Chimerix Inc (CMRX) 2023 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Chimerix third- quarter 2023 earnings conference call. I would now like to introduce you to your host for today's call, Michelle LaSpaluto, Vice President of Strategic Planning and Investor Relations at Chimerix. Please proceed.

早安，女士們、先生們，歡迎參加 Chimerix 2023 年第三季財報電話會議。現在我想向您介紹今天電話會議的主持人，Chimerix 策略規劃和投資者關係副總裁 Michelle LaSpaluto。請繼續。

Thank you, [Jhon]. Good morning, everyone, and welcome to the Chimerix third quarter 2023 financial and operating results conference call. This morning, we issued a press release related to our third quarter update. You can access the press release in our Investors section of our website. With me on today's call are President and Chief Executive Officer, Mike Andriole, Chief Medical Officer, Allen Melemed, and our Chief Technology Officer, Josh Allen.

謝謝你，[約翰]。大家早安，歡迎參加 Chimerix 2023 年第三季財務與營運業績電話會議。今天早上，我們發布了與第三季更新相關的新聞稿。您可以在我們網站的投資者部分存取新聞稿。與我一起參加今天電話會議的有總裁兼執行長 Mike Andriole、首席醫療官 Allen Melemed 以及我們的首席技術長 Josh Allen。

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

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包括 1995 年《私人證券訴訟改革法案》含義內的前瞻性陳述，這些陳述受到風險、不確定性和其他因素的影響。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 would now like to turn the call over to our President and Chief Executive Officer, Mike Andriole,

現在，我想將電話轉給我們的總裁兼執行長 Mike Andriole，

Thank you, Michelle, and good morning, everyone. The third quarter was marked by continued execution across our pipeline, including continued enrollment in our global Phase 3 ACTION study of ONC201, and Phase 1 dose escalation studies for our second-generation compound ONC206.

謝謝米歇爾，大家早安。第三季的特點是我們的產品線持續執行，包括繼續參與我們的 ONC201 全球 3 期 ACTION 研究，以及我們的第二代化合物 ONC206 的 1 期劑量遞增研究。

I'll start with ONC201 and the ACTION study. We now have 113 sites open across 12 countries and tracking ahead of our prior guidance of activating 100 sites by September 30. Enrollment is progressing with site activation, and we continue to expect first and second interim overall survival data as well as PFS data in 2025.

我將從 ONC201 和 ACTION 研究開始。我們現在在12 個國家開設了113 個站點，並領先於我們先前的指導，即在9 月30 日之前激活100 個站點。隨著站點激活，註冊工作正在進行中，我們繼續預計2025 年將獲得第一和第二個中期總體生存數據以及PFS 數據。

Geographically, we now have about an equal number of sites activated in Europe as the US. This past September, we participated in the European Association for Neuro-Oncology Conference, also known as EANO in the Netherlands. And at that conference, we hosted a symposium on the current diagnosis treatment strategies and clinical trials for H3 K27M mutant glioma, and engage with the neuro-oncology community broadly to drive ongoing awareness and interest in the action study.

從地理位置來看，我們現在在歐洲啟動的網站數量與美國大致相同。去年九月，我們參加了歐洲神經腫瘤學協會會議，在荷蘭也稱為 EANO。在那次會議上，我們主辦了一場關於 H3 K27M 突變神經膠質瘤當前診斷治療策略和臨床試驗的研討會，並與神經腫瘤學界廣泛接觸，以提高人們對行動研究的持續認識和興趣。

I was very pleased with the level of enthusiasm across the European community for this program and the degree of support from so many investigators who recognize the very high unmet need in this patient population. I was also reminded of the value to our industry of being back in person at medical conferences following the pandemic as attendance Adiana was at a new record high and we have seen a nice increase in site activity across Europe in the weeks since that conference ended.

我對整個歐洲社會對該計劃的熱情程度以及眾多研究人員的支持程度感到非常滿意，他們認識到該患者群體中存在非常高的未滿足需求。我還想起了在大流行之後親自參加醫學會議對我們行業的價值，因為阿黛安娜的出席人數創下了新的歷史新高，而且自會議結束以來的幾週內，我們看到整個歐洲的現場活動有了很大的增加。

That increases in addition to already strong engagement prior to EANO, we are now turning to North America, the annual meeting for the Society for Neuro-Oncology also known as SNO will occur in Vancouver, Canada in just a couple of weeks where we are also planning a large presence. I'll let Josh comment on our plans around this conference. So we're looking forward to seeing many of our investigators in the action study as well as other program collaborators later this month.

除了 EANO 之前已經有很強的參與度之外，我們現在將目光轉向北美，神經腫瘤學會（也稱為 SNO）的年度會議將在幾週後在加拿大溫哥華舉行，我們也將在那裡舉行計劃大規模存在。我會讓喬希評論一下我們圍繞這次會議的計劃。因此，我們期待在本月晚些時候看到行動研究中的許多研究人員以及其他專案合作者。

Our efforts in enrolling the ACTION study are also underpinned by a robust publication strategy that includes a recently published manuscript in cancer discovery this quarter. Which focused on frontline ONC201 survival data and further expand its mechanism of action.

