Cardiff Oncology Inc (CRDF) 2024 Q2 法說會逐字稿

Welcome to the Cardiff Oncology Second Quarter 2024 Financial Results and Business Update Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded.

歡迎參加卡迪夫腫瘤學 2024 年第二季財務表現與業務更新電話會議。（操作員指示）請注意，今天的會議正在錄製中。

I would now like to turn the conference call over to Kiki Patel of Gilmartin Group. Please go ahead.

我現在想將電話會議轉交給吉爾馬丁集團的琪琪·帕特爾。請繼續。

Thank you, operator. Joining us on the call today from Cardiff Oncology, our Chief Executive Officer, Mark Erlander, and Chief Financial Officer, Jamie Levine.

謝謝你，接線生。今天，我們的執行長馬克·埃蘭德 (Mark Erlander) 和財務長傑米·萊文 (Jamie Levine) 加入了來自卡迪夫腫瘤學的電話會議。

During this conference call, management will make forward-looking statements, including, without limitation, statements related to guidance, results and the timing of data readouts for onvansertib clinical trials. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties.

在本次電話會議期間，管理層將做出前瞻性聲明，包括但不限於與 onvansertib 臨床試驗的指導、結果和數據讀出時間相關的聲明。這些前瞻性陳述是基於公司目前的預期，本質上涉及重大風險和不確定性。

Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties.

由於這些風險和不確定性，我們的實際結果和事件發生的時間可能與此類前瞻性陳述中的預期有重大差異。

Factors that could cause results to be different from these statements include factors the company described in the section titled Risk Factors in its annual report on Form 10-K filed with the SEC for year ended December 31, 2023. Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events or changes in its expectations.

可能導致結果與這些陳述不同的因素包括該公司在向 SEC 提交的截至 2023 年 12 月 31 日止年度的 10-K 表格年度報告中標題為“風險因素”的部分中描述的因素。卡迪夫腫瘤學不承擔因新資訊、未來事件或預期變化而更新任何前瞻性陳述的責任或義務。

With that, I turn the call over to Chief Executive Officer, Mark Erlander. Mark?

說完，我將電話轉給執行長馬克‧埃蘭德 (Mark Erlander)。標記？

Thank you, Kiki, and good afternoon, everyone, and thank you for joining our business update conference call for the second quarter of 2024. These are certainly energizing times at Cardiff Oncology as we activate sites, enroll patients in our CRDF-004 trial in RAS-mutated metastatic colorectal cancer or mCRC.

謝謝 Kiki，大家下午好，謝謝您參加我們的 2024 年第二季業務更新電話會議。卡迪夫腫瘤中心無疑是充滿活力的時刻，因為我們激活了站點，將患者納入我們針對 RAS 突變的轉移性結直腸癌或 mCRC 的 CRDF-004 試驗。

The interactions we're having with the physicians and other professionals at the trial site reinforce has the potential to bring a more effective therapy to this large patient population of nearly 50,000 new patients a year in the U.S. alone. Specifically, the totality of the data from our Phase [Ib II] and ONSEMBLE second-line mCRC trials demonstrates onvansertib has the potential to shift the treatment paradigm for all RAS-mutated mCRC, not just subgroups to pair us.

我們與試驗現場的醫生和其他專業人員加強的互動有可能為僅在美國每年就有近 50,000 名新患者的龐大患者群體帶來更有效的治療。具體來說，我們的 [Ib II] 期和 ONSEMBLE 二線 mCRC 試驗的全部數據表明 onvansertib 有潛力改變所有 RAS 突變 mCRC 的治療模式，而不僅僅是與我們配對的亞群。

We say this because, first, there have been no new therapies approved for these patients over the past 20 years. Second, there are no competing clinical trials for this patient population. And third, unlike prior PLK1 inhibitors, onvansertib is well tolerated when combined with chemotherapy, which also opens the door to other chemo combinations for additional cancer indications. So let's dive in.

