CRDF - NASDAQ

Welcome to the Cardiff Oncology First 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 over to Kiki Patel of Gilmartin Group. Please go ahead.

Thank you, operator. Joining us on the call today from Cardiff Oncology are 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 describes in the section titled Risk Factors in our 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 statement 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?

Well, thank you, Kiki, and good afternoon, everyone, and thank you for joining our conference call for the first quarter of 2024 business update. It was less than a year ago that we announced that our clinical development plan for onvansertib was focused on the first-line treatment of RAS-mutated metastatic colorectal cancer or mCRC. The data we shared last August supported this move. And our focus on first-line mCRC addresses a large patient population, almost 50,000 new patients a year in the United States, for whom there have been no new therapies approved in 20 years. In the first quarter of 2024, 3 data sets added to the body of evidence supporting our first line focused strategy. First was the ONSEMBLE data, which served as an independent and randomized data set that replicated the efficacy signal in bev-naive patients observed in our Phase Ib/II trial. Second was our 5 posters presented at the annual meeting of the American Association for Cancer Research or AACR. And finally was the publication of data in the peer-reviewed journal Clinical Cancer Research from the Phase Ib portion of our Phase Ib/II KRAS-mutated mCRC trial. I want to emphasize our conclusion that the collective data released in Q1 strongly supports our finding that adding onvansertib to standard of care, FOLFIRI and bevacizumab, which I will refer to as bev, has significantly -- has significant efficacy in RAS-mutated mCRC patients that are bev-naive, that is, patients that have had no prior treatments with bev. Now during today's call, we have 3 topics to cover. First, I will provide a summary of the promising data we presented last month at AACR. Next, we will discuss our lead program in mCRC and provide updates around our ongoing CRDF-004 trial. And finally, we'll talk about our financial position that we disclosed today in our Form 10-Q. So let's begin. Last month, the American Association for Cancer Research held its 2024 Annual Meeting in San Diego, in which Cardiff Oncology presented a total of 5 posters, all of which are available on our website. One poster describes the design of our ongoing CRDF-004 trial. A second poster presented data that supports our first line strategy in mCRC by providing new translational data from our Phase Ib/II trial in second-line KRAS-mutated CRC. Three additional posters shared promising preclinical data in other cancer indications, including RAS wild-type mCRC, small cell lung cancer and ovarian cancer, demonstrating the broad opportunity we see for onvansertib. I would like to highlight some of the important data we presented in the poster on our lead program in RAS-mutated mCRC. In this poster, we presented both clinical data from the Phase Ib/II trial and subsequent data from preclinical studies that forms the basis of the scientific rationale for our clinical findings. We also demonstrated that bev-naive patients within this trial had a higher objective response rate and a longer progression-free survival. The additional preclinical data disclosed at AACR provides further evidence that onvansertib and bev have their pharmacological effect at 2 different nodes of the hypoxia pathway. We hypothesized that onvansertib and bev work in a synergistic manner, giving a 1-2 punch to the tumor. Our hypothesis was further strengthened by our preclinical in vivo data in 3 KRAS-mutant mCRC xenograft models. Combination treatment with onvansertib plus bev resulted in significant superior antitumor activity compared to monotherapy with either agent. And importantly, the combination treatment also resulted in a greater decrease in tumor vascularization compared to either agent alone. This finding provides rationale for further exploration of the combination of onvansertib and bev in additional indications where bev is FDA approved. Collectively, the clinical and preclinical data presented at AACR in RAS-mutated second-line mCRC provides further validation of our ongoing CRDF-004 trial. We believe onvansertib will have a significant impact in the first-line setting given that all patients are bev-naive. Now let's move on to our additional posters presented at AACR in therapeutic areas outside of our core focus of RAS-mutated mCRC. To date, most of the data we have generated in mCRC has been in RAS-mutated patients, and we are often asked if our therapy could work for patients who do not have a RAS mutation. At AACR, we shared encouraging preclinical data in RAS wild-type mCRC, meaning these models were derived from patients who did not have a RAS mutation. Preclinical study in RAS wild-type mCRC patient-derived