句話說，您能否幫助我們了解第三階段設計的哪些部分已經確定，哪些因素仍有待討論？

Now that's a very important question and distinction, and I would have our CMO, Sam take a crack at it.

這是一個非常重要的問題和區別，我希望我們的首席行銷長 Sam 能夠嘗試一下。

Yes. I would just say that we can't, obviously, at this point, articulate definitive guidance on the FDA design. But I can tell you that our Phase II study is open to patients, whether they're noncytoreductive or not, and the common theme is patients who require too many phlebotomies. So while patients are divided into high and low-risk categories, patients are divided into those who are receiving cytoreductive agents like hydroxyurea, interferon and those that aren't. The commonality between all the patients is that they're receiving frequent phlebotomy. I'll also ask Suneel Gupta, if he wants to say anything else about the clinical design.

是的。我只想說，顯然，目前我們無法就 FDA 設計提供明確的指導。但我可以告訴你，我們的第二階段研究對患者開放，無論他們是否為非細胞減滅性，共同的主題是需要過多放血療法的患者。因此，雖然患者被分為高風險和低風險類別，但患者又分為接受羥基脲、幹擾素等細胞減滅劑治療的患者和未接受該藥物治療的患者。所有病人的共同點是他們都要頻繁接受放血治療。我也會詢問 Suneel Gupta，他是否想談談臨床設計的其他內容。

I think you've covered all the important aspects. I think there's nothing more to add.

我認為您已經涵蓋了所有重要方面。我認為沒有什麼好補充的了。

Yes. I think the short answer is from the Phase II study, it seems the drug is very effective in both populations. So obviously, we want to have as broad a utility as possible. Our theme is basically -- this is a drug for choice where the current therapy is ineffective.

是的。我認為簡短的回答是從第二階段的研究來看，該藥物似乎對兩組人群都非常有效。顯然，我們希望擁有盡可能廣泛的實用性。我們的主題基本上是——這是一種針對當前療法無效的可選藥物。

That's very helpful. And as a follow-up, based on your discussions with the FDA, do you believe that the FDA and the EMA view the regulatory pathway in PV through the same lens?

這非常有幫助。另外，根據您與 FDA 的討論，您是否認為 FDA 和 EMA 對 PV 的監管途徑的看法相同？

Well, the unknowns are the unknowns. And I think we sound like a broken record, but I think it's still the most meaningful statement. The dialogue is ongoing. And when we have clarity, we'll share it with everybody, the whole world, and we believe that should happen in the first half of this year.

嗯，未知就是未知。我覺得我們聽起來像是一張破唱片，但我認為這仍然是最有意義的聲明。對話仍在進行中。當我們有了明確的結論時，我們會與所有人、全世界分享，我們相信這應該會在今年上半年發生。

Of course, the only historical comparison one could make -- we can't talk about, again, our own discussions. But the only historical comparison one could make would be to Jakafi, which was registered in both the EU and the U.S. And shortly, you may have a comparison of ropeginterferon, which is available in Europe and is on file in the U.S. Not that those are directly relevant to us, but those are the historical comparisons.

當然，我們唯一能做的就是進行歷史比較——我們不能再談論我們自己的討論。但唯一可以進行的歷史比較是與 Jakafi 進行比較，該藥物已在歐盟和美國註冊。

Great. That's very helpful. And as a last question, can you tell us what other indications beyond PV and HH for which rusfertide will make mechanistic sense for?

偉大的。這非常有幫助。最後一個問題，您能否告訴我們，除了 PV 和 HH 之外，rusfertide 對哪些其他適應症具有機制意義？

Yes. We've been thinking about 2 general areas, not to get specific here, but just generally, and they're kind of self-evident, if you think about it, based on the results with PV. One is diseases that are treated with phlebotomy and the other diseases that are -- one of the hallmarks of the disease is erythrocytosis. So obviously, in PV, those patients have erythrocytosis of a particular type, and they need phlebotomy. So we're trying to think about both of those as avenues for further development in other indications, and there are multiple diseases in each of those categories.

是的。我們一直在考慮兩個一般性領域，這裡不做具體闡述，只是一般性闡述，如果您根據 PV 的結果仔細思考一下，它們是不言而喻的。一種是用放血療法治療的疾病，另一種疾病——疾病的標誌之一是紅血球增多症。因此顯然，在 PV 中，這些患者患有特定類型的紅血球增多症，並且需要進行放血療法。因此，我們試圖將這兩者視為其他適應症進一步發展的途徑，並且每個類別中都有多種疾病。

Yes. So the triangulation of phlebotomy as a therapy, iron overload and excessive erythrocytosis.

