Cardiff Oncology at Noble Capital: Promising Results for Onvansertib

On Thursday, 09 October 2025, Cardiff Oncology (NASDAQ:CRDF) presented at the Noble Capital Markets Emerging Growth Virtual Investor Conference, unveiling promising developments for its lead asset, onvansertib. The company highlighted a significant 49% objective response rate in their Phase II trial for RAS-mutated metastatic colorectal cancer, while also addressing future plans and financial stability. However, challenges remain as the company prepares for a Phase III program and navigates competitive landscapes.

Key Takeaways

• Cardiff Oncology reported a 49% objective response rate in its Phase II CARDIFF-004 trial, marking a nearly 20% improvement over the control group.
• The company plans to discuss a Phase III program with the FDA, aiming for accelerated approval.
• Cardiff’s collaboration with Pfizer includes a $15 million investment and strategic support in trial operations.
• Cardiff Oncology holds $71 million in cash, funding operations into early 2027.
• Analysts project peak sales for onvansertib between $2 billion and $3 billion annually.

Financial Results

• As of June 30, 2025, Cardiff Oncology maintains a robust cash position of $71 million.
• This financial reserve is expected to sustain company operations into early 2027.
• Analysts estimate that onvansertib could achieve peak sales ranging from $2 billion to $3 billion per year.

Operational Updates

• The Phase II CARDIFF-004 trial concluded enrollment in April, with a 49% objective response rate observed.
• Cardiff is preparing to launch a Phase III program and will consult with the FDA for potential accelerated approval based on response rates.
• The company has secured two new U.S. patents, extending its colorectal cancer treatment runway to 2043.
• Pfizer Ignite serves as the contract research organization for the trial, with Pfizer holding a 3% stake in Cardiff and participating in strategic discussions.

Future Outlook

• Cardiff Oncology anticipates releasing further data from the CARDIFF-004 trial in the first quarter of 2026, focusing on duration of response and progression-free survival.
• The primary focus remains on first-line RAS-mutated metastatic colorectal cancer due to the promising clinical data.
• The company is also exploring additional indications through investigator-initiated trials in triple-negative breast cancer, small cell lung cancer, and pancreatic cancer.

Q&A Highlights

• Cardiff Oncology’s focus on RAS-mutated MCRC is due to the unique interaction of PLK1 inhibition with RAS-mutated tumor cells.
• The company does not view current competitive trials as a threat in the first-line RAS-mutated MCRC population.
• Future plans include broadening clinical trials to other cancer types, leveraging the promising results seen in MCRC.

For more detailed insights, readers are encouraged to refer to the full transcript of the conference call.

Full transcript - Noble Capital Markets Emerging Growth Virtual Investor Conference:

Robert, Host, Noble: Kabbinavar, the Chief Medical Officer. Please proceed.

Mark, Cardiff Oncology: Thank you, Robert, and thank you to Noble for this opportunity for us to talk to you about what we’re doing here at Cardiff Oncology. We will be making some forward-looking statements. Let me just get us started here before I turn the mic over to Dr. Fairooz Kabbinavar. Cardiff Oncology has its lead asset, a molecule called onvansertib. Onvansertib targets a very well-known cancer therapy target called PLK1. There is no question that PLK1 is a great cancer target. Inhibiting it in the past has been rather difficult simply because the compounds that have been generated to inhibit it have been, quite frankly, toxic. What Cardiff Oncology is offering is onvansertib, which is really the first in its class to be very well tolerated. That enables us to combine it with such things as chemotherapy in our first-line colorectal cancer program.

You can see here on the slide as well that it is a small molecule, and very importantly, it’s oral. Also, on the right-hand side of the slide, we’re showing that there are other PLKs that are evolutionarily related, PLK2 and PLK3. If you see the 10 versus 0.002, that’s the 10 divided by 0.002. That’s a 5,000-fold greater specificity for PLK1 than other PLKs. We believe that is one of the central reasons why this drug, onvansertib, is so well tolerated and really separates it from past PLK inhibitors, which were pan-inhibitors that hit all the PLKs. With that, I think what we’re going to do today is really three things. We’re going to first talk to you about our first-line program, which Dr. Fairooz Kabbinavar will be doing. Very exciting data.

I will come back if we have time to talk a little bit about the incredible and exciting new mechanism of action that we discovered along the way that got us to this first-line trial. Then Jamie Levine will come in and really close the session talking about our coming catalysts in cat. With that, Dr. Fairooz Kabbinavar.