我們這麼說是因為，首先，過去 20 年來沒有批准用於這些患者的新療法。其次，沒有針對該患者族群的競爭性臨床試驗。第三，與先前的 PLK1 抑制劑不同，onvansertib 與化療聯合使用時具有良好的耐受性，這也為其他癌症適應症的其他化療組合打開了大門。那麼就讓我們深入了解一下吧。

On today's call, we will cover 4 topics. First, I will discuss our lead program in nCRC and provide updates around our ongoing CRDF-004 trial. Second, I will provide an update on our pancreatic cancer program. Third, I will provide a brief overview of our continued encouraging preclinical data demonstrating onvansertib's activity in other cancer indications with unmet clinical need beyond RAS-mutated mCRC.

在今天的電話會議上，我們將討論 4 個主題。首先，我將討論我們在 nCRC 中的主導項目，並提供有關我們正在進行的 CRDF-004 試驗的最新資訊。其次，我將提供有關我們胰腺癌計劃的最新資訊。第三，我將簡要概述我們持續令人鼓舞的臨床前數據，這些數據證明了 onvansertib 在除 RAS 突變 mCRC 之外尚未滿足臨床需求的其他癌症適應症中的活性。

And finally, we will talk about our financial position that we disclosed today in our Form 10-Q. So let's begin.this quarter, we have been intensely focused on the clinical execution of our CRDF-004 trial, evaluating the contribution of onvansertib in first-line RAS-mutated mCRC.

最後，我們將討論今天在 10-Q 表格中披露的我們的財務狀況。讓我們開始吧。

As a reminder, CRDF-004 is our ongoing Phase II trial evaluating onvansertib in combination with current standard of care, which consists of either FOLFIRI plus bev or FOLFOX plus bev. The trial is currently active in 33 sites, and we plan to enroll 90 patients who will be randomized to receive either a 20-milligram or a 30-milligram dose of onvansertib plus standard of care for standard of care alone.

提醒一下，CRDF-004 是我們正在進行的 II 期試驗，評估 onvansertib 與目前護理標準的結合，其中包括 FOLFIRI 加 bev 或 FOLFOX 加 bev。該試驗目前在 33 個地點進行，我們計劃招募 90 名患者，他們將被隨機分配接受 20 毫克或 30 毫克劑量的 onvansertib 加標準護理（僅標準護理）。

Our team at Cardiff Oncology alongside our clinical execution partner, Pfizer Ignite is diligently working on the enrollment of the trial. We continue to leverage Pfizer's resources and capabilities in multiple areas to drive enrollment.

我們卡迪夫腫瘤學團隊與我們的臨床執行夥伴輝瑞 Ignite 正在努力進行試驗的註冊工作。我們繼續利用輝瑞在多個領域的資源和能力來推動註冊。

We also appreciate the commitment and the clinical efforts of our enthusiastic investigators who have been judiciously screening patients across our active sites.

我們也感謝我們熱情的研究人員的承諾和臨床努力，他們一直在我們的活動中心明智地篩選患者。

Based on the current pace of enrollment over the past few months, we continue to plan on releasing an initial data readout later this year as we previously guided. We expect this will include objective response rate data for approximately half of the patients we plan to enroll in the trial.

根據過去幾個月目前的註冊速度，我們繼續計劃按照我們先前的指導，在今年稍後發布初步數據。我們預計這將包括我們計劃參加試驗的大約一半患者的客觀緩解率數據。

Now I'd like to turn to our second agenda item, an update on our pancreatic cancer program focused on metastatic pancreatic ductal adenocarcinoma or PDAC. In September of last year, we released data from our Phase II trial for metastatic PDAC in the second-line setting. In this single-arm trial, patients received onvansertib in combination with the chemotherapy regimen of liposomal, irinotecan, leucovorin and 5-FU.

