Cardiff Oncology, Inc.

Welcome to the Cardiff Oncology fourth quarter and full year 2023 financial results and corporate update conference call. At this time, all participants are in 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 11 on your telephone. You will then 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 Lawrence Watts of the Gilmartin Group. Please go ahead.

Thank you, Operator. Joining us on the call today from the Department of Oncology are Chief Executive Officer, Mark Erlander, Chief Medical Officer, Dr. Farooz Kabinova, 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 on-ventative 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 for the year ended December 31, 2023, filed with the SEC earlier today. Cardiac 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. Slides for today's investor call can be found on the homepage and the events and presentations tab of the Cardiff Oncology website at www.cardiffoncology.com. With that, I will turn the call over to Chief Executive Officer Mark Allender.

Thank you. Thank you, Lawrence. Good afternoon, everyone, and thank you for joining the call. We have some very important new clinical data to share on the call today which we think is highly relevant to our current first-line metastatic colorectal cancer program. As you may be aware, last year we made a highly consequential decision to shift our MCRC program from the second line to the first-line setting. There were three factors that drove our decision. The first was the clinical signal from our second-line MCRC trial. The second was the new mechanism of action we discovered for our advanced retic. And the third was a strong support from the FDA for the first-line clinical development plan. What's new today is that for the first time, we are releasing data from our Ensembl trial, adding powerful support to our first-line strategy. And as we'll discuss, what's different with the Ensembl clinical data is that it's independent, it's randomized, and it's prospective. You'll hear more about each of these attributes today and by the end. I hope you've agreed that ensemble data has substantial support for our first-time program. So let's dive in. Slide two shows the three topics we'll cover on today's call. First, we'll talk briefly about 2023 and what a transformational year it has been for cardiac oncology and for the clinical development of our drug, on to answer tip. Secondly, as I mentioned, We'll share clinical data from our randomized second-line ensemble trial. And then finally, we'll talk about our financial position that we disclosed today in our Form 10-K. On slide four, we show the highlights of the significant announcements we made in 2023. In August, we provided our MCRC clinical update, where we announced the discovery of a novel mechanism of action for our advanced RTIP, which was previously unknown. and the critical role that it plays in the HIP-1-alpha pathway inhibiting vascularization of tumors. The data we presented, showing evidence for complementary mechanisms of action for imbacitib and bevacilumab, which we will refer to as BEV, could explain the strength of our clinical data in NCRC. And after discussing the clinical and underlying mechanism with the FDA in June of last year, we received strong support setting further we announced the pfizer through its pfizer ignite program which means providing cheap clinical execution for the carnet 004 trial at the time we made all these decisions we were already enrolling patients in the ensemble trials in the second line setting so in august we announced we would discontinue the trial to focus our efforts and resources on the larger patient population and the significant unmet need in the first-line setting. In September of last year, we held a second update call to announce state-of-the-art programs outside of MCRC. From our second-line pancreatic cancer trial, we announced four initial partial responses from the 21 patients, and today we can provide an update on those four patients by sharing that three of the four initial responses were confirmed on a subsequent scan. We also announced our decision to shift our pancreatic program to a first-line setting with an investigator-initiated trial combining Onvansertib with standard care gemabraxate. Finally, we announced new data from our refractory extensive stage small lung cancer investigator-initiated trial where we observed a confirmed PR among the first seven patients. Importantly, this is the first clinical data generated using Onvansertib as a single agent. Looking at the range of our announcements in 2023, you can believe that the year was a truly transformational for Cardiff Oncology. Just have this break for a second. I'm sorry, but I am losing my voice. So I'm going to ask my CFO, James, to continue with his remarks on the call. I'll be available for Q&A at the end of the call. Thank you.

