Cardiff Oncology at TD Cowen Conference: Onvansertib’s First-Line Shift

On Wednesday, 05 March 2025, Cardiff Oncology (NASDAQ: CRDF) presented at the TD Cowen 45th Annual Healthcare Conference, highlighting a strategic shift in its clinical development path. The focus was on advancing onvansertib, a PLK1 inhibitor, from a second-line to a first-line treatment for RAS-mutated metastatic colorectal cancer. While promising trial data was shared, challenges such as control arm performance were also addressed.

Key Takeaways

• Cardiff Oncology is advancing onvansertib for first-line treatment in RAS-mutated CRC, driven by promising trial data.
• A seamless Phase 3 trial is planned, with FDA feedback expected in the second half of the year.
• The company maintains a strong cash position, with a runway into Q1 2027.

Financial Results

• Cardiff Oncology reported having $92 million in cash at the end of the year.
• The company anticipates a quarterly burn rate of $10 million.
• This financial strategy provides a cash runway extending into Q1 2027.

Operational Updates

• Trial 004 has stopped screening, aiming for 90 evaluable patients, with full enrollment by the end of March.
• Initial data from Phase 2 trial 004 shows potential dose effects, with the 30mg dose outperforming the 20mg dose and control arm.
• Two patients have left the trial for surgery with curative intent.

Future Outlook

• Cardiff Oncology plans to update efficacy and safety data from trial 004 in Q2.
• FDA feedback on the design of trial 005 is expected in the second half of the year.
• The company aims to confirm dosing for the registrational trial and secure FDA sign-off on the trial 005 protocol.

Q&A Highlights

• Concerns about control arm performance were attributed to a low number of patients.
• Preclinical models show synergy with both FOLFOX and FOLFIRI chemotherapy regimens.
• Updates on small cell lung cancer and triple-negative breast cancer trials may be reported later this year.

For more detailed insights, please refer to the full transcript below.

Full transcript - TD Cowen 45th Annual Healthcare Conference:

Mark Fran, TD Cowen Biotech Team, TD Cowen: All right. Welcome back to the forty fifth annual TD Cowen Healthcare Conference. I’m Mark Fran from the TD Cowen Biotech team. Next session, we’re really happy to have the team from Cardiff Oncology. The plan is to have about twenty minutes of presentation, kind of higher level program updates, and then we’ll have about ten minutes of Q and A.

And with that, I’ll turn it over to the CEO, Mark Erlander, to do the presentation.

Mark Erlander, CEO, Cardiff Oncology: Thank you, Mark. I really appreciate it and really great to have an opportunity to speak at your conference here. So let me get started. Today, I want to talk to you about onvansertib and the opportunity that there is in onvansertib here at Cardiff Oncology. So ovansertib is a small molecule.

It’s oral. And as you can see here, it’s really, ovansertib inhibits a serine three named kinase called PLK one. And PLK one is overexpressed in a lot of different tumor types. It’s actually a way that, the tumors actually hijack PLK one because PLK one is involved in the cell cycle. So it allows tumors to have a higher proliferative rate and that sort of thing and also metastasis.

So it’s really, that’s really the origins and why it is considered a great target for cancer therapy. On the right hand side, you can see that, PLK1, we have a high specificity to just PLK1. There are other evolutionarily related PLKs, but we have, as you can see there with the IC50s on the right side, about 5,000 fold greater specificity. So very specific for just PLK1. You know, in the first start of the two first two slides, really just gonna tell tell you the journey, and how this the genesis of this program, and then I’m gonna jump to the most recent data, that we released in December tenth of last year.

Really, this whole program started with an unexpected but exciting finding in a in a second line trial we were doing in, KRAS mutated metastatic colorectal cancer in second line. And what we found there was that there was a patient population that did extremely well, and I’ll talk a little bit more about that later. It was called the BEV naive patients. They were patients who had not received bevosumumab or BEV in first line when they came into our second line trial. Now, because of that finding, we then had to really go into understanding the the background of that from a preclinical point of view, the mechanism.

And then that actually turned out to, we found a new mechanism of action for on vansertib that not only led to the issuance of a, now a patent from USPTO that’s that’s very important for us, but also, that one and two here was actually published in Journal Clinical Oncology, the ASCO flagship journal back in October of last year as well. And just as a sidebar, it’s free, so enjoy. Now once we had that finding, then we went to the FDA, and with the FDA meeting in June of a Type C meeting in June of twenty three, we really ended up pivoting our trial, our whole clinical development plan into first line. And then on top of that, also Pfizer was very interested in being, through their Pfizer IGNITE program to run that first line trial, and that’s the data that I’m gonna talk to you about right now. So then we did put out in initial data on December tenth of last year, and that’s the data that you’re gonna see today.

