Chimerix Inc (CMRX) 2024 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Chimerix second quarter 2024 earnings conference call.

早安，女士們、先生們，歡迎參加 Chimerix 2024 年第二季財報電話會議。

I would now like to introduce to you to your host for today's call Will O'Connor of Stern Investor Relations. Please proceed.

現在我想向您介紹今天電話會議的主持人斯特恩投資者關係部的威爾·奧康納。請繼續。

Thank you, operator. Good morning, everyone, and welcome to the Chimerix second quarter 2024 financial and operating results conference call. This morning, we issued a press release related to our second quarter operating update. You can access the press release in our Investors section of the Chimerix website.

謝謝你，接線生。大家早安，歡迎參加 Chimerix 2024 年第二季財務與營運績效電話會議。今天早上，我們發布了與第二季度營運更新相關的新聞稿。您可以在 Chimerix 網站的投資者部分存取新聞稿。

With me on today's call are President and Chief Executive Officer, Mike Andriole; Chief Financial Officer, Michelle LaSpaluto; and Chief Technology Officer, Josh Allen. We also have Allen Melemed, our Chief Medical Officer; and Tom Riga, our Chief Operating and Commercial Officer for question.

與我一起參加今天電話會議的有總裁兼執行長 Mike Andriole；財務長米歇爾‧拉斯帕魯托；和首席技術官喬許艾倫。我們還有我們的首席醫療官 Allen Melemed；和我們的營運長和商務長湯姆·裡加（Tom Riga）回答問題。

Before we begin, I'd like to remind you that the statements made on today's call will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties and other factors.

在我們開始之前，我想提醒您，今天的電話會議中所做的陳述將包括 1995 年《私人證券訴訟改革法案》含義內的前瞻性陳述，並受到風險、不確定性和其他因素的影響。

These risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties.

這些風險和不確定性以及其他因素可能導致實際結果與前瞻性陳述中提到的結果有重大差異。請參閱我們向 SEC 提交的文件，以更完整地揭露這些風險和不確定性。

At this time, I'll now turn the call over to Chimerix's President and Chief Executive Officer, Mike Andriole.

現在，我將電話轉給 Chimerix 的總裁兼執行長 Mike Andriole。

Thanks, Will. Good morning, everyone, and thank you for joining us. It's been a busy summer at Chimerix and we continue to make meaningful progress across our clinical programs. Starting with our lead program, dordaviprone.

謝謝，威爾。大家早安，感謝您加入我們。這是 Chimerix 一個忙碌的夏天，我們的臨床計畫繼續取得有意義的進展。從我們的主導項目多達維酮開始。

Our team continues to be laser-focused on the execution and enrollment of the Phase 3 ACTION study, which is on track for the first interim overall survival readout in the third quarter of next year. We're executing with urgency as there remains a significant need for patients battling this lethal disease.

我們的團隊繼續專注於 3 期 ACTION 研究的執行和招募，該研究預計將在明年第三季公佈第一個中期整體存活率數據。我們正在緊急執行，因為仍然非常需要與這種致命疾病作鬥爭的患者。

With no approved treatment options available that have proven clinical benefit beyond radiation therapy, we're keenly aware of the importance of speed in addressing this unmet need. It's because of this need that we continuously evaluate registration pathways globally to accelerate commercial access to dordaviprone where possible.

由於沒有經過批准的治療方案已證明除了放射治療之外具有臨床益處，我們敏銳地意識到速度在解決這一未滿足的需求方面的重要性。正是由於這種需要，我們不斷評估全球註冊途徑，以盡可能加快多達維隆的商業化進程。

Earlier this year, we initiated the evaluation process for dordaviprone to be considered for provisional registration in Australia. Provisional registration is a three-step process that begins with a pre-submission meeting to evaluate current data, the status of pivotal studies, and other program features.

今年早些時候，我們啟動了多達維酮的評估流程，考慮在澳洲進行臨時註冊。臨時註冊是一個三步驟過程，從提交前會議開始，評估當前資料、關鍵研究的狀態和其他專案特徵。

Following a supportive pre-submission meeting earlier in the year, our team recently initiated the second step in this process, the filing of a provisional determination application. Should the regulators in Australia approve this application, the final step is to apply for provisional registration.

繼今年稍早舉行的支持性預提交會議之後，我們的團隊最近啟動了該流程的第二步，即提交臨時裁決申請。如果澳洲監管機構批准此申請，最後一步就是申請臨時註冊。

If we proceed to this final step, it's expected that an NDA filing could occur as early as year-end 2024 with possible commercial availability in early 2026.