Thanks, Mark. On slide five, we transition to our second item on the agenda, the new clinical data we're announcing today. Recall that our MCRC program includes three clinical trials, and we want to very clearly discuss what's significant in each one. The Phase 1b2 trial in KRAS-mutated MCRC generated the initial signal of efficacy on which we based our MCRC clinical development program, and the trial is now complete. Based on the strength of the preliminary data from the single-arm Phase 1b2 trial, we proceeded with our originally designed next step of our clinical development program by implementing the second line ensemble trial, which would provide randomized data comparing on vansertib plus standard of care to standard of care alone. However, as the phase 1b2 data matured, we saw a powerful and unexpected positive signal from the data. We identified a subgroup of patients, specifically those who had not had prior treatment with Bev in the first line setting, that achieved higher response rates than what would have been expected. As we state on slide eight, we discussed our findings, including both the phase 1B2 clinical data and the new mechanism of action I mentioned at the start of the call with the FDA, which led to their strong support for us to discontinue the ensemble trial and shift our clinical program to the first-line setting. CARTF-004 is our randomized first-line RAS-mutated MCRC trial for which we just announced the first patient was dosed, and Pfizer Ignite is providing clinical executions. As you see on slide nine, today we are sharing new clinical data from the CARTF003 Ensembl trial. We had enrolled 23 patients in Ensembl prior to making the decision to discontinue this trial. While we closed the trial to new enrollment, those patients who are already enrolled continued treatment for protocol, and the majority of the patients enrolled remain on the trial today. As you'll see, there are important findings in the Ensembl clinical data that validate our decision to shift to the first line. I'll now turn the call over to Dr. Farooz Kabinavar, our Chief Medical Officer, to review our clinical data. As a reminder, Dr. Kabinavar is a medical oncologist with 35 years of experience who led the colorectal cancer program at UCLA and who was heavily involved in the registrational trials that led to the approval of BEV in metastatic colorectal cancer.

