Cardiff Oncology at H.C. Wainwright: Onvansertib’s Promising Path

On Tuesday, 09 September 2025, Cardiff Oncology (NASDAQ:CRDF) presented at the H.C. Wainwright 27th Annual Global Investment Conference. The focus was on their lead drug candidate, onvansertib, and its potential in treating first-line RAS mutant metastatic colorectal cancer. While the company showcased promising trial data, they also acknowledged the need for further funding to advance their Phase 3 trial.

Key Takeaways

• Cardiff Oncology’s lead drug, onvansertib, shows promise in treating RAS mutant mCRC.
• Updated trial data indicates potential for deeper tumor shrinkage with onvansertib.
• The company plans to start a Phase 3 trial and expects a regulatory update in Q1 next year.
• Cardiff has enough cash to operate until Q1 2027 but will need more funds for the Phase 3 trial.
• Onvansertib shows synergy with chemotherapy without adding significant toxicity.

Financial Results

• Cardiff Oncology has a cash runway until the first quarter of 2027.
• Additional funding is anticipated for the upcoming Phase 3 trial.

Operational Updates

• The CRDF-004 trial, investigating onvansertib with chemotherapy, enrolled its last patient in April.
• A Phase 3 trial (CRDF-005) is in planning, with updates expected in Q1 next year.
• Ongoing trials are exploring onvansertib in pancreatic and small cell lung cancers.

Future Outlook

• The CRDF-005 trial design will be finalized pending FDA feedback, focusing on overall survival.
• Cardiff is exploring onvansertib for other cancers, including triple-negative breast cancer.
• Commercialization efforts aim to integrate onvansertib with standard chemotherapy.

Q&A Highlights

• A 10-12% improvement in objective response rate (ORR) over standard care is a success marker.
• PAN-RAS inhibitors are not seen as direct competitors due to differing focus and toxicity issues.
• Onvansertib adds no incremental toxicity to standard chemotherapy, a key advantage.

In conclusion, Cardiff Oncology’s strategic focus on onvansertib positions it well for future growth, though funding needs remain. For more details, refer to the full transcript below.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Marc Erlander, CEO, Cardiff Oncology: There you go. Perfect.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Hi, and welcome to our next Fireside Chat. I’m Robert Burns, a Managing Director and Senior Biotech Analyst at HC Wainwright. I’m joined by Marc Erlander, the CEO of Cardiff Oncology. Marc, great to see you.

Marc Erlander, CEO, Cardiff Oncology: Robert, once again, great to talk with you again, and thank you for the invite here at the Wainwright Conference. It’s really a pleasure to talk to all of you here that are here today about what’s going on here at Cardiff Oncology. With that, let’s begin.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: All right. For those who may be unfamiliar with Cardiff Oncology, could you provide a brief overview of the company and its pipeline?

Marc Erlander, CEO, Cardiff Oncology: Absolutely. Let me move the slides over to, you know, Cardiff Oncology based in San Diego. We have an incredible molecule called onvansertib. Onvansertib is a very specific inhibitor of PLK1, which is a serine threonine kinase. PLK1 is integral to the cell cycle. In tumor cells, they overexpress it, and by overexpressing it, they allow tumor cells to have uncontrollable growth and metastasis. There’s been no question over the years that PLK1 is a great target for cancer therapy. The issue has been in previous PLK1 inhibitors, they have been toxic. The reason that I’m talking to you today is that onvansertib is the first in class of a PLK1 inhibitor that is well tolerated with no incremental toxicity when combined with chemotherapy in first-line metastatic colorectal cancer. We think that the reason why that is the case is on the right-hand side of that slide.

We show great specificity, 5,000-fold greater specificity to the other PLKs that are in the human genome. Also, in the middle, we have a 24-hour half-life. Previous PLK inhibitors were pan-inhibitors. They had PLK1, 2, and 3, and they also had long half-lives of five days. This is really a transformation as far as PLK inhibition, and that’s why we believe that we’re showing such a good, well-tolerated drug and also seeing great efficacy.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: I know one of the things that differentiates onvansertib is its clinical profile. Why do you think it is, what is the scientific underpinning that we’re seeing? Why is the addition of onvansertib to FOLFIRI really demonstrating a greater efficacy profile in BEV naive patients consistently versus the Avastin experienced patients?