xenograft, or PDX, models aimed to assess the efficacy of onvansertib as monotherapy and in combination with the eGFR inhibitor, cetuximab, which is the standard of care for RAS wild-type mCRC patients. We evaluated models that were both sensitive to cetuximab and resistant to cetuximab. In summary, onvansertib displayed robust antitumor activity as a single agent in cetuximab-sensitive and resistant PDX models. As for combination therapy, efficacy was enhanced when onvansertib and cetuximab were combined, compared to monotherapy of either agent alone. In combination, onvansertib and cetuximab induced tumor stasis of regression in 90% or 18 of the 20 PDX models. Overall, we are exceptionally pleased with our RAS wild-type preclinical data presented at AACR as it emphasized that onvansertib have broad spectrum activity in mCRC, independent of RAS mutational setting. This provides sound rationale for us to consider future clinical trials in RAS wild-type mCRC. I now would like to share the data we presented at AACR demonstrating onvansertib's antitumor activity across multiple tumor types outside of mCRC. If you recall, last September, we shared clinical data from our investigator-initiated trial in extensive-stage small cell lung cancer, where onvansertib as a single agent demonstrated a confirmed partial response with 50% shrinkage of patients' tumor among the first 7 patients treated on the trial. While we were impressed by onvansertib's single-agent activity, we believe a combination strategy would be the optimal approach to treating this aggressive disease. At that time, we disclosed that our clinical path forward in small cell lung cancer would be the combination strategy of onvansertib and paclitaxel, which is one of the standards of care for second-line small cell lung cancer. At AACR, we presented preclinical evidence that supports this clinical plan. In vitro, the combination of onvansertib plus paclitaxel synergistically inhibited tumor proliferation in cell lines for small cell lung cancer. In vivo, the combination was well tolerated and highly effective in cisplatin-sensitive and resistant PDX models for small cell lung cancer. These findings support the scientific rationale for a planned investigator-initiated trial combining onvansertib with paclitaxel as a promising treatment strategy for extensive-stage small cell lung cancer patients. Our final poster presented at AACR evaluated the combination of onvansertib plus carboplatin or gemcitabine in high-grade serious ovarian cancer models where both of these agents are standard of care. In vitro, onvansertib was synergistic in combination with carboplatin as well as with gemcitabine in an ovarian cell line. In vivo, both combinations demonstrated antitumor activity in platinum-resistant ovarian cancer PDX models and were well tolerated. Overall, we believe that these data support the potential of onvansertib to improve standard of care treatment for platinum-resistant ovarian cancer patients. At the moment, we are still determining our path forward in this indication. So in summary, the data we presented at AACR this year provided strong scientific rationale for the clinical development of onvansertib across multiple tumor types and various combinations. And our RAS-mutated mCRC data provided further validation of our lead program in our ongoing CRDF-004 clinical trial. Now, turning to our second agenda item. CRDF-004 is our ongoing Phase II trial evaluating first-line patients with RAS-mutated mCRC. Onvansertib is being added to the standard care -- current standard of care, which is either FOLFIRI plus bev or FOLFOX plus bev. We plan to enroll a total of 90 patients, who will be randomized to receive either 20 mgs of onvansertib plus standard of care, 30 mgs of onvansertib plus standard of care, or standard of care alone. We are working closely with our partner, Pfizer Ignite, who is conducting the clinical execution of the trial. And we are highly confident in Pfizer's ability to operationally execute given their track record of success. Currently, we have 24 activated clinical trial sites. In August of 2023, when we decided to move forward with the CRDF-004 trial, we forecasted that we would be able to share initial data from the trial in the Q2, Q3 2024 time frame. As of today, and based on the actual enrollment trends at our activated sites for the past few months, our expectation for the timing of an initial readout is now in the second half of this year, or Q3, Q4. I want to make it clear that this timing for the readout is solely based on the pace of enrollment. We, together with Pfizer Ignite, feel confident in our ongoing site activation and enrollment efforts, and we believe that we have all the resources to meet this timing. We anticipate this initial top line data release will include objective response rate for approximately half of the 90 patients we expect to enroll in the trial. Now I would like to turn the call over to Jamie to discuss our third agenda item, our first quarter 2024 financial update.

