Iterum Therapeutics PLC (ITRM) 2022 Q4 法說會逐字稿

Hello, everyone, and welcome to the Iterum Therapeutics Fourth Quarter and Full Year 2022 Financial Results and Business Update. My name is Charlie and I'll be coordinating the call today. (Operator Instructions) I will now hand over to your host, Louise Barrett, SVP, Legal Affairs, to begin. Louise, please go ahead.

大家好，歡迎收看 Iterum Therapeutics 第四季度和 2022 年全年財務業績和業務更新。我叫查理，今天我將負責協調電話會議。 （操作員說明）我現在將交給您的主持人，法律事務高級副總裁 Louise Barrett，開始。露易絲，請繼續。

Thank you, Charlie. Good morning, and welcome to Iterum Therapeutics Fourth Quarter and Full Year 2020 Financial Results and Business Update Conference Call. Our press release with our fourth quarter and full year 2020 results was issued early this morning and can be found on our website.

謝謝你，查理。早上好，歡迎來到 Iterum Therapeutics 第四季度和 2020 年全年財務業績和業務更新電話會議。我們今天凌晨發布了包含 2020 年第四季度和全年業績的新聞稿，可以在我們的網站上找到。

We are joined this morning by Corey Fishman, CEO; and Judy Matthews, CFO. Corey will provide some opening remarks, Judy will provide details on our financial results, and then we will open the lines to some Q&A.

今天上午，首席執行官 Corey Fishman 加入了我們的行列；和首席財務官 Judy Matthews。 Corey 將提供一些開場白，Judy 將提供我們財務結果的詳細信息，然後我們將開放一些問答環節。

Before I begin, I would like to remind you that this call will contain forward-looking statements concerning our plans, strategies and prospects for our business, including the development, therapeutic and market potential of sulopenem; the timing, conduct, progress and results of our ongoing REASSURE clinical trials; the expected timing of resubmission of our NDA; the term and coverage provided by our patents and other intellectual property rights; and the sufficiency of our cash resources. Actual results may differ material with those indicated by these forward-looking statements as a result of various important factors, including uncertainties inherent in the design, initiation and conduct of clinical development, including the REASSURE clinical trials; the availability and timing of data from the REASSURE clinical trials; changes in regulatory requirements due decisions of regulatory authorities; the timing or likelihood of regulatory filings and approvals, including the potential resubmission of our NDA for oral sulopenem; changes in public policy or legislation and commercialization plans and time line since oral sulopenem is produced; the actions of third-party clinical research for organization suppliers and manufacturers; the efficacy of our expectations regarding how far into future our cash on hand will fund our ongoing operations; and other factors discussed under the caption Risk Factors in our annual report filed this morning. In addition, any forward-looking statements represent views only as of the date of this call and should not be reliant on that representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements.

在開始之前，我想提醒您，本次電話會議將包含有關我們業務的計劃、戰略和前景的前瞻性陳述，包括舒羅培南的開發、治療和市場潛力；我們正在進行的 REASSURE 臨床試驗的時間安排、實施、進展和結果；重新提交保密協議的預期時間；我們的專利和其他知識產權提供的期限和覆蓋範圍；以及我們的現金資源是否充足。由於各種重要因素，包括 REASSURE 臨床試驗在內的臨床開發設計、啟動和實施中固有的不確定性，實際結果可能與這些前瞻性陳述所表明的結果存在重大差異； REASSURE 臨床試驗數據的可用性和時間安排；由於監管機構的決定而改變監管要求；監管備案和批准的時間或可能性，包括可能重新提交我們的口服磺羅培南 NDA；自生產口服硫羅培南以來公共政策或立法以及商業化計劃和時間表的變化；組織供應商和製造商的第三方臨床研究活動；我們對未來多長時間手頭現金將為我們的持續運營提供資金的預期的有效性；以及我們今天上午提交的年度報告中風險因素標題下討論的其他因素。此外，任何前瞻性陳述僅代表截至本次電話會議之日的觀點，不應依賴於代表我們截至任何後續日期的觀點。我們特別聲明不承擔任何更新此類聲明的義務。

We will also be referring to non-GAAP financial measures during the call. We have provided reconciliations of GAAP reported to non-GAAP adjusted information in the press release issued this morning. That said, I'll turn it over now to Corey for some opening remarks.