Thank you, Jamie, and thank you, Mark. It's my pleasure to present the new randomized clinical data from a CARDEX-003 ensemble trial On slide 10, you can see the ensemble trial design. This trial enrolled second-line grass-mutated metastatic colorectal cancer patients with unresectable but measurable disease. Patients were randomized across three arms. One was a control arm where patients received standard-of-care chemotherapy consisting of Fulfuri plus Bev. In the two experimental arms, patients received a dose of 1,1-Certiv in each of the first five days following the full 3D plus BEV infusion. One arm included a 20 milligram daily dose of 1,1-sertab. The other arm included a 30 milligram daily dose of 1,1-sertab. The primary endpoint was objective response rate, and the dosing schedule was the same as in our phase 1B2 trial. Looking at the enrollment at the top of slide 11, you can see that at the time the ensemble trial was discontinued, 23 patients had been randomized across the three arms. Importantly, one patient was never treated because the patient withdrew consent and left the trial prior to receiving any therapy. This reduced the treated patient population available for safety to 22 patients only. Also, one additional patient withdrew consent and left the trial before receiving any post-baseline scan, so 21 of the 23 patients were now available for efficacy. Both patients who left the trial were randomized to the control arm, and both were BEV-exposed, so their withdrawal from the trial does not impact any of the conclusions drawn from the data on the following slides. On slide 12, I'd like to define exactly what we mean by BEV-naive and BEV-exposed. In our second line MCRC trials, enrolled patients would have already received first-line therapy that may or may not have included BEV. A Bev-naive patient is simply a patient whose prior therapy did not include Bev. So these patients would have received only full force chemotherapy in their first-line treatment before coming into our second-line trial. In our second-line ensemble trial, seven of our 21 patients evaluable for efficacy were Bev-naive. We referred to the other 14 evaluable patients in our trial as Bev-exposed. meaning that prior first-line therapy included BEV in addition to full FOX chemotherapy. So the critical question we had as we watched the ensemble trial data mature over the past six months is, will the high response rates we saw for BEV-naive patients in our Phase 1 B2 single-arm trial continue to be observed in the ensemble randomized trial? And I'm excited to show you the results of the next slide. Slide 13. is the waterfall plot, which shows each patient's best response to therapy over the course of their treatment. As you can see, the answer to my question, the BEV9 patients receiving on one sedative with Folfiri Plus BEV once again had the most robust response to treatment. Now, allow me to walk you through what this slide is showing. Starting from the top of the slide, you can see that we have segregated the 21 available patients into two groups. So the seven BEV-naive patients are on the left, and the 14 BEV-exposed patients are on the right, which each of these cohorts, within each of these cohorts, we further divide the data into experimental arm patients who received on-one-certed plus standard-of-care Polfury plus BEV, and the control arm patients on Polfury plus BEV without on-one-certed. Looking at the graph, The bars above the midline represent tumor growth, and the bars below the midline represent tumor shrinkage. A teal colored bar represents an objective partial response, meaning the patient had 30% of greater reduction in the tumor size. A light red bar represents progressive disease, which is an increase of more than 20% in the tumor size. And a yellow bar represents stable disease, which is between these two numbers. At the bottom of the slide, you can see the dose of On1 Certib received by each experimental arm patient, either 20 milligrams or 30 milligrams, shown in blue boxes above the patient number. And the first three digits of the patient number is the clinical trial site number. As you scan from left to right on the waterfall plot, you can see that the three patients with the greatest tumor shrinkage observed are Bev-naive patients receiving on one CERDIB plus standard of care. This is highly encouraging and consistent with what we would have expected based on our prior phase 1b2 trial data. On the next few slides, we'll part this waterfall plot into sections and draw additional conclusions. As you call out on slide 14, you can see that for the Bev-naive patients, The only objective responses we observed were in patients that received standard of care plus on one CERDIP. Given this is a randomized trial, it's also important to point out that we did not see any responses in the control arm of BEV-9 patients that received standard of care alone without on one CERDIP. In addition, by looking at the first three digits of each patient number, you can see that each BEV-naive patient was enrolled at a different trial site, so that the BEV-naive finding is not the result of any bias coming out of the single trial site. Specifically, in the BEV-naive patients that did respond, one patient on one side demonstrated a 44% reduction in the tumor site, and the second patient had a 43% reduction. Importantly, both these patients have confirmed partial responses, and we see this partial responses at both 20 milligram and 30 milligram dose of Onvanserdib. A third Vag9 patient who received Onvanserdib had a 20% reduction in the tumor size, which is very close to the 30% threshold to qualify for a partial response. I would like you to keep this patient in your mind as I'll provide more detail in the next few slides. On slide 15, We focus on the 14 patients in the BEV-exposed cohort, and you can see that in both the experimental and control arms, there were no objective responses observed. And certainly, the size of the effect appears to be less than what we see in the BEV-naive cohort. And on slide 16, you can see that the BEV-naive and BEV-exposed control arm patients appear to have very similar responses to the standard of care therapy. On slide 17, we are looking at the spider plots for the BEV-naive patients. You can see that on the left are patients in the experimental arm. The teal lines in the plot allow you to see the trajectory of the two patients with confirmed partial responses. The plot on the right shows the BEV-naive control arm patients who did not receive on one CERDIP. Importantly, the two control arm patients with tumor shrinkage at their two-month scan both subsequently progressed at the four-month scan and left the trial. Now on slide 18, I'd like to provide some context around the patient I mentioned earlier, who had a 27% reduction in the tumor size at the six-month scan. On this six-month scan, a suspicious pneumatocytic lesion was noted in the patient's lung. So the treating physician decided to discontinue on one certum but continued treating the patient with standard of care for Fury Plus Bell. The lung lesion was later confirmed by a biopsy to be a value fewer fungal infection, unrelated to the patient's cancer and not a new tumor lesion. At the patient's 8-month scan, the tumors increased sufficiently for it to be considered progressive disease. But more importantly, during this two-month period, between the six-month and eight-month scan, when the tumor progressed, the patient was not receiving any On1 CERDIP, but was only on Folpuri plus Bev. In summary, on slide 19, I'd like to reiterate the three attributes of the On1 CERDIP, the On1 CERDIP data that Mark and JB mentioned at the start of the call, now that you have seen all the data. The ensemble trial was independent because it's the second clinical trial at a different point in time than our earlier phase one B2 trial, showing once again that BEV-naive patients have a strong response to therapy that includes on one CERDEV with Folfuri and BEV. Second, the ensemble trial was a randomized trial, thereby removing all clinical bias, where we see that BEV-naive patients in the control arm of Folfuri plus BEV without had no objective responses. And finally, the ensemble trial was prospectively designed. The original finding in the phase one B2 trial was from a retrospective look back at the data. However, we had seen the BEV9 signal before enrolling the ensemble trial and had prospectively planned to evaluate the differences in response rates between the BEV9 and BEV exposed patients in a randomized fashion. And importantly, when we look at the safety data that is included in the appendix of this material, we see that ON1-SERDIP when combined with chemotherapy plus bio is well tolerated with no major unexpected toxicity that was observed. On slide 20, I'll conclude my remarks reminding of the new mechanism of action we discovered for ON1-SERDIP and that mark mentioned at the start of the call. This mechanism of action explains why we believe we are seeing this clear efficacy signal in BEV9 patients. As we discussed in detail in August, we believe that the robust responses we are seeing are due to a novel mechanism of action that we have discovered for On1Certib's role in the hypoxia response pathway. It is well known that tumors outgrow their blood supply and become hypoxic. meaning they become starved of oxygen and nutrients. Tumors respond to this hypoxic stress by producing the HIF-1 alpha protein. HIF stands for hypoxia inducible factor 1 alpha protein, which turns on hundreds of genes that allow the tumor to survive in the hypoxic environment. One of those mechanisms involves the tumor secreting vascular endothelial growth factor A, or VEGF-A, to promote the formation of creation of new blood vessels to bring oxygen and nutrients to the cancer cell. As you can see on slide 21, BEV works by neutralizing VEGF-A, inhibiting the creation of new vasculature. But on one third, it plays a role upstream of VEGF by inhibiting HIF-1-alpha directly and thereby blocking all its downstream effects. This shows why on 131 beva complementary in a bev9 setting by deploying two separate hits on the tumor angiogenic pathway and its survival mechanisms. In conclusion, in my 35 years as a medical oncologist, I've never been as excited as I am now to see the kind of efficacy signal we are observing across our clinical trials. Now I'm going to hand this call back over to Jamie to continue on the discussion further. Jamie? Thank you, Peruz.

