Cardiff Oncology Inc (CRDF) 2023 Q3 法說會逐字稿

Welcome to the Cardiff Oncology third-quarter 2023 financial results and corporate update conference call. (Operator Instructions) As a reminder, this call is being recorded today, November 2, 2023.

歡迎參加卡迪夫腫瘤學 2023 年第三季財務業績和公司更新電話會議。 （操作員說明）謹此提醒，此通話將於今天（2023 年 11 月 2 日）錄音。

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 are Chief Executive Officer, Mark Erlander, and Chief Financial Officer, Jamie Levine.

謝謝你，接線生。今天來自卡迪夫腫瘤學的執行長 Mark Erlander 和財務長 Jamie Levine 參加了我們的電話會議。

During this conference call, management will make forward-looking statements, including without limitations, statements related to guidance, results, and the timing of the area for our advantage and clinical trials.

在本次電話會議期間，管理層將做出前瞻性聲明，包括但不限於與指導、結果以及我們的優勢領域和臨床試驗的時間表相關的聲明。

These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. 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.

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。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 describes in the section entitled Risk Factors in our annual report on Form 10-K for the year ended December 31, 2022, filed with the SEC on March 2, 2023.

可能導致結果與這些陳述不同的因素包括公司在 2023 年 3 月 2 日向 SEC 提交的截至 2022 年 12 月 31 日的 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。

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. Slides for today's investor call can be found on the homepage and Events and Presentations tab on the Cardiff Oncology website at www.cardiffoncology.com. With that, I'll turn the call over to Chief Executive Officer, Mark Erlander. Mark?

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。今天投資者電話會議的幻燈片可以在卡迪夫腫瘤學網站 www.cardiffoncology.com 的主頁以及「活動和簡報」標籤上找到。接下來，我會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 third-quarter 2023 financial results and the corporate update conference call. As you can see on slide 3, this past quarter was transformational for Cardiff Oncology.

謝謝你，琪琪，大家下午好。感謝您參加我們的 2023 年第三季財務業績和公司更新電話會議。正如您在幻燈片 3 中看到的那樣，過去一個季度對卡迪夫腫瘤學來說是一場變革。

In August, we announced strong data from our lead program in KRAS-mutated metastatic colorectal cancer, the conclusions from a highly supportive meeting with the FDA, and expansion of our relationship with Pfizer. Then in September, we released data with two earlier stage programs in pancreatic cancer and small cell lung cancer, which included a clear efficacy signal from onvansertib monotherapy in both indications.

8 月，我們宣布了 KRAS 突變轉移性結直腸癌主導計畫的強勁數據、與 FDA 高度支持的會議得出的結論，以及擴大我們與輝瑞的關係。然後在 9 月份，我們發布了胰腺癌和小細胞肺癌兩個早期項目的數據，其中包括 onvansertib 單藥療法在這兩個適應症中的明確療效信號。

Today, we would like to put all of this in context and explain our strategy to you all and demonstrate how we can create shareholder value going forward. As we all know, these are challenging times for publicly listed biotech companies, but Cardiff Oncology has a collection of strengths from which to build value.

今天，我們希望將所有這些放在背景下，向大家解釋我們的策略，並展示我們如何能夠創造未來的股東價值。眾所周知，對於上市生技公司來說，現在是充滿挑戰的時期，但卡迪夫腫瘤學擁有一系列可以創造價值的優勢。

As we list on slide 4, these include, first and foremost, our drug onvansertib, has shown clear signals of efficacy and tolerability in combination with chemotherapies and as a single agent in our clinical trials across multiple indications.

正如我們在幻燈片4 中列出的，這些首先包括我們的藥物onvansertib，在我們針對多種適應症的臨床試驗中，它已顯示出與化療聯合使用以及作為單一藥物的療效和耐受性的明確信號。

Second, onvansertib is the only PLK1 specific inhibitor in clinical development, meaning onvansertib is the first-in-class molecule for this well-understood target for cancer therapy. Third, onvansertib can combine synergistically with and is well tolerated in many first-line and second-line standard of care regimens.

其次，onvansertib 是臨床開發中唯一的 PLK1 特異性抑制劑，這意味著 onvansertib 是針對這一眾所周知的癌症治療標靶的一流分子。第三，onvansertib可以與許多第一線和二線標準護理方案協同結合，並且具有良好的耐受性。

This enables us to address some of the most common and deadliest cancer indications in early lines of therapy where there are the large patient populations that could be positively impacted. The fact that we are targeting first-line patients in both metastatic colorectal cancer and pancreatic cancer are good examples of that.