我們還將在電話會議期間提及非 GAAP 財務指標。我們在今天上午發布的新聞稿中提供了 GAAP 報告與非 GAAP 調整後信息的對賬。也就是說，我現在將把它交給 Corey 做一些開場白。

Thanks, Louise. Welcome, and thanks for joining us today. I want to share some highlights from 2022 and talk about our 2023 activities. We made significant progress in 2022 to move the clinical development of sulopenem forward. We worked with the FDA to align on a design for an additional Phase III clinical trial for oral sulopenem to address certain deficiencies the FDA noted in their complete response letter we received in July 2021.

謝謝，路易絲。歡迎並感謝您今天加入我們。我想分享 2022 年的一些亮點，並談談我們 2023 年的活動。我們在 2022 年取得了重大進展，推動了 sulopenem 的臨床開發。我們與 FDA 合作，共同設計了一項針對口服磺羅培南的額外 III 期臨床試驗，以解決 FDA 在我們於 2021 年 7 月收到的完整回复信中指出的某些缺陷。

We are conducting our new Phase III clinical trial under a special protocol assessment, SPA, agreement with the FDA. The SPA agreement provides that the design and planned analysis of the clinical trial as set out in the protocol submitted to the FDA adequately addresses the objectives necessary to support the potential resubmission of the company's new drug application for oral sulopenem.

我們正在根據與 FDA 達成的特殊協議評估 SPA 協議進行新的 III 期臨床試驗。 SPA 協議規定，提交給 FDA 的協議中規定的臨床試驗的設計和計劃分析充分解決了必要的目標，以支持公司可能重新提交口服硫羅培南的新藥申請。

As a brief reminder, our new Phase III clinical trial known as REASSURE, comparing oral sulopenem to oral Augmentin for the treatment of uncomplicated urinary tract infections is currently enrolling subjects. The REASSURE study is designed as a noninferiority trial comparing oral sulopenem and oral Augmentin in the Augmentin-susceptible population and is expected to enroll approximately 1,966 patients.

簡要提醒一下，我們名為 REASSURE 的新 III 期臨床試驗比較了口服硫羅培南和口服奧格門汀治療單純性尿路感染的效果，目前正在招募受試者。 REASSURE 研究被設計為一項非劣效性試驗，在 Augmentin 易感人群中比較口服 sulopenem 和口服 Augmentin ，預計將招募約 1,966 名患者。

In the REASSURE trial, patients will be randomized to receive either oral sulopenem twice daily for 5 days or oral Augmentin twice daily for 5 days. The primary endpoint is the overall response, clinical and microbiologic combined response at day 12 of the trial.

在 REASSURE 試驗中，患者將被隨機分配接受每天兩次口服硫羅培南，持續 5 天或每天兩次口服 Augmentin，持續 5 天。主要終點是試驗第 12 天的總體反應、臨床和微生物學綜合反應。

We expect to complete enrollment in the first half of 2024. And if successful, we'll resubmit our NDA to the FDA in the second half of 2024. If the resubmission addresses all the deficiencies in the Complete Response Letter we received in July 2021 from FDA, then the FDA's review and action should occur 6 months from receipt of our resubmission.

我們預計在 2024 年上半年完成註冊。如果成功，我們將在 2024 年下半年向 FDA 重新提交我們的 NDA。如果重新提交解決了我們在 2021 年 7 月從FDA，然後 FDA 的審查和行動應該在收到我們重新提交後的 6 個月內發生。

It's important to note that the need for new oral treatments in an uncomplicated urinary infection therapy area remains high. Although the market is quite large with approximately 33 million prescriptions in the U.S. annually, almost all currently available oral treatment options face safety and efficacy challenges, including increasing resistance, leading community physicians seeking new and effective treatment options.

重要的是要注意，在不復雜的尿路感染治療領域對新的口服治療的需求仍然很高。儘管市場相當大，美國每年約有 3300 萬張處方，但目前幾乎所有可用的口服治療方案都面臨安全性和有效性挑戰，包括耐藥性增加，導致社區醫生尋求新的有效治療方案。

We are very pleased to share that Iterum has been granted 2 U.S. patents, 1 directly to the composition of the bilayer tablet of oral sulopenem, which contains sulopenem etzadroxil and probenecid in a single bilayer tablet; and 1 patent directed to the method of use of oral sulopenem in treating with multiple diseases, including uncomplicated urinary tract infections. Both of these patents will provide protection into 2039, which allows for a substantial runway to protect the value of oral sulopenem in the U.S.