現在我想談談我們的第二個議程項目，即我們的胰腺癌項目的最新情況，重點是轉移性胰腺導管腺癌或 PDAC。去年 9 月，我們發布了二線治療轉移性 PDAC 的 II 期試驗數據。在這項單組試驗中，患者接受了 onvansertib 聯合脂質體、伊立替康、亞葉酸和 5-FU 化療方案。

After discussing the results with our investigators, we decided the next step of our PDAC program would be an investigator-initiated trial in the first-line study combining onvansertib with standard of care Gem-Abraxane, Today, we are sharing an update to our plans in metastatic PDAC because earlier this year, NALIRIFOX was approved for first-line metastatic PDAC after the NAPOLI III trial showed significantly greater improvement in overall survival and progression-free survival with first-line NALIRIFOX compared to Gem-Abraxane.

在與我們的研究人員討論結果後，我們決定 PDAC 計劃的下一步將是由研究者發起的一線研究試驗，將 onvansertib 與標準護理 Gem-Abraxane 相結合，今天，我們將分享我們計劃的更新今年早些時候，NAPOLI III 試驗顯示，與Gem-Abraxane 相比，一線NALIRIFOX 在總生存期和無進展生存期方面有顯著更大的改善，之後，NALIRIFOX 被批准用於轉移性PDAC。

As a result of this change to the first-line standard of care, we have decided to support a first-line investigator-initiated PDAC trial that combines onvansertib with NALIRIFOX. And recall that three of the four drugs that comprise the NALIRIFOX first-line regimen for the same drug combined with onvansertib in our prior second-line PDAC trial.

由於第一線護理標準發生變化，我們決定支持第一線研究者發起的將 onvansertib 與 NALIRIFOX 結合的 PDAC 試驗。回想一下，在我們先前的二線 PDAC 試驗中，構成 NALIRIFOX 一線方案的四種藥物中的三種與 Onvansertib 聯合使用。

This new trial will replace the first-line PDAC investigator initiated trial combining onvansertib with Gem-Abraxane, which was still in an early stage and have not started to enroll patients. We will provide further updates on the onvansertib NALIRIFOX investigator-initiated trial in the coming months.

這項新試驗將取代第一線 PDAC 研究者發起的 onvansertib 與 Gem-Abraxane 聯合試驗，該試驗仍處於早期階段，尚未開始招募患者。我們將在未來幾個月內提供有關 onvansertib NALIRIFOX 研究者發起的試驗的進一步更新。

Now I'd like to transition to the third item on our agenda, which is our continued success in identifying other cancer indications where onvansertib may be clinically efficacious. Previously, in preclinical studies, onvansertib has been shown to have activity in RAS wild-type mCRC ER-positive breast cancer, triple-negative breast cancer and platinum-resistant ovarian cancer.

現在我想轉向我們議程上的第三個項目，即我們在確定 onvansertib 可能在臨床上有效的其他癌症適應症方面不斷取得成功。先前，在臨床前研究中，onvansertib已被證明對RAS野生型mCRC ER陽性乳癌、三陰性乳癌和鉑類抗藥性卵巢癌具有活性。

Last month, we published preclinical data on a new indication within ovarian cancer in the peer-reviewed journal Cell Death and Disease, which is a portfolio member of the Journal, Nature. Specifically, the data evaluated onvansertib in ovarian cancers that are resistant to PARP inhibitors.

上個月，我們在同行評審期刊《細胞死亡與疾病》上發表了有關卵巢癌新適應症的臨床前數據，該期刊是《自然》雜誌的投資組合成員。具體來說，數據評估了 onvansertib 在對 PARP 抑制劑抗藥性的卵巢癌中的作用。

In the published study, the combination of onvansertib and olaparib, a PARP inhibitor approved in ovarian cancer was tested both in vitro and in vivo and BRCA1-mutated and wild-type ovarian cancer models.

在已發表的研究中，onvansertib 和奧拉帕尼（一種被批准用於卵巢癌的 PARP 抑制劑）的組合在體外和體內以及 BRCA1 突變和野生型卵巢癌模型中進行了測試。

In vitro, the combination of onvansertib and olaparib was synergistic in ovarian cancer cell lines and demonstrate inhibition of tumor growth. In vivo, the combination was well tolerated, low tumor progression and prolonged survival in patient-derived xenograft models resistant to olaparib.