We'll conclude the call with a few comments about CARTF004. Turning now to slide 23, you can see that colorectal cancer is a major public health issue. It's both a highly prevalent form of cancer and it is challenging to treat, and recently there have been a number of reports that CRC is becoming more common in younger adults, thus increasing our responsibility to develop more effective therapies beyond the current standard of care. And on the right side of the slide, you can see how our decision to move from second line to first line substantially increases the number of metastatic colorectal cancer patients who may benefit from adding Onvansertib to the current standard of care. On slide 24, You can see that the first-line standard of care for RAS-mutated MCRC consists only of chemotherapy with Bev, a regimen that hasn't changed in 20 years. So this large patient population is in need of new therapies directed at all RAS mutations. Slide 25 provides the study design for a CARTF004 trial. Similar to the Ensembl trial, CARTF004 includes MCRC patients whose tumors have a RAS mutation and are unresectable. A key difference for CARDF004 is that all patients are first line and therefore have not previously been exposed to BEV. The trial will randomize 90 patients across three arms. First, a control arm consisting of standard of care with Pulfury BEV or Folfox BEV, and then two experimental arms looking at standard of care chemotherapy plus BEV and a 20 milligram or a 30 milligram daily dose of Onvansertib, the same doses as in the ensemble trial. Our primary endpoint for the trial will be objective response rate, and the secondary endpoints are duration of response and progression-free survival. Let me provide a few additional details about the CARTF004 enrollment. Our clinical operations efforts, together with Pfizer Ignite, are going well with a critical mass of 20 clinical trial sites activated as of today. And as we announced, we've dosed our first patient. Based on the current robust screening activity observed, and our current enrollment projections, we expect to meet our goal of releasing data from the trial in mid-2024, and we anticipate this initial release will include objective response rate data for approximately half the patients we expect to enroll on the trial. On slide 26, I'll cover our third agenda item, our financial position, as of December 31, 2023. As we disclosed today in our Form 10-K filing, we had $74.8 million in cash and investments as of December 31, 2023, and our cash used in operating activities was $7.1 million in Q4-23. Today, we have greater clarity on our expected future expenses, and so we can be more precise about our forecasted cash runway. Specifically, we believe that our current cash resources provide us with cash runway into the third quarter of 2025, which is beyond the expected readout from the Cardiff 004 trial. Finally, on slide 27, we summarize why the ensemble data we released today is so relevant for our first line MCRC strategy and our ongoing Cardiff 004 trial. Ensembl is the second independent and randomized data set reproducing the robust efficacy signal for Onvansertib plus standard of care in Bev-naive patients. And this supports our currently enrolling first-line trial where all patients are Bev-naive. Secondly, no Bev-naive patients in the Ensembl control arm showed an objective response to treatment without Onvansertib, suggesting Onvansertib is critical to the robust responses observed in the experimental arms. And finally, both of the two on vancitive doses appear to be active, which suggests the two experimental arms of the CARDF004 trial could be combined when evaluating the trial data for efficacy. For all these reasons, we continue to believe our shift to the first-line setting is the best strategy for all of our stakeholders, particularly the large number of patients, 48,000 per year in the U.S., with RAS-mutated MCRC that may benefit from a new approach to treating their disease. With that, we'll open the call up for questions. Operator?