如果我們繼續進行最後一步，預計最早可能會在 2024 年底提交 NDA 申請，並可能在 2026 年初投入商業使用。

This morning, we're also excited to provide a safety and PK update from our other clinical program, the second generation of imipridone ONC206. We're making great strides advancing this program through Phase 1 studies, which recently began dosing within an expected therapeutic range, and we are now enrolling the first of two remaining dose cohorts.

今天早上，我們還很高興提供我們的另一個臨床計畫第二代咪咪酮 ONC206 的安全性和 PK 更新。我們正在透過一期研究取得重大進展，該計劃最近開始在預期治療範圍內給藥，我們現在正在招募剩餘兩個劑量組中的第一個。

As we escalate and intensify the dose within this range, we're encouraged by ongoing pharmacokinetic data that is in line with modeled expectations for delivering dose-proportionate exposures for extended durations. Importantly, these exposures have not been associated with dose-limiting toxicities thus far.

當我們在這個範圍內逐步增加和加強劑量時，我們對持續的藥物動力學數據感到鼓舞，這些數據與延長持續時間提供劑量成比例的暴露的模型預期一致。重要的是，迄今為止，這些暴露尚未與劑量限制性毒性相關。

With these data, we have increasing confidence in the safety profile and therapeutic window for ONC206, and we look forward to completing enrollment in our dose escalation trials by the end of the year.

有了這些數據，我們對 ONC206 的安全性和治療窗口越來越有信心，我們期待在今年年底前完成劑量遞增試驗的註冊。

I'll now turn the call over to Josh for more detailed discussion on the ONC206 data we announced this morning. Josh?

現在我將把電話轉給 Josh，以便對我們今天早上公佈的 ONC206 數據進行更詳細的討論。喬許？

Thank you, Mike, and good morning, everyone. I'm delighted to provide an update on the program for our next generation product, ONC206, that is being evaluated in ongoing Phase 1 clinical trials. I'll start with a reminder that this is a small molecule that shares the novel ClpP and DRD2 binding targets with its parent compound or dordaviprone and exhibits a tenfold increase in potency while retaining favorable safety and oral administration attributes.

謝謝你，麥克，大家早安。我很高興為我們的下一代產品 ONC206 提供最新的計劃，該產品正在正在進行的 1 期臨床試驗中進行評估。首先我要提醒大家，這是一種小分子，與其母體化合物或多達維酮共享新型 ClpP 和 DRD2 結​​合靶點，並且效力提高了十倍，同時保留了良好的安全性和口服給藥特性。

It also maintains the relatively rare ability to penetrate the blood-brain barrier and has shown encouraging activity in non-clinical studies of specific forms of cancer both within and outside of the central nervous system.

它還保持了相對罕見的穿透血腦屏障的能力，並在中樞神經系統內外特定形式癌症的非臨床研究中顯示出令人鼓舞的活性。

In the ongoing Phase 1 trials for pediatric and adult CNS tumors, we have previously completed dose escalation on a once per week administration schedule at doses reaching up to 350 milligrams. That experience demonstrated the desired peak plasma concentrations and safety in patients that we expected based on our non-clinical models.

在正在進行的兒童和成人 CNS 腫瘤的 1 期試驗中，我們之前已按每週一次的給藥計劃完成了劑量遞增，劑量達到 350 毫克。這一經驗證明了我們根據我們的非臨床模型所期望的患者的預期峰值血漿濃度和安全性。

In parallel to the clinical evaluation of this dose schedule, non-clinical studies suggested that the anti-cancer activity of this compound could be enhanced by prolonging the duration of time that tumor cells are exposed to biologically active concentrations.

在對該劑量方案進行臨床評估的同時，非臨床研究表明，可以透過延長腫瘤細胞暴露於生物活性濃度的時間來增強該化合物的抗癌活性。

This appeared to potentially be achievable through dosing on a twice per day for three consecutive days per week administration schedule based on our modeling, and we have been busy testing this in the clinic this year.

根據我們的模型，這似乎可以透過每週連續三天每天兩次給藥的給藥方案來實現，今年我們一直忙於在診所進行測試。

We have now generated human data for safety in pharmacokinetics or PK for short, at doses reaching up to 100 milligrams at this intensified administration schedule. We are happy to report that the tolerability of the compound continues to be favorable as we continue dose intensification with no meaningful changes in the overall adverse event profile as the dosing has either escalated up or become more frequent.

我們現在已經產生了藥物動力學（簡稱 PK）安全性的人體數據，在這種強化給藥方案中，劑量高達 100 毫克。我們很高興地報告，隨著我們繼續增加劑量，化合物的耐受性仍然良好，並且隨著劑量的增加或變得更加頻繁，整體不良事件特徵沒有發生有意義的變化。

The most frequent treatment-related adverse events are fatigue, vomiting, and lymphopenia that have occurred in a minority of patients and are largely low grade. With respect to PK results, our goal was to sustain biologically active concentrations for a prolonged duration of time, and that is indeed what we have accomplished with the intensified dose schedule.