Fairooz Kabbinavar, Chief Medical Officer, Cardiff Oncology: Thank you, Mark. Thank you to Noble for this opportunity. Here we wanted to provide just some background on the disease setting. We’re talking about colorectal cancer, which is the third most common cancer worldwide. Unfortunately, it is actually increasing in incidence, especially in younger people under the age of 50 in the United States. In terms of when patients have metastatic colorectal cancer, the median progression-free survival or PFS time is usually less than 12 months, with a relatively low five-year overall survival time. In particular, for RAS-mutated MCRC, which represents approximately half of the overall opportunity in colorectal cancer, there has been a dearth of innovation for these patients with the only targeted medicine that’s been approved in combination with chemotherapy, that is bevacizumab, which was 20 years ago. We certainly have a very high unmet need situation here.

To talk a little bit about KRAS and RAS mutation, as some of you may know, there are specific inhibitors of specific mutations in KRAS that are approved in colorectal cancer in later lines of treatment, but target a very narrow subset of the overall population. In terms of the RAS mutant subtype, it’s approximately half of the MCRC cases that are seen clinically. Onvansertib has the opportunity to address all of the known RAS mutant MCRC based on its mechanism of action. In terms of the clinical picture, we wanted to provide some background in terms of what have either molecules that have been approved or had positive phase III studies reported in terms of the objective response rates in particular that were associated with clinical benefit in the RAS mutants population.

What we learned is that these are actually been associated with fairly modest improvements in objective response rates, but were strongly associated with improvements in progression-free survival. Just some numbers to keep in mind as we go through our clinical presentation of our data. The CARDIFF-004 trial is a phase II study in the first-line RAS-mutated metastatic colorectal cancer. The primary objective of the study was to show proof of concept in combination with chemotherapy and bevacizumab and to select a dose to move into a registration-enabling phase III studies. The enrollment criteria are listed: previously untreated metastatic colorectal cancer, no prior bevacizumab, and it’s a six-arm trial. Two different chemotherapy backbones, which are commonly used in the U.S.: FOLFIRI bevacizumab and FOLFOX bevacizumab. Two different doses of onvansertib, 20 milligrams and 30 milligrams.

The primary endpoint is objective response rate, with secondary objectives of duration of response and progression-free survival. Importantly, response is assessed by blinded independent central review, and patients’ tumors are scanned every eight weeks. In terms of the key data that we updated in July, we actually are able to show the confirmed objective response rate of 49%, which is a nearly 20% improvement over the control. We think that that is certainly clinically meaningful, especially when you take into account the previously reported positive phase III studies in the first-line RAS-mutated population that we showed on a prior slide. This slide is actually also the waterfall plot, which shows patients’ best response on trial.

You can see compared to the control for the 20 and the 30 milligram arms, we are certainly achieving significantly better depth of response that we know is correlated to improvements in durability like PFS down the road. Another great way of showing what is happening over time is the spider plot. We can see in the control arms on the left that it is active chemotherapy and patients do respond. You can see the change from baseline in terms of the tumor reduction on the y-axis over time. On the x-axis, the patients are responding but tend not to deepen those responses over time. When we have the onvansertib added to standard of care, you can see a very impressive difference in terms of patients having complete responses, even 100% partial responses, and improving the depth of response over time beyond just the RECIST 30% requirement.

We’ve spoken to many different key opinion leaders in the metastatic colorectal cancer space, and they have been the most impressed by the depth of response that we’re seeing. They don’t commonly see this when adding agents to standard of care. We know that it’s strongly associated with improvements in durability with more follow-up. Just to give you a sense of who were our best responding patients, we wanted to know if, for example, these were maybe patients who are likely to respond to chemotherapy anyway, possibly with low burden disease. This actually wasn’t the case. We actually learned that when onvansertib was added either to FOLFOX, bevacizumab, or FOLFIRI bevacizumab, either at the 20 or 30 milligram doses, patients that would be considered difficult to treat had these incredibly deep responses.