是的。因此，放血療法是一種三角療法，可治療鐵超載和紅血球增多症。

Your next question comes from the line of Chris Howerton with Jefferies.

您的下一個問題來自 Jefferies 的 Chris Howerton。

Great. And obviously, congratulations on all the progress across the board. So maybe as a first question, just as a follow-up to some of that questioning with respect to PV and the regulatory path. If we could focus on the primary endpoint here, like, what are kind of the key features that you need to come to alignment on with the FDA with respect to the primary endpoint? Is it the specific endpoint that you want to go after? Is it the duration on therapy and follow-up? And I guess, what is your initial view in terms of what are the kind of categories that one needs to satisfy to get a registrational study completed?

偉大的。顯然，我要祝賀我們在各方面的進步。因此，也許作為第一個問題，只是作為對光伏和監管路徑的一些問題的後續答案。如果我們可以在這裡關注主要終點，那麼，就主要終點而言，您需要與 FDA 達成一致的關鍵特徵有哪些？這是您想要追求的特定終點嗎？是治療和追蹤的持續時間嗎？我想，您對於完成註冊研究需要滿足哪些類別的條件的初步看法是什麼？

Yes. So I'll make a general statement and then Sam will chime in. But the current data we have from the ongoing Phase II study leads us to believe and it's self-evident that they have amazing hematocrit control and joined to the -- with that observation is a drastic reduction in the phlebotomy requirement, and that has been sort of the cornerstone in this disease indication. So we are good with whatever the final outcome would be. But Sam?

是的。因此，我將做一個總體陳述，然後 Sam 會插話。所以無論最終結果如何，我們都很滿意。但是薩姆？

Yes. I mean, this is a chronic disease. And so we believe that we'll need data over a reasonable period of time. And as Dinesh said, the hallmark is keeping the hematocrit below 45%. That's what's in every guideline. That's what is in every medical textbook. And so 24/7 keeping it before -- keeping it under 45% over a significant period of time will be an important aspect of the primary endpoint.

是的。我的意思是，這是一種慢性疾病。因此我們相信我們需要合理時間內的資料。正如 Dinesh 所說，標誌是將血球比容保持在 45% 以下。每條指導方針都是如此。每本醫學教科書上都講到這一點。因此，全天候保持在相當長的一段時間內將其保持在 45% 以下將是主要終點的一個重要方面。

How it's defined, how it's analyzed, what else could be in there, we're not ready to say that. But again, from historical precedent and just from what we know about the disease, it's clear to us that the backbone of the primary endpoint will involve keeping the hematocrit below 45%.

如何定義它，如何分析它，它裡面還可能包含什麼，我們還沒準備好說出來。但是，從歷史先例以及我們對這種疾病的了解來看，我們可以清楚地知道，主要終點的關鍵是將血球比容保持在 45% 以下。

Okay. All right. That's very clear. And maybe as a second question, if we can maybe shift our focus to PN-943 or the IBD, I think, obviously, there's been recent recognition and focus of early-stage receptor occupancy data. And I think one of the questions that I've received numerous times from investors is, how does this mechanism work from a systemic versus a local or gut-restricted activity? And kind of how does that work? It seems like there's some confusion out there. So it might be helpful if you could compare and contrast local delivery in a gut-restricted manner versus systemic and kind of what you see in terms of the relevance of receptor occupancy data.

好的。好的。這非常清楚。也許作為第二個問題，如果我們可以將重點轉移到 PN-943 或 IBD，我認為，顯然，最近人們已經認識到並關注早期受體佔用率數據。我認為投資人多次向我提出的一個問題是，這種機制從系統性角度而非局部性或直覺性限制性活動的角度如何發揮作用？那麼它是如何運作的呢？看起來好像那裡有些混亂。因此，如果您可以比較和對比腸道限制方式的局部輸送與全身輸送，以及從受體佔用率數據的相關性方面觀察的結果，可能會有所幫助。

Thanks, Chris. That's a very important question. It is also one of the most common questions that we are receiving in recent days. And I'll give some general answer to it. And then our CSO, David Liu, will chime in with some more details. The way we look at alpha-4-beta-7 integrin is -- obviously, it's a validated target. It's one of the most safe and IBD-specific target as established by ENTYVIO from Takeda.