Thank you, Mark. Earlier today, we issued a press release summarizing our financial results for the first quarter ending March 31, 2024. You can also find additional information in our Form 10-Q for the first quarter filed with the SEC earlier today. Turning to our balance sheet. Cash and short-term investments as of March 31, 2024 totaled $67.2 million. And our cash used in operating activities was $7.7 million in Q1 2024. We believe that our current cash resources provide us with cash runway into the third quarter of 2025, which is well beyond the updated timing for the initial readout from the CRDF-004 trial Mark just discussed. With that, I'll turn the call back over to Mark.

Thank you, Jamie. Let me close the call by emphasizing our conviction in our clinical development strategy to add onvansertib to the standard of care in first-line RAS-mutated mCRC. We followed the data that was available at the time, and with the ONSEMBLE clinical data and the AACR data announced this quarter, our confidence continues to grow. And that brings us to where we are today, our ongoing CRDF-004 trial for the treatment of first-line RAS-mutated mCRC. Overall, we believe that the initial data readout of CRDF-004 has the potential to be an important value inflection point for Cardiff Oncology and for the nearly 50,000 patients diagnosed with RAS-mutated mCRC each year. We look forward to sharing an update on the trial later this year. With that, I will now open the call up for questions. Operator?

[Operator Instructions] Our first question comes from Marc Frahm with TD Cowen.

Maybe just to start off on the tweak to guidance on when the interim data might become available. Can you just maybe clarify how much of the small pushout was really kind of the enrollment pace once sites are open versus maybe just some delays getting the sites up and running as quickly as you'd hoped?

Well, yes, let me just -- thanks, Marc, for the question. And let me just step back for a minute and just talk about the CRDF-004 trial. Over the last month or so, Dr. Fairooz Kabbinavar, our Chief Medical Officer, and I have been going across the country and visiting with the principal investigators that are participating in our trial. And Fairooz has actually been taking them through the previous data of the Phase Ib/II and the ONSEMBLE data. And what I would say to you, universally, is that there is a high amount of enthusiasm with all of the principal investigators we have met. And the reason for that is not only because of the actual data that they're seeing building up to the trial that they are participating in now, but also that the onvansertib does provide a novel new option for first-line -- in the first-line setting where, as you know, there have been no new therapies for 20 years. Also, one of the key things that makes them enthusiastic is the actual design of the trial, because we are adding onvansertib, we're building it on to current standard of care and not replacing standard of care. And finally, also, there are no competing trials for a first-line RAS-mutated mCRC. So as I was saying earlier in the call, when we started -- when we made the decision in the summer of '23 to basically start CRDF-004, that's when we then announced in August of '23, prior to the trial starting, the forecast to share data in the Q2, Q3 time frame of 2024. Now that we've got several months of the enrollment and the pace of enrollment, we are able to now make a more accurate projection of the data share, and that is more in the Q3, Q4. And so -- and I think one thing, last thing I would say, Marc, is that -- why are we so confident of this timing? That's really because we are leveraging Pfizer's resources, Pfizer Ignite's resources, their techniques and their capabilities in multiple areas around the execution of this trial. And we are very confident of their ability to execute.

All right. Great. That's helpful. And then maybe just as we get to that data, can you kind of review some of the scenario planning that you and the team are kind of going through in terms of the data? I know it's not a formal statistical analysis there, but is there a scenario where it could get shut down either more kind of from a futility perspective or also, on the other end of the spectrum, make you want to kind of accelerate plans to open up 005 even faster and not have to wait for all 90 patients?

Yes. I mean I think right now, of course, what we're saying is that we will be looking to share initial data in the Q3, Q4 time frame. And we should have approximately half the patients of the trial approximately that -- with at least 1 post-baseline scan. I mean one thing I would say about that timing, it's a good -- it's a great question, Marc, is that the 004, from the FDA's point of view, is really a dose confirmation trial of Project Optimus. And so the faster we can get to the FDA with a dose, of course, the better off we are and better off we are as far as our time lines of going into our registrational trial.

Our next question comes from the line of Joe Catanzaro with Piper Sandler.