在體外，onvansertib 和 olaparib 的組合在卵巢癌細胞系中具有協同作用，並顯示出對腫瘤生長的抑製作用。在體內，該組合在對奧拉帕尼抗藥性的患者來源的異種移植模型中具有良好的耐受性、較低的腫瘤進展和較長的生存期。

Resistance to olaparib has been observed in clinical studies and has been a challenge to overcome. Moreover, these findings underscore the ability of onvansertib to overcome resistance to PARP inhibitors in high-grade serious ovarian carcinoma, which could make a significant impact in the treatment landscape for ovarian cancer.

臨床研究中已觀察到對奧拉帕尼的抗藥性，這一直是需要克服的挑戰。此外，這些發現強調了 onvansertib 克服高級別嚴重卵巢癌對 PARP 抑制劑抗藥性的能力，這可能對卵巢癌的治療前景產生重大影響。

Overall, we are still determining our path forward in ovarian cancer. However, we are highly encouraged by the totality of the data generated from our recent publication and AACR poster that demonstrates onvansertib's ability to effectively resensitize ovarian cancer to treatment.

總體而言，我們仍在確定卵巢癌治療的方向。然而，我們最近的出版物和 AACR 海報產生的全部數據令我們深受鼓舞，這些數據證明了 onvansertib 能夠有效地使卵巢癌對治療重新敏感。

Now I would like to turn the call over to Jamie to discuss our final agenda item, our second quarter 2024 financial update.

現在我想將電話轉給 Jamie，討論我們的最後一個議程項目，即 2024 年第二季的財務更新。

Thank you, Mark. Earlier today, we issued a press release and filed a Form 10-Q with the SEC, which contain our financial results for the second quarter ending June 30, 2024.

謝謝你，馬克。今天早些時候，我們發布了新聞稿並向 SEC 提交了 10-Q 表格，其中包含我們截至 2024 年 6 月 30 日的第二季度的財務業績。

Turning to our balance sheet. Cash and short-term investments as of June 30, 2024, totaled $60.3 million, and our cash used in operating activities was $9.2 million in Q2 2024. Today, we're also updating our cash runway guidance based on our most up-to-date cash forecast.

轉向我們的資產負債表。截至 2024 年 6 月 30 日，現金及短期投資總額為 6,030 萬美元，2024 年第二季我們用於經營活動的現金為 920 萬美元。今天，我們也根據最新的現金預測更新了現金跑道指南。

As a result, we believe that our current cash resources provide us with runway through the end of the third quarter of 2025, whereas previously, we had expected runway into the third quarter of 2025.

因此，我們認為，我們目前的現金資源為我們提供了到 2025 年第三季末的跑道，而之前我們預計可以到 2025 年第三季末。

With that, I'll turn the call back over to Mark.

這樣，我會將電話轉回馬克。

Thank you, Jamie. I would now like to close the call by emphasizing our confidence in our clinical development strategy for our lead program in RAS-mutated mCRC and enthusiasm for our upcoming data readout of CRDF-004 later this year.

謝謝你，傑米。現在，我想在結束這次電話會議時強調我們對 RAS 突變 mCRC 主導計畫的臨床開發策略的信心，以及對今年稍後即將推出的 CRDF-004 數據讀出的熱情。

Collectively, the data we have released throughout the past year from our Phase [Ib/II] study ONSEMBLE trial and as AACR gives us conviction that adding onvansertib to standard of care has the potential to change the treatment paradigm for the entire first-line RAS-mutated mCRC patient population. And we believe that such an outcome would create enormous step for our stakeholders and positively impact the large population of patients living with RAS-mutated mCRC.