最常見的與治療相關的不良事件是疲勞、嘔吐和淋巴細胞減少，這些不良事件發生在少數患者中，而且大多是低度的。關於 PK 結果，我們的目標是長時間維持生物活性濃度，這確實是我們透過強化劑量方案所實現的目標。

At 100 milligrams twice a day for three days per week, the human PK results show that biologically active concentrations of ONC206 were sustained for beyond 24 hours in plasma, and that peak plasma concentrations are well in excess of the compounds IC50 and vitro, as well as exposures associated with in vivo efficacy in oncology models.

以 100 毫克每天兩次、每週三天的劑量，人體 PK 結果顯示 ONC206 的生物活性濃度在血漿中持續超過 24 小時，且血漿峰值濃度遠遠超過化合物的 IC50 和體外濃度。的體內功效相關的暴露。

Keep in mind that this is all based on plasma concentrations and that many target tissues are expected to have even higher exposure based on prior distribution studies in [rodents]. For example, brain tissue showed a two-fold higher drug concentration relative to plasma, and that's before considering disruptions to vasculature in the tumor microenvironment that are expected to further augment drug delivery.

請記住，這一切都是基於血漿濃度，根據先前的分佈研究，許多目標組織預計會有更高的暴露量。[囓齒動物]。例如，腦組織的藥物濃度相對於血漿高出兩倍，而且這是在考慮腫瘤微環境中脈管系統的破壞之前的情況，預計這會進一步增強藥物輸送。

While that is already promising at the current dose, our modeling suggests that we may be able to push the dose up even a bit further to fully optimize the pharmacologic activity of the compound. We therefore have two more dose level to enroll that we expect to top out at 200 milligrams twice a day for three consecutive days per week by the end of the year.

雖然在目前的劑量下這已經很有希望，但我們的模型表明，我們也許能夠進一步提高劑量，以充分優化該化合物的藥理活性。因此，我們還有兩個劑量等級可供招募，預計到年底，每週連續三天每天兩次，最高劑量為 200 毫克。

This enrollment is on top of the more than 75 patients dosed to date that have provided a robust safety and PK data set. Following this, we will make a determination of how to best advance the compound into efficacy studies in selected populations.

此次入組是迄今為止超過 75 名接受給藥的患者的基礎上的，這些患者提供了可靠的安全性和 PK 數據集。在此之後，我們將確定如何最好地將化合物推進到選定人群的功效研究中。

Establishing safety and PK are the primary goals of these studies. However, we are all, of course, keen to look for objective responses whenever possible, and we have an eye on this in the current and future cohorts.

確定安全性和 PK 是這些研究的主要目標。然而，當然，我們都熱衷於盡可能尋找客觀的回應，並且我們在當前和未來的群體中關注這一點。

These are Phase 1 trials that enroll patients at various doses with many different forms of CNS cancer and at different time points in their disease journey that often involve surgery, radiotherapy, and chemotherapy. Therefore, assessment of response needs to be handled very carefully to avoid misinterpretation.

這些是一期試驗，以不同劑量招募患有多種不同形式中樞神經系統癌症的患者，並在其疾病歷程的不同時間點招募患者，通常涉及手術、放射治療和化療。因此，需要非常謹慎地處理反應評估，以避免誤解。

Response assessment may be appropriate in the subset of patients who meet certain criteria, including those who have a CNS tumor that has progressed on prior therapy, received monotherapy ONC206 without concurrence or very recent anti-cancer interventions are naive to imipridone treatment, have achieved adequate exposure to ONC206 and have disease characteristics that are valuable by conventional response criteria for CNS tumors such as RANO.

療效評估可能適用於符合某些標準的患者亞群，包括患有中樞神經系統腫瘤且在先前治療中進展的患者、未經同意接受ONC206 單藥治療的患者或最近接受過亞咪啶酮治療的抗癌幹預措施、已取得足夠療效的患者暴露於 ONC206，並且具有根據中樞神經系統腫瘤的傳統反應標準（例如 RANO）有價值的疾病特徵。

The ongoing trials have recently begun enrolling patients who meet these specific criteria. And we expect some patients enrolled in the two remaining dose cohorts may also meet these criteria for appropriateness to evaluate objective response.

正在進行的試驗最近開始招募符合這些特定標準的患者。我們預計參加剩餘兩個劑量組的一些患者也可能符合評估客觀反應的適當性標準。

This is an exciting opportunity to get an initial glimpse into the potential of ONC206 to treat CNS tumors, and we are carefully monitoring these patients in these higher dosing cohorts, in particular those who are starting to stay on study beyond the typical window of time for DLT assessment when we would otherwise expect further disease progression.