Marc Erlander, CEO, Cardiff Oncology: Yeah, it’s a great question. I think just really to begin that story, it was really our journey in colorectal cancer. As you can see on this slide, we had an unexpected finding. We were in second line. We were combining onvansertib with FOLFIRI and BEV. The unexpected finding was that those patients that came into our trial that had not received bevacizumab or BEV in first line had an incredible response rate, 73%, versus those that were BEV exposed was more in the 20%. This led us to then a preclinical work, which was really identifying a new mechanism of action of onvansertib. That data together is what then led us to going to the FDA. The FDA looked at the data. What came out of that, that was two years ago.

What came out of that meeting was that they recommended that we shift our entire clinical development path to first line, because in first line, all patients are BEV naive. That’s really how we got to first line was through this data that we found in second line and the meeting with the FDA. From there, we then went on to do a data release, and we just had a recent data release on July 29th. I think that that’s part of the answer. I think the other part was the background story of what really was going on. Why were we seeing this interaction with BEV naive patients where we saw this incredible response rate? It came down to one of the hallmarks of cancer, which is hypoxia.

You can see here on the slide, on the left-hand side, a cartoon of a tumor growing, and you can see in the middle, there’s hypoxic conditions, not enough oxygen. Normal cells would die, but tumor cells survive through an adaptive process where they turn on this big new genetic pathway that’s driven by the HIF1α, which is in essence, for those of you that are scientists in the room, that’s a transcriptional factor. It drives a lot of new gene expression. Why am I telling you all of this? Because we know that BEV neutralizes VEGF, which is one of the outputs of this genetic program that’s driven by HIF1α. It allows you to attract new blood vessels. What we didn’t know until we got into the clinical data and then went and did the preclinical was that, in fact, onvansertib shuts down the whole HIF1α pathway.

What we’re seeing here is that, and this was a new finding, what we’re seeing is that onvansertib and BEV are working in concert, in essence, to shut down the angiogenesis. This is important because it was actually, this was all published in the ASCO flagship, JCO, came out in October of last year. Even more importantly, it was a new invention, and we’ve now had two new issued patents for patient selection in colorectal cancer, basically patients who are BEV naive and onvansertib naive. That was very exciting because that’s extending the IP runway out to 2043 in colorectal cancer. I’ve given you a long answer, Robert, but you knew that was coming.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: I know I did.

Marc Erlander, CEO, Cardiff Oncology: Thank you for your patience as I waded through all those slides.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: It’s okay. You mentioned before that you recently released data or updated data from the CRDF 004 trial. Maybe provide an overview of that data and how it has evolved over time from the initial data cut to now.

Marc Erlander, CEO, Cardiff Oncology: Right. Let me set back and level set and sort of talk a little bit about what’s known in first line for RAS mutant patients. First of all, just before we even start talking about it, for RAS mutant patients in first line metastatic colorectal cancer, the last drug approved was over 20 years ago, and it was Avastin. Patients have been getting FOLFIRI or FOLFOX, which are chemo cocktails with Avastin or BEV, bevacizumab BEV, since 2004. When you look back on those trials, and I’m showing you here on the slide, the first one is the approval of BEV. You can see that I’m showing you here that, with all intent to treat patients, the delta of response rate was, at best, 10%. If you look below that, there’s the FOLFOXIRI, which is really a practice-changing trial. In there, the delta was around 11%.

Both those deltas led to stat-sig on PFS, patient outcome, and also led to approval. That gives you the context of what are we talking about here as far as the bar of what are we looking for here if we’re going to add onvansertib on top of the current standard of care. I think that that’s, do you want me to talk about the trial now?

