CRDF - NASDAQ

Welcome to the Cardiff Oncology Fourth Quarter 2024 Financial Results and Business Update Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the conference call over to Kiki Patel of Gilman Group – I am sorry, Gilmartin Group, my reading. 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, 2024. 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. The fourth quarter of 2024 was significant for Cardiff Oncology. On December 10, we released an initial CRDF data from our ongoing CRDF-004 trial in first-line RAS-Mutated Metastatic Colorectal Cancer or mCRC, which we believe was highly encouraging and served as a basis for us to successfully complete a $40 million capital raise. On today's call we address four topics. First, we will briefly review the data we previously released from our lead program in mCRC and then provide an update on CRDF-004 enrollment activity and our registrational plans for onvansertib. Second we'll discuss our intellectual property strategy including the advances made in 2024 and what we expect for 2025. Third, we will share highlights from two preclinical posters we presented at the San Antonio Breast Cancer Symposium in December. And finally we'll discuss our financial position that we disclosed today in our Form 10-K filing. I begin with a review of the previously disclosed data from CRDF-004, which is our ongoing randomized Phase 2 trial in first-line RAS-mutated mCRC evaluating two dose levels of onvansertib combined with current standard of care regimens FOLFIRI or FOLFOX plus bevacizumab or bev versus standard of care alone. In December, we released an initial data set as of November 26, 2024 for the first 30 patients on the trial. Overall, we were pleased with the efficacy signal observed in the trial. First, as of the data cutoff date patients on the 30 mg dose of onvansertib demonstrated a 64% ORR compared to a 33% ORR in the control arm. Second, the 30 mg arm demonstrated deeper tumor responses than the other arms. Specifically, the five deepest tumor regressions seen across the entire trial are in patients receiving the 30 mg dose of onvansertib. Based on the data released, we believe this correlation between the dose of onvansertib and the magnitude of therapeutic effect serves as an initial signal that onvansertib is a biologically active drug candidate for the treatment of mCRC. Finally, I would like to highlight onvansertib's favorable safety profile, which is an important differentiating factor over previous PLK1 inhibitors that have failed in the clinic due to toxicity concerns. Over 380 patients have been dosed with onvansertib across multiple clinical trials to date and the treatment has been well tolerated. For the full CRDF-004 clinical trial results from the initial data cut, please refer to our corporate presentation or the investor call from December 10, posted on our Investor Relations website. We continue to expect to release additional clinical data from the CRDF-004 trial, in the first half of 2025. Next, I will share the current status of our mCRC program, as it pertains to enrollment and our registrational strategy. First, regarding enrollment. In December, we mentioned that we expected to complete enrollment of the 90 evaluable patients planned in the CRDF-004 trial, in early 2025. Today, I can share that this week, we closed the trial to new patients entering screening. We anticipate complete enrollment in the trial, in the next few weeks. Secondly, there is an important FDA approval in Q4 2024 from another company that validates our registrational strategy for the approval of onvansertib in mCRC. Specifically, Pfizer announced the results from its BREAKWATER trial, evaluating its drug encorafenib in first-line mCRC patients, with a BRAF mutation. And to be clear, this is a totally separate patient population from our RAS-mutated mCRC focus. Pfizer's BREAKWATER trial achieved accelerated approval using ORR from a subset of patients, at an interim time point and subsequently achieved a statistically significant and clinically meaningful improvement, in progression-free survival, which is their endpoint for full approval. The regulatory pathway used by Pfizer to pursue accelerating full approval for encorafenib, from a single trial, is the same as our registrational plans agreed with FDA for onvansertib and therefore, reinforces the validity of our strategy. I now move on to our second agenda topic, our intellectual property strategy. In Q4, 2024, we strengthened our intellectual property portfolio for onvansertib, with the issuance of a new patent. The claims cover the method of using onvansertib in combination with bev for the treatment of KRAS-mutated mCRC patients, who have not previously been treated with bev. The patent aligns with the target patient population of our lead mCRC program, and has an expected expiration date of no earlier than 2043. We believe the new patent underscores the groundbreaking nature of our discovery, demonstrating onvansertib's powerful synergy with bev in inhibiting angiogenesis. We continue to explore new opportunities to convert the novel discoveries, we have made regarding the role of PLK1 inhibition into new intellectual property and you could expect to hear more on these efforts, later this year. Now, I will move to the third item of our agenda. In December, we presented two poster presentations at the San Antonio Breast Cancer Symposium, reporting preclinical data from our breast cancer program. The objective of the first poster was to evaluate onvansertib in combination with paclitaxel, as a potential therapeutic strategy for hormone receptor positive or HR-positive breast cancer patients, after progression on endocrine therapy and CDK4/6 inhibitors. In vitro onvansertib demonstrated synergistic activity, with paclitaxel and HR-positive breast cancer cell lines. In vivo, the combination exhibited robust antitumor activity in eight patient-derived xenograft or PDX models resistant to first-line therapies. The second poster evaluated the combination of onvansertib and ENHERTU in drug-resistant HR-positive breast cancer PDX models. The combination of onvansertib plus ENHERTU was well tolerated, overcame ENHERTU resistance and displayed enhanced antitumor activity compared to each monotherapy. Overall, the combination of ENHERTU with onvansertib, represents a promising therapeutic strategy for HR-positive breast cancer patients resistant to first-line therapies. We believe these posters highlight the broad potential of onvansertib, some of which we are currently evaluating through our investigator-initiated trials. For our last agenda item, I will turn the call over to Jamie to talk about our fourth quarter financials. Jamie?