這是一個令人興奮的機會，可以初步了解 ONC206 治療中樞神經系統腫瘤的潛力，我們正在仔細監測這些較高劑量隊列中的這些患者，特別是那些開始在典型時間窗口之外繼續研究的患者當我們預期疾病進一步進展時進行DLT 評估。

Given the need to confirm responses and the importance of characterizing their durability, initial readout of objective response is expected to occur in the first half of 2025.

鑑於需要確認應對措施以及表徵其持久性的重要性，預計將在 2025 年上半年首次公佈客觀應對措施。

We are very excited about the current stage of the study where ONC206 is now safely achieving sustained biologically active concentrations in patients, some of which have forms of CNS cancer that are expected to be responsive to ONC206 based on preclinical models and some of which have never been tested before in the clinic with either ONC206 or even ONC201.

我們對目前階段的研究感到非常興奮，ONC206 現已在患者中安全地達到持續的生物活性濃度，其中一些患者患有中樞神經系統癌症，根據臨床前模型預計這些癌症會對ONC206 產生反應，而其中有些患者從未有過反應。

An example of that is medulloblastoma where ONC206 has consistently shown compelling in vivo efficacy as a monotherapy in mouse models and we have just enrolled our first patient with this tumor type. We look forward to updating you more on this program in the future that is evaluating the potential of ONC206 in indications beyond that of dordaviprone.

髓母細胞瘤就是一個例子，其中 ONC206 作為單一療法在小鼠模型中始終表現出令人信服的體內療效，我們剛剛招募了第一位患有這種腫瘤類型的患者。我們期待將來向您提供有關該計劃的更多最新信息，該計劃正在評估 ONC206 在多達維酮以外的適應症中的潛力。

With that, I will turn the call over to Michelle for an update on financial results.

這樣，我將把電話轉給米歇爾，以了解最新的財務表現。

Thank you, Josh. We continue a balanced approach of investing in R&D while keeping a tight control on G&A expenses, which has essentially been flat year-on-year. This discipline has allowed us to maintain an average burn for the past six months of about $16 million a quarter.

謝謝你，喬許。我們繼續採取平衡的研發投資方式，同時嚴格控制一般管理費用，該費用與去年同期基本持平。這項紀律使我們能夠在過去六個月中保持每季約 1600 萬美元的平均消耗。

We expect this rate to increase modestly in the quarters to come as we begin to make investments in launch readiness in advance of the interim OS assessment next year. As always, we remain confident in our ability to make smart investment decisions as we approach upcoming catalyst.

我們預計，隨著我們在明年的中期作業系統評估之前開始對發布準備進行投資，這一比率將在未來幾個季度小幅增長。一如既往，當我們接近即將到來的催化劑時，我們仍然對自己做出明智投資決策的能力充滿信心。

Now turning to the financial results for the quarter. Earlier today, we issued a press release containing our financial results for second quarter of 2024. The second quarter of 2024, we reported a net loss of $20.7 million compared to a net loss of $18.6 million in the second quarter of 2023.

現在轉向本季的財務表現。今天早些時候，我們發布了一份新聞稿，其中包含 2024 年第二季的財務表現。2024 年第二季度，我們報告淨虧損 2,070 萬美元，而 2023 年第二季淨虧損 1,860 萬美元。

Research and development expenses increased to $18.4 million for the second quarter of 2024 compared to $16.9 million for the same period in 2023. This was driven primarily by increases in spending in the ACTION study.

2024 年第二季的研發費用增至 1,840 萬美元，而 2023 年同期為 1,690 萬美元。這主要是由於行動研究支出的增加所致。

General and administration expenses remained essentially flat at $4.5 million for the second quarter of 2024 compared to $4.4 million for the same period in 2023. We ended the second quarter with just over $171 million in cash and cash equivalents. Under our current operational plan, we expect to have cash into 4Q of 2026.

2024 年第二季的一般和管理費用基本上持平，為 450 萬美元，而 2023 年同期為 440 萬美元。第二季結束時，我們的現金和現金等價物略高於 1.71 億美元。根據我們目前的營運計劃，我們預計 2026 年第四季將有現金。

With that, I will now turn the call back over to Mike.

這樣，我現在將把電話轉回給麥克。

Thanks, Michelle. Throughout the remainder of 2024, we will continue to focus on the execution and enrollment of the Phase 3 ACTION study to accelerate this potentially life-altering drug to patients as quickly as possible and we'll continue to advance our discussions with regulators in Australia and hope to reach agreement on filing for provisional registration before year's end.

