Theratechnologies Inc (THTX) 2021 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and thank you for standing by. Welcome to Theratechnologies Third Quarter Fiscal Year 2021 Earnings Call. (Operator Instructions)

早上好，女士們，先生們，感謝你們的支持。歡迎來到 Theratechnologies 2021 財年第三季度財報電話會議。 （操作員說明）

I would now like to remind everyone that this conference call is being recorded today, Wednesday, October 13, 2021, at 8:30 a.m. Eastern Time.

我現在想提醒大家，本次電話會議是在東部時間今天 2021 年 10 月 13 日星期三上午 8 點 30 分錄製的。

I will now turn the call over to Theratechnologies Head of Investor Relations, Leah Gibson. Ms. Gibson, please go ahead.

我現在將電話轉給 Theratechnologies 投資者關係主管 Leah Gibson。吉布森女士，請繼續。

Thank you, Catherine, and welcome, everyone. Mr. Paul Lévesque, President and Chief Executive Officer of Theratechnologies; and Mr. Philippe Dubuc, Senior Vice President and Chief Financial Officer, will be the speakers on today's call. A Q&A session will follow their prepared remarks.

謝謝你，凱瑟琳，歡迎大家。 Theratechnologies 總裁兼首席執行官 Paul Lévesque 先生；高級副總裁兼首席財務官 Philippe Dubuc 先生將在今天的電話會議上發言。問答環節將遵循他們準備好的發言。

Before we begin, I would like to remind everyone that Theratechnologies' remarks today contain forward-looking statements about its current and future plans, expectations and intentions, results, levels of activity, performance, goals or achievements or other future events and developments. In preparing these forward-looking statements, several assumptions were made by Theratechnologies, and there are risks that actual results obtained by the company will differ materially from those statements. As a result, the company cannot guarantee that any forward-looking statement will materialize, and you are cautioned not to place undue reliance on them.

在我們開始之前，我想提醒大家，Theratechnologies 今天的評論包含有關其當前和未來計劃、預期和意圖、結果、活動水平、績效、目標或成就或其他未來事件和發展的前瞻性陳述。在準備這些前瞻性陳述時，Theratechnologies 做出了多項假設，並且存在公司獲得的實際結果與這些陳述存在重大差異的風險。因此，公司不能保證任何前瞻性陳述都會實現，請注意不要過分依賴它們。

Theratechnologies refers current and potential investors to the forward-looking information section of its management's discussion and analysis issued this morning, available at sedar.com and on EDGAR at sec.gov. Forward-looking statements represent their technologies expectations as of October 13, 2021. Except for that, which is required by securities laws, Theratechnologies does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Theratechnologies 將當前和潛在投資者引向其管理層今天上午發布的討論和分析的前瞻性信息部分，這些信息可在 sedar.com 和 EDGAR 上的 sec.gov 上獲取。前瞻性陳述代表他們截至 2021 年 10 月 13 日的技術預期。除此之外，證券法要求，Theratechnologies 不承擔任何更新任何前瞻性陳述的義務，無論是由於新信息、未來事件或其他。

I would now like to turn the call over to Paul. Paul?

我現在想把電話轉給保羅。保羅？

Thank you, Leah. Good morning, everyone, and thank you for being with us today. I'm very pleased to provide an update on where Theratechnologies stands in our effort to build upon the clear and strong operational results that have been achieved in fiscal 2021 thus far. At the beginning of the fiscal year, we set forth the logical strategic plan to lead the company toward inevitable growth and transformation and our commercial and investigational pipelines. As we move well into the back half of our fiscal year, our efforts are beginning to show fruit.

謝謝你，利亞。大家早上好，感謝你們今天和我們在一起。我很高興提供有關 Theratechnologies 在我們努力基礎上在 2021 財年迄今取得的明確而強大的運營成果的基礎上所處的最新情況。在本財年開始時，我們制定了合理的戰略計劃，帶領公司走向不可避免的增長和轉型，以及我們的商業和研究渠道。隨著我們進入本財年的後半段，我們的努力開始見效。

We are continuing to further unlock the unrealized value, held in our commercial business through product life cycle management and innovation, while at the same time, building on the vital quality of proof-of-concept work needed to advance the promising therapeutic potential of our investigational oncology portfolio and Phase III development programs in NASH. Through this end, we are extremely excited about the progress made in the Phase I study, evaluating our novel peptide drug conjugate, TH1902, for the treatment of sortilin-positive cancers.

我們將繼續通過產品生命週期管理和創新進一步釋放我們商業業務中未實現的價值，與此同時，以推進我們有前途的治療潛力所需的概念驗證工作的重要質量為基礎NASH 的研究性腫瘤學組合和 III 期開發計劃。為此，我們對第一階段研究取得的進展感到非常興奮，該研究評估了我們的新型肽藥物偶聯物 TH1902，用於治療分選蛋白陽性癌症。

As you recall, we received Fast Track designation from the FDA in January 2021, recognizing TH1902 and our SORT1+ Technology as a broadly applicable cancer agnostic treatment for patients with sortilin-expressing solid tumors. This morning, we provided an interim safety update noting that to date, we have dosed several patients in Part A of the study, with some participants receiving more docetaxel when conjugated to TH1902 than the indicated dose of docetaxel alone. Additionally, patients that have received up to 300-milligram per square meter of TH1902, which is equivalent to approximately 1.5x the indicated therapeutic dose of docetaxel, have not experienced any Grade 2 adverse events. The last patient that was dosed in the trial received 420 milligrams per square meter of TH1902 or approximately 2x the indicated dose of docetaxel.

您還記得，我們於 2021 年 1 月獲得了 FDA 的快速通道指定，承認 TH1902 和我們的 SORT1+ 技術是一種廣泛適用於表達分揀蛋白的實體瘤患者的癌症不可知論治療。今天早上，我們提供了一份臨時安全更新，指出迄今為止，我們已經在研究的 A 部分給幾名患者服用了劑量，其中一些參與者在與 TH1902 結合時接受的多西他賽比單獨使用指定劑量的多西他賽要多。此外，每平方米接受高達 300 毫克 TH1902（相當於多西紫杉醇指示治療劑量的約 1.5 倍）的患者未出現任何 2 級不良事件。在試驗中接受給藥的最後一位患者接受了每平方米 420 毫克的 TH1902 或大約 2 倍的多西紫杉醇指示劑量。

And at that level, the patient experience Grade 4 neutropenia. We are now awaiting all safety information to come in, so we may assess the next dosing level and pursue the study as per the approved protocol design. As a reminder, Part A dose escalation study of the Phase I trial is primarily met to establish a maximum tolerated dose. While we have not yet identified what the maximum tolerated dose will be, what we have observed thus far is very encouraging because it seems that TH1902 is better tolerated than docetaxel alone.

在那個水平上，患者會出現 4 級中性粒細胞減少症。我們現在正在等待所有安全信息的到來，因此我們可以評估下一個劑量水平並根據批准的方案設計繼續研究。提醒一下，I 期試驗的 A 部分劑量遞增研究主要是為了確定最大耐受劑量。雖然我們尚未確定最大耐受劑量是多少，但迄今為止我們觀察到的結果非常令人鼓舞，因為似乎 TH1902 的耐受性優於單獨使用多西紫杉醇。

Furthermore, in our preclinical work, we have demonstrated that TH1902 can potentially penetrate the cancer cell far more effectively than docetaxel alone and increase the concentration of docetaxel specifically [where it helps] in the cancer cells. TH1902 is targeting the SORT1 receptor, which is a very prominent receptor in many solid tumors.