我們在招募 ACTION 研究方面所做的努力也得到了強有力的出版策略的支持，其中包括本季度最近發表的關於癌症發現的手稿。其中重點在於一線ONC201生存數據並進一步擴展其作用機制。

Data from this peer-reviewed publication further strengthens our confidence in the ACTION trial and also further supports its enrollment. I'll let Josh speak more to the details included in this recent manuscript. As we continue to enroll the ACTION study, we're also simultaneously preparing the company and the market for ONC201's potential commercialization.

這份同儕審查出版物的數據進一步增強了我們對 ACTION 試驗的信心，並進一步支持其入組。我將讓喬許更多地談論這份最新手稿中包含的細節。在我們繼續招募 ACTION 研究的同時，我們也為公司和市場為 ONC201 的潛在商業化做好準備。

To that end we're in the process of finalizing recruitment of a Chief Commercial Officer, and I'm excited that that process is nearing completion. In fact, I expect to announce the hiring of that individual before the end of the year.

為此，我們正在最終確定首席商務官的招募工作，我很高興這個過程即將完成。事實上，我希望在年底前宣布聘用該人。

Turning briefly to ONC206, the protocol amendments for each of our dose escalation studies have been approved as expected during the third quarter. These amendments allow for a more intense dosing schedule that includes twice-a-day dosing up to three consecutive days weekly in order to increase the duration of therapeutic exposure.

簡單談談 ONC206，我們每項劑量遞增研究的方案修正案均已如預期在第三季獲得批准。這些修正案允許更嚴格的給藥方案，包括每天兩次給藥，每週最多連續三天給藥，以增加治療暴露的持續時間。

We expect the continual 72-hour exposure of ONC206 to potentially generate additional monotherapy activity, both in CNS tumors and potentially tumors outside of the CNS based on emerging in vivo data. The PNOC in NIH studies are enrolling at the more frequent dose levels, and we expect dosing to be complete in the first half of 2024.

根據新出現的體內數據，我們預期 ONC206 的持續 72 小時暴露可能會在中樞神經系統腫瘤和中樞神經系統以外的潛在腫瘤中產生額外的單一治療活性。 NIH 研究中的 PNOC 正在以更頻繁的劑量水平入組，我們預計給藥將在 2024 年上半年完成。

As you may recall, we previously reported the GBM response on the once a week schedule starting at Dose level 2, and that patient's response remains ongoing as the patient's dose level has increased. Since these studies began enrolling. Again, I'm also happy to report we have observed no dose-limiting toxicities thus far.

您可能還記得，我們​​之前報告了從劑量水平 2 開始每週一次的 GBM 反應，並且隨著患者劑量水平的增加，患者的反應仍然持續。自從這些研究開始招募以來。我也很高興再次報告，迄今為止我們尚未觀察到劑量限制性毒性。

Before I turn the call over to Josh, I'd like to reiterate our deliberate disciplined approach to capital allocation. We ended the quarter with $217 million in cash and equivalents, which is on plan to meet our previous guidance of approximately $200 million in cash at the end of the year.

在我把電話轉給喬許之前，我想重申我們在資本配置方面採取的審慎、嚴格的方法。截至本季末，我們擁有 2.17 億美元的現金及等價物，計劃在年底達到我們先前約 2 億美元現金的指引。

We continue to expect our cash balance to be sufficient to support operations into the end of 2026, and through each of the expected action clinical endpoints. For more details on our third quarter balance sheet and income statement, please refer to the press release which we released earlier today.

我們仍然預計我們的現金餘額將足以支援到 2026 年底的營運以及每個預期行動臨床終點。有關我們第三季資產負債表和損益表的更多詳細信息，請參閱我們今天早些時候發布的新聞稿。

With that, I'll turn the call over to Josh to provide additional color on our recent publication in Cancer Discovery and our recent engagements with the neuro-oncology community.

接下來，我將把電話轉給喬什，為我們最近在《癌症發現》雜誌上發表的文章以及我們最近與神經腫瘤學界的合作提供更多資訊。

Josh?

喬許？

Thank you Mike. So we continue to see benefit from our connections to the global neuro-oncology community. As Mike mentioned, over the last quarter, we held a symposium at the European Association for Neuro-Oncology conference in the Netherlands. There, we met with leading neuro oncologist and active clinical trial investigators in addition to holding a symposium for presentations by thought leaders related to H3 K27M-mutant glioma, including the ACTION study.

謝謝你，麥克。因此，我們繼續受益於我們與全球神經腫瘤學界的聯繫。正如麥克所提到的，上個季度，我們在荷蘭的歐洲神經腫瘤學協會會議上舉辦了一次研討會。在那裡，我們會見了領先的神經腫瘤學家和活躍的臨床試驗研究人員，此外還舉辦了一場研討會，由與 H3 K27M 突變神經膠質瘤相關的思想領袖發表演講，包括 ACTION 研究。

Later this month, we will be similarly present at the Annual Society for Neuro-Oncology meeting in Vancouver, where we are planning a large presence, including a symposium on future directions of the diagnosis and treatment of H3 K27M-mutant glioma, as well as supporting our collaborators who will be making a series of oral presentations on preclinical and clinical studies of ONC201, in different treatment settings.

