Cardiff Oncology, Inc. Q2 FY2024 Earnings Call

Welcome to the Cardiff Oncology Second Quarter 2024 Financial Results and Business Update Conference Call. Please be advised that today's conference is being recorded. I would now like to turn the conference call over to Kiki Patel of Gilmartin Group. Please go ahead.

Thank you, operator. Joining us on the call today from Cardiff Oncology, our Chief Executive Officer, Mark Erlander, and Chief Financial Officer, Jamie Levine. 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. 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. 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 the 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. With that, I turn the call over to Chief Executive Officer, Mark Erlander. Mark?

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 and enroll patients in our CRDF-004 trial in RAS-mutated metastatic colorectal cancer, or mCRC. The interactions we're having with the physicians and other professionals at the trial site reinforce that onvansertib 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 that onvansertib has the potential to shift the treatment paradigm for all RAS-mutated mCRC, not just subgroups. 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 chemotherapy combinations for additional cancer indications. So let's dive in. On today's call, we will cover four topics. First, I will discuss our lead program in mCRC 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. 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. As a reminder, CRDF-004 is our ongoing Phase II trial evaluating onvansertib in combination with the 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 or standard of care alone. 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. We also appreciate the commitment and the clinical efforts of our enthusiastic investigators who have been judiciously screening patients across our active sites. 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. 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. 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. 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. Recall that three of the four drugs that comprise the NALIRIFOX first-line regimen are the same drugs combined with onvansertib in our prior second-line PDAC trial. 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 had not started to enroll patients. We will provide further updates on the onvansertib NALIRIFOX investigator-initiated trial in the coming months. 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. Last month, we published preclinical data on a new indication within ovarian cancer in the peer-reviewed journal Cell Death and Disease, which is part of the portfolio of the Nature journal. Specifically, the data evaluated onvansertib in ovarian cancers that are resistant to PARP inhibitors. 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 in BRCA1-mutated and wild-type ovarian cancer models. In vitro, the combination of onvansertib and olaparib was synergistic in ovarian cancer cell lines and demonstrated inhibition of tumor growth. In vivo, the combination was well tolerated, showed low tumor progression, and prolonged survival in patient-derived xenograft models resistant to olaparib. 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 serous ovarian carcinoma, which could make a significant impact in the treatment landscape for ovarian cancer. 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, which demonstrates onvansertib's ability to effectively resensitize ovarian cancer to treatment. Now, I would like to turn the call over to Jamie to discuss our final agenda item, our second quarter 2024 financial update.

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

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. 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. We believe that such an outcome would create enormous value for our stakeholders and positively impact the large population of patients living with RAS-mutated mCRC. With that, I will now open the call up for questions. Operator?

Please be advised that there are no further questions at this time. I will now turn the conference back over to Mark Erlander for closing remarks.

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?

Thanks, Marc. Enrollment is tracking quite well and is tracking with our guidance of having an initial look at the data later this year. 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 to drive enrollment. I think the other things that really do help, which I mentioned earlier on the call, is that there have been no new drugs for 20 years for these RAS-mutated patients in first-line mCRC. Importantly, there are no competing trials. So to answer your question, yes, we're on track with the guidance of an initial look later this year.

Okay. That's very helpful. And then maybe on the pancreatic trial that you are going to start up. I think NALIRIFOX has 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 of broad standard of care. So I guess why be aggressive in adopting that now for this initial proof of concept for pancreatic versus maybe using some of the older regimens that are also potentially a bit better tolerated than that regimen?

Yes. Really two answers to that question. The first is that the NALIRIFOX regimen includes three of the four chemo agents we've already combined with onvansertib in second-line and have good data from that. So we believe that along with our preclinical work in this area, that's really the first part of the answer to the question. The second is that we are showing really good tolerability of onvansertib in combination with these chemotherapy agents. The only chemotherapy that we haven't combined with is oxaliplatin, which is part of the NALIRIFOX regimen. However, oxaliplatin does not have any overlapping toxicities with onvansertib. Therefore, we do feel confident that we can come in with this more aggressive chemotherapy, combining and adding value because we believe that this is really the type of regimen that shows superiority in efficacy in the first line.

Maybe extend from Marc's question earlier in the call. Just curious about whether you could comment on the level of scientific validation with the change of the investigator-initiated trial in pancreatic cancer. Obviously, I think it's well validated that onvansertib synergy with irinotecan is now included in the regimen, whereas it was not part of the Gem-Abraxane regimen before. I'm curious about your view on that. And then in terms of the potential ovarian cancer entry, there's obviously new therapies for ovarian cancer in the form of antibody-drug conjugates (ADCs). So have you looked at chemotherapy, targeted therapy combinations, and PARP? I am just curious about whether you've done or plan to do any sort of combinatorial work in the ADC field as well.

Thanks, Andy, for both of those questions. To answer your first question, the irinotecan synergy is one of the main reasons we are going with the combination with NALIRIFOX in first line. Additionally, the investigator conducting the new investigator-initiated trial has experience from our second-line pancreatic trial and has been a huge proponent of going into the first line. He knows our drug, is aware of its tolerability, and is very excited about the move to the first line. Regarding your other question about ovarian cancer and ADC combinations, we are currently preclinically looking at ADCs in combination with onvansertib, not only in ovarian but also in several other areas where ADCs have been approved.

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

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

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