此外，在我們的臨床前工作中，我們已經證明 TH1902 可能比單獨使用多西紫杉醇更有效地穿透癌細胞，並增加多西紫杉醇在癌細胞中特異性 [有幫助的地方] 的濃度。 TH1902 靶向 SORT1 受體，這是許多實體瘤中非常重要的受體。

In terms of next steps for this program, we will plan to provide another update of the Phase I Part A study when we have reached the maximum tolerated dose of TH1902, at which time we may have early signs of efficacy data to report. We continue to expect initiating the Part B basket trial in the U.S. and Europe in early 2022.

就該計劃的後續步驟而言，我們將計劃在達到 TH1902 的最大耐受劑量時提供 I 期 A 部分研究的另一次更新，屆時我們可能會報告療效數據的早期跡象。我們繼續期望在 2022 年初在美國和歐洲啟動 B 部分籃子試驗。

As one of the only biotech companies currently targeting SORT1 receptor in the treatment cancer, we are fully committed to this journey of pioneering a novel and potentially transformational treatment to a broad class of hard-to-treat cancers. Therefore, we're taking the same approach to garnering scientific support for this program as we did for our Phase III program in NASH. Aligned with this strategy follows the appointment of Dr. Mace Rothenberg as a scientific adviser for our SORT1+ technology oncology platform. We are very excited to have Mace as part of our team as he brings more than 30 years' experience across government, academia and the biopharmaceutical industry, most recently serving as Chief Medical Officer at Pfizer, before his retirement earlier this year where I've had the opportunity to work with him.

作為目前在治療癌症中靶向 SORT1 受體的僅有的幾家生物技術公司之一，我們完全致力於為廣泛的難以治療的癌症開創一種新穎且可能具有變革性的治療方法。因此，我們正在採用與 NASH III 期計劃相同的方法來為該計劃爭取科學支持。為配合這一戰略，任命 Mace Rothenberg 博士為我們的 SORT1+ 技術腫瘤學平台的科學顧問。我們很高興 Mace 成為我們團隊的一員，因為他在政府、學術界和生物製藥行業擁有 30 多年的經驗，最近擔任輝瑞公司的首席醫療官，今年早些時候他退休了有機會和他一起工作。

During his time at Pfizer, as CMO, the company initiated completed and obtained emergency use authorization for its COVID-19 vaccine and obtained regulatory approvals for 11 new cancer medicines. Mace will no doubt be an important adviser to Theratechnologies as we advance our oncology platform through development and towards approval.

在輝瑞擔任首席營銷官期間，該公司發起完成並獲得了 COVID-19 疫苗的緊急使用授權，並獲得了 11 種抗癌新藥的監管批准。隨著我們通過開發和批准推進我們的腫瘤學平台，梅斯無疑將成為 Theratechnologies 的重要顧問。

We are also looking at additional opportunities to expand the regulatory and commercial scale for TH1902 in other geographies. Currently, we are exploring potential cooperation and alliances with China-based organizations to evaluate TH1902 in patients in greater China that are suffering from sortilin-expressing cancers.

我們也在尋找更多機會擴大 TH1902 在其他地區的監管和商業規模。目前，我們正在探索與中國組織的潛在合作和聯盟，以評估 TH1902 在大中華區患有表達 sortilin 的癌症的患者中的作用。

By gaining the support and scientific expertise of a locally based organization to help us develop TH1902, we are better positioning ourselves to bring this potential treatment to patients faster and more effectively, which is at the foundation of our oncology strategy.

通過獲得本地組織的支持和科學專業知識來幫助我們開發 TH1902，我們可以更好地定位自己，更快、更有效地為患者提供這種潛在的治療方法，這是我們腫瘤學戰略的基礎。

As we think about the future objectives of our SORT1+ Technology platform, there are a number of additional value-driving opportunities that we will work toward, including evaluating different dosing schedules, such as weekly or intermittently that may potentially increase the therapeutic window in terms of safety and efficacy; exploring the possibility of conjugating with different anticancer agent, including cytotoxins, like SN-38 and irinotecan and TKI in evaluating synergistic partnerships; and finally, exploring the rational combination with other cancer treatments, especially immunotherapies. But for the near term, we remain focused and committed to completing our first 1 -- or Phase I trial as quickly as possible.

當我們考慮 SORT1+ 技術平台的未來目標時，我們將努力爭取許多額外的價值驅動機會，包括評估不同的給藥方案，例如每週或間歇性給藥，這可能會增加治療窗口安全性和有效性；探索與不同抗癌劑結合的可能性，包括細胞毒素，如 SN-38、伊立替康和 TKI，以評估協同合作關係；最後，探索與其他癌症治療尤其是免疫療法的合理結合。但就近期而言，我們仍然專注於並致力於盡快完成我們的第一個 - 或第一階段試驗。

Turning to our Phase III program in NASH. The company continues to evaluate our options to most effectively execute the Phase III clinical trial of tesamorelin for the treatment of NASH, which includes seeking a potential partner. As we announced in our last earnings call, an external U.S.-based biopharma advisory firm was retained to assist in identifying the potential partnership with this program, and we also explore other opportunities to initiate the trial in a timely manner.

轉向我們在 NASH 中的 III 期計劃。公司繼續評估我們的選擇，以最有效地執行 tesamorelin 治療 NASH 的 III 期臨床試驗，其中包括尋找潛在的合作夥伴。正如我們在上次財報電話會議上宣布的那樣，我們聘請了一家總部位於美國的外部生物製藥諮詢公司，以協助確定與該項目的潛在合作夥伴關係，我們還探索了及時啟動試驗的其他機會。

In support of these initiatives, we recently hosted a virtual NASH webinar featuring Dr. Rohit Loomba, Stephen Harrison, and Steve Grinspoon, who are key opinion leaders in hepatology, endocrinology and NASH. The event provided a deep dive into our innovative approach to treating NASH and tesamorelin and also demonstrated the distinct support this program has from these leading disease and industry experts. We look forward to updating you on the advancement of our NASH program soon.

為了支持這些舉措，我們最近舉辦了一場虛擬 NASH 網絡研討會，由 Rohit Loomba 博士、Stephen Harrison 和 Steve Grinspoon 博士主持，他們是肝髒病學、內分泌學和 NASH 領域的關鍵意見領袖。該活動深入探討了我們治療 NASH 和替沙莫林的創新方法，並展示了該計劃得到這些領先疾病專家和行業專家的獨特支持。我們期待盡快向您通報我們 NASH 計劃的最新進展。

Moving on to the commercial side. We're happy to report on the uptick in activity and demand for EGRIFTA SV for the treatment of lipodystrophy. While the COVID pandemic was an unfortunate and unforeseeable event, which has no doubt materially impacted most of the health care industry, we want to know that in many ways, the pandemic's transformational pressures have only accelerated the health care industry's need to move toward digital health, which has been an ongoing presence in health care for the past decade. Engagement between HCPs and the patient care journey have increasingly shifted toward new behavioral patterns that are largely driven by a need for better technology and immediate access to HCPs.