本月晚些時候，我們將類似地出席在溫哥華舉行的神經腫瘤學年會，我們計劃在該會議上進行大規模的活動，包括關於H3 K27M 突變神經膠質瘤的診斷和治療的未來方向的研討會，以及支持我們的合作者，他們將在不同的治療環境中就 ONC201 的臨床前和臨床研究進行一系列口頭演講。

We're looking forward to seeing many of our investigators and collaborators in person as we drive continued engagement in the ACTION study and keep a close eye on emerging treatment strategies in molecularly- defined glioma.

我們期待與許多研究人員和合作者見面，推動繼續參與 ACTION 研究，並密切關注分子定義的神經膠質瘤的新興治療策略。

In addition to these larger Neuro- Oncology conferences, we also remain actively engaged on the scientific front, including presentation of non-clinical data that reflect our deepening understanding of the novel mechanism of action of methadone at the AACR Special Conference in Cancer Research for brain cancer held in Minneapolis just a few weeks ago.

除了這些較大的神經腫瘤學會議外，我們還積極參與科學前沿，包括在 AACR 腦部癌症研究特別會議上展示非臨床數據，這些數據反映了我們對美沙酮新作用機制的加深理解幾週前，癌症在明尼阿波利斯舉行。

As Mike mentioned, our research manuscript co-authored by numerous academic investigators in Chimerix recently published in the journal Cancer Discovery that reflects several years of clinical translational and mechanistic investigations of ONC201 as a first-in-class therapy for H3 K27M-mutant glioma. The manuscript describes data that support a range of important conclusions for ONC201 and H3 K27M-mutant glioma that span its mechanism of action, its biological activity within patients' tumors and its clinical activity that extends beyond the prior efficacy analyses in the recurrent setting.

正如Mike 所提到的，我們由Chimerix 的眾多學術研究人員共同撰寫的研究手稿最近發表在《Cancer Discovery》雜誌上，該手稿反映了ONC201 作為H3 K27M 突變神經膠質瘤的一流療法多年的臨床轉化和機制研究。該手稿描述了支持ONC201 和H3 K27M 突變神經膠質瘤的一系列重要結論的數據，這些結論涵蓋其作用機制、其在患者腫瘤內的生物活性及其臨床活性，超出了先前在復發環境中的療效分析。

Starting with the mechanistic finding, the data provide a step-by-step understanding of why ONC201 is uniquely poised to address this disease that starts with the engagement of its [clip, P]. binding target in the mitochondria and ends with reversal of the H3 K27M trymethyl [loss] event in the nucleus. Reversal of this epigenetic hallmark is remarkable as it is the direct consequence of the H3 K27M mutation and is thought to be the path of physiological driver of the disease.

從機制發現開始，這些數據提供了為什麼 ONC201 能夠獨特地解決這種疾病的逐步理解，而這種疾病始於其 [夾子，P] 的參與。粒線體中的結合目標，並以細胞核中 H3 K27M 三甲基[丟失]事件的逆轉結束。這種表觀遺傳標誌的逆轉是引人注目的，因為它是 H3 K27M 突變的直接結果，並被認為是疾病的生理驅動因素。

These findings were consistent across disease models and importantly, reversal of H3 K27M trymethyl loss was robustly evident across all tumor biopsies obtained from ONC201 treated patients.

這些發現在各種疾病模型中是一致的，重要的是，在從 ONC201 治療的患者獲得的所有腫瘤活檢中，H3 K27M 胰甲基缺失的逆轉是非常明顯的。

Turning to clinical outcomes, the survival of H3 K27M mutant glioma patients who received ONC201 the frontline setting following radiotherapy, which I'll notice is the same setting of the ACTION trial was reported as 21.7 months from diagnosis, in contrast to 12 months for patients who did not receive ONC201.

談到臨床結果，在放射治療後接受ONC201 一線設定的H3 K27M 突變神經膠質瘤患者的生存期（我注意到與ACTION 試驗的設定相同）據報告從診斷起為21.7 個月，而患者的生存期為12 個月未收到 ONC201 的人。

Favorable survival outcomes among ONC201 treated patients were consistently observed across a variety of sensitivity and subgroup analyses. It is worth noting that while the previously disclosed results for ONC201 in the recurrent setting were skewed towards adult patients in Thalamic primary tumor locations. This front line data set described in the manuscript were skewed towards pediatric patient and Brainstem tumor locations.

在各種敏感性和亞組分析中，一致觀察到 ONC201 治療患者的良好存活結果。值得注意的是，雖然先前揭露的 ONC201 在復發環境中的結果偏向於丘腦原發腫瘤位置的成年患者。手稿中描述的前線資料集偏向兒科患者和腦幹腫瘤位置。

Aggregately these findings demonstrate that ONC201 is the first-in-class therapy for H3 K27M mutant glioma that consistently reverses the major driver of the disease pathology and appears to be associated with compelling outcomes in uncontrolled trials across multiple clinical settings.