So really, what was the we had a shift then. Our shift was really from a second line clinical development path to a first line. So talk a little bit about that. Most of you already probably know this, but on left left hand side, colorectal cancer is the fourth most, diagnosed, a cancer in United States. But on the right side, it is the number two killer in The United States.

And the reason I bring that up is because when you look at the patients that we are targeting, which are the RAS mutated patients within first line colorectal cancer, which is about half the population. There really has nothing been nothing new, since ’2, 02/2004 when Avastin or bevacizumab or what people call just called Bev was approved back in 02/2004. So over twenty years have gone by, for these patients with no new therapies. And then also, I think some of you probably know about the fact that there have been some, g twelve c inhibitors, and there was one recently approved in second line, the Amgen case, KRAS G twelve c inhibitor. But as I point out here in the pie chart, it really represents a very small sliver of the RAS mutated tumors in colorectal cancer.

And the reason that’s important is because on Vansertib on the right side really goes after all of the RAS mutations. And the reason for that is that PLK one is downstream of RAS pathway. So we’re able to really affect the entire, all the different mutations of RAS. So with that, let me move into the this trial. So this is the trial that we reported our initial look on in December 10.

Left side, you can see that the enrollment has is first line. It’s all RAS mutated, unresectable, and, of course, no prior bev. And then in the middle of it, you see that we actually have six arms that was randomized to, and within that six, they can really group those into three groups. And the three groups, of course, are standard of care, which is either full FURY BEV or full FOXBEV. Both of those chemo regimens are approved for first line, and that’s why we did that.

And then then you’re looking at the 20 and the 30 MIG on top of that. Importantly, on the bottom of this slide is two things. One, ORR is the primary endpoint. Two, all the data you’re going to see is through blinded independent central review or what we call BICR. This is really important, because we do have 41 sites across The United States where this trial is currently being run.

On the right side, you can see that really what the dosing is. We overlay on vansertib on top as an oral drug on top of the existing standard of care, which is really the chemotherapy plus bev, which is every every fourteen days, two fourteen days equal one cycle. Now the objectives of this trial on right side, were pretty straightforward. First of all, we wanted to look at efficacy because it is a randomized trial. Secondly, and really the point of this trial was through Project Optimus with the FDA was to really confirm a dose, twenty mg or thirty mg.

And then finally, really, of course, looking at safety as well. Now one of the things that we show here is just simply, I’m not going to go into it, but we’re really showing that even though it’s just 30 patients, they’re relatively balanced between the three different major arms, and that’s important because that allows us then to compare between, these these three different groups. Now this is an initial look at the data. This is a standard waterfall plot, where you see that once a tumor shrinks to 30% or greater, it turns to a teal color, which then is an objective response. And you can see here that in the control arm, we had a 33% versus experimental arms.

That’s combining both the twenty mg and the thirty mg together with 57%. One thing so what I’m going to do now in the next two slides is I’m going to parse this data two different ways. I’m going to first ask, is there a difference in the chemo backbones? And then secondly, the more important question is, is there a difference in dose? So first, when we looked at the backbones of the chemotherapy, you can see on the left, these are obviously small numbers of patients.

So what I what I what we have taken from this and the really the what the takeaway from this slide is really that when you add on vansertib on top of either full FURY BEV or full FOXBEV, you are seeing an increase in signal. And so that’s really what we take away from this at this point. And we think that that is good news because that means that potentially in our registrational trial, we’ll be able to have more of an investigator choice as far as the chemo backbone. Now the second way to look at this data is, of course, by dose. And so what you’re seeing here is the control on the left and then twenty and thirty mgs.

And one of the things that we noticed right away at this was that there does appear to be, potentially a dose effect when you see this when you see this data. When you go from a twenty MIG to a thirty MIG, there are a greater number of responses and also they appear deeper. Now a way to really look at this, I think in a better way is with the traditional spider plots. The spider plot, as you can see on the x axis, you’re looking at the cadence of the scan. So, standard of care, we we get, for these patients and the standard of care is a scan every eight weeks or every every two months.