Maybe first one, with the slight push in the initial readout from 004, I'm wondering if there's a possibility of maybe seeing another cut of the ONSEMBLE cohort before them just -- before then, just getting longer follow-up and a better sense of the durability of responses and how that's shaking out between the arms of the trial, the bev-naive, bev-experienced. So any thoughts there would be helpful. And I might have a follow-up.

Yes. Thanks, Joe, for the question. I mean as we sit here today, we did announce the data on February 29 for the ONSEMBLE trial. And we felt that that was a very robust data set that propelled us with even greater confidence into our 004. As we sit here now, we don't have plans to have a continued follow-up of the ONSEMBLE data.

Okay. And then maybe my follow-up is on the preclinical work at AACR on the RAS wild-type CRC scenario setting. I recall years back, the synthetic lethality, the idea of PLK1 inhibition in the context of mutant RAS. It seems like you're sort of thinking outside of that, and you mentioned potentially exploring it. Maybe you could just elaborate whether there's opportunity to explore that clinically and think about that population of patients within the context of a potential future pivotal frontline trial.

Yes. Great question, Joe. I'd say, first of all, the -- when you look at RAS wild-type and RAS-mutant tumors in colorectal, those are very different beasts, very different animals in the sense of the biology. And so as you know, we did -- we have shown synthetic lethality in the RAS mutant background. In RAS wild-type, I think it's a different biology, and I think that we are seeing a very interesting finding where we are combining with cetuximab. And so I think as we sit here today, we are evaluating what kind of trial design that would be in the wild-type setting. But we have not made any move yet in that area. Our focus as we sit here today continues to be 004 and getting the data toward the registrational trial.

Our next question comes from Andy Hsieh with William Blair.

Great. A couple of quick ones from us, if you don't mind. So in terms of clinical sites, I believe, Mark, you said 24 sites right now. I believe it was 20 before. And is your end-goal being 30 total by the end of the enrollment completion?

Yes. Thanks, Andy, for that question. So you're right, as of today we have 24. And our goal actually in working with Pfizer Ignite is to activate 35 sites. And we are also looking at some additional sites. But one of the things to keep in mind with this is this is a very dynamic process, in the sense that we continue to evaluate sites. And if the site is not performing, then that site would be replaced with another site. So it's -- the number is not always static. It's really more dynamic as we go through this trial and continue to activate sites.

Okay. That's helpful. And just kind of a follow-up on Mark's question before, you mentioned about Project Optimus, 2 doses in the 004 study. Is it conceivable to bring 2 doses in the pivotal study? Is that a potential scenario? And I guess from an FDA perspective, beyond kind of confirmation of safety, efficacy, what else are they looking at before giving you the okay to start a pivotal study?

Right. Thanks for the question. Just to answer those questions kind of linearly, first off, we don't expect to go into the registrational trial with 2 doses. We plan to have a single dose. And you're right, what the FDA looks for is, really, is there a difference between the efficacy between the 2 doses? And is there a difference in the safety? Both those things we will be continuing to evaluate, not only using our existing data, but also the -- obviously, the 004 data. And like I said to Marc, our goal -- the gate to the registrational trial is this confirmation of dose with the FDA. And so of course, we are very focused on getting that as soon as possible.

Great. And maybe, like, my last question has to do with catalyst events. So Jamie, you talked about Q3 2025 being the cash runway. Perhaps, can you give us maybe a big-picture view? Obviously, 004 study happening in the second half of this year. Any other potential data readouts that you can expect in the first 3 quarters of 2025 that could allow us to better appreciate the clinical activity of onvansertib?

It's a great question. We are not prepared at this point to set dates of some of the investigator-initiated trials that we do actually have ongoing right now. Those could be potentially, but we're just not prepared to set foot out in the public, okay, this is the time that we would announce data on those trials. But clearly, we are looking at those as well as we continue to keep laser-focused on the 004 trial.

Got it. I understand. All right. Thanks so much for answering all of our questions.

Thank you, Andy.

And I will conclude the Q&A session as I see no further questions, and hand them back to Mark Erlander. Thank you.

Thank you, operator. And this concludes our conference call. Thank you once again, everyone, for joining us this afternoon. Have a good day.