Thank you, Mark. Earlier today, we issued a press release and filed a Form 10-K with the SEC which contain our financial results for the full year ending December 31, 2024. Turning to our balance sheet. Cash and short-term investments as of December 31, 2024 totaled $91.7 million, which includes the net proceeds of the $40 million capital raise, we successfully completed in December with new and existing health care dedicated institutional investors. Our cash used in operating activities was $10.3 million in Q4 2024, which is in line with our typical quarterly cash burn. Based on the cash spend forecasted for our ongoing clinical programs, we believe that our current cash resources provide us with runway into the first quarter of 2027. Finally, I'd like to point out that today we also filed a shelf registration statement on Form S-3, which replaces our previous shelf that was due to expire in April of this year. It has always been our practice to maintain an active shelf registration statement. And for clarity the S-3 we filed today did not involve the issuance of any shares. With that, I'll turn the call back over to Mark.

Thank you Jamie. As you could hear from our remarks today, we are highly encouraged by the efficacy results from the CRDF-004 trial and that we shared in December and we look forward to sharing additional updates from the trial in the first half of this year. With that I would like to take a moment to thank the clinical investigators and importantly, the patients and their families whose participation in the trial is enabling our clinical development efforts. We continue to believe that onvansertib has the potential to change the treatment paradigm for the large number of patients who are diagnosed with RAS-Mutated mCRC each year. With that, I will now open the call up for questions. Operator?

Great. Thank you. At this time, we will conduct the question-and-answer session. [Operator Instructions] Our first question comes from Marc Frahm with TD Cowen. Your line is now open.

Hi. This is Alex [ph] on for Mark. Thanks for taking my question. So can you give us any sense of when exactly in the first half that data update is coming and in what context? And then in that update how many new patients do you expect will become valuable for ORR? And also how mature do you expect those PFS curves to be? Thank you.

Thanks Alex for that question. At this point in time, what our goal is to really to our next update to actually give a more mature and substantive update since the 30-patient update. So at this point that's really what we have planned to do. When it comes to PFS, I think that this is probably too early for PFS within the first half of this year. But that's something that, obviously, we will be updating beyond this first half.

Great. Thank you.

Please standby for the next question. Our next question comes from Joe Catanzaro at Piper Sandler. Your line is now open.

Great. Hey, everybody. Thanks for the update. Thanks for taking my question. Maybe a couple for me here. Can you just speak to your thoughts around when you will make the dose selection decision and whether that will come together with your interactions with the FDA and converting 004 to a potential registrational trial. Just maybe walk through the cadence of those decision points? And then I have a follow-up. Thanks.

Thanks Joe for that question. Really our goal as you know this is the -- CRDF-004 is based on Project Optimus. And our goal really is to get in front of the FDA as soon as possible. And there's really two topics that we will be talking to the FDA about. The first, of course, is the dose which is 30 versus 20. And then the second really is the -- really finalizing the trial design for the registrational trial the 005. So, I mean from our point of view our goal is to get to the FDA as soon as possible. This may or may not be all 90 patients. It could be less. Of course it will depend on looking at that signal with the 30 and 20. So I think that that's really where we are right now. And of course that after that meeting with the FDA that will give us clarity and that will be the gating factor for going into the registrational 005 trial.