總的來說，這些發現表明ONC201 是H3 K27M 突變神經膠質瘤的一流療法，能夠持續逆轉疾病病理的主要驅動因素，並且似乎與多個臨床環境中的非對照試驗中令人信服的結果相關。

These findings boost our confidence in the prospective randomized controlled evaluation of ONC201 the ongoing action study, which is further strengthened by inclusion of dose intensification to twice-weekly dosing.

這些發現增強了我們對 ONC201 正在進行的行動研究的前瞻性隨機對照評估的信心，透過將劑量強化納入每週兩次給藥，該評估進一步得到加強。

With that, I'll turn the call back over to Mike for closing remarks.

之後，我會將電話轉回給麥克，讓其致閉幕詞。

Thanks, Josh. During the third quarter, we've continued to execute our plan with a focus on bringing ONC201 to patients as soon as possible. We're beginning to prepare our organization to potentially launch ONC201 and are excited about the promise to further broaden our pipeline in the future by advancing ONC206 and or through business development. With that, operator, we'll open the call question.

謝謝，喬許。第三季度，我們繼續執行我們的計劃，重點是盡快將 ONC201 帶給患者。我們正在開始準備我們的組織可能推出 ONC201，並對未來透過推進 ONC206 和/或透過業務開發進一步拓寬我們的產品線的承諾感到興奮。接線員，我們將開始通話問題。

(Operator Instructions) We will pause for just a moment to compile the Q&A roster. Thank you.

（操作員說明）我們將暫停片刻來整理問答名單。謝謝。

Maury Raycrof, Jefferies.

莫里‧雷克羅夫，傑弗里斯。

Hi, this is James on for Maury. Congrats on the progress and thanks for taking our question. Can you talk more about the progress on site initiation, enrollment, feedback from investigators, specifically in Western Europe and also Canada? And can you bookend timeframes for when you could reach full enrollment of the 450 patients needed for the study?

大家好，我是莫里的詹姆斯。恭喜您的進展，並感謝您提出我們的問題。您能否多談談網站啟動、註冊、調查人員回饋的進展，特別是在西歐和加拿大？您能否預定何時能夠實現研究所需的 450 名患者的全部入組？

Sure. And thanks for the question, James. Engagement in Western Europe, actually across all of Europe, has been strong, I think, as evidenced by the speed of site activations to date in that part of the world. I'd say Canada has been a little bit slower, but from a regulatory perspective, that's not entirely unusual. But engagement at sites with investigators has been quite strong in both geographies.

當然。謝謝你的提問，詹姆斯。我認為，西歐（實際上是整個歐洲）的參與度一直很高，迄今為止該地區網站啟動的速度就證明了這一點。我想說加拿大的速度有點慢，但從監管的角度來看，這並不完全不尋常。但在這兩個地區，現場與調查人員的互動都相當強烈。

In terms of when we would expect full enrollment in the study. We haven't given that guidance, but continue to reinforce our guidance to have first interim efficacy overall survival data in the first half of 2025. So you might expect it would be similar timeframe. If you just look at the number of events required to hit that in timelines.

就我們預計何時全面參與研究而言。我們尚未給予該指導，但會繼續強化我們的指導，以便在 2025 年上半年獲得第一個中期療效總體生存數據。因此，您可能預計時間範圍會類似。如果您只查看時間軸中達到該目標所需的事件數量。

Got it. Thanks. And where are you in enrollment for the consecutive dosing Phase cohorts, ONC206? Do you anticipate that you would press release that data at an earnings call have a separate event of that or would you present that data at an upcoming medical conference?

知道了。謝謝。您在哪裡報名參加連續給藥階段隊列 ONC206？您是否預計會在財報電話會議上發布該數據，或者您會在即將舉行的醫學會議上展示該數據？

Yes, good question. We've got two separate arms, Pediatric, Recurrent. Frontline and the Pediatrics. PNOC study and then a separate, obviously study with the NIH. So for three different in a way arms ongoing with that Phase 1 studies, James. And so we're not going to give a play-by-play on where we are with each one, but all three are enrolling and we continue to expect that will have enrollment completed in the first half of '24.

是的，好問題。我們有兩個獨立的部門，兒科，復發。前線和兒科。 PNOC 研究，然後是與 NIH 進行的單獨的、顯然的研究。因此，詹姆斯，對於正在進行第一階段研究的三個不同的部門。因此，我們不會逐一透露我們在每個項目中的情況，但所有三個項目都在註冊，我們仍然預計將在 24 年上半年完成註冊。

I think that will likely top line the safety data to the extent that there's efficacy insights that we can gather from that. We'll do that at that time. But I want to probably set expectations that if you look at the least the parent compound ONC201 and the recurrence setting, there was an 8.3-month time to onset of response.

我認為這可能會成為安全資料最重要的部分，因為我們可以從中收集到功效見解。到時候我們就這麼做。但我想大概設定一個預期，如果您至少查看母體化合物 ONC201 和復發設置，您會發現有 8.3 個月的時間才會出現反應。

And so there's a natural lag between maturity of those patients into our response and when we might have safety data. So there's probably a two-step process in terms of identifying safety data and an additional insight from an efficacy, a responder perspective.