Thank you. As a reminder, if you'd like to ask a question, please press star 1-1. If your question hasn't answered and you'd like to remove yourself from the queue, please press star 1-1 again. Our first question comes from Mark Fram with TD Cowan. Your line is open.

Thanks for taking the questions and congrats on the data that you were able to release. First off, obviously, just the first patient today, but any sense for how much data you'll be able to release in the middle of the year from the 004 trial? And then for the data today from Ensembl, any characteristics you can provide on the baseline? Were there any differences in left and right sidedness and things like that that might explain a little bit of the difference in response rate?

I can start. First of all, like we said on the call, we're going to be putting data out when we have approximately about half of the patients enrolled in the trial. And the second thing was regarding the ensemble data. We have looked at that. We haven't seen any differences from the side of this, but we did opposite that here.

Okay, and sorry, just on that update, is that once you've enrolled or that you have mature response data on HAP? That's the question.

We're looking at at least one scan after the baseline. Okay, thanks. That's helpful.

Thank you. Our next question comes from Joseph Catanzaro with Piper Sandler. Your line is open.

Hey, everybody. Thanks for taking the questions and the update. First, on the ensemble data, I'm wondering if you guys performed a PFS analysis. I'm looking at the swimmer's plot, and even sort of considering both BEV-naive and BEV-exposed, it feels like there's a pretty good even maybe merging PFS signal that you're seeing in this randomized data. So I'm wondering if you did that analysis and maybe what it's saying. Thanks, and I have maybe one follow-up.

Thanks, Joe, for that question. We have not looked at it rigorously. We were waiting for a little bit more follow-up for us to look at that since it's a small number of patients. But we agree with you that it looks like there isn't a emerging signal.

Okay, thanks. And then for the frontline trial, is there any safety running on the backbone of FOLFOX? Just trying to get a sense of maybe historically how the neutropenia compares you know, with Fulfox relative to Fulfuri, and then maybe relatedly the expected split between Fulfuri and Fulfox. As a backbone, I'm thinking back to some, you know, earlier preclinical data from a couple years back that, you know, suggested on Vanstertib and Renotecan, you know, there's some cooperativity there. So hopefully that question makes sense.

Yeah. Joe, let me first start by talking about the preclinical data, we actually have shown publicly that we have synergy with both oxaloplatin as well as Avena-Tcan in people modeled preclinically. And we have not seen any toxicity as well. For your questions regarding the full FOX in our first-line trial, I'm going to turn it over to Firuz, our CMO here.