這使我們能夠在早期治療中解決一些最常見和最致命的癌症適應症，大量患者群體可能會受到積極影響。我們的目標是轉移性大腸直腸癌和胰臟癌的第一線患者，這一事實就是一個很好的例子。

Fourth, we have clear third-party support for our plan, and this includes the FDA and Pfizer. And finally, we have the financial resources to pursue our strategy in a thoughtful and methodical manner with the cash runway into 2025.

第四，我們的計劃得到了明確的第三方支持，其中包括 FDA 和輝瑞。最後，我們擁有財務資源，可以深思熟慮、有條不紊地實施我們的策略，並擁有直至 2025 年的現金跑道。

As we go to slide 5, we show the three objectives for Cardiff Oncology that we believe will create value for all of our stakeholders. And let me be very clear. Our primary focus is our lead program in RAS-mutated metastatic colorectal cancer. We are currently working closely with Pfizer Ignite to execute the clinical development plan that the FDA has agreed to, and to generate data from our first-line CRDF-004 clinical trials in mid-2024.

當我們轉到幻燈片 5 時，我們展示了卡迪夫腫瘤學的三個目標，我們相信這將為所有利益相關者創造價值。讓我說得很清楚。我們的主要重點是 RAS 突變轉移性大腸直腸癌的主導項目。我們目前正在與輝瑞Ignite密切合作，執行FDA已同意的臨床開發計劃，並在2024年中期從我們的一線CRDF-004臨床試驗中產生數據。

Our second objective is to continue to generate additional clinical data from our trials in pancreatic cancer, small cell lung cancer, and triple-negative breast cancer, which we plan to do in a capital-efficient manner through investigator initiated trials.

我們的第二個目標是繼續從我們的胰腺癌、小細胞肺癌和三陰性乳腺癌試驗中產生更多的臨床數據，我們計劃透過研究者發起的試驗以資本有效的方式做到這一點。

Finally, our third objective is rooted in our conviction that PLK1 inhibition has an even larger role to play in cancer therapy. As we have for other clinical programs, we will make data-driven decisions with strong commercial logic to explore new promising combinations and cancer indications. Our current efforts focused on cost effective preclinical study.

最後，我們的第三個目標植根於我們的信念：PLK1 抑制在癌症治療中發揮更大的作用。正如我們對其他臨床項目所做的那樣，我們將做出具有強大商業邏輯的數據驅動決策，以探索新的有希望的組合和癌症適應症。我們目前的工作重點是具有成本效益的臨床前研究。

By executing towards these objectives, we can create significant value for all of our stakeholders, and we believe that data and the plans we announced in the third quarter from a shareholder perspective, reduce the risk of our clinical development plan while increasing the reward potential given the larger commercial opportunity that we are now pursuing.

透過實現這些目標，我們可以為所有利益相關者創造巨大的價值，我們相信，從股東的角度來看，我們在第三季度宣布的數據和計劃可以降低我們臨床開發計劃的風險，同時增加給予的獎勵潛力我們現在正在追求的更大的商業機會。

Let's move to slide 6. Here, we're summarizing the key accomplishments during the third quarter of our lead program in metastatic colorectal cancer. As you as you know, in August, we shared a series of findings from our second-line Phase 1b/2 clinical trial in KRAS-mutated metastatic colorectal cancer. About a quarter of the patients who came into our second-line trial were not treated with bevacizumab or bev in their prior first-line treatment.

讓我們轉到幻燈片 6。如您所知，8 月份，我們分享了 KRAS 突變轉移性結直腸癌二線 1b/2 期臨床試驗的一系列結果。參加我們二線試驗的患者中約有四分之一在先前的第一線治療中未接受貝伐單抗或 bev 治療。

For this bev naive patient, we saw strong responses to the combination of our drug onvansertib with the second-line standard of care, which includes bev, specifically 73% of bev naive patients had a confirmed objective response to treatment versus historical controls that had demonstrated a rate of around 25%. And these patients also remained on our trial for a median time of 15 months before their disease progressed versus historical controls of seven to eight months.

對於這位未接受過Bev 治療的患者，我們看到對我們的藥物onvansertib 與二線標準治療（包括BeV）的組合產生了強烈的反應，特別是73% 的未接受過BeV 治療的患者對治療有明確的客觀反應，而歷史對照已證明比率約為25%。這些患者在疾病進展之前繼續參加我們的試驗的中位數時間為 15 個月，而歷史對照組為 7 至 8 個月。

We were highly encouraged by these data, which suggested that there was a new mechanism of action of onvansertib at blood that was previously unknown. Observing a threefold increase in response rate, a doubling in the median PFS in bev naive patients was a signal too strong for us to ignore.