So you can see on the x axis two, four, six, eight corresponding to months, And then you can look at the depth of the change in the tumor size or the targeted lesions by looking at, each one of these lines. And each line here represents a patient. If the line has turned to teal, that means that that patient now has an objective response. What you can see right away with this is that there are deeper and greater number in the, thirty mg versus the twenty mg and the control arm. Another way to look at this is in the actual swimmer, plots where you can see that each lane here is a patient.

I don’t expect you to be looking at this from where you are right now, but if this is on our corporate, as on our website. And what you’ll like about this, I think, is that we actually put in the percent of decrease of the tumor at each scan. So you can see those numbers there that you can maybe barely make out. Those are the actual number versus baseline. So allows you to really look at every single patient here.

One thing I will point out is that two patients have already gone off trial for surgery with the curative intent. So one at the twenty mg and one at the thirty mg. So excited for those patients. We do expect more of that to happen, but already seeing two patients have left the trial because of that. And the other question really is this is the numbers.

I mean, our number thirty three percent is a little lower than what the historical controls are. Historical controls for RAS mutated, is thirty eight to forty four percent. So in the forties, would be appropriate. We are at thirty three percent, which is a little lower, but it’s not too far off from it at this point. And the other, what we also, the characteristics, I won’t go into it, but we’re not seeing anything here that’s unusual.

And then safety slide, very busy slide, but the bottom line here is that we’re not really seeing any increase in neutropenia with onvancertib being added, which is, neutropenia would be an on target toxicity of a PLK inhibitor, and we’re not seeing that, an added amount of neutropenia with, the chemotherapies. Where are we going with this? So this on the left hand side is 004. That is a trial that we’re talking about today. As you know, as I mentioned, we did have a meeting with the FDA, a a type c meeting, where we came out of that, excuse me, was really not only the project optimist for the four, but then also, we agreed with the FDA agreed with us that we would have a seamless one trial, the five for the registration of where ORR and duration of response would be the primary endpoint for the accelerated approval and PFS and OS note showing no detriment would be the primary endpoint for full approval all in one trial.

So, looking at our time, is that thirteen minutes? Is that like the for the whole thirty minutes? Yeah. Okay. Let me just hit a little a couple of things here.

You know, one thing that, from this the shift was the we went into a deep dive into the science. It was very exciting what came out of it. As I mentioned, we had this unexpected finding, and we did, that came from the second line trial. And really the bottom line here was that we didn’t know at the time we were doing the second line trial that we had two different types of patients coming in. There were those that were bev naive and bev exposed.

And in fact, that made a big difference when you looked at the bev naive in the left side, response rates were much higher, seventy three percent versus sixteen percent with the Bev exposed. And also that we saw the median PFS was at fifteen months versus, really around seven to eight. So that really led us to preclinical research. And so we did the obvious experiment. We said, okay, there’s something going on between a a tumor that has not seen bev and has not seen on vancertib.

So we did the obvious experiment, looked and showed that on vancertib plus bev did have an effect that was greater than either agent alone. Well, we decided, okay, let’s do a couple more models and see if we see the same thing. We saw the same thing. In those last two models, we said to the CRO that was doing, we said, look, why don’t you do a gross dissection of their tumors and take a photo of it and send it to us? They did.

And so what you can see here is that in the control, very vascular, your eyes go down to the bottom, and you can see that when you have the ONVANCER to bev together, they’re the most pale tumors, and they’re obviously smaller, but a lot more pale. That was what we call a hint and a clue that what was really going on. And what was really going on, that we all know that tumors on the left side here, that they get hypoxic because they outpace the vascularization of the tumor. And so the way they adapt is they turn on a whole new set of genes through a transcriptional factor called HIF one alpha. HIF one alpha is really a master switch, turns on over 200 genes that increases your your not only your angiogenesis of secretes VEGF, but also survival and proliferation.

Well, we know how BEV works, and that is really well known. But what we didn’t know is that on Vansertib inhibits the inducibility of one alpha. So it’s a one two punch is what we discovered. And this, as I said earlier, was all published in, JCO, and it’s a really a great way to if you wanna know the background story of this whole of this whole program, this article really lays it all out for you. With that, what I’d say is that we do have other programs in PDAC, small cell and triple negative breast cancer ongoing.

These are all investigator initiated trials, and we hope to give updates on those at some point. They’re a little slower because they are investigator initiated and not sponsored. And we also do have, two different types of relationship with the Pfizer. On the left hand side, they did do an equity investment through the breakthrough growth initiative. And then that, like I said earlier, they are really in essence acting as our CRO, and we have a great relationship with them, of them running our current trial.