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah, let’s go into the trial now that you’ve laid the groundwork, the background information.

Marc Erlander, CEO, Cardiff Oncology: When we met with the FDA, they wanted us to do, based on Project Optimus, they wanted us to go into first line, like I was telling you earlier. What was that trial really about? That trial was really, you can see in the middle of the slide, was actually six arms of randomization where we were looking at standard of care and then standard of care plus 20 mg, standard of care and 30 mg of onvansertib. Why two different chemos? Because both FOLFOX and FOLFIRI are approved for first line. We wanted to make sure that we looked at both of those combinations. The other thing to keep in mind here is on the left-hand side, it really just tells you the enrollment. It’s really, it’s first line, RAS mutant only. Importantly, unresectable, as well as no prior BEV.

Patients who come into first line are, by definition, and through NCCN guidelines, BEV naive. The other really important thing that I want to point out here is all of this data is central reviewed. It’s basically blinded, independent central review. Let’s keep that in mind. This data goes through that more rigorous process of actually the analysis. With that, let’s talk a little bit about it. This is a busy slide, but I’m going to basically focus on the first three rows of this slide. First of all, before I start, though, keep in mind that this is a snapshot of an ongoing trial. This trial is, the last patient in was in April of this year. Now, no more patients are coming in, but it is an ongoing trial, and this will continue to change.

We tried to give you here a little glimpse into what’s now and what might be coming. The top, you know, basically, first of all, we’re looking at intent to treat population. That’s what the FDA is going to be looking at when we visit them. We’re also one, the FDA wants us to look at confirmed PRs, which means there are confirmed responses, which means that they had a response, and then in a subsequent scan, they showed that that response was still there. What you can see here right away is that in the control arm, we had 30% response rate, and if you go all the way to the right, you had a 19% increase with the highest dose.

The other thing, the second row, which is really important, is we’re showing you a snapshot with what we call a landmark analysis, which a lot of you are familiar with. What we’re saying there is in the first six months, how many patients basically had confirmed PRs? What that means is you have scans every two months. A patient had to have a response either in the first scan or the second scan to be able to be confirmed by the third, which would be six months. What you can see right away is that in the control arm, you only had 22% of patients who had confirmed PRs within the first six months, whereas in the 30 mg, it was more than double. What does that mean?

That means that response rates are happening, the responses are happening more rapidly in the experimental arm, particularly the 30 mg versus the control. This is good news. Faster responses usually mean longer time, a better outcome. The third line row is important because what we do there is we say this is a snapshot of the trial. Let’s look at responses that were confirmed, plus patients who have had a response, but they still have the ability to confirm within the trial. It’s really looking forward. You can see that they’re 43% versus 59%. 43% for a control arm, that’s about, that’s coming in right about where we expected standard of care to come in. The trial is continuing to go. We expect these response rates across all three to go up even a little bit more.

We expect to see even maybe more widening with the 30 mg versus the control. That’s really the high level. I think what I’d like to show, though, I think this is, Robert, is what has really gotten us excited at Cardiff Oncology, is this slide here. This is known as a spiral plot, but what it really is, is it’s looking at every single patient over time. In the Y-axis, what you’re looking at there is the actual tumor shrinkage versus baseline. If it is a teal color, that means that patient had at least a 30% shrinkage. That is an official partial response or 30% or greater, so they turn to a teal color. Gold color means it’s basically stable disease. There are two things that come out of this immediately when you look at this. Number one, the control arm has a different pattern than both experimentals.

The second point that you come out of is that the 30 mg has much even greater, deeper responses than the 20 mg. That is to say, there is a dose effect. What we’re seeing here is that in the standard of care, yes, they do get responses, but look how they level out. That means that they have a more, unfortunately for those patients, they may progress much quicker. Whereas you can see in the 30 mg, we have patients that are still going down as far as the tumor shrinkage. On top of that, what we do see in the experimental arms, which you don’t see in the control, is we see already in this data here, seven patients that had their targeted lesions that were being measured disappear 100%. This is really exciting for us.