這些數據讓我們深受鼓舞，這些數據表明 onvansertib 在血液中存在一種以前未知的新作用機制。觀察到反應率增加了三倍，未接受過治療的患者中位無惡化存活期 (PFS) 翻倍，這是我們無法忽視的強烈訊號。

So as a next step, we investigated the underlying science through a 12-month, multi-phase preclinical program. The preclinical work led us to conclude that both onvansertib and bev have independent mechanisms of action that work together to restrict a tumor's blood supply, thereby significantly decrease the tumor growth.

因此，下一步，我們透過為期 12 個月的多階段臨床前計畫研究了基礎科學。臨床前工作使我們得出結論，onvansertib 和 bev 都有獨立的作用機制，共同限制腫瘤的血液供應，從而顯著減少腫瘤的生長。

We next asked, why is this clinical finding only observed in bev naive patients and not in patients who were treated with bev -- in bev in the first line setting? To answer this question, we engaged an independent research firm called Tempus to conduct a clinical study that analyzed tumor biopsy data from 135 KRAS-mutated metastatic colorectal patients -- cancer patients.

接下來我們問，為什麼這項臨床發現僅在未接受過 Bev 治療的患者中觀察到，而在接受過 Bev 治療的患者中沒有觀察到——在一線治療中？為了回答這個問題，我們聘請了一家名為 Tempus 的獨立研究公司進行一項臨床研究，分析了 135 名 KRAS 突變的轉移性結直腸癌患者（癌症患者）的腫瘤活檢數據。

This analysis showed that once patients were exposed to bev in the first line setting, the tumor genomics were changed. And this change is consistent with generating tumor resistance to onvansertib and death in the second line setting. We believe this explains why we observed strong positive clinical results in our Phase 1b/2 trial in the bev naive, but not the bev-exposed patient populations.

該分析表明，一旦患者在一線環境中接觸貝韋病毒，腫瘤基因組就會發生變化。這種變化與腫瘤對 onvansertib 產生抗藥性以及二線治療中的死亡是一致的。我們相信這解釋了為什麼我們在 1b/2 期試驗中在未接觸過 bev 的患者群體中觀察到了強烈的陽性臨床結果，但在暴露於 bev 的患者群體中卻沒有觀察到強烈的陽性臨床結果。

Now armed with these findings, we shared our clinical and preclinical data with the FDA in a Type C meeting in June of this year. The FDA suggested we move our clinical development program of onvansertib up to the first line where all patients are bev naive and where we have the opportunity to positively impact the largest patient population of RAS-mutated metastatic colorectal cancer.

現在有了這些發現，我們在今年 6 月的 C 類會議上與 FDA 分享了我們的臨床和臨床前數據。 FDA 建議我們將 onvansertib 的臨床開發計劃移至一線，所有患者均未接受過治療，我們有機會對最大的 RAS 突變轉移性結直腸癌患者群體產生積極影響。

We responded to the FDA's suggestion by proposing a development plan with two clinical trials. The first trial, CRDF-004, will provide randomized data for both efficacy and dose confirmation. Then, we can conduct a subsequent registrational CRDF-005, where the FDA provided clear guidance for a path to both accelerated approval and full approval from one trial.

我們響應 FDA 的建議，提出了一項包含兩項臨床試驗的開發計畫。第一項試驗 CRDF-004 將為療效和劑量確認提供隨機數據。然後，我們可以進行後續的註冊 CRDF-005，FDA 為一項試驗的加速批准和完全批准路徑提供了明確的指導。

Finally, we shared the full data package and FDA conclusions with members of our Scientific Advisory Board, which includes the representative from Pfizer. As you know, Pfizer initially invested in Cardiff Oncology two years ago, having seen full development of the clinical, preclinical, and FDA response I just described, they proposed to us that Pfizer Ignite conduct the CRDF-004 first-line clinical trial.

最後，我們與科學顧問委員會成員（其中包括輝瑞公司的代表）分享了完整的資料包和 FDA 結論。如你所知，輝瑞最初於兩年前投資了 Cardiff Oncology，在看到我剛才描述的臨床、臨床前和 FDA 反應的全面發展後，他們向我們建議輝瑞 Ignite 進行 CRDF-004 一線臨床試驗。

Now, every partnership that Pfizer Ignite considers undergoes close internal scrutiny by the Chief Scientific Officer, along with other key scientific team members at Pfizer. They gauge the potential of each project, ensuring collaborations are mutually beneficial and aligned with Pfizer's broader goals.