Hi, Joe. So the question about regarding any safety run-in for the full FOX BEV plus on one Saturday balance. Yes, for the first nine patients, after the first nine patients have been dosed, and those patients will be evaluated by the safety review committee. And once it is determined that full FOX plus on one Saturday plus BEV, and there's no additional toxicity beyond what is expected of full-force PEV, then that arm will continue to accrue to its full completion of the full complement of the patients. So yes, there is a safety valve built into this trial. And we don't expect, based on how on one certain partners with other chemotherapy drugs, we don't expect any major toxicity issues. And I'm giving you a lot more detailed information, even though there were two patients with neutropenia that was seen in the ensemble trial. It was at the lower dose, at 20 milligrams, not at the 30. And then these patients, their neutropenia resolved just by holding the treatment or delaying the treatment for seven, in one patient, seven days, and another patient, 10 days. And those patients still continue on treatment without any of those reductions.

Oh, good. Thank you. That's all very helpful. Thanks again for taking my questions.

Thank you. Our next question comes from Andy Tsai with William Blair. Your line is open.

Great. Thanks for taking our questions. Mark, I hope you feel better soon. I just want to dig a little deeper Just want to dig a little deeper into the ensemble top-down results, maybe on two topics. One is on lipid metastases and maybe second on dose response. Maybe I'll go first on the dose response. Maybe, you know, perhaps you can comment on, you know, whether you see some sort of dose response or if both are active and how do you think about, you know, both doses going forward. Specifically on the liver metastases, I think if I did the calculation right, it's about 77% of the patients have some sort of liver metastases. That's kind of on the higher side. Have you looked at the two responders? Do they have liver metastases and You know, I think the emerging data is suggesting that these patients are particularly hard to treat and maybe there's a potential hypothesis on the mechanistic side of the advantage of that's active in this population and a couple of follow ups.

Okay, well, thanks, Andy, for the dose response. If I understood your question correctly, We are seeing similar activity, albeit small data numbers, but we are seeing similar activity between the two doses, the 20-meg and the 30-meg, if that's what you're asking. And so, you know, from that, that's why we're concluding that we can combine those arms together to look at efficacy in the 004 trial. As far as the liver meth, we have not... analyzed that um robustly yet but i would say that um in our phase 1b2 trial we showed that there was no difference uh in the response in bed nagi benadi patients who had a liver mat versus those that didn't um that there was no um no no division of the response there is irrespective of the liberation but um yeah so so andy just building up on what mark just said

uh in the phase one b2 trial we looked at multiple other factors trying to see were there any other uh features uh that would impact these responses that we're seeing in uh bed night patients and to give you a very short answer absolutely no clinical feature appeared to play a role in the significant robust responses that we've seen in in the bed night patients so we looked at Lactality of the tumors, right and left tumors, both responded equally. We looked at patients with liver mets, without liver mets, they all seemed to respond well. We looked at patients who had a gender, did not impact the outcome. So we think at this point, based on what we have seen with the phase 1b2 trial, and that it's the Bev-Naegi, if you will, that plays a significant role in the dramatic synergy that you're seeing between Bev, and online survey plus chemotherapy.

I see. That's very helpful. So maybe moving out of the – sorry, before we move on. So in terms of managing neutropenia for the ongoing 004 study, are you considering doing growth factor prophylaxis for patients?

so uh it's it's the well the three the three things that we normally would use uh hold the dose uh or delay the next dose allow the bone marrow to recover if if it doesn't recover then we use growth factors according to asco guidelines and then subsequently i mean we also have the option of doing dose reduction depending on which which drug is causing is the is the culprit but Again, going back to 1B2 trial and others, we have not found a reason for us to those decrease. So we have all three options that will standard that we would normally use in managing these patients. But at this point, we don't think it's going to be a big issue.

Got it. That's helpful. And then so outside of CRC, I believe small cell lung cancer in the September update was 1PR3, stable disease. Patients, do you have any updates on that cohort, or that's kind of the latest data?

I can say that we don't have any updates. The PI has moved to another academic institution, and so that has somewhat slowed down the accrual in that particular trial.

I see. Great. Thank you so much for taking all of our questions, and congratulations on the progress.

Thank you. Thank you, Andy.

Thank you. There are no further questions at this time. I'd like to turn the call back over to Jamie Levine for closing remarks.

Thank you, operator. This concludes our conference call, and thanks again for joining us this afternoon. Bye-bye.

Thank you for your participation. This does include the program. You may now disconnect. Good day.