轉向商業方面。我們很高興地報告 EGRIFTA SV 用於治療脂肪代謝障礙的活動和需求的增加。雖然 COVID 大流行是一個不幸且不可預見的事件，它無疑對大多數醫療保健行業產生了重大影響，但我們想知道，在許多方面，大流行的轉型壓力只會加速醫療保健行業向數字醫療邁進的需要，在過去十年中一直存在於醫療保健領域。 HCP 與患者護理旅程之間的參與越來越多地轉向新的行為模式，這在很大程度上是由對更好的技術和立即訪問 HCP 的需求驅動的。

When I came on board at Theratechnologies, we made the conscious decision to move the company towards this path and coincidentally at the start of the pandemic. Since then, we have challenged the fundamentals of our business, developing a mature business acumen, which includes a more focused field force and digitalized training and product education tools and have ultimately created a solid go-to-market model. As a result, sales increased nearly 30% in the third quarter over 2021 over last year, supported by a 65% increase in EGRIFTA SV sales. The improvement in EGRIFTA SV sales is a direct result of a return to some face-to-face meetings and greater and more efficient digital campaigning at (inaudible) education, which also led to a 40% increase in new prescribers during the quarter. Based on this momentum, we believe we have begun to revert back to a pre-COVID sales environment, but with a much better level of cross-functional team execution, creating a springboard for growth for our approved medicines.

當我加入 Theratechnologies 時，我們有意識地決定將公司推向這條道路，而且恰逢大流行開始時。從那時起，我們挑戰了我們的業務基礎，發展了成熟的商業頭腦，包括更專注的現場工作人員以及數字化培訓和產品教育工具，並最終創建了穩固的上市模式。因此，在 EGRIFTA SV 銷售額增長 65% 的支持下，2021 年第三季度的銷售額比去年增長了近 30%。 EGRIFTA SV 銷售額的提高是恢復一些面對面會議以及在（聽不清）教育領域開展更大、更高效的數字營銷活動的直接結果，這也導致本季度新開處方者增加了 40%。基於這種勢頭，我們相信我們已經開始恢復到 COVID 之前的銷售環境，但跨職能團隊執行水平要高得多，為我們批准的藥物的增長創造了跳板。

In terms of market expansion in HIV beyond our existing markets, we have also made progress toward securing pricing and reimbursement agreements for Trogarzo in several countries outside of the U.S., including Italy, most recently, which is an integral part of our Trogarzo growth strategy. Specific to our progress in the Italian market, Theratechnologies and the Italian Medicines Agency recently reached a reimbursement agreement for Trogarzo, and we expect that this medicine will become commercially available to all eligible patients in Italy by the end of fiscal year 2021.

在我們現有市場以外的 HIV 市場擴張方面，我們還在美國以外的幾個國家（包括最近的意大利）確保 Trogarzo 的定價和報銷協議方面取得了進展，這是我們 Trogarzo 增長戰略的一個組成部分。具體到我們在意大利市場取得的進展，Theratechnologies 和意大利藥品管理局最近就 Trogarzo 達成了報銷協議，我們預計到 2021 財年末，該藥將在意大利上市銷售給所有符合條件的患者。

Our life cycle management strategy for Trogarzo is also progressing nicely. Most recently, we announced results for the TMB-302 study evaluating an IV push mode of administration of Trogarzo in HIV-1 patient. This internal study achieved consistent and statistically significant results demonstrating that there was no difference in pharmacokinetics between the IV push and the current IV infusion mode of administration. This more convenient IV push mode administration requires only 2 quick infusions per month, offering patients a rapid infusion type, thereby potentially increasing patient compliance and allowing patients to benefit from long-acting protection against HIV-1 when Trogarzo is administered with other antiretrovirals.

我們的 Trogarzo 生命週期管理策略也進展順利。最近，我們公佈了 TMB-302 研究的結果，該研究評估了 HIV-1 患者的 Trogarzo 靜脈推注給藥模式。這項內部研究取得了一致且具有統計學意義的結果，證明 IV 推注和當前 IV 輸注給藥模式之間的藥代動力學沒有差異。這種更方便的 IV 推動模式給藥每月僅需 2 次快速輸注，為患者提供了一種快速輸注類型，從而有可能提高患者的依從性，並使患者在 Trogarzo 與其他抗逆轉錄病毒藥物聯合給藥時受益於針對 HIV-1 的長效保護。

Based on the results of the IV push study, we plan to file an sBLA with the FDA during this quarter. In addition, patients screening to evaluate an intramuscular or IM method administration of Trogarzo is also planned to begin this quarter.

根據 IV push 研究的結果，我們計劃在本季度向 FDA 提交 sBLA 。此外，還計劃在本季度開始對患者進行篩查，以評估 Trogarzo 的肌內或 IM 方法給藥。

Further supporting our growth strategy for Trogarzo is our plan to initiate a post-authorization studies named the Trogarzo PROMISE trial that will evaluate the real-world, long-term efficacy and safety of Trogarzo in combination with other antiretrovirals. This study is expected to enroll patients in the EU during this quarter, while a similar study we'll be initiating in the U.S. in the first quarter of [2022], enhancing our portfolio of real-world evidence with Trogarzo. We'll provide our field force with additional and important market data to support their discussions with patients and HCPs.

我們計劃啟動一項名為 Trogarzo PROMISE 試驗的授權後研究，進一步支持我們的 Trogarzo 增長戰略，該試驗將評估 Trogarzo 與其他抗逆轉錄病毒藥物聯合使用的真實、長期療效和安全性。這項研究預計將在本季度在歐盟招募患者，而我們將在 [2022 年] 第一季度在美國啟動一項類似的研究，以加強我們與 Trogarzo 的真實世界證據組合。我們將為我們的現場工作人員提供額外的重要市場數據，以支持他們與患者和 HCP 的討論。

Based on today's business update, it is clear to see that we are proceeding as planned and executing against the polls that we have rolled out at the beginning of this year. In oncology, we are extremely pleased and encouraged by the early indication that the Phase I Part A study in TH1902 have demonstrated and look forward to both interim and full data readouts in this program over the next several quarters.

根據今天的業務更新，可以清楚地看到我們正在按計劃進行並執行我們在今年年初推出的民意調查。在腫瘤學方面，我們對 TH1902 的第一階段 A 部分研究已經證明的早期跡象感到非常高興和鼓舞，並期待在接下來的幾個季度中對該計劃的中期和完整數據讀出。

We're also encouraged by the current commercial landscape that has begun to show signs of recovery and expanding market penetration as we continue to unlock the intrinsic value held in our EGRIFTA SV and Trogarzo medicines for HIV. And we continue to work tirelessly to evaluate opportunities to most effectively execute our ready-to-proceed Phase III program in NASH and advance this exciting program towards a potential approval.

隨著我們繼續釋放 EGRIFTA SV 和 Trogarzo 治療 HIV 藥物的內在價值，當前的商業格局已經開始顯示出複蘇和擴大市場滲透的跡象，這也令我們感到鼓舞。我們將繼續不知疲倦地評估機會，以最有效地執行我們在 NASH 中準備好進行的 III 期計劃，並將這一令人興奮的計劃推進到潛在的批准。

With that, I will turn the call over to Philippe, who will provide the Q3 financial summary. Philippe?

有了這個，我將把電話轉給菲利普，他將提供第三季度的財務摘要。菲利普？

Thank you, Paul, and good morning, everyone.