現在，輝瑞 Ignite 考慮的每項合作關係都經過首席科學長以及輝瑞其他關鍵科學團隊成員的嚴格內部審查。他們評估每個專案的潛力，確保合作互利並符合輝瑞更廣泛的目標。

As we announced in August, our new relationship with Pfizer Ignite allows us to leverage their clinical development horsepower to execute our CRDF-004 clinical trial, while importantly, Cardiff Oncology maintains full economic ownership and control of onvansertib.

正如我們在8 月宣布的那樣，我們與輝瑞Ignite 的新關係使我們能夠利用他們的臨床開發能力來執行我們的CRDF-004 臨床試驗，同時重要的是，卡迪夫腫瘤學保持對onvansertib 的完全經濟所有權和控制權。

This month, November, the first group of our planned 30 clinical trial sites across the United States for CRDF-004 will be open to enrollment. We anticipate enrolling patients shortly thereafter and plan to report preliminary results in the middle of next year.

本月，也就是 11 月，我們計劃在美國設立 30 個 CRDF-004 臨床試驗中心的第一批臨床試驗中心將開放註冊。我們預計不久後將招募患者，並計劃在明年年中報告初步結果。

With this, I'd like to turn now to our earlier-stage programs, which are highlighted on slide 7. In September, we announced signals of efficacy in metastatic pancreatic cancer from two clinical trials, which support our planned path forward in the first line setting.

說到這裡，我現在想談談我們的早期項目，這些項目在幻燈片7 中突出顯示。個項目中規劃的前進道路線路設定。

The first trial CRDF-001, as you know, evaluate onvansertib's efficacy and tolerability in the second line setting of pancreatic ductal adenocarcinoma or metastatic PDAC. From CRDF-001, we reported four of our 21 patients were 19% achieved an objective partial response or PR.

如您所知，第一個試驗 CRDF-001 評估了 onvansertib 在胰腺導管腺癌或轉移性 PDAC 二線治療中的療效和耐受性。根據 CRDF-001，我們報告 21 名患者中有 4 名患者的 19% 達到了客觀部分緩解或 PR。

As of the data cutoff of September 13, 2023, three of the four patients with PRs were still awaiting their confirmatory scan. As of today, November 2, one of these three patients, patient 42, has now shown the further deepening of response at their four-month scan, therefore, representing a second confirmed PR on this trial.

截至 2023 年 9 月 13 日資料截止，四名 PR 患者中的三名仍在等待確認掃描。截至今天，即11 月2 日，這三名患者中的一名（42 號患者）在為期四個月的掃描中顯示出進一步加深的反應，因此，這是該試驗中第二次確認的PR 。

We are still awaiting confirmatory scans for the remaining two patients with an unconfirmed PR who remained on treatment, one for about eight months and another for over nine months. This is much longer than historical median progression survival -- free survival of 3.1 months for second line.

我們仍在等待其餘兩名未確診 PR 的患者進行確認掃描，他們仍在接受治療，其中一名患者接受了大約八個月的治療，另一名患者則接受了九個多月的治療。這比歷史中位惡化存活期（二線治療的無存活期 3.1 個月）長得多。

Overall, for all evaluable patients, we reported a median progression-free survival of five months, which is encouraging since this approaches the benchmark of the first-line median PFS, which is 5.5 months, indicating yet another strong signal of efficacy in this indication.

總體而言，對於所有可評估的患者，我們報告的中位無惡化存活期為5 個月，這是令人鼓舞的，因為這接近一線中位PFS 的基準，即5.5 個月，表明該適應症的另一個強烈的療效訊號。

The second trial in pancreatic cancer is an investigator-initiated biomarker discovery trial in metastatic PDAC, where onvansertib effect on tumors is being evaluated as a single agent. As you recall from our last call, the data we presented in September showed effects on tumor biomarkers with onvansertib monotherapy after only 10 days of treatment.

第二項針對胰臟癌的試驗是一項由研究者發起的轉移性 PDAC 生物標記發現試驗，其中正在評估 onvansertib 作為單一藥物對腫瘤的作用。正如您在我們上次電話會議中所記得的那樣，我們在 9 月提供的數據顯示，僅治療 10 天后，onvansertib 單藥療法就對腫瘤生物標記產生了影響。

Because of these encouraging results that we observed today with onvansertib from both trials, we plan to move to the first line setting through a new investigator-initiated trial to be conducted at the Oregon Health and Science University Knight Cancer Institute. This first-line design enables us to potentially have the greatest opportunity to impact these challenging diseases at an earliest possible stage, when the chances of patients responding to treatment are the highest.