因此，在這些患者對我們的反應成熟度與我們可能獲得安全數據之間存在自然的滯後。因此，在識別安全資料和從功效、回應者角度獲得額外見解方面，可能有一個兩步驟流程。

The other insight I'll make is some of those patients who will qualify for those studies may have seen ONC201 previously. And so we could have resistance mechanisms built in that would make assessing response more difficult.

我要提出的另一個見解是，一些有資格參加這些研究的患者可能以前已經看過 ONC201。因此，我們可以建立內建的抵抗機制，這將使評估反應變得更加困難。

We also have some patients in the PNOC study that are in the frontline setting and therefore, confounding a response assessment, really making the money valuable for response. And so we're really focused on the recurrent setting in patients who are naive to the methadone class and assessing response. So we'll look at the totality of the data at the time, but I think that's likely the top line safety data first and that we would press release and then followed perhaps by mature and efficacy data.

在我們的 PNOC 研究中也有一些處於前線環境的患者，因此，混淆了反應評估，確實使這筆錢對反應有價值。因此，我們真正關注的是未接受美沙酮類藥物的患者的復發情況並評估反應。因此，我們將查看當時的全部數據，但我認為這可能首先是最重要的安全數據，我們將發布新聞稿，然後可能是成熟的功效數據。

Great. Thank you for taking our questions. I'll hop back in the queue.

偉大的。感謝您接受我們的提問。我會跳回到隊列中。

Sure.

當然。

Naureen Quibria with Capital One. Please go ahead.

諾琳·奎布里亞與第一資本。請繼續。

Hi, good morning. Thanks for taking my question. I guess I'll start first with ONC206, the patient response --the GBM patient responder, you see the patients still on study, you know, how long has the patient been on therapy? And can you comment on what dose, how many doses they've received the different level?

早安.感謝您提出我的問題。我想我會先從 ONC206 開始，即患者反應——GBM 患者反應者，您看到患者仍在研究中，您知道，患者接受治療多久了？您能否評論一下他們接受了多少不同劑量的劑量？

The patient's been -- yeah Naureen, well first, thanks for the question, Naureen. That patient has been on study for about a year and a half at this point. So it's been quite some time, a very durable response. They have continued to dose escalate.

病人是－－是的，諾琳，首先，謝謝你的提問，諾琳。到目前為止，該患者已經接受了大約一年半的研究。所以已經有一段時間了，這是一個非常持久的反應。他們的劑量繼續增加。

Last I heard I'll ask Allen or Josh to weigh in on this, but I my understanding is they graduated to dose level four. It was the last piece of information I had on that patient. Josh, do you have other insights?

上次我聽說我會請艾倫或喬什對此進行權衡，但我的理解是他們已升級到第四級劑量。這是我掌握的關於那個病人的最後一則訊息。喬什，你還有其他見解嗎？

Not much to add I know that that patient has had dose escalated at least twice since the initial dose level at 100 milligrams. I know the investigators reported a deepening of response at that dose escalation has occurred in that patient, which is very encouraging.

無需補充太多，我知道該患者自初始劑量水平 100 毫克以來，劑量至少增加了兩次。我知道研究人員報告稱，該患者劑量增加後反應加深，這是非常令人鼓舞的。

But overall, I think the macro messages we're compelled by this idea that ONC206 continues at the preclinical level to show signs of efficacy outside of H3 K27M mutant glioma. Clearly, that was a strong indication that can translate at least in that patient.

但總的來說，我認為這種宏觀訊息迫使我們相信 ONC206 繼續在臨床前層級顯示出 H3 K27M 突變神經膠質瘤以外的療效跡象。顯然，這是一個強烈的跡象，至少可以轉化為該患者。

As Mike has pointed to, we look forward to continuing execution at this intensified dose schedule and taking a careful look within the response valuable population in the study. To see what the path forward looks like outside of H3 K27M. So great news for that one patient and look forward to see more of that.

正如麥克所指出的，我們期待繼續執行這項強化劑量計劃，並仔細研究研究中有價值的人群的反應。看看 H3 K27M 以外的前進道路是什麼樣的。對那位患者來說這是個好消息，並期待看到更多這樣的消息。

Great. And thanks, Josh. And maybe this one's for you or Allen. Do you -- can comment on what type of data on this patient and any of the preclinical type of data that we presented at the upcoming SNO conference.

偉大的。謝謝，喬許。也許這個適合你或艾倫。您能評論一下該患者的什麼類型的數據以及我們在即將舉行的 SNO 會議上提供的任何臨床前類型的數據嗎？

Go ahead, Josh, I think you're closest to that. Go ahead.

來吧，喬什，我想你最接近那個了。前進。

I'll start with SNO, Naureen and just mentioned that we expect at least three oral presentations to occur at SNO on ONC201 two of them are related to positioning until one as a combinatorial backbone, right? Given the DMGs, right? Given the signal from the monotherapy that this drug has produced its safety profile, its oral administration, et cetera.