謝謝你，保羅，大家早上好。

Theratechnologies has posted strong overall results for the third quarter of 2021, registering 27% growth over the same period in 2020. We recorded sales of $17.9 million for the quarter and $51.1 million for the first 9 months of the year. Sales of EGRIFTA performed well as the effects of the pandemic are showing signs of wearing off. We recorded sales of $11.2 million for EGRIFTA in the third quarter, up 64% from the same period last year, a period which had been negatively affected by the transition to EGRIFTA SV from the original version.

Theratechnologies 公佈了 2021 年第三季度的強勁整體業績，與 2020 年同期相比增長了 27%。我們本季度的銷售額為 1790 萬美元，今年前 9 個月的銷售額為 5110 萬美元。 EGRIFTA 的銷售表現良好，因為大流行的影響正在消退。我們在第三季度錄得 EGRIFTA 的銷售額為 1120 萬美元，比去年同期增長 64%，這一時期受到從原始版本過渡到 EGRIFTA SV 的負面影響。

Sales of Trogarzo for the quarter were down 7.8% compared to last year and came in at $6.6 million. As mentioned in the past, Trogarzo's new prescriptions have been more impacted by COVID as patients have been more reluctant to visit health care facilities. Sales were also impacted by the entry of a new competitor in the multidrug-resistant market. We are encouraged by the new prescription numbers we are seeing since the start of the fourth quarter.

本季度 Trogarzo 的銷售額與去年同期相比下降了 7.8%，為 660 萬美元。正如過去所提到的，Trogarzo 的新處方受到 COVID 的影響更大，因為患者更不願意去醫療機構就診。新競爭對手進入耐多藥市場也影響了銷售額。我們對自第四季度開始以來看到的新處方藥數量感到鼓舞。

Cost of goods sold in the third quarter of 2021 amounted to $4.3 million, down slightly from $4.6 million for the same quarter last year. This is due in large part to a higher proportion of sales of EGRIFTA, which carries a lower cost of goods sold and a lower cost of goods sold for Trogarzo, which decreased from 62% to 52% during the third quarter of last year.

2021 年第三季度的銷售成本為 430 萬美元，略低於去年同期的 460 萬美元。這在很大程度上是由於 EGRIFTA 的銷售額比例較高，其銷售成本較低，而 Trogarzo 的銷售成本較低，在去年第三季度從 62% 降至 52%。

As we advance the development of our SORT1+ technology in oncology with the initiation of our Phase I trial for TH1902 and we continue to get ready for the launch of our Phase III trial for tesamorelin in NASH, R&D expenses are increasing. In Q3 2021, they stood at $8.3 million compared to $4.2 million for the same quarter last year. R&D expenses also included expenses related to the medical science liaison team and medical education activities in the U.S. and in Europe as well as the development of the F8 formulation of EGRIFTA and the multi-dose pen injector.

隨著我們通過啟動 TH1902 的 I 期試驗推進我們在腫瘤學中的 SORT1+ 技術的發展，並且我們繼續準備啟動我們在 NASH 中的替沙莫林的 III 期試驗，研發費用正在增加。 2021 年第三季度為 830 萬美元，而去年同期為 420 萬美元。研發費用還包括與美國和歐洲的醫學科學聯絡小組和醫學教育活動相關的費用，以及 EGRIFTA 的 F8 製劑和多劑量筆式註射器的開發。

Selling expenses in the third quarter of 2021 were up 9%, standing at $7.7 million compared to $7 million for the same period last year. This is mainly associated with increased activities in Europe as we gear up for a number of country launches in the upcoming quarters. G&A expenses grew to $3.6 million in the third quarter of 2021 compared to $2.7 million for the same quarter last year. The increase in G&A expenses was mainly associated with an overall increase in business activities, senior hires to support our sales activities in the U.S. and head office functions as well as increased activity in Europe.

2021 年第三季度的銷售費用增長了 9%，為 770 萬美元，而去年同期為 700 萬美元。這主要與歐洲活動的增加有關，因為我們正在為即將到來的幾個季度在多個國家/地區發布做準備。 G&A 費用在 2021 年第三季度增至 360 萬美元，而去年同期為 270 萬美元。 G&A 費用的增加主要與業務活動的整體增加、支持我們在美國的銷售活動和總部職能的高級僱員以及歐洲活動的增加有關。

In Q3 2021, net finance costs amounted to $2.3 million compared to $799,000 in Q3 of 2020. Finance costs mostly represented interest on the senior convertible notes issued in June 2018 and a foreign currency loss as opposed to foreign currency gain in the third quarter of 2020. For the third quarter of 2021, we recorded a net loss of $9.5 million or $0.10 per share compared to a net loss of $6.8 million or $0.09 per share for the same period last year.

2021 年第三季度，淨財務成本為 230 萬美元，而 2020 年第三季度為 799,000 美元。財務成本主要是 2018 年 6 月發行的高級可轉換票據的利息，以及與 2020 年第三季度的外匯收益相對的外匯損失2021 年第三季度，我們錄得淨虧損 950 萬美元或每股 0.10 美元，而去年同期為淨虧損 680 萬美元或每股 0.09 美元。

During our third quarter of 2021, our operations, including working capital variations, used $3.1 million, which includes a positive impact of $1.4 million from changes in operating assets and liabilities. Our financial position remains strong with $51.6 million in cash and bonds at the end of the third quarter.

在 2021 年第三季度，我們的運營（包括營運資本變動）使用了 310 萬美元，其中包括運營資產和負債變化產生的 140 萬美元的積極影響。我們的財務狀況依然強勁，截至第三季度末，我們擁有 5160 萬美元的現金和債券。

I will now turn the call back to Paul for some closing remarks.

我現在將把電話轉回給保羅，聽取一些結束語。

Thank you, Philippe. From a commercial perspective, we are very pleased with the improvements made since the beginning of 2021, and we are optimistic for future growth based on our third quarter results.

謝謝你，菲利普。從商業角度來看，我們對 2021 年初以來取得的進步感到非常滿意，並且根據我們第三季度的業績，我們對未來的增長持樂觀態度。

In terms of our operational and pipeline performance, we've had 3 quarters of solid progress that have been transformational for the organization. Looking ahead, we remain committed to building out our clinical and commercial assets and achieving a valuation for the company that is much better aligned with the opportunities ahead of us.

就我們的運營和管道績效而言，我們已經取得了 3 個季度的穩固進展，這些進展對組織來說是變革性的。展望未來，我們將繼續致力於建立我們的臨床和商業資產，並為公司實現更符合我們面前機遇的估值。

I look forward to continuing to report on the positive progress that the team of Theratechnologies has worked so hard to achieve.

我期待著繼續報告 Theratechnologies 團隊努力取得的積極進展。

With that, we will now open the call up to questions from the audience. As a reminder, questions can be submitted in written form via the webcast platform. We will also take analysts question via the conference call line. Operator?

有了這個，我們現在將開始聽眾提問。提醒一下，問題可以通過網絡直播平台以書面形式提交。我們還將通過電話會議熱線回答分析師的問題。操作員？

(Operator Instructions) And our first question over the phone comes from Andre Uddin with Research Capital.

（操作員說明）我們通過電話提出的第一個問題來自 Research Capital 的 Andre Uddin。

Paul, Philippe and Christian, I just had a couple of questions. In terms of Trogarzo, I was just hoping you could elaborate a little bit more on the pricing of it in the EU. And also, is the U.S. Trogarzo competitor, is that Rukobia in terms of the competitor there?