We think that, and we have some of the PIs that have had these patients, I’ve been working with our Chief Medical Officer here, Roger Sadu, who happens to be in the front row. Wave to him. If you have any real questions, ask him, not me. I was going to say that he’s already been talking to some of the PIs. They’re very excited about their patients. I think I’ve gone on and up.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: I think you have. You know, the spiral plot, at least from my perspective, it’s really telling about the story of onvansertib and how it adds to the depth of tumor response here. A more high-level question maybe, because I know that you’re giving potentially two different chemotherapy regimens in combination with onvansertib. Are you seeing any differential efficacy profile between the FOLFOX plus onvansertib versus the FOLFIRI plus onvansertib?

Marc Erlander, CEO, Cardiff Oncology: I mean, so far, no, we’re seeing that additive or increased response with onvansertib in both chemo backbones. Obviously, we’re going to have to see how that goes. We’ve got, this is a snapshot. There’s more to come. We’ll have to, we will be continuing to evaluate that. That’s why we did that in this phase II, what we call proof of concept trial in first line. We knew we had two different chemo backbones, and we wanted to know that before we went into the registrational trial for approval of what that looked like. So far, we’re seeing increased activity in both backbones.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Okay. When you laid the groundwork for the historical, what we see within the frontline setting of colorectal cancer, I think that investors should then be able to extrapolate what you might define as success in the CRDF 005 trial, which is going to be your phase III trial for this agent. Would it be correct to assume a 10 to 12% or delta is what you define as success? How are you designing that trial?

Marc Erlander, CEO, Cardiff Oncology: I mean, I think number one is that would be the low end of that. I mean, that’s really what we’re seeing as the bar is that 10% to 12% delta in ORR. I think that as far as the design goes, we are going to be giving an update, a regulatory update, as well as an update on this trial in Q1 of next year. At that point, we’ll have a lot more information about the trial design because I don’t want to come out and say something now, and then when we meet with the FDA in several months, we basically have to retract that, obviously. What I’m telling you is that we will have an update on this. Roger, our CMO here, has been working very hard and has come up with a trial design.

Until we get the nod from the FDA, we really are not going to be talking about it at this point.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Okay. One of the things that I find interesting was one of the guidance documents that the FDA recently released on overall survival and how they’re really pushing for it to be one of the primary endpoints, at least within certain tumor types. It seems to me that it’s really more for the tumors where you generally don’t have a prolonged overall survival. Would colorectal cancer be one of those types where they’re really going to push for an OS? Just your thoughts on that.

Marc Erlander, CEO, Cardiff Oncology: We don’t think so. We think that, you know, clearly, and from looking at the guidance and talking with Roger, our CMO, about it, our feeling is that we just, it has to just be a little bit more formal looking at OS. What I’m showing you here is what came out of our meeting two years ago with the FDA. This was all in play. This guidance was even in play during that time. What they’re really looking for is on the bottom there, you can see is really the lack of detriment on overall survival. We feel that if we just formalize that, maybe we have a little bit of alpha spend on that, that that will be fine. You know, because when you think about it, we are in first line, median OS for these patients is two years. It’s not a short situation.

I think that the FDA is more focused on those indications and those lines of therapy where you’re seeing very short OS, less than a year.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah, no, that makes sense. You know, one of the things that has always fascinated me about onvansertib is you’re not isolating one type of KRAS mutation or NRAS mutation. You’re going across the spectrum here. Talk to me a little bit about the breakdown of KRAS mutations across colorectal cancer. Obviously, a lot of, there’s been a lot of investor interest in these PAN-RAS, PAN-KRAS agents. How do you see those, you know, do you even view them as competitive threats, considering the line of therapy that you’re in currently?

