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Cardiff Oncology, Inc. isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).

Operator: 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 speakers’ presentation, there will be a question-and-answer session. [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 Gilmartin Group. Please go ahead.

Kiki Patel: 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 limitations, statements related to guidance, results, and the timing of the 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 entitled 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 will turn the call over to Chief Executive Officer, Mark Erlander. Mark?

Mark Erlander: 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 rat 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, 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 data sets added to the body of evidence supporting our first line focus strategy. First was the ONSEMBLE data, which served as an independent and randomized data set that replicated the efficacy signals in bev naïve patients observed in our Phase 1b/2 trial.

Second was our five 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 K-RAS mutated mCRC trial. I want to emphasize our conclusion that the collective data released in Q1 strongly supports our findings 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 naïve, 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. 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 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 1b2 trial and 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 1b2 trial and subsequent data from preclinical studies that forms the basis of the scientific rationale for our clinical findings. We also demonstrated that bev naïve 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 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 mutated 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 naïve. Now let’s move on to our additional posters presented at AACR in therapeutic areas outside of our core focus of RAS mutated mCRC.

Today, 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 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 anti-tumor 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 stages of regression in 90% or 18 of the 20 PDX models. Overall we were 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 mutation set. 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 anti-tumor activity across multiple tumor types outside of mCRC. If you recall, last September, we shared clinical data from our investigator initiated trials 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 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 providing 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 the gemcitabine in an ovarian cell line. In vivo, both combinations demonstrated anti-tumor activity and 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 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 2 trial evaluating first line patients with RAS mutated mCRC. Onvansertib is being added to the 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 care, 30 megs of onvansertib plus standard care or standard 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 trials, 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 enrollment efforts, and we believe that we have all the requisite 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.

Jamie Levine : 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 : Thank you, Jamie. Let me close the call by emphasizing our conviction in our clinical development strategy to add onvansertib to the standard 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?

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Operator: [Operator Instructions]. One moment for our first question. It comes from Mark Frahm with TD Cowen.

Mark Frahm: Maybe just start off on the tweak to guidance on when the interim data might become available. Can you just clarify how much of the small push out was really 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: 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 1b2 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’re participating in now, but also that onvansertib does provide a novel new option 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’re 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 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. I think one thing, last thing I’d say, Mark, 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.

Mark Frahm: Maybe just as we get to that data, can you 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 CRDF-005 even faster and not have to wait for all 90 patients?

Mark Erlander: I think, right now, of course, what we are saying is that we will be looking to share data, initial data in the Q3/Q4 timeframe and we should have approximately half the patients of the trial, approximately that, with at least one post-baseline scan. One thing I would say about that timing – it’s a great question, Mark – is that the CRDF-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 going into our registration trial.

Operator: One moment for our next question, please. And it comes from the line of Joe Catanzaro with Piper Sandler.

Joseph Catanzaro: 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 ONSEMBLE cohort before then just getting longer follow-up and better sense of the durability of responses and how that’s shaking out between the arms of the trial, the bev naïve, bev experienced. So, any thoughts there would be helpful.

Mark Erlander: As we sit here today, we did announce the data on February 29th for the ONSEMBLE trial and we felt that that was a very robust data set that propelled us with even greater confidence into our CRDF-004. As we sit here now, we don’t have plans to have a continued follow-up of the ONSEMBLE data.

Joseph Catanzaro: Maybe my follow-up is on the pre-clinical work at AACR on the RAS wild type CRC scenario/setting. I recall years back the synthetic lethality 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 elaborate whether there’s opportunity to explore that clinically and think about that population of patients within the context of a potential future pivotal front line trial?

Mark Erlander: I’d say, first of all, 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. So 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 have not made any moves yet in that area. Our focus, as we sit here today, continues to be CRDF-004 and getting the data toward the registrational trial.

Operator: One moment for our next question. It comes from Andy Hsieh with William Blair.

Andy Hsieh: 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?

Mark Erlander: 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 a site is not performing, then that site will be replaced with another site. So the number is not always static. It’s really more dynamic as we go through this trial and continue to activate sites.

Andy Hsieh: And just kind of follow up on Mark’s question before. You mentioned about Project Optimus, two doses in the CRDF-004 study. Is it conceivable to bring two 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?

Mark Erlander: Just to answer those questions kind of literally, first off, we don’t expect to go into the registration trial of the two 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 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 obviously the CRDF-004 data. And like I said to Mark, our goal – 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: Maybe like my last question has to do with catalyst events. Jamie, you talked about Q3 2025 being the cash runway. Perhaps can you give us maybe a big picture view? Obviously, CRDF-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?

Jamie Levine: We’re not prepared at this point to set dates on 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 our laser focused on the CRDF-004 trial.

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

Operator: Thank you, operator. And this concludes our conference call. Thank you once again, everyone, for joining us this afternoon. Have a good day. Thank you. You may all disconnect.