謝謝，米歇爾。在 2024 年剩餘的時間裡，我們將繼續專注於 3 期 ACTION 研究的執行和招募，以盡快將這種可能改變生命的藥物推向患者，我們將繼續推進與澳洲和澳洲監管機構的討論。希望年底前就臨時註冊申請達成協議。

The safety and PK progress we reported today from the ONC206 program furthers our conviction and the potential for the second generation of imipridone, and we look forward to enrolling the remaining two-dose cohorts yet this year.

我們今天報道的 ONC206 計畫的安全性和 PK 進展進一步增強了我們對第二代咪咪酮的信心和潛力，我們期待今年招募剩餘的兩劑組。

Lastly, as we move past the midpoint of the year, I'd like to take a brief moment to thank all of my fellow employees at Chimerix who are working tirelessly to bring this pipeline to fruition. Thank you for your dedication to our mission. It's this shared sense of purpose that drives our continued progress now and into the future.

最後，在今年年中過去之際，我想花一點時間感謝 Chimerix 的所有員工，他們為使這條管道取得成果而不懈努力。感謝您對我們使命的奉獻。正是這種共同的使命感推動我們現在和未來不斷進步。

With that, Dustin, we'll open the call to questions.

達斯汀，接下來我們將開始提問。

(Operator Instructions) Maury Raycroft, Jefferies.

（操作員說明）Maury Raycroft，Jefferies。

Hi. Good morning. Congrats on the progress, and thanks for taking my questions. Maybe I'll start with 206. So for the higher dose cohorts for 206, could you potentially backfill any of those cohorts and maybe talk more about the first half of the 2025 update?

你好。早安.恭喜您的進展，並感謝您提出我的問題。也許我會從206開始。因此，對於 206 年的較高劑量隊列，您是否可能回填這些隊列中的任何一個，並可能更多地談論 2025 年更新的上半年？

Can you talk about the number of patients that you could report on the amount of follow-up goals that you have? And just how you plan on doing that disclosure as well?

您能談談您可以報告的患者數量以及您的後續目標數量嗎？您打算如何進行揭露？

Yeah. Thanks, Maury, for the question. I'm going to turn that over to Josh, to answer both of them. Josh?

是的。謝謝莫里提出的問題。我會把這個問題交給喬什，由他來回答他們兩個。喬許？

Yeah. Happy to do that. Maury, good to hear from you. In terms of backfilling cohorts for the remaining couple that we're going through, we'll be looking at treatment naive patients. I mean, there's the opportunity on the pediatric trial for some intrapatient dose escalation after naive patients have completed their DLT window.

是的。很高興這樣做。莫里，很高興收到你的來信。就我們正在經歷的剩餘夫婦的回填隊列而言，我們將關注未接受過治療的患者。我的意思是，在兒科試驗中，在未接受 DLT 治療的患者完成 DLT 窗口期後，患者體內的劑量有可能增加。

So by and large, we're looking really to load in patients that are in the treatment naive setting. In terms of how many patients and how much follow-up we're looking at, in general, these are especially as we get into the final cohorts of the study tend to follow more of the three-plus-three paradigm.

因此，總的來說，我們確實希望對那些未曾接受過治療的患者進行治療。就我們正在研究的患者數量和追蹤情況而言，一般來說，尤其是當我們進入研究的最後隊列時，它們傾向於更多地遵循三加三範式。

And keep in mind there's two different trials, two different enrollment settings for pediatrics. So we should have an experience that follows somewhere in that range with about three cohorts following roughly a three-plus-three design.

請記住，兒科有兩個不同的試驗、兩個不同的入組設定。因此，我們應該有一個在該範圍內某個地方的體驗，其中大約三個隊列遵循大致三加三的設計。

In terms of the amount of follow up the DLT window keeping in mind safety is the primary goal of this study lands at around a month. So that's what you need for safety (inaudible) assessment like I mentioned in my prepared remarks takes a little more time to confirm and characterize durability. So we're looking more at the first half of 2025 when we look at how long we would need to follow some of those patients out in these final cohorts for initial look at response.

就追蹤時間而言，考慮到安全性，本研究的主要目標是 DLT 窗口期約一個月。因此，這就是您需要進行的安全（聽不清楚）評估，就像我在準備好的評論中提到的那樣，需要更多的時間來確認和表徵耐久性。因此，我們將更多地關注 2025 年上半年，當時我們需要對這些最終隊列中的一些患者進行多長時間的跟踪，以初步觀察療效。

Got it. Okay. And anything more you're seeing about the types of tumors that could be in that update any baseline trends that you're seeing they can comment on?