我將從 SNO 開始，Naureen，剛才提到我們預計在 ONC201 的 SNO 上至少會進行 3 場口頭演講，其中 2 場與定位相關，直到 1 場作為組合骨幹，對吧？考慮到DMG，對吧？鑑於單一療法的信號表明該藥物已產生其安全性、口服給藥等。

Really physicians that is an ideal backbone therapy. So some of the mechanistic data, pre-clinical rationale and been available emerging clinical safety and outcomes associated with [200], as a backbone therapy will be presented in SNO. I think that's going to be the subject of a couple of those studies. So you'll expect to see more of that at SNO.

確實對醫生來說這是一種理想的骨幹療法。因此，作為骨幹療法的一些機制數據、臨床前原理以及與[200]相關的可用新興臨床安全性和結果將在 SNO 中呈現。我認為這將成為其中一些研究的主題。因此，您會期望在 SNO 上看到更多這樣的內容。

Terrific. Okay. And just one more. Can you just remind me with the ONC206 trials that are ongoing, the dose escalation. Is it just post radiation or do they receive a little bit of Temozolomide as well?

了不起。好的。還有一個。您能提醒我一下正在進行的 ONC206 試驗嗎？劑量遞增。是只是放療後還是他們也接受了一點替莫唑胺？

There are arms that have -- that are in the frontline setting post radiation and also arms that are at recurrence. I believe Temozolomide is allowed prior to initiation of [ONC206]

有些手臂在放療後處於前線環境，有些手臂則處於復發狀態。我相信在開始 [ONC206] 之前允許使用替莫唑胺

Mike, I can answer that. The Phase 1 studies, it's a little more open on the inclusion criteria as we are trying to get safety for this patient population. I think bonuses if we did some signs of activity needed evaluate where we are seeing this activity, and that will help us decide vertical for future.

麥克，我可以回答。第一階段研究的納入標準更加開放，因為我們正在努力確保該患者群體的安全。我認為，如果我們做了一些需要的活動跡象，那麼獎金就會評估我們在哪裡看到這項活動，這將幫助我們決定未來的垂直方向。

Okay. Thanks so much.

好的。非常感謝。

Soumit Roy, Jones Research

蘇米特羅伊，瓊斯研究中心

Good morning, everyone, and congratulations on all the progress. On ONC206, excuse me. Could you remind us the dose escalation is going to be with 100 milligram dose level twice weekly? And how much does exposure increase do you expect on the prior schema?

大家早安，祝賀所有的進展。抱歉，在 ONC206。您能否提醒我們，劑量將每週兩次增加至 100 毫克劑量水平？您預計在先前的架構上曝光率會增加多少？

Yes, Soumit, I'll have Josh, perhaps contribute to this, too. But we have a slide in our deck that essentially lays out the dose frequency and schedule. So the next two dose levels following reactivation of this new protocol are evaluating similar. Essentially similar exposures and dose levels that were given once a week, but doing it fractionated over three days and then escalating up from there. Big picture, we'll end up at about four times the dose on a weekly basis if we make it all the way to dose level 11, Josh, anything to add?

是的，蘇米特，我會讓喬希也為此做出貢獻。但我們的幻燈片中有一張幻燈片，基本上列出了劑量頻率和時間表。因此，在重新活化該新方案後，接下來的兩個劑量水準的評估結果相似。每週一次的暴露量和劑量水平基本上相似，但在三天內分次進行，然後逐漸增加。總體而言，如果我們一直達到劑量水平 11，我們最終每週的劑量將是原來的四倍，喬什，有什麼需要補充的嗎？

No, I think you covered it.

不，我想你已經涵蓋了。

Okay, So and then with the time to response being about eight months or so, and I'm expecting this patient just got the dose escalation part just got initiated. So the data is most likely we are thinking end of '24. Is that a correct assumption? The efficacy data?

好的，那麼反應時間大約是八個月左右，我預計這位患者剛開始劑量遞增部分。所以我們認為的數據很可能是 24 年底的數據。這是一個正確的假設嗎？功效數據？

I think to the extent that we have valuable efficacy data, it will come in likely after completion of of the safety analysis. Right, Soumit and so we'd expect that, as we said in the first half or middle part of next year. And we'll share what efficacy insights response insights we have at that time. And we'll update that during the course of the year as those patients continue to be followed.

我認為，只要我們有有價值的療效數據，它就可能在安全性分析完成後出現。是的，Soumit，所以我們預計會出現這種情況，正如我們在明年上半年或中期所說的那樣。我們將分享我們當時擁有的功效見解和回應見解。隨著對這些患者的持續跟踪，我們將在這一年中更新這一情況。

And one last question, in terms of the location of the tumor itself, we should expect a broad range, right between anything between the PON, DIPG, Stem?

最後一個問題，就腫瘤本身的位置而言，我們應該期待一個廣泛的範圍，介於 PON、DIPG、Stem 之間嗎？

Yeah this is looking at primary CNS tumors. So it's going to be a fairly heterogeneous patient population.

是的，這是在研究原發性中樞神經系統腫瘤。因此，這將是一個相當多樣化的患者群體。

The only exception is -- Soumit this is Allen. The only exception as we are excluding patients, how you typically see with [CNS] disease [or] looking outside of that, but otherwise the broader sort of CNS disease.