Paul、Philippe 和 Christian，我剛剛有幾個問題。就 Trogarzo 而言，我只是希望你能詳細說明它在歐盟的定價。還有，美國的Trogarzo是競爭對手嗎，Rukobia是那裡的競爭對手嗎？

Thank you, Andre for your questions. Well, we have achieved a very solid price in Italy in our negotiation. The price is not public at this time. I don't believe it is. However, we're very pleased with this because it's going to be an anchor point in Europe. So this is a good start for us. We're happy. And actually, the negotiation in Italy was pretty stunning because despite the COVID environment over there, it won't -- only god knows how much they were affected by that. We ended up ahead of schedule and in negotiating pricing and reimbursement and, as I said, at a pretty solid anchor point that will be very important for the rest of Europe in our negotiation.

謝謝安德烈的提問。好吧，我們在意大利的談判中取得了非常穩固的價格。價格暫時不公開。我不相信是這樣。然而，我們對此感到非常高興，因為它將成為歐洲的一個錨點。所以這對我們來說是一個好的開始。很高興。實際上，在意大利的談判非常令人震驚，因為儘管那裡有 COVID 環境，但它不會——只有上帝知道他們受到了多大的影響。我們提前結束了談判定價和報銷，正如我所說，在一個非常穩固的錨點上，這對歐洲其他國家的談判非常重要。

When it comes down to Rukobia, Rukobia is a competitor to Trogarzo, as you said. It has made some significant inroads in the U.S. based on their field force presence and also the trial that they had that was significantly large and ended up creating a bolus of patients for them at the beginning. But I remain optimistic that Steve is going to help us expand and extend that segments of multidrug resistance. And I think that we're trying to find a way to continue to be relevant, and I'm very optimistic about the future. John, do you want to add a few things?

說到 Rukobia，正如你所說，Rukobia 是 Trogarzo 的競爭對手。它在美國取得了一些重大進展，基於他們的現場力量存在以及他們進行的試驗非常大，並最終在開始時為他們創造了大量患者。但我仍然樂觀地認為，史蒂夫將幫助我們擴大和擴展多重耐藥性領域。而且我認為我們正在努力尋找一種繼續保持相關性的方法，我對未來非常樂觀。約翰，你想補充幾件事嗎？

The only thing I'd add, Paul, is that we do see a shift in the MDR market to long-acting. And as you know, Trogarzo is the first long-acting agent. And so as more long-acting agents come out, I think that we're going to see more interest and more movement in that direction. But the landscape in the multidrug in the HRD space is changing, and there are competitors that are coming out that are going to impact that.

保羅，我唯一要補充的是，我們確實看到了耐多藥市場向長效藥物的轉變。如您所知，Trogarzo 是第一種長效藥物。因此，隨著更多長效藥物的問世，我認為我們會看到更多的興趣和朝著這個方向的更多行動。但是 HRD 空間中多藥的格局正在發生變化，並且出現的競爭者將對其產生影響。

Thank you for your question.

謝謝你的問題。

Okay. And then just in terms of the Canadian market, do you have any foreseeable plan there for partnerships or launches? If you could elaborate a little bit on that? And then if you could just also give us a bit of a business development update as well in terms of out-licensing and in-licensing, that'd be great.

好的。然後就加拿大市場而言，您是否有任何可預見的合作夥伴關係或推出計劃？你能詳細說明一下嗎？然後，如果您也可以在外向許可和內向許可方面向我們提供一些業務發展更新，那就太好了。

Thank you. Philippe, I'll turn to you for the BD in a moment. When it comes to the Canadian market, EGRIFTA is approved here, but it's only its previous formulation. And since you know that we have DSP, but we are committed to shifting and transitioning to the F8, a more convenient mode of administration next year, that's probably where we're going to kind of revamp our plan for Canada. We're not turning our back to Canada, but this is not our priority at the moment. And when it comes down to the clinical development, we'll see at what stage we want to have or not some Canadian centers involved in our programs. But we're well grounded in Canada, and we'll continue to look for opportunities. Philippe, business development.

謝謝。 Philippe，稍後我會向你求助 BD。說到加拿大市場，EGRIFTA在這裡獲得批准，但這只是它以前的配方。既然你知道我們有 DSP，但我們致力於轉移和過渡到明年更方便的管理模式 F8，這可能是我們要修改加拿大計劃的地方。我們不會拒絕加拿大，但這不是我們目前的首要任務。當涉及到臨床開發時，我們將看到在什麼階段我們希望或不希望一些加拿大中心參與我們的項目。但我們在加拿大有很好的基礎，我們將繼續尋找機會。菲利普，業務發展。

Yes. Well, as Paul mentioned on the NASH program, the outreach is continuing, and we have had some discussions with potential partners. But there's no real update at this point. On the oncology, we've had some -- we hired adviser as well for Greater China. We have received some inbound interest from Chinese companies, and we decided to go out much broader than just dealing with 1 or 2. And so we've initiated a process, a formal process. There's quite a bit of interest in China for the oncology platform. Again, very early to report anything substantial, but we're frankly pretty encouraged with the interest that we've seen.

是的。好吧，正如保羅在 NASH 計劃中提到的那樣，外展活動仍在繼續，我們已經與潛在合作夥伴進行了一些討論。但目前還沒有真正的更新。在腫瘤學方面，我們有一些——我們也為大中華區聘請了顧問。我們收到了一些來自中國公司的入境興趣，我們決定走出去，而不僅僅是處理 1 或 2 家公司。因此我們啟動了一個流程，一個正式的流程。中國對腫瘤學平台很感興趣。同樣，很早就報告任何實質性的事情，但坦率地說，我們對所看到的興趣感到非常鼓舞。

On the in-licensing side, it's a little less active, although we have been approached with some very interesting earlier stage projects. So we're not quite ready to discuss that. But there is -- one of the plans that we have is to act as a catalyst for research that is being done here in Quebec in addition to in-licensing other technologies. And I think we're starting to have pretty good name here. So we're having -- we're seeing some very interesting science come our way.

在許可方面，它不太活躍，儘管我們已經接觸了一些非常有趣的早期項目。所以我們還沒有準備好討論這個問題。但是，我們的計劃之一是作為在魁北克這裡進行的研究的催化劑，除了許可其他技術。而且我認為我們在這裡開始有了很好的名聲。所以我們有——我們看到一些非常有趣的科學出現了。

We have a question from Edward Nash with Canaccord Genuity.

Canaccord Genuity 的愛德華納什向我們提出了一個問題。

I wanted to just ask -- I guess my first question is just one about model housekeeping. Philippe, I know you mentioned with regards to the increase in R&D. There were several things in there, obviously, sortilin 1 and then the pen injector. I look at things like the pen injector is kind of a one-off, one-in-dime-type thing. But obviously, as you guys are now starting to ramp up with the oncology side of things, the number we saw in the third quarter, is that a pretty reasonable run rate we should expect over the next quarter and then the rest of next year? Or should we expect it to be variable?

