Cardiff Oncology - Q1 2024

Transcript

Operator (participant)

Welcome to the Cardiff Oncology First Quarter 2024 financial results and business update conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone, and you will hear an automated message advising your hand is raised. 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.

Kiki Patel (Head of Investor Relations)

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

Mark Erlander (CEO)

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 would focus 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, three datasets added to the body of evidence supporting our first line focus strategy.

First, was the ONSEMBLE data, which served as an independent and randomized dataset that replicated the efficacy signal in bev-naive patients observed in our phase 1b/2 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 1b portion of our phase 1b/2 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 significant efficacy in RAS mutated mCRC patients that are bev-naive, that is, patients that have had no prior treatment with bev. Now, during today's call, we have three 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. 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 five posters, all of which are available on our website. One poster described 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 1b/2 trial in second-line KRAS-mutated mCRC.

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 1b/2 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, clinical data disclosed at AACR provides further evidence that onvansertib and bev have their pharmacological effect at two different nodes of the hypoxia pathway.

We hypothesized that onvansertib and bev work in a synergistic manner, giving a one-two punch to the tumor. Our hypothesis was further strengthened by our preclinical in vivo data in three 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. Our 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 or 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 emphasizes that onvansertib has broad-spectrum activity in mCRC, independent of RAS mutational status. 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 patient's tumor among the first seven 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 serous 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 care treatments 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. Our RAS-mutated mCRC data provided further validation of our lead program and 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 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 mg of onvansertib plus standard of care, 30 mg 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 then we would be able to share initial data from the trial in the Q2, Q2, Q2, Q3 2024 timeframe. 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 right 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.

James Levine (CFO)

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.

Mark Erlander (CEO)

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 onvansertib clinical data and the AACR data announced this quarter, our confidence continues to grow. 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 (participant)

Thank you so much, and as a reminder, press star one one to get in the queue and wait for your name to be announced. One moment while we compile the Q&A roster. One moment for our first question. It comes from Marc Frahm with TD Cowen. Please proceed.

Marc Frahm (Biotechnology Equity Research Analyst)

Hi. Thanks for taking my questions. Maybe just start off on the tweak to guidance on when the interim data might become available. Can you just maybe clarify, you know, how much of the small push out was really, you know, 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?

Mark Erlander (CEO)

Well, yeah, 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 in the Phase 1b/2 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.

You know, the reason for that is not only because of the actual data that they're seeing building up to the trial that they're participating in now, but also that the onvansertib does provide a novel new option for first line in a 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're adding onvansertib, we're building it onto 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 you know, as I was saying earlier in the, in the call, you know, when we made the decision in the summer of 2023, to basically start CRDF-004, that's when we then announced in August of 2023, prior to the trial starting, the forecast to share data in the Q2, Q3 timeframe 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 I think one thing, last thing I'd say, Mark, is that, you know, 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.

Marc Frahm (Biotechnology Equity Research Analyst)

All right, great. That, 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? You know, I know it's not a formal statistical analysis there, but, you know, is there a scenario where, you know, it, 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, even faster and not have to wait for all 90 patients?

Mark Erlander (CEO)

Yeah, I mean, I think, right now, of course, what we're saying is that we will be looking to share data, initial data, in the Q3, Q4 timeframe. And we should have approximately, you know, half the patients of the trial, approximately that, with at least one post-baseline scan. I mean, one thing I would say about that timing, it's a great question, Mark, is that, you know, the 004, from the FDA's point of view, is really a dose confirmation trial with 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 timelines of going into our registrational trial.

Marc Frahm (Biotechnology Equity Research Analyst)

Okay, thanks.

Operator (participant)

Thank you. One moment for our next question, please. It comes from the line of Joe Catanzaro with Piper Sandler. Please proceed

Joseph Catanzaro (Senior Biotech Equity Analyst)

Hey, everybody, thanks for taking my questions here. Maybe first one, with the slight push in the initial readout from CRDF-004, I'm wondering if there's a possibility of maybe seeing another cut of the onvansertib cohort before then, just getting longer follow-up and better sense of the durability of responses and how that's shaking out between, you know, the arms of the trial, the bev-naive, bev-experienced. So any thoughts there would be helpful, and I might follow up

Mark Erlander (CEO)

Yeah, thanks, Joe, for the question. I mean, as we sit here today, you know, 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. You know, as we sit here now, we don't have plans to have a continued follow-up of the ONSEMBLE data. Yeah.

Joseph Catanzaro (Senior Biotech Equity Analyst)

Okay, thanks. Then maybe my follow-up is on the preclinical work at AACR and the RAS wild type CRC scenario, setting. Mm-hmm.

You know, I recall years back, the synthetic lethality idea of PLK1 inhibition in the context of a 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.

Mark Erlander (CEO)

Yeah, great question, Joe. I'd say, you know, first of all, you know, When you look at RAS wild type and RAS mutant tumors in colorectal, those are very different beasts or very different animals in the sense of the biology. And so, you know, as you know, 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 haven't, you know, 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.

Joseph Catanzaro (Senior Biotech Equity Analyst)

Okay, got it. That's all helpful. Thanks, for taking my questions.

Mark Erlander (CEO)

Oh, absolutely. Thanks, Joe.

Operator (participant)

Thank you. One moment for our next question. It comes from Andy Hsieh with William Blair. Please proceed.

Andy Hsieh (Biotechnology Research Analyst)

Great. Thanks for taking our questions. A couple of quick ones from us, if you don't mind.

Mark Erlander (CEO)

Sure.

Andy Hsieh (Biotechnology Research Analyst)

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?

Mark Erlander (CEO)

Yeah. Thanks, thanks, Andy, for that question. So, you know, as... You're right. As of today, we have 24, and our, 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, with this, is this is a very dynamic process, in the sense that, we continue to evaluate sites, and if a site is not performing, then that site could be replaced with another site. So it's, you know, the number is not always static. It's really more dynamic as we go through this trial and continue to activate sites.

Andy Hsieh (Biotechnology Research Analyst)

Okay, that's helpful. Thank you. And just kind of follow up on Mark's question before, you mentioned about Project Optimus, two doses in the 004 study. Is it conceivable to bring two doses in the pre-pivotal study? Is that a potential scenario? And I guess, you know, 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?

Mark Erlander (CEO)

Right. Thanks for the question. And just to answer those questions kind of linearly, first off, we don't expect to go into the registrational trial with two doses. We plan to have a single dose. And you're right, what the FDA looks for is really there a difference between the efficacy between the two 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 004 data, obviously. And like I said to Mark, our goal, you know, the gate to the registrational trial is this confirmation of dose with the FDA. So of course, we are very focused on getting that as soon as possible.

Andy Hsieh (Biotechnology Research Analyst)

Great. And maybe like my last question has to do with catalyst events. So Jamie, you talked about Q3 2025 being the cash runway. You know, 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 three quarters of 2025 that could allow us to better appreciate the clinical activity of onvansertib?

Mark Erlander (CEO)

Well, 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, put 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 our laser focused on the 004 trial.

Andy Hsieh (Biotechnology Research Analyst)

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

Mark Erlander (CEO)

Thank you, Andy.

Operator (participant)

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

Mark Erlander (CEO)

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

Operator (participant)

Thank you. You may all disconnect.