知道了。好的。您還看到了有關腫瘤類型的更多信息，可以更新您看到的任何基線趨勢，他們可以對此發表評論嗎？

Not too much to say, other than I mentioned that the methylated glioblastoma example there. I'll just note that ONC206 within CNS tumors was largely limited in its exploration to glioblastoma and H3 K27M mutant glioma.

沒什麼好說的，除了我提到的甲基化膠質母細胞瘤的例子。我只想指出，CNS 腫瘤內的 ONC206 在很大程度上僅限於對膠質母細胞瘤和 H3 K27M 突變膠質瘤的探索。

Given some of the initial stages of escalation with 206 when it started in its program at a time ACTION wasn't open, there was a variety of tumors that may have come into that initial experience, but we really think there's a lot of other CNS tumors that have never been tested before with either ONC206 or ONC201 that could make sense based on the mechanism and non-clinical data.

考慮到 206 在行動未開放的情況下開始其計劃時的一些升級的初始階段，可能存在多種腫瘤，但我們確實認為還有很多其他中樞神經系統疾病以前從未用ONC206 或ONC201 測試過的腫瘤，根據機制和非臨床數據可能有意義。

So we're really excited in these final cohorts to get into some of these tumor types that we think could make sense that we've never tested before. Methylated glioblastoma is just one example of that I mentioned there and look forward to seeing if we get more patients that fit that profile and updating on them in the future.

因此，我們對這些最後的隊列感到非常興奮，能夠研究其中一些我們認為可能有意義但我們以前從未測試過的腫瘤類型。甲基化膠質母細胞瘤只是我在那裡提到的一個例子，期待看到我們是否有更多符合這種情況的患者，並在未來對他們進行更新。

Got it. Okay, and maybe I'll ask one question on 201 and hop back in the queue. Just for the new guidance for the interim overall survival data in third quarter of this year -- of 2025, are you seeing event rates stabilized or is there anything else on clinical metrics that you can comment on that you're seeing in the study?

知道了。好的，也許我會在 201 上問一個問題，然後跳回隊列。對於今年第三季（即 2025 年）中期整體存活數據的新指導，您是否看到事件發生率穩定下來，或者您在研究中看到的臨床指標是否還有其他可以評論的內容？

Yes. Thanks, Maury, for the question. Certainly, seeing enrollment rates are consistent, stable and predictable at this point. Event rates, blinded event rates are just now beginning to come in. So I'd say still early days on blinded event rates, but stay tuned in the coming quarters for updates there.

是的。謝謝莫里提出的問題。當然，目前入學率是一致、穩定且可預測的。事件率、盲事件率現在才剛開始出現。因此，我想說，關於盲事件發生率還處於早期階段，但請繼續關注未來幾季的更新。

We have enough confidence to project out about a year when we expect that first interim OS, but more to follow on blinded event rates and observed event rates as we get into the next quarter. I think it will be instructive.

我們有足夠的信心來預測第一個臨時作業系統大約在一年內推出，但隨著我們進入下一個季度，我們將進一步關注盲態事件率和觀察到的事件率。我認為這將是有啟發性的。

Got it. Okay. Thanks for taking my question.

知道了。好的。感謝您提出我的問題。

Soumit Roy, Jones Research.

蘇米特·羅伊，瓊斯研究中心。

Good morning, everyone, and congrats on all the progress. Sorry I missed the comment on the last question. Did you provide any color on the enrollment status, like how far along is it that Phase 3 ACTION trial is enrolled? And will you be providing any baseline characteristics in a blinded fashion ahead of -- well ahead of the data?

大家早安，祝賀所有的進展。抱歉，我錯過了對最後一個問題的評論。您是否提供了任何關於註冊狀態的顏色，例如第 3 階段 ACTION 試驗的註冊進行了多久？您是否會在數據之前以盲目的方式提供任何基線特徵？

Hey Soumit, thank you for the question. Yeah. Enrollment, we continue to be excited about the level of engagement from investigators around the world, not just in the US but a really balanced enrollment between the US, Europe and Asia are really proportional. So continues to be very encouraging.

嘿，蘇米特，謝謝你的提問。是的。入學方面，我們繼續對世界各地研究人員的參與程度感到興奮，不僅在美國，而且美國、歐洲和亞洲之間的入學情況非常平衡，而且是成比例的。所以還是非常令人鼓舞。

We're seeing meaningful contributions geographically around the world. We haven't provided exact guidance on where we are with enrollment, but we're on track to meet that first interim OS assessment in Q3 of next year. With respect to early disclosures of patient characteristics, we're not planning to do that. That will be part of the final data readout.

我們在世界各地看到了有意義的貢獻。我們尚未就註冊情況提供準確的指導，但我們預計在明年第三季完成第一次中期作業系統評估。關於早期披露患者特徵，我們不打算這樣做。這將是最終資料讀出的一部分。

Okay. One last question. Would you be providing any color on screen failure rate? Is it matching up with your prior experience or if anything changed by geographic location or any other metrics?