Okay, got it. So my follow-up relates to your comments Mark on the BREAKWATER trial of encorafenib. Not terribly familiar with the data off the top of my head here. So, my question is whether the response rate delta that they observed in that trial that supported an accelerated approval aligns with what you've seen thus far in the 004 study?

Yes. Certainly Joe great question. Certainly is consistent. Their ORR was 61% versus 40%. So I think that it's certainly consistent with what we have shown so far with the first 30 patients.

Okay, great. That’s it for me. Thanks for taking my question.

Thank you, Joe. Appreciate it.

Thank you. Our next question comes from Andy Hsieh at William Blair. Your line is now open.

Thanks for the update and taking our questions. Two for me if you don't mind. One is really kind of your evolving thinking in terms of the velocity of tumor size reduction. So basically looking at the December data one of the most obvious observations is really the slope of the control arm is relatively flat over time. And then it deepens as you alluded to Mark on the call for the 20-milligram and 30 milligram. So, I'm curious if that data based on some of the prior CRC experience could de-risk or inform how you think about endpoints approvable endpoints such as PFS and OS. So that's question number one. Question number two has to do with also BREAKWATER. So in that trial the patient number that's required for the accelerated approval was about 100 patients each arm. So, I'm curious if that's kind of that could potentially form the framework of your upcoming discussion with the FDA in the context of the accelerated approval pathway? Thank you.

Thanks Andy for both of those questions. Yes going after that first one clearly there has been data in CRC first line in previous trials showing that earlier responses and deeper responses have a correlation and are associated with greater PFS and OS. So that's something that is known. And I think moving on to the BREAKWATER well certainly their 110 per arm was what they went after for their interim. Certainly we are looking at that. We will be of course talking to the FDA to finalize the specifics around our assumptions and our trial design when we do meet with them. But certainly one point that you make Andy, which is a good one is that what BREAKWATER showed was that fewer patients are needed for the accelerated and of course the full approval. So, thank you for both those questions.

Great. Thank you.

Thank you.

Thank you. Our next question comes from Robert Burns at H.C. Wainwright. Your line is now open.

Hi guys. Thanks for taking my questions and again congrats on the amazing data that you reported late last year. I guess just one follow-up for me. So obviously we know about the CodeBreak 301 trial. And although KRAS G12C is a minor component in colorectal cancer I wanted to get your thoughts as to how you view that agent especially also the pan-RAS agents that are also being developed in the space?

Great. Robert thanks for both those questions. The G12C inhibitors as you mentioned, there is an approval of the Amgen's drug last year but that was really in second line. And that of course is just with G12C, which you know is a very small sliver of the KRAS and RAS-mutated patients. It's about – makes up about 4% of RAS-mutated patients. So I think that from what we look at there it's really – it's not really too – it doesn't really impact what we're doing in first line, since they are in second line and such a small. And we also do have G12C mutations patients with those mutations within our trials. So that's the – with the RevMed, the G12X program, clearly the signal is in the non-small cell as well as the pancreatic or the PDAC. And so we don't see as much activity with their agents for what they've reported in the colorectal but we certainly are keeping an eye on their progress and what they're doing in this space.

Awesome. Thanks for taking my questions and congrats again.

Thank you, Robert.

Thank you. Please stand-by for the next question. The next question comes from Albert Lowe with Craig-Hallum. Your line is now open.

Hi, everyone. Thanks for taking my question. I was just wondering it's great to see the enrollment is going to complete over the next few weeks here. So do you think we'll be able to see all of the 90 patients included in this first half update?

Yes. Albert, thank you for that question. Yes, we are very pleased and excited that we're really within a couple of weeks of finishing the enrollment. We did have 60 patients dosed by – in December, when we reported out the 30 patients which had at least one post-baseline scan. And so we continue to – obviously, we'll be continuing to treat these patients. And our goal really for this first half and reporting out the next update is really to make sure it's a substantive and really more mature update from the trial. So we leave it at that at this point.

Okay. I see. Thank you.

Thanks, Albert.

[Operator Instructions] All right. I'm showing no other questions at this time. So this will conclude the question-and-answer session. I would now like to turn it back to Mark for closing remarks.

Thank you operator, and thank you all again for – everyone here for joining us this afternoon for this call.