由於我們今天在兩項試驗中觀察到了 onvansertib 的這些令人鼓舞的結果，我們計劃透過在俄勒岡健康與科學大學奈特癌症研究所進行的一項由研究者發起的新試驗進入一線治療。這種第一線設計使我們能夠有最大的機會儘早影響這些具有挑戰性的疾病，此時患者對治療做出反應的機會最高。

Finally, and important, this approach allows us to generate data in a capital-efficient manner. In September, we also presented the first look at data from an investigator-initiated trial in refractory extensive-stage small cell lung cancer. The trial treats patients with onvansertib monotherapy and is being conducted at the University of Pittsburgh Medical Center.

最後，也是重要的是，這種方法使我們能夠以資本效率高的方式產生數據。九月，我們也首次展示了研究者發起的難治性廣泛期小細胞肺癌試驗的數據。該試驗在匹茲堡大學醫學中心進行，並以 onvansertib 單藥療法治療患者。

Of the first seven patients that have been treated as of September 26, 2023, one had a confirmed partial response, three stable disease, and three progressive disease. Seeing a confirmed partial response, which the investigator assessed as a 50% shrinkage of the tumor from treatment with onvansertib monotherapy, provides a clear signal of onvansertib's efficacy in this challenging disease.

截至 2023 年 9 月 26 日，首批接受治療的 7 名患者中，1 名患者已確認部分緩解，3 名患者病情穩定，3 名患者病情進展。看到確認的部分緩解（研究人員評估為使用 onvansertib 單藥治療後腫瘤縮小了 50%），這為 onvansertib 對這種具有挑戰性的疾病的療效提供了明確的信號。

Our current plans are to continue enrollment in this trial, but as we reported in September, our expectation is that a future clinical path forward in small cell lung cancer is most likely to include a combination regimen of onvansertib with second-line standard of care paclitaxel.

我們目前的計劃是繼續參加這項試驗，但正如我們在 9 月報導的那樣，我們的預期是，小細胞肺癌的未來臨床路徑最有可能包括 onvansertib 與二線標準護理紫杉醇的聯合治療方案。

Finally, the investigator-initiated trial in triple negative breast cancer continues to enroll, and we'll provide data from that trial when it becomes available.

最後，研究者發起的三陰性乳癌試驗繼續入組，我們將在該試驗可用時提供該試驗的數據。

Okay, so, so far, I've discussed our ongoing programs and plans, but our third objective to create value for our stakeholders is to investigate new therapeutic indications for onvansertib. For example, the recent discovery of the power of the onvansertib-bev combination indicates that we should aggressively explore, through preclinical models, indications where bev is FDA approved. This includes RAS, wild-type colorectal cancer, lung, liver, kidney, cervical, and ovarian cancer.

好的，到目前為止，我已經討論了我們正在進行的項目和計劃，但我們為利益相關者創造價值的第三個目標是研究 onvansertib 的新治療適應症。例如，最近發現的 onvansertib-bev 組合的功效表明我們應該透過臨床前模型積極探索 bev 獲得 FDA 批准的適應症。這包括 RAS、野生型結直腸癌、肺癌、肝癌、腎癌、子宮頸癌和卵巢癌。

We also know that onvansertib is anti-mitotic, given that PLK1 plays a critical role in cellular mitosis, which is the process through which a cancer cell divides from one cell to two. There is extensive literature suggesting the combination of two anti-mitotic agents could be synergistic, and we have been exploring this combination in preclinical models with dramatic results.

我們也知道 onvansertib 具有抗有絲分裂作用，因為 PLK1 在細胞有絲分裂中發揮關鍵作用，細胞有絲分裂是癌細胞從一個細胞分裂為兩個細胞的過程。有大量文獻顯示兩種抗有絲分裂藥物的組合可能具有協同作用，我們一直在臨床前模型中探索這種組合，並取得了顯著的結果。

To give one example, I will share some new preclinical data for hormone-receptor positive, or HR-positive, breast cancer. These results are shown on slide 8. Breast cancer is the most common form of cancer diagnosed today in the United States, and hormone-receptor, or HR-positive breast cancer represents about 80% of breast cancer cases. In metastatic HR-positive breast cancer, tumor cells can develop resistance to first-line treatment, in part by overexpressing PLK1.