Marc Erlander, CEO, Cardiff Oncology: Right. Yeah, we don’t see them as competitive as we sit here today. I think everybody knows that there are G12C inhibitors that are approved in second-line colorectal cancer. As I show on the left-hand side of this slide, it’s a very small sliver of metastatic colorectal cancer, 4%. You might say, what about RevMed and the G12X and the PANRAS inhibitor programs? Based on their company calls, their data is really in pancreatic cancer. Their focus in colorectal cancer has been really more to combine their G12C inhibitor with their G12X PAN inhibitor to focus on specifically G12C patients. What we’re looking at there is a really small patient population there as well. I’d say that we are in first line.

Keep in mind that in first line, there are a couple of things that are roadblockades for other competitors or to be competitors in the sense that you have to then really, in essence, replace the standard of care, which is either FOLFOX or FOLFIRI, which actually is quite active, 40% to 45% response rate, as you know. What we do differently with onvansertib is because we have synergy with the standard of care, and we are really adding on top of the current standard of care. We’re not replacing it. That also speaks to the commerciality of this product, this drug as well. We’re not replacing standard of care. We’re adding on top of it. I haven’t shown you the slide. I do have it, but is that really showing that we have also very well tolerated. We have no incremental toxicity when we do add on top.

That I think is important. The trial we’re doing right now, 42 sites across the United States, we’ve not had any competitive trials because we’re in RAS mutant. There are trials going on in RAS wild type, but not RAS mutant, which is 50% of the population.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah, no, I think that that’s a particularly salient point that you just made, right? That incremental toxicity that we see with these PANRAS and KRAS specific inhibitors, you know, will they really be able to add on to chemotherapy? We’ve seen some data sets in other indications where, you know, that toxicity sort of precludes them from really pursuing that type of combination in full depth and breadth.

Marc Erlander, CEO, Cardiff Oncology: Yeah, I mean, I think also, you know, if you, we just had at ASCO of this year, one of our investigators at Harvard, they presented data from triple negative breast cancer where they combined onvansertib with current standard of care for triple negative, which is in essence paclitaxel, which is a chemotherapy. What they show there is that it’s very well tolerated. In fact, in the highest dose of onvansertib with paclitaxel, we had a 40% response. We are very excited about that. It’s a different topic. Obviously, our focus is colorectal cancer. That’s where we’re going. It’s really great to see that we have other opportunities in other areas where we think that onvansertib can play.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Yeah, it’s not just triple negative breast cancer. I believe there’s also prostate or was it pancreatic? Which one was it?

Marc Erlander, CEO, Cardiff Oncology: We also have an investigator-initiated trial in first line pancreatic cancer. We’ll see how that goes. We also have an investigator-initiated trial in small cell lung cancer, and we’ve already reported out some really incredible data there. We’re showing that onvansertib as a single agent, as a monotherapy, has activity. You know, that’s something that people have asked. You’re doing a combination in colorectal. What about, does it have single agent activity? Yes, it does. In fact, out of the first seven patients of the basically relapsed small cell lung cancer, a very aggressive disease, as you know, we had a patient that had a confirmed response with greater than 50% tumor shrinkage with onvansertib as a single agent. We’re really excited about that as well. Those are other future indications as we go forward.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: I guess the last question for me is, you know, we know that a data update from the CRDF 004 phase II trial is coming in the first quarter. There’s also going to be a regulatory update coming later this year. What is your cash on hand as of right now, and what sort of operational runway does that provide?

Marc Erlander, CEO, Cardiff Oncology: Right. Bottom line is that we have cash into the first quarter of 2027. Obviously, those of you that are following Cardiff Oncology do know that we are talking about a registrational trial before that. There is an obvious, you know, sort of question there of us, you know, somehow basically raising funds for that trial. Yes, we have runway into 2027. We do, we will expect that we will be raising additional funds for that registrational trial.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: That’s really all the questions I had. Marc, thank you for joining us. I’ll open up the floor to any questions if anyone has any.

Marc Erlander, CEO, Cardiff Oncology: Okay.

Robert Burns, Managing Director and Senior Biotech Analyst, HC Wainwright: Awesome. Thanks, Marc.

Marc Erlander, CEO, Cardiff Oncology: All right. Thank you very much for your attention.

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