Patients with not just target disease in the liver, but with more advanced disease like disease in the peritoneum or even disease spread in distant organs, which we think really speaks to the power of the response that we’re seeing. Some of these patients were actually referred to curative surgery when they originally were considered unresectable. We also reported the progression-free survival time, or PFS. We considered this immature at the time based on the degree of follow-up. We had approximately a median follow-up time of six months for patients at this data cut. We know from the disease history that we would expect the median progression-free survival time to be anywhere from 10 to 12 months in this disease. We did encouragingly see some early signs of separation in the PFS curves, especially for the 30 milligram dose versus the control.

We expect to be more informative with more follow-up, in particular in the Q1 time frame when we get closer to one year of follow-up on all the patients. What we can say is that, as I mentioned before, in the metastatic colorectal cancer literature, it’s been published in some of the top journals, large retrospective analyses in terms of how both early tumor shrinkage, which is defined as at least a 20% reduction in tumor size at the first imaging time point, and also depth of response are strongly associated with improvements in progression-free survival. These analyses were done retrospectively across both bevacizumab and EGFR studies that combined with the similar chemotherapies that we are studying in the 004 trial. Another important characteristic is safety. In a great way, we’re actually seeing very little additive toxicity on top of standard-of-care chemotherapy.

We would expect from the mechanism of action, one of the important adverse events of interest would be hematologic, in particular events of neutropenia. We’ve highlighted those in the chart. Especially in terms of grade III or higher adverse events, we’re not really adding much to the background chemotherapy rates as we observed them in the trial. For example, with neutropenia, we haven’t seen events of febrile neutropenia or discontinuation of onvansertib due to onvansertib-related adverse events. We think this is also important for durability down the road as patient compliance with therapy has been relatively high given how it’s very well tolerated and easy to administer, given it’s an oral medication on top of standard-of-care chemotherapy.

In terms of next steps, as we highlighted, the 004 study really was imagined and designed after interaction with the FDA in 2023, where a novel finding in the second-line metastatic colorectal cancer was observed where patients that had not had prior bevacizumab seemed to have much better response. That has led to the 004 study. We also were able to discuss the key elements of a phase III program that employ an objective response rate for accelerated approval and progression-free survival for full approval. We’re in the process of designing a phase III program or a clinical trial that we plan to discuss with the FDA. With that, I will turn it over to Mark to talk about the rationale for our shift from second line.

Mark, Cardiff Oncology: Thank you, Roger. I think the question really comes down to we have this exciting data that Roger just showed you, these really deep responses, 100% decrease in basically tumors going away. What is the fundamental mechanism of how is this happening? This is actually another journey that we had, actually that we started obviously prior to this 004 first-line data that you just heard. It really started by looking at our understanding of what was the synergy between onvansertib and bevacizumab or BEV or Avastin. You can see here, this is a very typical experiment done preclinically where you put human tumors on a mouse in the hind leg. You measure the growth of that tumor versus what you give that mouse. You can see here that on the curve here on the y-axis, you’re looking at tumor volume. On the x-axis, looking at days.

You can see right away that onvansertib plus BEV gives you much greater control and an inhibition of tumor growth. We just said, that’s very interesting. Let’s take a look at a couple more. We kept seeing the same thing over and over again. That is to say, onvansertib and BEV were somehow working in concert to really inhibit tumor growth. We actually asked the CRO that was doing the study, we said, you know what? Why don’t you do gross dissection at the end of the study and take a photo of the actual tumors and send that to us? They did. What you can see on the top is a very large bloody kind of tumor, kind of gross. If your eyes go to the bottom, you will notice right away that the combination, not only are they a lot smaller, but importantly, they’re really pale.

What that meant to us was there’s something going on that onvansertib was working in concert with BEV to be able to inhibit angiogenesis. That is to say, vasculature coming in and basically feeding the tumor. That was inhibiting that. The next slide really shows you a lot of work that what we did, we then began to understand what was happening was that one of the very well-known hallmarks of cancer and tumor growth is that a tumor grows so fast on the left-hand side there, you can see that it basically becomes hypoxic. It doesn’t have enough oxygen. What does it do? It survives. It adapts. How does it do that? By increasing this whole new genetic program that was really started by this HIF1 alpha transcriptional factor at the top right. That then drives all kinds of new genes to get turned on.

One of them is VEGFA, which as we know is inhibited, neutralized by bevacizumab. VEGF is an angiogenic factor. It detracts vascularization. What about onvansertib? Where does onvansertib fit in? It actually is at the master switch. It actually shuts down the whole program. These two work in concert to, we believe, to be this is the reason we’ve seen the underlying clinical data. The next slide really shows this whole work was actually published last year in ASCO’s flagship journal, JCO. On top of that, because it was a novel finding, we actually have two new U.S. patents issued that actually give us runway in colorectal cancer out to 2043. We’ve been very excited about this. With that, I’m now going to turn it over to Jamie to talk about Catalysts and Cash.