舉一個例子，我將分享一些荷爾蒙受體陽性或 HR 陽性乳癌的新臨床前數據。這些結果顯示在幻燈片 8 中。在轉移性 HR 陽性乳癌中，腫瘤細胞可能會對第一線治療產生抗藥性，部分原因是過度表現 PLK1。

Paclitaxel, an anti-mitotic agent, is a common second-agent therapy, making it an ideal drug to explore in combination with onvansertib in this setting. The data on slide 6 shows how treatment with onvansertib, paclitaxel, and the two agents combined impacts patient-derived xenograft models resistant to first-line treatment with palbociclib in HR-positive breast cancer.

紫杉醇是一種抗有絲分裂藥物，是一種常見的第二藥物治療，使其成為在這種情況下與 onvansertib 聯合探索的理想藥物。第 6 張投影片上的數據顯示了 onvansertib、紫杉醇以及兩種藥物聯合治療如何影響 HR 陽性乳癌患者對 Palbociclib 一線治療產生抗藥性的異種移植模型。

We observed highly significant tumor regression with the combination, with over 50% of the tumors within each model having a complete response to the combination treatment. As we look at this here at Cardiff Oncology, we believe this data supports our broader vision for onvansertib, and we remain committed to a cost-effective approach using preclinical models to validate additional indications and combinations.

我們觀察到合併治療後腫瘤顯著消退，每個模型中超過 50% 的腫瘤對合併治療有完全反應。當我們在卡迪夫腫瘤學看到這一點時，我們相信這些數據支持我們對 onvansertib 的更廣泛願景，並且我們仍然致力於使用臨床前模型來驗證其他適應症和組合的具有成本效益的方法。

Now, I will turn it over to our CFO, Jamie Levine, to go over the financial results for the third quarter, 2023. Jamie?

現在，我將把它交給我們的財務長傑米·萊文 (Jamie Levine)，讓他審查 2023 年第三季的財務表現。

Thank you, Mark. Earlier today, we issued a press release summarizing our financial results for the third quarter, and on slide 9, we share the financial highlights. You can also find additional information in our Form 10-Q for the third quarter filed with the SEC earlier today.

謝謝你，馬克。今天早些時候，我們發布了一份新聞稿，總結了第三季的財務業績，並在投影片 9 上分享了財務亮點。您還可以在今天早些時候向 SEC 提交的第三季 10-Q 表格中找到更多資訊。

Turning to our balance sheet, cash and short-term investments as of September 30, 2023 totaled $81.4 million and net cash used in operating activities for the third quarter of 2023 was approximately $8 million. Based on our current expectations and projections, we believe our cash resources are sufficient to fund operations into 2025.

轉向我們的資產負債表，截至 2023 年 9 月 30 日，現金和短期投資總額為 8,140 萬美元，2023 年第三季經營活動使用的淨現金約為 800 萬美元。根據我們目前的預期和預測，我們相信我們的現金資源足以為 2025 年的營運提供資金。

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. And we close today, you can see from the data we have generated today, we here at Cardiff Oncology truly believe we have a pipeline in a product, and we have found highly capital efficient ways to explore the efficacy signals.

謝謝你，傑米。我們今天結束，您可以從我們今天產生的數據中看到，我們在卡迪夫腫瘤學真正相信我們擁有產品管道，並且我們已經找到了高度資本效率的方法來探索功效訊號。

And with data expected mid-next year from our first-line RAS-mutated metastatic colorectal cancer trial, we have an important near-term catalyst from our lead program. So while we recognize the challenges facing the broader biotech industry, we believe that the strength of our data, the clarity and support we received from our recent FDA meeting, our expansion of our relationship with Pfizer, and our strong financial position clearly show that Cardiff Oncology has the potential to create enormous value for our stakeholders, including our shareholders, and most importantly, the patients we intend to serve.

我們的一線 RAS 突變轉移性結直腸癌試驗預計將於明年中期公佈數據，我們的主導項目將在近期產生重要的催化劑。因此，雖然我們認識到更廣泛的生物技術行業面臨的挑戰，但我們相信，我們的數據強度、我們從最近的FDA 會議獲得的清晰度和支持、我們與輝瑞關係的擴展以及我們強大的財務狀況清楚地表明，卡迪夫腫瘤學有潛力為我們的利害關係人創造巨大的價值，包括我們的股東，最重要的是，我們打算服務的病人。

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) Mark Frahm, TD Cowen.