我們很高興地與大家分享，Iterum 已獲得 2 項美國專利，1 項直接涉及口服磺胺培南雙層片的成分，其中在單個雙層片中含有磺胺嘧啶和丙磺舒； 1 項專利涉及口服硫羅培南治療多種疾病的方法，包括無並發症的尿路感染。這兩項專利都將提供到 2039 年的保護，這為在美國保護口服磺羅培南的價值留出了一條可觀的跑道。

Outside the U.S., we have pending patent applications, including in Europe, China, Japan and parts of South America, which were submitted following receipt of the Written Opinion on the International Search Authority indicating that several claims directed to the composition of the bilayer tablet of oral sulopenem are novel and inventive.

在美國以外，我們有待審專利申請，包括在歐洲、中國、日本和南美洲部分地區，這些申請是在收到國際檢索機構的書面意見後提交的，表明多項權利要求針對雙層片的成分口服磺羅培南具有新穎性和創造性。

Additionally, we continue to evaluate potential new areas where there is an unmet medical need and where sulopenem could be an important potential alternative in treating those patients. We will share additional details as and when this plan develops further.

此外，我們繼續評估未滿足醫療需求的潛在新領域，以及磺羅培南可能成為治療這些患者的重要潛在替代品。當這個計劃進一步發展時，我們將分享更多細節。

Our cash position remains solid with a balance of approximately $61 million as of year-end 2022. We expect that our current cash, cash equivalents and short-term investments will be able to fund our operations into mid-2024.

截至 2022 年底，我們的現金狀況保持穩定，餘額約為 6100 萬美元。我們預計，我們目前的現金、現金等價物和短期投資將能夠為我們的運營提供資金，直至 2024 年年中。

In summary, we are pleased to have aligned with the FDA and begun enrollment in our REASSURE clinical trial and are looking forward to potentially bringing the first new oral sulopenem to the market in order to help address a serious medical need in the community.

總之，我們很高興與 FDA 保持一致並開始註冊我們的 REASSURE 臨床試驗，並期待著可能將第一個新的口服磺羅培南推向市場，以幫助解決社區的嚴重醫療需求。

Now I'll turn the call over to Judy for additional details on our financial results.

現在我會把電話轉給朱迪，了解我們財務業績的更多細節。

Thanks, Corey. Total operating expenses were $7.9 million and $30.4 million in the fourth quarter and full year 2022 compared to $6.8 million and $24.5 million in the fourth quarter and full year 2021. Operating expenses include research and development expenses and general and administrative expenses. R&D costs were $5.8 million for the fourth quarter and $17.6 million for the full year 2022 compared to $3.7 million and $10.7 million for the same period in 2021.

謝謝，科里。第四季度和 2022 年全年的總運營費用分別為 790 萬美元和 3040 萬美元，而第四季度和 2021 年全年的運營費用分別為 680 萬美元和 2450 萬美元。運營費用包括研發費用以及一般和行政費用。第四季度的研發成本為 580 萬美元，2022 年全年的研發成本為 1760 萬美元，而 2021 年同期為 370 萬美元和 1070 萬美元。

The primary driver of the increase in R&D expense for the fourth quarter and full year with cost to support our REASSURE trial, which began enrollment in October 2022. G&A cost was $2.1 million for the fourth quarter of 2022, which is $1 million lower than G&A costs of $3.1 million in the fourth quarter of 2021 due primarily to lower share-based compensation expense.

第四季度和全年研發費用增加的主要驅動因素是支持我們的 REASSURE 試驗的成本，該試驗於 2022 年 10 月開始註冊。2022 年第四季度的 G&A 成本為 210 萬美元，比 G&A 低 100 萬美元2021 年第四季度的成本為 310 萬美元，這主要是由於基於股份的薪酬費用較低。

Full year G&A costs were $12.8 million in 2022, which is $1 million lower than G&A costs of $13.8 million in 2021, primarily due to the cost of pre-commercialization activities carried out in 2021 prior to receipt of the CRL and the decrease in consultant is to support our general and administrative functions, partially offset by an increase in legal fees associated with the lawsuit filed in August 2021, which was dismissed with prejudice in January 2023, which means the case cannot be brought back to court.