謝謝，克里斯。這是一個非常重要的問題。這也是我們最近幾天收到的最常見的問題之一。我將對此給出一些一般性的回答。然後我們的首席策略長 David Liu 將會介紹更多細節。我們看待 alpha-4-beta-7 整合素的方式是——顯然，它是一個經過驗證的目標。它是武田公司的 ENTYVIO 確定的最安全且最針對 IBD 的目標之一。

Now there are 2 types of approaches over here. One is where the action is through systemic exposure. And over there, we have the injectable antibody drugs and orally bioavailable small molecule drugs. The other approach, which Protagonist has undertaken, and in fact, Protagonist is the only company in that space, is the gut-restricted approach. So now the main action is not in the blood compartment, but rather tackling the target in the GI tissue compartment.

現在這裡有兩種方法。一種是透過系統性暴露採取行動。我們有註射抗體藥物和口服生物可利用的小分子藥物。 Protagonist 採取的另一種方法是直覺限制法，事實上，Protagonist 是該領域唯一的公司。因此現在的主要行動不是在血液區，而是解決胃腸道組織區中的目標。

So while we are the only presence over here, then the question is, is that a risky proposition? The answer, in our opinion, is no, because, as you know, with our previous first-generation drug PTG-100, we already established clinical proof-of-concept in a Phase IIa study in ulcerative -- in moderate-to-severe disease ulcerative colitis patients, where we got clinical remission rates of 16%, similar to ENTYVIO in a Phase IIa study, and from the biopsy samples, colonic biopsy samples of these patients, we got 44% histologic remission.

因此，當我們是這裡唯一的存在時，問題是，這是一個冒險的提議嗎？我們認為答案是否定的，因為如您所知，對於我們之前的第一代藥物 PTG-100，我們已經在潰瘍性結腸炎（中度至重度潰瘍性結腸炎）患者的 IIa 期研究中建立了臨床概念驗證，我們的臨床緩解率為 16%，與 IIa 期研究中的 ENTYVIO 相似，並且從這些患者的活檢中獲得了樣本的研究、4% 4%。

So yes, ours is a unique approach. And -- but we already have the clinical proof-of-concept from the first-generation drug. And now we are moving forward with the second-generation drug 943, which is at least threefold more potent by all in vitro, in vivo preclinical and even Phase I, blood receptor occupancy measurements that we have conducted so far between these 2 drugs.

是的，我們的方法很獨特。而且——但我們已經有了第一代藥物的臨床概念驗證。現在我們正在推進第二代藥物 943，到目前為止，我們在兩種藥物之間進行的所有體外、體內臨床前甚至 I 期血液受體佔有率測量都表明，943 的藥效至少是前者的三倍。

The blood receptor occupancy component, this is where David, you may want to chime in and take over the conversation.

血液受體佔有率成分，這就是戴維，你可能想加入並接管談話的地方。

Yes. Thank you, Dinesh. So I think everything that Dinesh mentioned that has been observed for the benefit of our approach in the clinic was presaged by all of the work that we did preclinically. So looking at trafficking, looking at pharmacodynamic responses that were associated with the trafficking with disease outcomes in -- as well as histological outcomes in preclinical models of colitis, and that was all basically predictive of what we eventually observed in the clinic.

是的。謝謝你，Dinesh。因此，我認為 Dinesh 提到的所有有利於我們在臨床上觀察的結果都是由我們在臨床前所做的所有工作所預測的。因此，觀察運輸、觀察與運輸相關的藥效學反應以及疾病結果——以及結腸炎臨床前模型中的組織學結果，基本上都可以預測我們最終在臨床上觀察到的情況。

With regard to the pharmacodynamic responses, as shown predominantly by receptor occupancy in the blood, we believe that the surrogate of essentially what was initially target -- high-target engagement is locally on the immune cells and residing in the gut. And as those cells are trafficking back out, they can't reenter because of the very tightly bound 943 to the surface of that cells on the integrin.

關於藥效動力學反應，主要透過血液中的受體佔有率來顯示，我們認為，本質上最初的目標——高目標參與的替代品是在局部免疫細胞上並駐留在腸道中。當這些細胞被運送回去時，它們無法重新進入，因為 943 與細胞表面的整合素結合非常緊密。

In addition, we think the high local target engagement engenders a very nice effect on cells that are trying to proliferate and be activated from alpha-4-beta-7 engagement as a co-stimulatory factor. And we can -- we have shown that from in vitro studies that we can certainly block that mechanism. So high local target engagement, blocking both trafficking and local activation of the T cells.