好的。最後一個問題。您能提供螢幕顏色故障率嗎？它是否與您之前的經驗相符，或者地理位置或任何其他指標是否發生了變化？

Thanks, Soumit. I'll turn that over to Allen for comment. Allen?

謝謝，蘇米特。我會將其轉交給艾倫徵求意見。艾倫？

Our screen failure rate is as we've been expecting it to. These are hard patients to get as this are rare patient population, and our enrollment does have specific criteria that is necessary to show activity. But our screen failure rate has been consistent throughout the study at this point.

我們的螢幕故障率正如我們所預期的那樣。這些患者很難獲得，因為這是罕見的患者群體，而且我們的入組確實有顯示活動所需的特定標準。但目前我們的螢幕故障率在整個研究過程中一直保持一致。

And it's pretty much in line with what we expected at the start of the study.

這與我們在研究開始時的預期非常一致。

Thank you so much.

太感謝了。

Ed White, H.C. Wainwright.

懷特，H.C.溫賴特。

Good morning. Thanks for taking my questions. Just a follow-up on the 206 study you had mentioned that the response data could be available in the first half of '25. What about the further PK final, PK and safety data? Would that be available before that? And if we were disclosed before that or just wait until you get the response rate data?

早安.感謝您回答我的問題。只是您提到的 206 研究的後續行動，響應數據可能會在 25 年上半年提供。進一步的PK最終、PK和安全性資料呢？在那之前可以使用嗎？如果我們在此之前披露，或者只是等到您獲得回覆率數據？

Yeah. Thanks, Ed, for the question. I'll turn that over to Josh. Josh?

是的。謝謝埃德提出這個問題。我會把它交給喬希。喬許？

Ed, nice to hear from you. Thanks for the question. The safety experience really requires about a month DLT window, right. So I mentioned that we planned to round out the risk of the dose escalation cohorts by the end of the year. So I would expect safety data and PK data to follow in the months to come after that.

艾德，很高興收到你的來信。謝謝你的提問。安全體驗確實需要大約一個月的 DLT 窗口，對吧。所以我提到，我們計劃在今年年底前完善劑量遞增隊列的風險。因此，我預計安全資料和 PK 資料將在接下來的幾個月內公佈。

Okay, thanks. And just on dordaviprone, if you could just discuss your ex-US strategy in particular Australia. I think you had mentioned prior that you were looking to get a distribution agreement for Australia. Are you making any progress there or any progress outside of the US?

好的，謝謝。就多達維酮而言，您能否討論一下您的前美國策略，特別是澳洲的策略。我想您之前曾提到您正在尋求獲得澳洲的分銷協議。你們在美國或美國以外取得了任何進展嗎？

Yeah. thanks Ed. We've been studying that commercial model outside of the US for some time. I'm going to ask Tom Riga to comment on our status there. Tom?

是的。謝謝埃德。一段時間以來，我們一直在研究美國以外的商業模式。我要請湯姆·裡加對我們在那裡的狀況發表評論。湯姆？

Hey, Ed, nice to hear from you. Yeah, we're doing a lot of work on that. I think the first step here is to work through the TGA process and subsequently the HTA process for reimbursement. But we are looking at a lean commercial model that could include distribution partners and other strategies that will minimize the expense here at Chimerix, but enable us to provide commercial availability. So more to follow as we progress through the regulatory process, but we are actively engaged in studying that business case.

嘿，艾德，很高興收到你的來信。是的，我們正在這方面做很多工作。我認為第一步是完成 TGA 流程，然後是 HTA 報銷流程。但我們正在尋找一種精益的商業模式，其中可能包括分銷合作夥伴和其他策略，這些策略將最大限度地減少 Chimerix 的費用，但使我們能夠提供商業可用性。因此，隨著我們在監管流程中取得進展，還有更多的事情要做，但我們正在積極研究該業務案例。

Okay. Thanks Tom. And my last question is just for Michelle, you had mentioned that you are making investments in the launch and expect to see operating expenses increases modestly. What kind of investments have been made towards the launch so far? And are these -- should we be thinking mostly for 2025 or will some of these expenses impact the back half of this year?

好的。謝謝湯姆。我的最後一個問題是問米歇爾的，您曾提到您正在對此次發布進行投資，並預計營運費用會小幅增加。到目前為止，已經為推出進行了哪些投資？我們是否應該主要考慮 2025 年的情況，或者其中一些費用是否會影響今年下半年？

Yeah. Thanks. So we have seen -- we've made a little bit of investment in this year, obviously, with Tom coming on board. And I do expect that, as I mentioned, to increase a little bit more this year, but obviously a little bit more as we continue into 2025. So Tom, did you want to maybe elaborate a little bit on some of the early investments?