唯一的例外是──蘇米特，這是艾倫。唯一的例外是我們排除了患者，即您通常如何看待[中樞神經系統]疾病[或]除此之外的其他疾病，但除此之外還有更廣泛的中樞神經系統疾病。

Understand that. Thank you so much and congrats again on the progress.

明白。非常感謝並再次恭喜取得的進展。

Thanks, Soumit.

謝謝，蘇米特。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Good morning. Hi, this is Ben on for Joe. Thanks for taking our questions. First question is what expense trajectory do you expect over the next few quarters?

早安.大家好，我是本為喬代言的。感謝您回答我們的問題。第一個問題是您預計未來幾季的支出軌跡如何？

Hi Ben. I'm sorry to clarify. Was that expense trajectory you asked?

嗨本。很抱歉要澄清一下。您問的是費用軌跡嗎？

Yes sir.

是的先生。

Yes, it will be it will be similar. I would expect if you look at our first half run rate in terms of cash burn in 2023. And this latest quarter, we're averaging $15 million, $16 million, $17 million a quarter. I would expect that to continue over the next couple of quarters (multiple speakers)

是的，將會是相似的。如果你看看我們 2023 年上半年的現金消耗率，我會預期。在最近一個季度，我們平均每季度燒錢 1500 萬美元、1600 萬美元、1700 萬美元。我預計這種情況將在接下來的幾個季度繼續下去（多位發言者）

I was just going to add as we begin to prepare for commercialization, you might see an uptick in expense. But I would say in the grand scheme of things, there would be just at the margin.

我只是想補充一點，當我們開始為商業化做準備時，你可能會看到費用上升。但我想說的是，從長遠來看，這只是邊緣而已。

Great. That's super helpful. And then I guess on the identification of biomarkers for ONC206 for future efficacy studies, would you expect the biomarkers to be similar to the biomarkers you showed for ONC201 Cancer Discovery publication or something different?

偉大的。這非常有幫助。然後我猜想，在為未來功效研究識別 ONC206 生物標記時，您是否期望這些生物標記與您在 ONC201 癌症發現出版物中展示的生物標記相似或有所不同？

Yes, really good question, then I'll let Josh weigh in on that. Josh?

是的，確實是個好問題，那麼我會讓喬希對此發表意見。喬許？

Yeah Ben great, great question. And as you would expect from, we've been working on ONC201 alone in this platform for a number of years now, and we're expecting to leverage all of that molecular information we've gathered from those efforts important into the ONC206 program.

是的，本，很好，很好的問題。正如您所期望的那樣，我們多年來一直在這個平台上單獨研究 ONC201，並且我們期望利用我們從那些對 ONC206 項目很重要的努力中收集到的所有分子資訊。

So what I'll say is we're really excited about what we're seeing with ONC206. We've been working hard in the lab ourselves and with collaborators and have generated a growing body of compelling in vitro and in vivo efficacy that we're excited about.

所以我要說的是，我們對 ONC206 所看到的一切感到非常興奮。我們自己和合作者一直在實驗室努力工作，並產生了越來越多令人信服的體外和體內功效，我們對此感到興奮。

As we've mentioned, the potency increase and the alternative engagement of additional target engagement interactions we've seen with ONC206 relative to ONC201. While that may not be a meaningful opportunity for H3 K27M mutant glioma, given that ONC201 is having on target saturation there. We think there's a lot of other opportunities outside of H3 K27M, both within the CNS and outside of the [CNS] that can be addressed by ONC206.

正如我們所提到的，相對於 ONC201，我們在 ONC206 中看到了額外目標參與互動的效力增加和替代參與。雖然這對 H3 K27M 突變神經膠質瘤來說可能不是一個有意義的機會，因為 ONC201 在那裡已經達到目標飽和度。我們認為，除了 H3 K27M 之外，在 CNS 內部和 [CNS] 之外還有很多其他機會可以透過 ONC206 來解決。

So we're seeing signs of that in preclinical studies. Clearly, we've reported on this one responder early in dose escalation in the Phase 1, for ONC206 that endorses that hypothesis. And what we're looking to do now is take some of these molecular biomarkers, some of which you're pointing to but good ideas can come from anywhere.

所以我們在臨床前研究中看到了這個跡象。顯然，我們已經在第一階段劑量遞增的早期報告了這一反應者，ONC206 證實了這一假設。我們現在要做的是採用一些分子生物標記物，其中一些是你指出的，但好的想法可以來自任何地方。

So we're trying to take for all of those ideas we have for specific molecular driver alterations in cancer that could be associated with ONC206 heightened activity and test some of those hypotheses against the de-compelling preclinical activity we're seeing so that we can run towards actionable alterations in follow-on trials. If that's appropriate.

因此，我們正在嘗試採納我們對癌症中可能與 ONC206 增強活性相關的特定分子驅動改變的所有想法，並針對我們所看到的令人信服的臨床前活性測試其中一些假設，以便我們能夠在後續試驗中爭取可行的改變。如果合適的話。

So good question. Good thinking, and we're hard at work testing a lot of these theories that include what we've learned from ONC201 and ONC206 over years.