2022 年全年 G&A 成本為 1280 萬美元，比 2021 年的 G&A 成本 1380 萬美元低 100 萬美元，這主要是由於 2021 年在收到 CRL 之前進行的商業化前活動的成本以及顧問的減少以支持我們的一般和行政職能，部分被與 2021 年 8 月提起的訴訟相關的法律費用增加所抵消，該訴訟於 2023 年 1 月因有偏見而被駁回，這意味著該案件無法重新審理。

Our net loss on a U.S. GAAP basis was $5.1 million for the fourth quarter of 2022 and $44.4 million for the full year. Impacting the full year net loss was a noncash charge of $17.4 million included in other income and expense in connection with the cancellation of share options. As we discussed last time, in July 2022, certain executives and employees agreed to the surrender and cancellation of previously granted share options in order to make available additional shares under the company's equity incentive plan, giving rise to this noncash charge.

我們 2022 年第四季度的美國公認會計原則淨虧損為 510 萬美元，全年為 4440 萬美元。影響全年淨虧損的是一筆 1740 萬美元的非現金費用，該費用包含在其他收入和支出中，與取消購股權有關。正如我們上次討論的那樣，在 2022 年 7 月，某些高管和員工同意放棄和取消先前授予的股票期權，以便根據公司的股權激勵計劃提供額外的股票，從而產生了這一非現金費用。

There was no impact of this adjustment on cash or cash runway, which I will turn to in a moment. On a non-GAAP basis, which excludes certain noncash adjustments, our net loss of $6.4 million and $22.9 million in the fourth quarter and full year 2022 compared to our non-GAAP net loss of $3.3 million and $19.4 million in the fourth quarter and full year of 2021. The $3.1 million and $3.5 million increase in our non-GAAP net loss for the fourth quarter and full year was primarily a result of higher R&D expenses related to our REASSURE trial.

這種調整對現金或現金跑道沒有影響，我稍後會談到這一點。在非公認會計原則的基礎上，不包括某些非現金調整，我們在第四季度和 2022 年全年的淨虧損分別為 640 萬美元和 2290 萬美元，而我們在第四季度和全年的非公認會計原則淨虧損分別為 330 萬美元和 1940 萬美元2021 年。我們第四季度和全年的非 GAAP 淨虧損增加了 310 萬美元和 350 萬美元，這主要是由於與我們的 REASSURE 試驗相關的研發費用增加。

At the end of December, we had cash, cash equivalents and short-term investments of $60.8 million, which based on our current operating plan will provide a cash runway until mid-2024. We expect to complete enrollment in the first half of 2024. And if the REASSURE trial is successful, we expect to resubmit to the FDA the NDA for oral sulopenem for the treatment of uUTI in the second half of 2024.

截至 12 月底，我們擁有 6080 萬美元的現金、現金等價物和短期投資，根據我們目前的運營計劃，這將提供一條現金跑道，直到 2024 年年中。我們預計將在 2024 年上半年完成註冊。如果 REASSURE 試驗成功，我們預計將在 2024 年下半年向 FDA 重新提交口服磺羅培南治療 uUTI 的 NDA。

As of December 31, 2022, we had approximately 12.6 million ordinary shares outstanding. Also as of the end of December 2022, we had approximately $12.6 million of exchangeable notes outstanding, which can be exchanged at the option of the noteholder for approximately 1.1 million shares. If the notes are not exchanged, we will pay the noteholders $12.6 million plus accrued interest in January 2025. Now I will turn it back over to Corey for some closing comments.

截至 2022 年 12 月 31 日，我們擁有約 1260 萬股已發行普通股。同樣截至 2022 年 12 月底，我們有大約 1260 萬美元的未償還可交換票據，票據持有人可以選擇將其交換為大約 110 萬股股票。如果不交換票據，我們將在 2025 年 1 月向票據持有人支付 1260 萬美元加上應計利息。現在我將把它轉回給科里，徵求一些結束意見。

Thanks, Judy. We'll open the line now to any questions.

謝謝，朱迪。我們現在將打開任何問題的線路。

(Operator Instructions) We have a question from Ed Arce of H.C. Wainwright.

（操作員說明）我們有來自 H.C. 的 Ed Arce 的問題。溫賴特。

This is Thomas Yip asking a couple of questions for Ed. First, regarding REASSURE. Can you tell us how patients have been enrolled so far? And if not, approximately what percentage enrollment has been achieved so far?