總的來說，我們在過去一年中發布的 [Ib/II] 期研究 ONSEMBLE 試驗和 AACR 的數據讓我們相信，將 onvansertib 添加到護理標準中有可能改變整個一線 RAS 的治療模式-突變的mCRC患者群。我們相信，這樣的結果將為我們的利害關係人邁出巨大的一步，並對大量 RAS 突變 mCRC 患者產生積極影響。

With that, I will now open the call up for questions. Operator?

現在，我將開始提問。操作員？

(Operator Instructions).

（操作員說明）。

Marc Frahm of TD Cowen.

TD Cowen 的 Marc Frahm。

Maybe first off, last quarter, you noted that kind of enrollment trends in the 004 trial had maybe been a bit slower than you'd anticipated when you opened the trial. Just curious, has that kind of held steady, has the enrollment held steady over the summer? Or have you seen some acceleration in that enrollment trend?

也許首先，上個季度，您注意到 004 試驗中的註冊趨勢可能比您開始試驗時預期的要慢。只是好奇，這種情況是否保持穩定，夏季的入學人數是否保持穩定？或者您看到入學趨勢有所加速？

Thanks, Marc. Enrollment is tracking quite well and is tracking with our guidance of having an initial look at the data later this year. And part of the reason why it's doing well is because we have Pfizer Ignite as a strong partner, and we've been able to leverage a lot of their capabilities and being able to drive the enrollment.

謝謝，馬克。註冊情況追蹤得很好，並且按照我們今年稍後初步查看數據的指導進行追蹤。它表現良好的部分原因是因為我們有輝瑞 Ignite 作為強大的合作夥伴，我們能夠利用他們的許多能力並能夠推動註冊。

I think the other things that really do help that I mentioned earlier on the call is that there are no new drugs for 20 years for these RAS-mutated patients in first-line mCRC. And also importantly, there are no competing trials. So to answer your question, yes, we're on track with the guidance of initial look later this year?

我認為我之前在電話會議中提到的其他真正有幫助的事情是，對於這些一線 mCRC 中的 RAS 突變患者來說，20 年來沒有新藥。同樣重要的是，沒有競爭性試驗。那麼，回答你的問題，是的，我們正在按照今年稍後初步審查的指導走上正軌？

Okay. That's very helpful. And then maybe on the pancreatic trial that you are going to start up. I think [NALIRIFOX] obviously been approved. But at least in our conversations with physicians, it's not 100% clear that it's going to get broadly adopted as a true kind broad standard of care. So I guess why be kind of aggressive on adopting that now kind of for this initial proof of concept for in pancreatic versus maybe using some of the older regimens that are also potentially a bit better tolerated than that regimen?

好的。這非常有幫助。然後也許您將要啟動胰臟試驗。我認為 [NALIRIFOX] 顯然已獲得批准。但至少在我們與醫生的對話中，並不能 100% 明確它是否會被廣泛採用作為真正的廣泛護理標準。所以我想為什麼現在要積極採用這種方案來進行胰臟的初步概念驗證，而不是使用一些較舊的方案，這些方案的耐受性也可能比該方案更好？

Yes. Really two answers to that question. I mean the first is that the NALIRIFOX really 3 of the 4 chemo agents. We've already combined with onvansertib in second line and have good data from that. And so we believe that with along with our preclinical work in this area. So that's really the first part of the answer to the question.

是的。這個問題確實有兩個答案。我的意思是，第一個是 NALIRIFOX 實際上是 4 種化療藥物中的 3 種。我們已經在第二行與 onvansertib 結合使用，並從中獲得了良好的數據。因此，我們相信這一點以及我們在該領域的臨床前工作。這其實是問題答案的第一部分。

The second is really that we are showing really good tolerability of onvansertib in combination with these chemo agents. And really, the only chemo that we haven't combined it with is the oxaliplatin, which is part of the NALIRIFOX. But really oxaliplatin really does not have any overlapping toxicities with onvansertib.