此外，我們認為較高的局部標靶參與度對試圖增殖並透過 alpha-4-beta-7 參與作為共刺激因子活化的細胞產生非常好的效果。我們可以—體外研究表明，我們可以阻斷這種機制。局部標靶參與度如此之高，可阻斷 T 細胞的運輸和局部活化。

And what I would add, Chris, is that for our gut-restricted approach, we have established, based on our clinical POC data, the efficacious dose in the ulcerative colitis study, that translated to 74% blood receptor occupancy in Phase I study in healthy humans. So that is our guideline for the gut-restricted integrin blocker approach. And in a Phase I study of 943, we know that we can surpass that 74% number easily at 3x lower doses versus the previous drug.

克里斯，我想補充的是，對於我們的腸道限制方法，我們已經根據臨床 POC 數據確定了潰瘍性結腸炎研究中的有效劑量，這在健康人的第一階段研究中轉化為 74% 的血液受體佔有率。這是我們針對腸道限制整合素阻斷劑方法的指導方針。在對 943 進行的 I 期研究中，我們知道，與先前的藥物相比，我們可以以 3 倍更低的劑量輕鬆超越 74% 這一數字。

Now for the systemic drugs, 100% RO, blood RO is a goalpost, but we know and we don't have to get into the details, but the minimal dose at which one can achieve 100% RO is significantly lower than the actual efficacy of dose that have been used for the systemic drugs.

現在對於全身性藥物來說，100% RO，血液 RO 是一個目標，但我們知道並且我們不必深入細節，但是能夠達到 100% RO 的最小劑量明顯低於已用於全身藥物的實際療效劑量。

Your next question comes from the line of Joseph Schwartz with SVB Leerink.

您的下一個問題來自 SVB Leerink 的 Joseph Schwartz。

This is Kelly Girskis on for Joe. Maybe one about indications outside of IBD for your oral IL-23 antagonist. How are you approaching or maybe thinking about the bioavailability differences that might be needed for more systemic indications versus those that are more gut-restricted? And are there any attributes of your new agents, PN-235 or 232 that you designed in or selected for that might lend themselves to a more gut-restricted or more systemic profile?

這是凱利吉爾斯基斯 (Kelly Girskis) 為喬主持的節目。也許其中一個是關於口服 IL-23 拮抗劑在 IBD 之外的適應症。您如何處理或考慮過系統性適應症與腸道限制性適應症所需的生物利用度差異？您設計或選定的新藥劑 PN-235 或 232 是否具有某些屬性，使其更符合直覺或更系統性的特性？

That's an excellent question, Kelly. Really appreciate it. And as you know, we are a peptide technology platform company, and we like to be the pioneers in the advancement of the field of peptidic science. So initially, we went on the journey of discovering peptides that were as potent as antibodies. The next step was that making peptides that are orally stable and gut-restricted. And maybe the ultimate holy grail in the field of peptides would be where we could make peptides orally bioavailable. So for the IL-23 program in general, our future undertakings, we would not be shying away from targets or approaches that actually require some sort of systemic oral bioavailability. That's how I would frame it.

這是一個非常好的問題，凱利。真的很感激。如您所知，我們是一家勝肽技術平台公司，我們希望成為勝肽科學領域進步的先驅。因此最初，我們踏上了尋找與抗體一樣有效的勝肽的旅程。下一步是製作口服穩定且腸道限制的勝肽。也許勝肽領域的最終目標就是使勝肽具有口服生物利用度。因此，就 IL-23 計劃總體而言，在我們未來的工作中，我們不會迴避實際上需要某種系統性口服生物利用度的目標或方法。這就是我的構思方式。

Your next question comes from the line of Anupam Rama with JPMorgan.

您的下一個問題來自摩根大通的 Anupam Rama。

Just 2 quick ones for me. First is more of a clarification question on PTG-300 Phase II. At the conference and then in your press release today, you talked about updates at medical conferences in 2021. So is this a EHA and ASH strategy or sort of ASH-only type of strategy post enrollment completion midyear? That's our first question.

對我來說只需快速問 2 個問題。首先是關於 PTG-300 第二階段的澄清問題。在會議上以及今天的新聞發布會上，您談到了 2021 年醫學會議的最新進展。這是我們的第一個問題。

Second one is one of the questions we've been getting a little bit on PTG-300 is in PV -- based on the profile that's emerging post ASH, where does this drug fit in the treatment paradigm based on your market research?