Robert, Host, Noble: Thanks, Mark. Thanks to Noble for allowing us to be here. Before I talk about cash, I thought I would just comment quickly on the relationship that Cardiff Oncology has with Pfizer. Back in 2021, Pfizer made a $15 million investment in the company. They currently hold a little over 3%. Importantly, along with that investment, Pfizer does appoint a member to our Scientific Advisory Board. They also have the right to see data before we make it public. Two days before we make it public, we show the data to Pfizer. We get their feedback.

When Pfizer saw in 2023 the fact that we were moving into this very large patient population of first-line RAS-mutated metastatic colorectal cancer, they proposed to us what you see on the right side of this slide, that Pfizer Ignite act as the contract research organization, effectively acting as the entity that would run the trial. We are paying Pfizer in cash like we would pay any other contractor that would assist us in running the trial. It does show the strategic interest in this molecule that Pfizer has. Importantly, we still retain full ownership and control of onvansertib. Pfizer does not have any rights in that area. We do have a close working relationship around the phase II CARDIFF-004 trial. Finally, looking at our cash and investments as of the end of June 30, 2025, we had $71 million in cash.

We’ve said that that cash funds us into early 2027. We’ve publicly guided that the next update from the 004 trial will be in the first quarter of 2026, so next quarter. The cash that we have on hand funds us into early 2027. We feel we are well funded with a year’s worth of cash after the next significant catalyst to fund the company’s operations and to make good decisions about the clinical path forward for onvansertib. With that, I think we’ll be turning it back to Robert, who can provide some Q&A.

Mark, Cardiff Oncology: Thank you very much. That was a very interesting presentation. One of the first questions is that when you’re adding this PLK1 inhibitor, the polo-like kinase inhibitor, you’re adding another mechanism of action to the standard of care, the FOLFOX and FOLFIRI with bevacizumab combination. Given the wide range of cancers where onvansertib could be effective, how did you choose to focus on the RAS-mutated metastatic colon cancer? Yeah.

I’ll take this one. This is a great question, Robert. You know, it really started at Harvard. One of the professors, Professor Ellerich at Harvard, published over a decade ago that there was a unique interaction between PLK1 inhibition and basically tumor cells from the colon, colorectal cancer tumors, that had a RAS mutation. That is to say, if you had a RAS mutation and you also inhibited PLK1, those cells died much more readily than if it was a RAS wild type background. That really got us started. That and the fact that in colorectal cancer, we knew that irinotecan, which is FOLFIRI, one of the chemos, we knew that that basically had synergy with onvansertib. We really put our first bet really in colorectal cancer because of basically the synthetic methodology between RAS mutation and PLK1 inhibition and the synergy with the chemotherapies already given in colorectal.

That’s where we got started. That’s why our focus is really in this area. Like you asked, there are other places that we are also looking at really going after simply based on some of the mechanisms we just talked to you about and also synergies with other chemotherapies as well. We recently basically presented work at triple-negative breast cancer at the most recent ASCO conference. Very exciting data in triple-negative breast cancer. We also have single-agent activity in small cell lung cancer, another very exciting area that we’re looking at very closely. We also are looking at other GI tumors. We’re also looking at, in essence, the other parts of colorectal cancer, like even wild type, because we think there’s actually something going on there that’s different that we just talked about as far as RAS mutants.

I think the answer to your question is that onvansertib is very well tolerated and is central to many different mechanisms that we can really leverage to going after and killing these tumor cells.

Do you have any plans to start clinical trials or any efficacy data in these indications?

We do. We’ve already started investigator-initiated trials. That was what was reported in triple-negative breast cancer work out of Dana-Farber at Harvard. That was really showing the activity of onvansertib in combination with paclitaxel, another very interesting basic science there of how that combination kills tumor cells. We reported that. We do have other investigator-initiated trials in small cell lung cancer as well as in pancreatic cancer. We’re doing those. We’re watching our resources. To be transparent, our focus is really on the colorectal cancer program in first line since we’re seeing such exciting data there. We are also exploring some of these other areas as investigator-initiated trials.