好問題。很好的想法，我們正在努力測試許多這些​​理論，其中包括我們多年來從 ONC201 和 ONC206 中學到的東西。

Great. Thanks for the insights also from us.

偉大的。也感謝我們的見解。

Troy Langford,TD Cowen

特洛伊·蘭福德，TD·考恩

Hi. Congrats on the progress this quarter and thanks for taking our questions. First one just on ONC206. So with respect to the Phase 1 dose escalation work, do you have any Phase 1 work for both the NIH sponsored study in the PNOC sponsored study to complete around the same time. And if not, would you need to wait for both of those to finish before you move forward with the program?

你好。恭喜本季取得的進展，並感謝您提出我們的問題。第一個就在 ONC206 上。因此，關於 1 期劑量遞增工作，您是否有 NIH 資助的研究和 PNOC 資助的研究的 1 期工作大約在同一時間完成。如果沒有，您是否需要等待這兩個任務完成才能繼續該計劃？

Yes, good question, Troy. We do expect them based on what we know right now to complete around the same time. I don't think we have any insight there. They would be materially different, of course, as we get closer and to the final dose levels, assuming that we don't have a safety event that would stop us earlier. At a particular dose level -- right now are planning for them to complete around the same time if that should change, then, of course, we'll update you accordingly.

是的，好問題，特洛伊。根據我們目前所知，我們確實希望它們能夠在大約同一時間完成。我認為我們對此沒有任何洞察力。當然，當我們越來越接近最終的劑量水平時，假設我們沒有發生會提前阻止我們的安全事件，它們將會有很大的不同。在特定的劑量水平上——現在正計劃讓它們大約在同一時間完成，如果情況發生變化，那麼，當然，我們會相應地更新您的資訊。

(multiple speakers), Allen is going to add. Allen?

（多個發言者），艾倫將補充。艾倫？

The only thing I would add is that on ONC206. So it's really how quickly can fill the cohort close the cohorts and then opening new cohort. So there's high demand here.

我唯一要補充的是ONC206。因此，問題實際上是如何快速地填充隊列、關閉隊列，然後打開新隊列。所以這裡的需求很高。

Okay. Great. And then just other one on ONC206. So with respect to some of the expansion opportunities for that compound, just provide any color around how you think about balancing investment into some of those other areas with the need to preserve the cash runway for the ACTION study?

好的。偉大的。然後是 ONC206 上的另一台。因此，關於該化合物的一些擴張機會，請提供一些關於您如何考慮平衡對其他一些領域的投資與保留行動研究現金跑道的需要的任何顏色？

Yes. Great. Great question. And so as we think about capital allocation, we have earmarked some capital on balance sheet for Phase 2 studies that could be ONC206. Could be another compound may be it may be that could be in-licensed as we've said in prior quarters Troy, the bar for business development, continues to be high because we continue to see early preclinical and clinical data with 206 that continues to raise the bar for anything else we would pull in and allocate capital to.

是的。偉大的。很好的問題。因此，當我們考慮資本配置時，我們在資產負債表上指定了一些資本用於第二階段研究，可能是 ONC206。可能是另一種化合物，可能是可能會獲得許可，正如我們在前幾季所說的那樣，Troy 業務發展的門檻仍然很高，因為我們繼續看到206 種早期臨床前和臨床數據，這些數據仍在繼續提高我們要吸引和分配資本的其他任何事物的標準。

Clearly if we the more substantial of a Phase 2 study, we might run with ONC206 would shorten the runway. And well, we'll evaluate that when we make that decision.

顯然，如果我們進行更實質的 2 期研究，我們可能會使用 ONC206 來縮短跑道。好吧，當我們做出決定時，我們會對此進行評估。

To what extent would we shorten the runway? What are access to other dilutive or nondilutive capital and in particular and any additional insight we might have on milestone payments that might be forthcoming from Emergent BioSolutions, with respect to the TEMBEXA divestiture we made last year all factor into that calculus.

我們會將跑道縮短到什麼程度？獲得其他稀釋性或非稀釋性資本的途徑是什麼，特別是我們對 Emergent BioSolutions 可能即將支付的里程碑付款的任何額外見解，以及我們去年剝離 TEMBEXA 的所有因素都納入了這項計算。

But it starts with how much conviction do we have in the data to date on ONC206, both preclinically and clinically and sharing that data with the market, making sure that conviction is shared externally as well.

但首先是我們對 ONC206 迄今為止的數據有多少信心，包括臨床前和臨床數據，並與市場分享這些數據，確保外部也分享這些數據。

Great. Thanks for all the extra color, and that's all for me.

偉大的。感謝所有額外的顏色，這就是我的全部。

Sure.

當然。

I will now turn the call back over to Mike Andriole for closing remarks.

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, John. Thank you, everyone, for your time this morning. For those of you attending the SNO conference this month. Please stand by our booth. Otherwise, we look forward to updating you again in the coming months.

謝謝，約翰。謝謝大家今天早上抽出時間。致本月參加 SNO 會議的各位。請大家站在我們的展位前。否則，我們期待在未來幾個月內再次為您提供最新資訊。

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。