我是 Thomas Yip 向 Ed 問了幾個問題。首先，關於 REASSURE。你能告訴我們到目前為止是如何招募患者的嗎？如果沒有，到目前為止大約達到了多少百分比的入學率？

Thomas, it's Corey. Thanks for the question. We're not going to disclose specifics around the study. We generally don't do that just in terms of trying to not get people out in a good or bad way. But what I would tell you is I think the study is progressing very nicely. We've got a significant amount of sites open, and we've had significant enrollment so far. So the piece that we will share and we have shared is that based on the current forecast of how that continues to go, we would expect to finish up enrollment in that first half of '24.

托馬斯，我是科里。謝謝你的問題。我們不會透露研究的具體細節。我們通常不會僅僅為了不讓人們以好的或壞的方式離開而這樣做。但我要告訴你的是，我認為這項研究進展非常順利。我們已經開放了大量的站點，並且到目前為止我們已經有大量的註冊。因此，我們將分享和分享的內容是，根據目前對這種情況繼續發展的預測，我們預計將在 24 年上半年完成註冊。

Got it. And then perhaps a question regarding the interim analysis. What type of data can we expect after this is analysis is finished? And is there any possible to adjust the trial based on the data?

知道了。然後可能是關於中期分析的問題。分析完成後我們可以期待什麼類型的數據？有沒有可能根據數據調整試驗？

Yes. So the purpose of the interim analysis is really just to determine the patient size and make sure that the power remains where we had wanted it. And that's really the only information we get. It's generally done on a blinded basis. So you're really not looking at any of the data. And of course, the company can never do that anyway. It's done by an outside data safety monitoring committee. So all they'll do is look at the blinded data and say, yes, based on what we see right now, you're on track to maintain your power or if you want to maintain this power, you need to add x patients. If you're below where you'd expect it to be. So that's really the only piece of information you'll get when there's an interim analysis. It's really not about the efficacy in terms of -- we aren't going to know anything specific for sure. It's all going to be on a blinded basis.

是的。因此，中期分析的目的實際上只是確定患者的體型並確保功率保持在我們想要的位置。這真的是我們得到的唯一信息。它通常是在盲法的基礎上完成的。所以你真的沒有在看任何數據。當然，無論如何，公司永遠無法做到這一點。它由外部數據安全監控委員會完成。所以他們要做的就是查看盲化數據並說，是的，根據我們現在看到的情況，你有望保持你的力量，或者如果你想保持這種力量，你需要增加 x 名患者。如果你低於預期的水平。因此，這實際上是進行中期分析時您將獲得的唯一信息。這真的與功效無關——我們不會確定知道任何具體的事情。這一切都將是盲目的。

Got it. Perhaps one last question. This one should be for Judy. A question about cash runway. You mentioned to mid-2024. Just wondering was this expected to include top line data readout from REASSURE?

知道了。也許是最後一個問題。這個應該是給朱蒂的。關於現金跑道的問題。你提到到 2024 年年中。只是想知道這是否包括來自 REASSURE 的頂線數據讀出？

Yes. Based -- we will definitely get to enrollment, as we said, in that first half of 2024, and we do expect to be able to fund up through data. So it's expected -- data is also expected shortly after, of course, within a few months of finishing enrollment.

是的。基於——正如我們所說，我們肯定會在 2024 年上半年開始招生，我們確實希望能夠通過數據籌集資金。所以這是意料之中的——當然，在完成註冊後的幾個月內，數據也會很快出現。

We currently have no further questions. So I hand back over to Corey for any final remarks.

我們目前沒有進一步的問題。所以我將任何最後的評論交還給 Corey。

Great. Thanks very much. In conclusion, we want to thank you for joining us today. We continue to remain confident in the value of oral sulopenem to treat multidrug-resistant infections in the community and we look forward to concluding our ongoing clinical work. And if successful, resubmitting our NDA to the FDA for this important treatment option for physicians and patients.

偉大的。非常感謝。最後，我們要感謝您今天加入我們。我們繼續對口服硫羅培南治療社區多重耐藥感染的價值充滿信心，我們期待著完成我們正在進行的臨床工作。如果成功，我們將重新向 FDA 提交我們的 NDA，以便為醫生和患者提供這一重要的治療選擇。

Ladies and gentlemen, this concludes today's call. Thank you for joining. You may now disconnect your lines.

女士們，先生們，今天的電話會議到此結束。感謝您的加入。您現在可以斷開線路。