Great. You mentioned that there’s an update from the trial expected in the first quarter of 2026. Can you tell us what to expect from that update?

Pass that over to Robert.

Fairooz Kabbinavar, Chief Medical Officer, Cardiff Oncology: That’s a great question. As we mentioned, there’s high interest in not only the strong objective response rate data we’re showing in terms of the improvement over control of nearly 20%, but also measures of durability, specifically duration of response and also progression-free survival. I think that this update that we provided was in the July time frame, approximately six months of follow-up. Towards the first quarter, we should get a lot closer to a year of follow-up, which we are hopeful will be more informative with respect to kind of the key measures of durability from the 004 study.

Mark, Cardiff Oncology: OK. We have a question from the floor from the audience asking whether all of the patients on the 30 milligram dose have completed their six-month scans, and if there’s any new data available for the cohort or any update on the ongoing RAS wild type.

Fairooz Kabbinavar, Chief Medical Officer, Cardiff Oncology: In terms of the patient disposition for 004, the study ended enrollment in April. We are expecting to have, as we mentioned in the Q1 time frame, an update not only on the objective response data but also on the duration of response and also for the PFS.

Mark, Cardiff Oncology: Great. OK. Thanks for explaining the relationship that you have with Pfizer. Are there other companies that Pfizer has invested through the Breakthrough Growth Initiative?

Robert, Host, Noble: Sure. Pfizer did make several investments through the Breakthrough Growth Initiative. One of the more notable is Trillium that was subsequently acquired by Pfizer. When you look at most of the analyst reports, we certainly see this as a very significant drug and have a dialogue with a number of the large pharma companies that are interested in GI oncology, which is particularly active in the pancreatic side. There’s not as much available in MCRC. Obviously, that’s where we feel we have very encouraging data.

Mark, Cardiff Oncology: Yeah. Just from the usage of the drugs in the clinical trial and other regimens, yeah, I would expect quite a lot. Could you talk a little bit about the commercial opportunity and the patient population for metastatic colon cancer?

Robert, Host, Noble: Sure. From a commercial opportunity, I guess I would highlight that most of the analysts that publish on onvansertib have a peak sales estimate somewhere between $2 billion and $3 billion a year. A very significant drug. In our current clinical trial, we do not see competitive trials for our patient population. We feel that in first-line RAS-mutated MCRC, we have a pretty open field. Maybe the last comment I would make is, as Robert described, we’re adding onvansertib to the current standard of care. We’re not taking anything away. We are showing that it’s very well tolerated.

In the commercial consulting work that we’re currently performing, the projections that we have are that we could have very fast adoption of onvansertib because if we show significantly improved efficacy, no additional toxicity for a patient population that has had nothing new in 20 years, we do feel like that sets up for a very attractive commercial opportunity potential for onvansertib.

Mark, Cardiff Oncology: Yes, I would agree with you. The fact that it fits in with their current practice for these patients and doesn’t add additional toxicities is a key factor that I would expect the doctors would be looking for and affect the decision to add it. Are there other drugs in development that would compete with onvansertib?

Robert, Host, Noble: Right now, as I said, we’re not seeing competitive trials against our first-line RAS-mutated population. We do see that, as Roger mentioned, there are potentially drugs targeting G12C, but that’s a small sliver of the RAS-mutated population. Right now, those aren’t drugs targeted at the first line. They’re in later lines of therapy. We do feel like we have a fairly open road for the commercial development of our drug onvansertib.

Mark, Cardiff Oncology: Great. OK. Just one other question about the market and acquisitions was that Meris announced that it was going to be acquired by GenMed for $8 billion. Does the Meris program in first-line metastatic colon cancer compete with your program?

Robert, Host, Noble: Thanks for pointing that out. I know that in the past, there has been a little confusion about this. As we said, RAS-mutated is about 50% of the patients in first-line MCRC, and that’s our target. Meris, in their CRC program, is targeting the other 48%. They’re looking at RAS wild type patients. In that positioning, we don’t see Meris as a competitor because they’re only focused on the wild type population.

Mark, Cardiff Oncology: Great. OK. In the interest of time, I’d like to thank you for participating in the conference and for this very informative discussion. Thank you very much.

Thank you.

Fairooz Kabbinavar, Chief Medical Officer, Cardiff Oncology: Thank you.

Robert, Host, Noble: Thank you, Robert.

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