我只想問——我想我的第一個問題只是關於模型管家的問題。 Philippe，我知道你提到了研發的增加。顯然，裡面有幾樣東西，sortilin 1，然後是筆式註射器。我看筆式註射器是一種一次性的、一分錢一分貨的東西。但很明顯，隨著你們現在開始在腫瘤學方面取得進展，我們在第三季度看到的數字是否是我們應該在下一季度和明年剩餘時間預期的相當合理的運行率？或者我們應該期望它是可變的嗎？

Yes. I think it's a good indicator. As you said, some of these projects will go away, but we have more -- like Paul mentioned, the PROMISE trial which we'll start in the EU and in North America as well. So I guess that level is sustainable even though there are certain projects that will be falling off activity, and activity should be ramping up in the oncology program as well. Because as you know, we've been enrolling patients one by one. And as we move deeper into Phase I, we'll be enrolling 3 by 3. And then when the expansion trial comes in, it's 40 patients. So next year, there should be a ramp-up on the oncology program.

是的。我認為這是一個很好的指標。正如你所說，其中一些項目將會消失，但我們還有更多——就像保羅提到的，我們將在歐盟和北美開始的 PROMISE 試驗。所以我想這個水平是可持續的，即使某些項目將停止活動，並且腫瘤學項目中的活動也應該增加。因為如你所知，我們一直在一個接一個地招募患者。隨著我們深入到第一階段，我們將招募 3 名 3 名患者。然後當擴展試驗開始時，有 40 名患者。所以明年，腫瘤學項目應該會有所增加。

Okay. That's helpful. And then just with regards to the PROMISE studies, which, I think, make a lot of sense. I guess my question is, was this more driven internally by you guys to try to help further educate physicians? Or were you actually getting the feed push from physicians to better understand how they would incorporate Trogarzo for those multidrug-resistant patients?

好的。這很有幫助。然後關於 PROMISE 研究，我認為這很有意義。我想我的問題是，這是否更多地是由你們內部推動的，以試圖幫助進一步教育醫生？或者您是否真的從醫生那裡得到了飼料推送，以更好地了解他們將如何為那些多重耐藥患者加入 Trogarzo？

Thank you, Edward, and I'll ask Christian to provide additional color. But you should know that, first of all, this is an obligation we have in Europe. It comes with the approval we got to get going with a post-marketing surveillance trial. But in my experience from a strategic point of view, this is great stuff because you actually give a chance to a lot of KOL to develop hands-on experience. And I think this is going to be a strategic activity for us in the upcoming years with Trogarzo. And our commitment is big. Christian, do you want to add anything?

謝謝你，愛德華，我會請克里斯蒂安提供額外的顏色。但你應該知道，首先，這是我們在歐洲的義務。它伴隨著我們開始進行上市後監督試驗的批准。但從戰略的角度來看，以我的經驗來看，這是一件很棒的事情，因為你實際上給了很多 KOL 發展實踐經驗的機會。我認為這將是我們未來幾年與 Trogarzo 合作的一項戰略活動。我們的承諾很大。克里斯蒂安，你想補充什麼嗎？

Yes. This is a very, very good tool of our clinical team. And as Paul mentioned, for Europe, it was requested by EMA. And in the U.S., we decided to implement the study with a slight change. We will do retrospective data entry in the patients that have been treated so far. Then this is a good tool to interact with our physicians. And hopefully, in the near future, maybe in a year from now, we'll be able to start reporting good long-term safety and efficacy data that it's a good tool to interact with the physician and potentially good publication on our own products.

是的。這是我們臨床團隊的一個非常非常好的工具。正如 Paul 提到的，對於歐洲，它是 EMA 要求的。在美國，我們決定稍微改變一下來實施這項研究。我們將對迄今為止接受過治療的患者進行回顧性數據錄入。那麼這是與我們的醫生互動的好工具。希望在不久的將來，也許一年後，我們將能夠開始報告良好的長期安全性和有效性數據，這是與醫生互動的好工具，並可能在我們自己的產品上發表好文章。

(Operator Instructions) We have a question from Endri Leno with National Bank.

（操作員說明）Endri Leno 向國家銀行提出了一個問題。

I'll start with Trogarzo. I was wondering if you guys could talk a little bit on the sales on the breakdown of that decline. I mean because -- we saw -- there was COVID-related drops even last year. Like is it safe to assume that most of the decline you saw this quarter is because of the competition?

我將從 Trogarzo 開始。我想知道你們是否可以談談銷售下降的細目。我的意思是因為——我們看到——甚至去年也出現了與 COVID 相關的下降。是否可以安全地假設您本季度看到的大部分下降是由於競爭？

Well, I think -- thank you for the question. I think we said in previous quarters, and we haven't changed our mind that there was a multifactor playing out. Trogarzo is an IV infusion. Patients were asked to stay home. They needed to go to the clinic, to the hospital at a time where physicians were telling them to stay at home. So that impacted, obviously, us capturing new patients, putting new patients on therapies. And at the same time, Rukobia came out in a pill mode. And although we absolutely believe that BID is more pills and patients are facing pill fatigue, so it's directionally incorrect. But for a short period of time, it was kind of favorable to them and unfavorable to us.

好吧，我想——謝謝你提出這個問題。我想我們在前幾個季度說過，我們沒有改變我們的想法，即有多種因素在起作用。 Trogarzo 是一種靜脈輸液。患者被要求待在家裡。他們需要去診所，在醫生告訴他們待在家裡的時候去醫院。因此，很明顯，這影響了我們吸引新患者，讓新患者接受治療。而與此同時，露可比亞以藥丸模式登場。雖然我們絕對相信 BID 是更多的藥片，但患者面臨藥片疲勞，所以它的方向是不正確的。但是在很短的時間內，對他們有利，對我們不利。

I think that now we see the situation changing a bit. And as I said before, what is absolutely important to me is that we team up in a way to make sure that the segment, the multidrug-resistant segment is opening up, so that we can both of us benefit from doctors being less lenient when it comes down to the viral load untreated and that they go about treating it. John, do you want to add anything?

我認為現在我們看到情況發生了一些變化。正如我之前所說，對我來說絕對重要的是我們以某種方式合作，以確保該細分市場，即多重耐藥細分市場正在開放，這樣我們雙方都可以從醫生不那麼寬容的情況下受益它歸結為未經處理的病毒載量，他們開始治療它。約翰，你想補充什麼嗎？

I think that's it, Paul. I mean COVID certainly had a major effect on any IV drug. There was many instances in other disease states like oncology, where there was a shift to oral agents. And so I think we were impacted by that certainly. But as Paul said, we have had a new competitor launch, and that has also had an impact.

我想就是這樣，保羅。我的意思是 COVID 肯定對任何靜脈注射藥物都有重大影響。在其他疾病狀態（如腫瘤學）中有許多實例轉向口服藥物。所以我認為我們肯定受到了影響。但正如保羅所說，我們推出了新的競爭對手，這也產生了影響。

Okay. Great. So the other question on Trogarzo is, if you can talk a little bit about the cadence of new reimbursement plans in Europe. I mean -- because there are several other countries I think that you've talked before to potentially target to France, Spain, U.K. Any color you can give me there in terms of timelines?

好的。偉大的。所以關於 Trogarzo 的另一個問題是，你能否談談歐洲新報銷計劃的節奏。我的意思是 - 因為我認為還有其他幾個國家/地區，我認為您之前已經談過可能以法國，西班牙，英國為目標。您可以在時間表方面給我任何顏色嗎？

He's wondering about the reimbursement and the successive launches in Europe, what we're seeing.