第二個問題是，我們確實表現出了 onvansertib 與這些化療藥物聯合使用的良好耐受性。實際上，我們唯一沒有將其與奧沙利鉑聯合使用的化療藥物，它是 NALIRIFOX 的一部分。但實際上奧沙利鉑確實與 onvansertib 沒有任何重疊的毒性。

So we do feel confident that we can come in with this more aggressive chemo and combining and adding value to that because we believe that this is really the type of regimen that is showing the superiority in efficacy in first line.

因此，我們確實有信心能夠採用這種更積極的化療，並將其結合起來並為其增加價值，因為我們相信這確實是一種在一線中顯示出療效優越性的治療方案。

Okay, thank you.

好的，謝謝。

Andy Hsieh of William Blair.

威廉布萊爾的謝安迪。

Maybe kind of extend from Marc's question earlier in the call. Just curious about whether you could comment on the level of kind of scientific validation with the change of the IST in pancreatic cancer. Obviously, I think it's well validated that onvansertib synergy with irinotecan, which is now included in the regimen versus the Gem-Abraxane regimen before. I'm curious about your view on that.

也許是馬克在電話會議早些時候提出的問題的延伸。只是好奇您是否可以對胰腺癌 IST 變化的科學驗證水平發表評論。顯然，我認為 onvansertib 與伊立替康的協同作用得到了充分驗證，與先前的 Gem-Abraxane 方案相比，現在將其包含在該方案中。我很好奇你對此的看法。

And then in terms of the potential ovarian cancer entry, there's obviously new therapy for ovarian cancer in the form of ADCs. So you looked at chemotherapy, you look at targeted therapy combinations, PARP. So just curious about whether you've done or plan to do any sort of commentatorial work in the ADC field as well.

然後就潛在的卵巢癌進入而言，顯然有 ADC 形式的卵巢癌新療法。所以你研究了化療，你研究了標靶治療組合，PARP。所以只是想知道您是否已經完成或計劃在 ADC 領域進行任何類型的評論工作。

Thanks, Andy, for both of those questions. I'd say, to answer your first question, really, the irinotecan synergy is one of the main reasons we are going with the combination with NALIRIFOX in first line. Also, our the TI that is that we're working with for this new investigator-initiated trial has already has experience in our second-line pancreatic trial and really was the huge proponent enthusiastic in going into first line. So that was really -- he knows our drug, he knows it's well tolerated, and he's very excited about going into first line.

謝謝安迪提出這兩個問題。我想說的是，為了回答你的第一個問題，伊立替康的協同作用是我們在一線與 NALIRIFOX 聯合使用的主要原因之一。此外，我們正在合作進行這項由研究者發起的新試驗的 TI 已經在我們的二線胰腺試驗中擁有經驗，並且確實是熱衷於進入一線的大力支持者。所以這真的是——他了解我們的藥物，他知道它的耐受性很好，而且他對進入一線感到非常興奮。

To answer your other question about ovarian cancer and ADC combination, we are currently preclinically looking at ADCs in combination with onvansertib, not only ovarian not specific to only ovarian, but we are really exploring that in several other areas that -- where ADCs have been approved.

為了回答您關於卵巢癌和 ADC 組合的其他問題，我們目前正在臨床前研究 ADC 與 onvansertib 的組合，不僅限於卵巢癌，而且我們正在其他幾個領域進行探索——ADC 已在這些領域中使用正式認可的。

That's helpful. Thank you so much.

這很有幫助。太感謝了。

Sure. Thanks, Andy.

當然。謝謝，安迪。

(Operator Instructions) There are no more questions. I will now turn the conference back over to Mark Erlander for closing remarks.

（操作員說明）沒有更多問題。現在我將把會議轉回馬克·埃蘭德致閉幕詞。

Thank you, operator, and this concludes our conference call. Thank you again, everybody, for joining us this afternoon. Good day.

謝謝接線員，我們的電話會議到此結束。再次感謝大家今天下午加入我們。再會。

Ladies and gentlemen, that concludes today's call and 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。