第二個問題是，我們在 PTG-300 上遇到的一個問題是 PV——基於 ASH 後出現的情況，根據您的市場調查，這種藥物在治療模式中處於什麼位置？

Sure. Let me -- I'm sure Sam will want to elaborate. But very quickly, no, we aren't going to just wait until the end of the year to present things at the ASH Conference. There are significant conferences in midyear and throughout the year. So it is our full intention to present updates at medical conferences throughout the year.

當然。讓我——我相信薩姆會想詳細說明。但很快，不，我們不會等到年底才在 ASH 會議上展示一些東西。年中和全年都有重要的會議。因此，我們全心全意地在全年的醫學會議上展示最新進展。

Yes. Remember, the first part of the study is an open-label Phase II study. So since it's open-label, we have no problem with reporting on it and being transparent over time. The second part, which is randomized and blinded, that would require the last person completing the study before we could update that part of the study.

是的。請記住，研究的第一部分是開放標籤 II 期研究。因此，由於它是開放標籤的，我們可以毫無問題地對其進行報告，並保持長期透明度。第二部分是隨機和盲法的，這就要求最後一個完成研究的人才能更新該部分研究。

With respect to where we see this being used, as we kind of said earlier, we're not trying to replace any particular therapy. We think that people who have too many phlebotomies have been demonstrated to have 2 things: One is too much time spent above a hematocrit of 45%. And we think that's a guideline for a reason medically in terms of preventing events. So we think that's not a good thing to be spending time above 45%.

關於我們看到這種藥物的用途，正如我們之前所說，我們並不是想取代任何特定的療法。我們認為，進行過多次放血的人已被證實有兩個問題：一是血球比容在 45% 以上的時間過長。我們認為從醫學角度而言，這是預防事件發生的指導方針。所以我們認為花的時間超過 45% 並不是一件好事。

And of course, the people who have many phlebotomies are the ones who have the highest degree of iron deficiency because, obviously, the more phlebotomies you're doing, the more iron you're taking out of the body on a regular basis. And those are the patients where we would expect to see -- if we see a certain improvement, obviously, that's where we would expect to see it the most is in the people who have the highest degree of iron deficiency.

當然，進行多次放血的人是缺鐵程度最高的人，因為顯然，進行多次放血的人越多，身體定期消耗的鐵就越多。我們希望看到這些患者——如果我們看到一定的改善，顯然，我們最希望看到的是那些缺鐵程度最高的患者。

So again, it's not a strategy of saying, don't use any particular other therapy. If you and your doctor decide any other therapy is useful and important for you, that's great. But what we see in the marketplace is with the existing therapeutics that are available, that there are many patients who are on other drugs and have too many phlebotomy or on phlebotomy alone and have too many phlebotomy, and those are our patients.

所以再說一遍，這並不是一個說不要使用任何其他特定療法的策略。如果您和您的醫生認為任何其他療法對您有用且重要，那就太好了。但我們在市場上看到的是，對於現有的治療方法，有很多患者正在服用其他藥物，並且進行了過多的靜脈穿刺，或者單獨進行靜脈穿刺，並且進行了過多的靜脈穿刺，這些人就是我們的患者。

Yes. So Anupam, the way I would phrase it is that essentially, this is a drug -- this could be a drug of choice when the current therapy is ineffective. And our Symphony data survey basically shows that majority of patients will fall in this category. And if you look at our current Phase II study, the data we presented at ASH on 18 patients, it's like 8 patients are on phlebotomy alone, then 7 patients are on hydroxyurea. We also have 3 patients that are on interferon. And remember, the qualification for getting into our study is in spite of those treatments, they require frequent phlebotomies, at least 3 or more phlebotomies in a 6-month period. So that translates to more than 6 phlebotomies annually. And it demonstrates 2 things. It's like the current treatments are ineffective and too many frequent phlebotomies is not a good thing for the patients ultimately. And that is where we would like to see the performance of our drug.