他想知道我們所看到的報銷和在歐洲的連續發射。

Okay. Well, I mean, as you know, we've got some cohorts in some countries now, France, in particular, where we are under ATU. So temporary authorization, the patients are reimbursed at full price. And meanwhile, we're doing the pricing and negotiation with the government. It's one of our major countries over there. But as I said before, in the midst of the pandemic, we were able to accelerate negotiation in Italy, and Italy came out as showing leadership. We have many KOLs on the ground that are coming forward and ended up being big advocate for us to get reimbursement. So that will be published in the next couple of weeks. And we believe that we're going to have by the end of this year reimbursement, and therefore, we'll start our activities on the ground.

好的。好吧，我的意思是，如你所知，我們現在在一些國家/地區有一些同夥，尤其是法國，我們在 ATU 的領導下。所以臨時授權，病人全價報銷。與此同時，我們正在與政府進行定價和談判。它是我們那邊的主要國家之一。但正如我之前所說，在大流行期間，我們能夠在意大利加快談判，意大利表現出了領導作用。我們有許多實地的 KOL 挺身而出，最終成為我們獲得報銷的大力倡導者。所以這將在接下來的幾週內發布。我們相信我們將在今年年底之前獲得報銷，因此，我們將在實地開始我們的活動。

Now most of the other countries will unfold in early and mid-2022. So we're gearing up now to really capitalize on this situation. And again, I think that in Europe, we are ahead of Rukobia in many countries. And the market dynamics are different. I think the KOLs in Europe are playing a much bigger role as opposed to the HIV providers in the U.S. So the go-to-market model may be different and may not require that we deploy a huge amount of resources to actually get going with our commercial model.

現在大多數其他國家/地區將在 2022 年初和中期展開。所以我們現在正準備真正利用這種情況。而且，我認為在歐洲，我們在許多國家/地區領先於 Rukobia。而且市場動態不同。我認為與美國的 HIV 提供者相比，歐洲的 KOL 發揮著更大的作用。因此，進入市場的模式可能不同，可能不需要我們部署大量資源來真正開始我們的商業模式。

Okay. Great. My next question is on TH1902. I was wondering if you guys can comment a bit in terms of if the -- if you saw the Grade 4 SAE on the 420-milligram dose, would that suggest that that could be the MTD? Or is it more work that you need to do there? Or do you need to see another SAE in that dose group to make that call?

好的。偉大的。我的下一個問題是關於 TH1902。我想知道你們是否可以評論一下——如果您在 420 毫克劑量上看到 4 級 SAE，這是否表明這可能是 MTD？還是您需要在那裡做更多的工作？或者您是否需要看到該劑量組中的另一個 SAE 才能做出決定？

Christian?

基督教？

Yes, absolutely. Well, this is -- we're not there yet with the MTD. The way it works is even like what we need to see is what we call a dose-limiting toxicity. And what we have seen so far is a neutropenia without fever. Therefore, it's not yet the DLT. Then once we reach like Grade 2 adverse events, we need to enroll more patients at that dose level. And once we have a total of 3 patients treated at that dose level, we decide if we can continue to increase or if we remain at the same dose or if we have to lower the dose. Then what I can say about this Phase I trial is at the moment, it is really what we have -- what we were expecting from the animal data that we had then.

是的，一點沒錯。好吧，這是 - 我們還沒有 MTD。它的工作方式甚至就像我們需要看到的是我們所說的劑量限制毒性。而我們目前看到的是沒有發燒的中性粒細胞減少症。因此，它還不是分佈式賬本技術。然後，一旦我們達到 2 級不良事件，我們需要在該劑量水平上招募更多患者。一旦我們總共有 3 名患者接受了該劑量水平的治療，我們將決定是否可以繼續增加劑量，或者是否保持相同劑量，或者是否必須降低劑量。那麼關於這個第一階段試驗，我現在可以說的是，它確實是我們所擁有的——我們對當時所擁有的動物數據的期望。

We are now at those levels that are in the range of about 2x docetaxel. We have dosed patients at 300 without Grade 2 adverse event, which means that we can administer up to 1.5x the dose of docetaxel when conjugated with TH1902 without having any adverse events. Then we're getting close to the MTD. That's the dose that we're expecting. Based on the animal model, we need a few more patients to be able to define our MTD. But it doesn't mean that in terms of efficacy that it wouldn't show efficacy at lower doses. Then we're on track. We continue MTD. We should probably reach the MTD towards hopefully the end of this year. And after that, we'll be able to initiate our basket trial beginning of 2022.

我們現在處於大約 2 倍多西紫杉醇範圍內的水平。我們已經給 300 名患者給藥，沒有發生 2 級不良事件，這意味著我們可以在與 TH1902 結合時給予高達 1.5 倍劑量的多西紫杉醇，而不會出現任何不良事件。然後我們接近 MTD。這就是我們期望的劑量。基於動物模型，我們需要更多的患者才能定義我們的 MTD。但這並不意味著就功效而言，它不會在較低劑量下顯示出功效。然後我們走上正軌。我們繼續 MTD。我們應該有望在今年年底達到 MTD。在那之後，我們將能夠在 2022 年初啟動我們的籃子試驗。

Thank you, Christian. It's got to be clear to everyone this morning that all of this is directionally correct. And quite frankly, we're very proud of where we are because it's a very least 1.5x the dose of docetaxel that we're able to carry without significant side effects. So we haven't reached the maximum targeted dose, Christian was clear on this. And it's very important that we carry on the dose escalation to find out what that is, which is going to inform the Part B of that Phase I trial. But for now, what we see is very encouraging. I'm going to say that again, because we can, it seems, give more docetaxel, better tolerated, and it is directionally very exciting. And hopefully, that is going to translate to the efficacy we saw in the animal model once we get further down into trial.

謝謝你，克里斯蒂安。今天早上每個人都必須清楚，所有這些都是方向正確的。坦率地說，我們為我們所處的位置感到非常自豪，因為它至少是我們能夠攜帶的多西紫杉醇劑量的 1.5 倍，而沒有明顯的副作用。所以我們還沒有達到最大目標劑量，Christian 對此很清楚。非常重要的是，我們進行劑量遞增以找出那是什麼，這將通知第一階段試驗的 B 部分。但就目前而言，我們所看到的是非常令人鼓舞的。我要再說一遍，因為我們似乎可以給予更多的多西紫杉醇，耐受性更好，這在方向上非常令人興奮。希望一旦我們進一步深入試驗，這將轉化為我們在動物模型中看到的功效。

Okay. Great. One more question there. I don't know if you have the data on it yet or even want to disclose at this point. But was there any difference in the sortilin expression between the patients that you've treated in terms of how they respond to the different doses?

好的。偉大的。還有一個問題。我不知道你現在是否有數據，甚至不想透露。但是，就您治療過的患者對不同劑量的反應而言，他們的分揀蛋白表達是否存在差異？

At the moment, we're, as I mentioned before, in discussion with FDA. We are not selecting patients based on the expression of the sortilin receptor, and this is normal. It was requested by the FDA because we need to assess eventually what will be the level of the sortilin receptor, like the association between the receptor and the efficacy.