（操作員說明）Mark Frahm，TD Cowen。

Thanks for taking my questions. Maybe first on the clinical side, at the last update, there were three unconfirmed PDAC responses. Just -- I'm not sure if maybe some of those patients have had a chance to have a confirmatory scan in the last month or two, and if so, were any of them able to confirm?

感謝您回答我的問題。也許首先是在臨床方面，在上次更新時，有三個未經確認的 PDAC 反應。只是——我不確定其中一些患者是否有機會在過去一兩個月內進行確認性掃描，如果有，他們中有人能夠確認嗎？

And then on the finance side, maybe, Jamie, can you just talk through the expense trajectory here as the first-line trial and colorectal starts to ramp up and some of these other ISTs? I know it's not a big lift on your part, but just as some of those start up as well.

然後在財務方面，Jamie，您能否談談隨著一線試驗和結直腸試驗開始增加以及其他一些 IST 的費用軌跡？我知道這對你來說並不是一個很大的提升，但就像其中一些啟動一樣。

Okay. Well, thanks, Mark, for your question. So regarding the CRDF-001 PDAC trial, as you as you stated, we had four PRs that we announced with one being confirmed on our September call. What we're announcing today is the continuing and following these patients. And now we have a second patient who had a deepening response and confirm -- and now has a confirmed PR.

好的。嗯，謝謝馬克的提問。因此，關於 CRDF-001 PDAC 試驗，正如您所說，我們宣布了四項 PR，其中一項在 9 月的電話會議上得到了確認。我們今天宣布的是對這些患者的持續追蹤。現在我們有第二位患者，他的反應加深並得到確認，現在已經確診為 PR。

We have two remaining patients who have not had their next scan, one's been on treatment for eight months and the other's still on treatment for over nine months. And so we planned at some date in the future, we will update that trial, but that's where we stand today.

我們還有兩名患者尚未進行下一次掃描，其中一名已經接受了八個月的治療，另一名患者仍在接受九個多月的治療。因此，我們計劃在未來的某個日期更新該試驗，但這就是我們今天的立場。

And I will now turn it to Jamie to -- unless, Mark, there's any more clarity you need on that.

我現在將把它交給傑米——除非馬克，你需要對此有更多的澄清。

No, no. That's very helpful. Thanks.

不，不。這非常有幫助。謝謝。

So Mark, from an expense trajectory, what we'd say is we have a few trials that are actually going to be winding down. As we've talked about, our plans in mCRC of the Phase 1b/2 trial, it's going to be winding down. We're also shifting away from our second line PDAC trial into the first line IIT that Mark talked about earlier on the call.

馬克，從費用軌跡來看，我們想說的是，我們有一些試驗實際上即將結束。正如我們所討論的，我們的 mCRC 1b/2 期試驗計劃即將結束。我們也將從二線 PDAC 試驗轉向 Mark 早些時候在電話會議中談到的一線 IIT。

So that's happening at the same time as we are ramping up our CRDF-004 trial. So when we look at our overall expenses, our net expenses going forward, we do expense -- we do expect that they're going to increase but not significantly. And I think when you put that together with the $81 million we have at the end of the third quarter, you can see, once again, we burned $8 million this quarter. That's in line with where we've been in the past. And so that is the basis on which we make the statement that our current cash extends into 2025.

因此，這發生在我們加大 CRDF-004 試驗的同時。因此，當我們審視我們的整體支出、未來的淨支出時，我們確實預期它們會增加，但不會大幅增加。我認為，當你將其與第三季末我們擁有的 8,100 萬美元放在一起時，你可以看到，我們本季再次燒掉了 800 萬美元。這與我們過去的情況一致。因此，這就是我們聲明我們目前的現金可以延續到 2025 年的基礎。

Great. Thanks, very helpful.

偉大的。謝謝，非常有幫助。

Sure.

當然。

Joe Catanzaro, Piper Sandler.

喬·卡坦扎羅，派珀·桑德勒。

Hey, everybody. Appreciate you taking my questions. Maybe just a couple from me on the 004 study. I would love to just get your sense around your level of competence around being able to generate these interim data by mid-'24, given dosing hasn't started yet. I'm wondering if you have any internal projections on how quickly you can enroll these planned 90 patients.

嘿，大家。感謝您回答我的問題。也許只是我對 004 研究的一些看法。鑑於劑量尚未開始，我很想了解您在 2024 年中期之前產生這些臨時數據的能力水平。我想知道您是否對如何快速招募這 90 名計劃中的患者有任何內部預測。

And then have you said whether this data readout is triggered by a specific number of patients reaching a specific amount of follow-up? Any details there would be helpful. Thanks.