是的。謝謝。所以我們已經看到——今年我們顯然做了一些投資，湯姆也加入了。正如我所提到的，我確實預計今年會增加一點，但隨著我們進入 2025 年，顯然會增加一點。湯姆，您想詳細說明一下一些早期投資嗎？

Yeah. We're going to -- we're taking a gated approach to our spend on launch that lines up to our development milestones. So in the early days, we're engaging key stakeholders. Obviously, the investigators and the customer base through ACTION as well as patient advocacy. And the third stakeholder here is the payer and starting to engage and have early conversations there.

是的。我們將——我們將採取一種封閉的方式來控制我們的發布支出，以符合我們的開發里程碑。因此，在早期，我們正在與主要利害關係人接觸。顯然，調查人員和客戶群透過行動以及患者的宣傳。這裡的第三個利害關係人是付款人，並開始在那裡參與並進行早期對話。

So I think what you can expect from a burn standpoint and the back half of this year is modest. That work will involve both sales for size, structure, forecasting work to round out, our early efforts in that regard. But it won't involve substantial increase in headcount and others. So we're going to take a measured approach here to make sure that we're ready for the first interim here in Q3 of next year.

因此，我認為從燃燒的角度來看，今年下半年的情況是溫和的。這項工作將涉及銷售規模、結構和預測工作，以完善我們在這方面的早期努力。但不會涉及人員數量和其他方面的大幅增加。因此，我們將在這裡採取謹慎的方法，以確保我們為明年第三季的第一次中期做好準備。

Okay. Thanks for taking my questions.

好的。感謝您回答我的問題。

Troy Langford, TD Cowen.

特洛伊·蘭福德，TD·考恩。

Hi. Congrats on all the progress this quarter and thanks for taking our questions. I just have two questions, both on dordaviprone. First, can you all just remind us how large you think the commercial opportunity for dordaviprone in Australia could be relative to that of the US and EU?

你好。恭喜本季取得的所有進展，並感謝您提出我們的問題。我只有兩個問題，都是關於多達維隆的。首先，您能否提醒我們，您認為多達維酮在澳洲的商業機會相對於美國和歐盟有多大？

And then related to that, do you think the TGA will want to see that first interim OS data from the ACTION study before they issue an approval?

與此相關的是，您認為 TGA 在發布批准之前是否希望查看 ACTION 研究中的第一個中期 OS 資料？

Thanks, Troy. It's Mike I'll start with that first question. I'll ask Tom to comment on the size of the commercial opportunity in Australia. But with respect to our interactions with TGA to date, it's been focused on the Phase 2, 50 patient registration cohort that we did the BICR on some time ago and the output of that.

謝謝，特洛伊。我是麥克，我將從第一個問題開始。我將請湯姆評論一下澳洲商業機會的規模。但就我們迄今為止與 TGA 的互動而言，重點是我們不久前進行的 BICR 的 2 期 50 名患者註冊隊列及其輸出。

So there is certainly within that window, the potential for that interim OS to readout. And yet that's not the basis of our discussions with regulators in Australia, it's really on the Phase 2 response rate data. Tom, do you want to talk about the commercial opportunity?

因此，在該視窗內，臨時作業系統肯定有可能進行讀出。然而，這並不是我們與澳洲監管機構討論的基礎，它實際上是基於第二階段的回應率數據。湯姆，你想談談商業機會嗎？

Yeah. Commercial opportunity in Australia is small relative to Europe and US, obviously, based on population. I think that proof of concept I think is important, both for gaining first regulatory approval as well as providing commercial access for patients in need. So that could be a business that is interesting if managed in a lean fashion from an overall operating expense, and we are looking forward to that potential opportunity.

是的。顯然，從人口角度來看，澳洲的商業機會相對於歐洲和美國來說很小。我認為概念驗證對於獲得首次監管批准以及為有需要的患者提供商業准入都很重要。因此，如果從整體營運支出中以精益方式進行管理，這可能是一項有趣的業務，我們期待著這一潛在機會。

Thank you. Seeing as there are no more questions in the queue. That concludes our question-and-answer session. I will now turn the call back over to Mike Andriole for closing remarks.

謝謝。看到隊列中沒有更多問題了。我們的問答環節到此結束。現在，我將把電話轉回給麥克安德里奧 (Mike Andriole)，他將發表結束語。

Thanks, Dustin, and thank you, everyone, for your time this morning. We look forward to updating you in the coming months.

謝謝達斯汀，也謝謝大家今天早上抽出時間。我們期待在未來幾個月內為您提供最新消息。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。