目前，正如我之前提到的，我們正在與 FDA 進行討論。我們不是根據分揀蛋白受體的表達來選擇患者，這是正常的。這是 FDA 要求的，因為我們需要最終評估分揀蛋白受體的水平，例如受體與功效之間的關聯。

On the other hand, we are collecting the information. We will do the staining with the immunohistochemistry test, and we will have the information. Then at the end of the MTD, if there are some patients that are responding or stabilizing, we'll be able to see if there's a correlation with the expression of the receptor. But those patients are not selected based on the expression of the receptor. And that's what we will do as well in the basket trial. It's very important to be able to determine what level of expression of the receptor is needed to show efficacy.

另一方面，我們正在收集信息。我們將通過免疫組織化學測試進行染色，我們將獲得信息。然後在 MTD 結束時，如果有一些患者正在響應或穩定，我們將能夠看到是否與受體的表達相關。但這些患者並不是根據受體的表達來選擇的。這也是我們將在籃子試驗中做的。能夠確定顯示功效所需的受體表達水平非常重要。

Thank you, Christian. This is a key, key, key fact to understand. The patients in the dose escalation are all comers. They are not selected based on their level of SORT1 expression. That's very important that people understand that. We take all comers, people that are at the end of the line when it comes down to their own treatment, and therefore, they are the patients that we're treating with TH1902. Any additional questions?

謝謝你，克里斯蒂安。這是要理解的關鍵、關鍵、關鍵事實。劑量遞增中的患者都是來者不拒。它們不是根據它們的 SORT1 表達水平來選擇的。人們理解這一點非常重要。我們接受所有來者，當涉及到他們自己的治療時處於隊伍末尾的人，因此，他們是我們正在用 TH1902 治療的患者。還有其他問題嗎？

And there are no other questions on the phone line.

電話線上沒有其他問題。

Okay. So there are quite a few questions on the webcast and most of them are related to the timing of the Phase I trial. So I think they have been addressed. But there's one here that I will ask Christian is, was the one Grade 4 SAE, the only one seen so far in the trial? Any reason why the trial seems to be a little behind schedule?

好的。所以網絡直播中有不少問題，其中大部分與一期試驗的時間安排有關。所以我認為他們已經得到解決。但是這裡有一個我要問克里斯蒂安的問題是，到目前為止在試驗中看到的唯一一個 4 級 SAE 嗎？審判似乎有點落後於計劃的原因是什麼？

Well, yes, this is the first time that we're seeing what we call in this case is the Grade 4 neutropenia, but it's a Grade 2 adverse event. And it's the first time that we see the Grade 2 adverse events since the initiation of the trial. And as you remember, we started with 30-milligram per day per meter square. And this is what we -- like we're able to increase -- double the dose, 1 additional patient, only 1 patient per dose as per the protocol. Once we reach the 200-milligram, it was the Fibonacci escalation dose theme that is no longer doubling the dose, but it is done because we know that we're getting closer to some toxicity, and we don't want to double the dose anymore.

嗯，是的，這是我們第一次看到我們在這種情況下所說的 4 級中性粒細胞減少症，但這是 2 級不良事件。這是自試驗開始以來我們第一次看到 2 級不良事件。你還記得，我們開始時每天每平方米 30 毫克。這就是我們 - 就像我們能夠增加 - 劑量加倍，增加 1 名患者，按照協議，每劑僅 1 名患者。一旦我們達到 200 毫克，斐波那契遞增劑量主題不再將劑量加倍，但這樣做是因為我們知道我們正在接近某種毒性，我們不想將劑量加倍了。

But as I said before, we're very happy that we reached the dose of 420-milligram per meter square. It shows that we can give more docetaxel with TH1902 than docetaxel alone. And if you remember from the animal data, we always mentioned that in the presence of the sortilin receptor, it looks like there are more drugs that enter the cancer cell than the noncancer cells, that if we give 1.5x the dose of docetaxel and there's more drug entering the cancer cell, hopefully, that will have an impact on the efficacy.

但正如我之前所說，我們很高興我們達到了每平方米 420 毫克的劑量。它表明與單獨使用多西他賽相比，我們可以使用 TH1902 提供更多的多西他賽。如果你還記得動物數據，我們總是提到在分選蛋白受體存在的情況下，進入癌細胞的藥物似乎比非癌細胞多，如果我們給予 1.5 倍劑量的多西紫杉醇，就會有希望更多的藥物進入癌細胞，這將對療效產生影響。

In terms of the timing, we're right on. The cycles are given every 3 weeks. But to recruit the following patient, we need to have all of the safety data. We need to look at data carefully, and it will take probably 4 to 5 weeks between each patients. And I must say that at the moment, we're right on target and probably even higher to some extent with the 420-milligram. And now we will decide once we have all of the information and safety, what will be the next dose for the following patients and if we need to enroll more patients at the following notice.

就時間而言，我們是對的。週期每 3 週進行一次。但是要招募以下患者，我們需要擁有所有的安全數據。我們需要仔細查看數據，每個患者之間可能需要 4 到 5 週的時間。我必須說，目前我們的目標是正確的，420 毫克可能在某種程度上更高。現在，一旦我們掌握了所有信息和安全性，我們將決定以下患者的下一次劑量是多少，以及我們是否需要在以下通知中招募更多患者。

Okay. Paul, you can close.

好的。保羅，你可以關門了。

Okay. Well, thank you very much for your questions and the enthusiasm this morning. I just want to wrap up in saying that, first of all, we had a solid order from a revenue point of view. This is really, really exciting to us coming out of the COVID, being able to deploy resources in an effective manner.

好的。嗯，非常感謝你今天早上的提問和熱情。我只想說，首先，從收入的角度來看，我們有一個穩定的訂單。這讓我們從 COVID 中走出來，能夠有效地部署資源，這真的非常令人興奮。

We are very enthusiastic about the progress of TH1902. This is very exciting. We carry on. We're not behind. We're where we thought we would be. And this early report tells us that it seems like our TH1902 is better tolerated than docetaxel alone. This is directionally correct. Very excited. And we're still committed to the NASH trial. And we've said many, many times that we're looking for a partner. We are in discussion. We want to see if there are some partners available where they would be a good fit from a capability and resourcing point of view. And we're committed to the trial. So if we don't find a partner, we'll find alternate way, responsible way for our shareholders to finance this trial.

我們對TH1902的進展非常熱情。這非常令人興奮。我們繼續。我們沒有落後。我們在我們以為我們會在的地方。這份早期報告告訴我們，我們的 TH1902 似乎比單獨使用多西紫杉醇的耐受性更好。這是方向正確的。很激動。我們仍然致力於 NASH 試驗。我們已經說過很多很多次我們正在尋找合作夥伴。我們正在討論中。我們想看看是否有一些可用的合作夥伴，從能力和資源的角度來看，他們是合適的。我們致力於審判。因此，如果我們找不到合作夥伴，我們會找到其他方式，對我們的股東負責的方式為這次試驗提供資金。

We are sitting on a Phase III ready-to-go program in NASH. It's one of the highest unmet medical need area, and I don't see why we would sit on it. So we're committed to finding a way to put that in the clinic.

我們正在進行 NASH 的 III 期準備就緒計劃。它是未滿足醫療需求最高的地區之一，我不明白我們為什麼要坐在上面。所以我們致力於尋找一種方法將其應用於臨床。

So again, thank you very much for attending today and looking forward to the next update at the next quarterly report. Thank you again.

再次，非常感謝您參加今天的會議，並期待下一季度報告的下一次更新。再次感謝你。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。