是的。所以 Anupam，我的說法是，本質上，這是一種藥物——噹噹前療法無效時，這可能是一種可選藥物。我們的 Symphony 資料調查基本上顯示大多數患者都屬於這一類。如果你看我們目前的第二階段研究，我們在 ASH 上展示的 18 位患者的數據，其中 8 位患者僅接受了靜脈切開術，7 位患者接受了羥基脲治療。我們還有3名患者正在接受干擾素治療。請記住，參加我們研究的資格是，儘管接受了這些治療，但仍需要頻繁進行放血，6 個月內至少進行 3 次或更多次放血。因此，這相當於每年進行超過 6 次的放血治療。它證明了兩件事。就好像目前的治療方法無效，而過於頻繁的放血最終對患者來說不是一件好事。這正是我們希望看到我們的藥物的效果。

Yes. We presented our Symphony data at ASH. It's in a poster at ASH that was presented by one of the key opinion leaders. And the punchline is where they use cytoreductive or use phlebotomy alone, many patients are not receiving treatment according to the treatment guidelines.

是的。我們在 ASH 上展示了我們的 Symphony 數據。它是在 ASH 上由一位關鍵意見領袖展示的海報中的內容。而關鍵在於他們只使用細胞減滅術或放血療法，許多患者並沒有按照治療指引接受治療。

Your next question comes from the line of Douglas Tsao with H.C. Wainwright.

您的下一個問題來自 H.C. 的 Douglas Tsao。溫賴特。

Hello?

你好？

Hi, Doug.

你好，道格。

Sorry. I was having a little trouble in my line. So just in terms of the new IL-23s that have been nominated by Janssen for development. Just curious, at what point should we start to get a sense of what indications that you're thinking about? And obviously, I would presume the horizons might be a little broader than just in IBD, just given how -- as you alluded to earlier, right, it might not just be sort of gut-restricted, obviously, Stelara has pretty wide use.

對不起。我在工作上遇到了一點麻煩。就楊森公司提名開發的新型 IL-23 而言。只是好奇，我們應該從什麼時候開始了解您正在考慮的跡象？顯然，我認為其應用範圍可能比 IBD 更廣泛一些，正如您之前提到的，它可能不僅限於腸道，顯然，Stelara 的用途非常廣泛。

Yes. Doug, it's an excellent question. And as you can imagine, over here, this is a partnership with Janssen. So we have to be mindful of the statements we make. But I would just like to phrase it this way. Our collaboration with Janssen is not on IBD. Our collaboration with Janssen is on IL-23 receptor antagonist. So wherever the IL-23 pathway -- intervention of the IL-23 pathway leads to a medical utility in a particular disease indication, that is where we are theoretically going with these multiple optionalities. And -- so the idea is like, "Hey, let's add a few promising candidates in the development bucket." We have at least 3 as of now. And then the various strategic and clinical options will become more clear down the road as we get more data from the current Phase I and Phase II studies that we are conducting with these candidates.

是的。道格，這是一個非常好的問題。正如您所想像的，這是與 Janssen 的合作。所以我們必須謹記我們所發表的言論。但我只想這樣表達。我們與 Janssen 的合作並不在 IBD 領域。我們與 Janssen 的合作涉及 IL-23 受體拮抗劑。因此，無論 IL-23 路徑—介入 IL-23 路徑對特定疾病指徵產生醫療效用，從理論上講，這就是我們利用這些多種選擇所要實現的目標。所以這個想法就像是，“嘿，讓我們在開發桶裡添加一些有前途的候選人。”截至目前我們至少有 3 個。隨著我們從目前正在針對這些候選藥物進行的 I 期和 II 期研究中獲得更多數據，各種策略和臨床選擇將變得更加清晰。

And Dinesh, you just sort of went way -- so I guess it sounds like what we learn from the Phase I in terms of bioavailability, PK profile, et cetera, will real sort of help determine which of those indications, especially outside of IBD might -- which the candidates might be best suited for?

還有 Dinesh，您剛才說到——所以我想這聽起來像是我們從第一階段的生物利用度、PK 特徵等方面了解到的信息，是否真的有助於確定哪些適應症，特別是 IBD 之外的適應症——哪些候選藥物最適合？

Yes, it will be hard to disagree with your logic.

是的，我很難不同意你的邏輯。

And with that, this concludes our Q&A section. And I would like to hand it over to Dinesh Patel for closing remarks.

我們的問答部分到此結束。現在我想將發言權交給 Dinesh Patel 先生，請他作最後發言。

Thank you, again, everybody, for joining us this afternoon, and this formally concludes our fourth quarter 2020 and full year 2020 conference call and webcast. Thank you.

再次感謝大家今天下午的參加，這正式結束我們的 2020 年第四季和 2020 年全年電話會議和網路廣播。謝謝。

This concludes today's conference call, and you may now disconnect.

今天的電話會議到此結束，您可以掛斷電話了。