然後您有沒有說過這個數據讀出是否是由特定數量的患者達到特定的追蹤量觸發的？任何細節都會有幫助。謝謝。

Well, hi, Joe. Yes, we remain very bullish in being able to put out the first interim data or preliminary data from the trial. As you know, we are working very closely with Pfizer Ignite. And Pfizer Ignite, we're very pleased because Pfizer Ignite is actually conducting and implementing and executing the CRDF-004 randomized trial. And so we are going off of where those projections are. And we do believe that we will be able to have data to talk about.

嗯，嗨，喬。是的，我們仍然非常樂觀地能夠發布試驗中的第一個中期數據或初步數據。如您所知，我們正在與輝瑞 Ignite 密切合作。輝瑞 Ignite，我們非常高興，因為輝瑞 Ignite 實際上正在進行、實施和執行 CRDF-004 隨機試驗。因此，我們將偏離這些預測。我們確實相信我們將能夠用數據來討論。

Now, keep in mind, we'll be watching the trial. The trial itself is an open-label trial. So we'll be able to watch the progress of that as we start to enroll patients. But we do remain confident to be able to give information sometime mid next year.

現在，請記住，我們將觀看審判。該試驗本身就是一項開放標籤試驗。因此，當我們開始招募患者時，我們將能夠觀察進展。但我們仍然有信心在明年年中的某個時候提供資訊。

Okay, that's helpful. And then in terms of the actual data readout, my follow-up there was whether that's triggered by something formerly in the protocol as it relates to the number of patients and the amount of follow-up.

好的，這很有幫助。然後就實際數據讀出而言，我的後續行動是這是否是由協議中先前的某些內容觸發的，因為它與患者數量和後續數量有關。

No, it's not. It's really we're watching as it's open label. So it's going to depend on the magnitude of the effect that we do see. So but there is no trigger in the protocol.

不，這不對。我們確實正在關注它，因為它是開放標籤。因此，這將取決於我們確實看到的影響的大小。但協定中沒有觸發器。

Okay, got it. That's very helpful. Thanks for taking my question.

好，知道了。這非常有幫助。感謝您提出我的問題。

Sure, Joe.

當然，喬。

Andy Hsieh, William Blair.

安迪謝，威廉布萊爾。

Great, thanks for taking my questions and congratulations on all the progress. Two questions, if you don't mind. One has to do with, Mark, I believe when you were conducting the Phase 1b/2 study before, there was a strategy employed to minimize the adverse event from switching between bolus 5-FU and infusional 5-FU. I'm just curious if that strategy is also being employed in 004 and 005.

太好了，感謝您提出我的問題並祝賀所有的進展。如果你不介意的話，有兩個問題。其中一個與馬克有關，我相信當您之前進行 1b/2 期研究時，採用了一種策略來最大限度地減少推注 5-FU 和輸注 5-FU 之間切換帶來的不良事件。我只是好奇004和005是否也採取了這個策略。

And then I'd love to hear, obviously with this expanded pipeline development plan, I'd love to hear your thoughts on the IP strategy in terms of market exclusivity. Thank you.

然後，我很想聽聽，顯然，透過這個擴大的管道開發計劃，我很想聽聽您對市場獨佔性方面的智慧財產權策略的想法。謝謝。

Okay. With the first question, Andy, regarding the bolus, we're continuing to have that be an optional for the treatment arms. And -- but in the control arm, the FDA has asked that they consider it to be standard care to have the 5-FU bolus. But we will continue to do what we've done in the Phase 1b/2 trial. Your second question, maybe, Andy, maybe you could repeat that again just so I make sure I answer that correctly.

好的。關於第一個問題，安迪，關於推注，我們將繼續將其作為治療組的可選選項。但在對照組中，FDA 要求他們將 5-FU 推注視為標準治療。但我們將繼續做我們在 1b/2 階段試驗中所做的事情。你的第二個問題，也許，安迪，也許你可以再重複一遍，這樣我就可以確保我的回答是正確的。

Thank you. At this time, I would now like to turn the conference back over to Mark Erlander for closing remarks.

謝謝。現在，我想將會議轉回馬克·埃蘭德（Mark Erlander）進行閉幕致詞。

Well, thank you all for your time, and this concludes our conference call and thank you once again for joining us this afternoon.

好的，感謝大家抽出寶貴的時間，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。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。