With that, I will just end with the classic slide on the bottom, how much cash do we have. As of the end of the year, we had over a little over 90 almost $92,000,000 We burn around $10,000,000 a quarter, and we have cash into Q1 of twenty twenty seven. With that, I have I think finished actually really on time. Perfect. That was twenty minutes.

That was blasting through. All right. Thank

Mark Fran, TD Cowen Biotech Team, TD Cowen: you. Thanks for that, Mark. So I have some questions, but obviously anybody in the audience, feel free to raise your hand if you want to ask yours as well. We’ll try to get those answered. Maybe to start off with Mark, in the presentation, you touched on this idea and then one of the push backs I’ve heard on sort of on your data is that control arm potentially having somewhat underperformed expectation.

Are there when you look at baseline factors and stuff, is there any anything that kind of jumps out that maybe explains why it might be at the low end or maybe even slightly below the low end of that expected range?

Mark Erlander, CEO, Cardiff Oncology: Yes. There’s nothing that jumps out at us. I think what we’re talking about here is just, really a low number of patients. And so you do have variability because of that. But I but I think I think that’s what it’s attributed to.

Mark Fran, TD Cowen Biotech Team, TD Cowen: Okay. And then on the differences in, Fulfurian and Fulfox, I mean, again, I know it’s small numbers, but it when you’ve done some of those preclinical experience experiences or any rationale for why this might the combo with Fulfurian might underperform Fulfox, the Fulfox combo a bit?

Mark Erlander, CEO, Cardiff Oncology: Yes. Preclinical in vivo models, we don’t we see a synergy with both the FOLFOX and the FOLFURY, the Arena Tecan and as well as the five FU. So, we don’t have any basis pre clinically to think that we would see a difference clinically. But obviously, we’ve got to work. It’s early days on this trial, so we’ll see how things pan out.

Okay. And then you’ll be updating data later with half, right, from

Mark Fran, TD Cowen Biotech Team, TD Cowen: the trial. I think the other day on your earnings call, you mentioned that enrollment is obviously picked up. Yes. And it’s accelerated as you’ve got this trial going. And you’re up at the 90 now or about to, I guess, if you

Mark Erlander, CEO, Cardiff Oncology: Yes. Screening. But Well, we’ve actually Yeah.

Mark Fran, TD Cowen Biotech Team, TD Cowen: We’ve stopped update that.

Mark Erlander, CEO, Cardiff Oncology: Yeah. We have stopped screening for patients in this trial. The goal of this trial was to have 90 evaluable patients. We have stopped screening, and we project that we will have full enrollment by the end of this month.

Mark Fran, TD Cowen Biotech Team, TD Cowen: And so what’s triggering to make to the next kind of disclosure of efficacy? Is it getting initial scans on all those 90 patients? Is it waiting for confirmatory scans for everyone? Just when what did we follow-up

Mark Erlander, CEO, Cardiff Oncology: to the At a minimum, what we’re looking at is that, as we mentioned in December 10 disclosure, we had 60 patients dosed with only with 30 of them with at least one post baseline scan. So that’s why we had 30 patients in the disclosure as far as data. We’ve noticed so far in the trial that the responses, the PRs that occur, they accrue either in the first scan or the second scan. There’s a there’s one patient that had a third, you know, in in the six month scan, but most of them are two months and four months. So we we think at a bare minimum, we would like to see, at least those 60 patients with at least two scans.

We would we have to we’d like to maybe see a little bit more than that. But that’s at least, we think a bare minimum as far as having another release that would be substantive.

Mark Fran, TD Cowen Biotech Team, TD Cowen: Okay. And you know, I know it won’t it certainly won’t be fully mature, but would you expect to start talking a bit about PFS with that or just or

Mark Erlander, CEO, Cardiff Oncology: I don’t think so. But you know, I mean, I never say never. Right? But I think that, you know, the median PFS for this patient population is nine to ten months in with standard of care historical data. So, you know, our first patient dosed was in February of twenty four.

But as you know, the enrollment is slow in the beginning. So we’ll have to see how things pan out. And as the PFS whether it

Mark Fran, TD Cowen Biotech Team, TD Cowen: is with this next update or the subsequent one. But as PFS matures, you mentioned that benchmark. What type of separation do you think you want to be able to show to really to maintain confidence for the five trial?

Mark Erlander, CEO, Cardiff Oncology: Well, I think we just had an ad board where we had seven KOLs, really commenting about the whole registrational trial. The consensus among them was that they want to see a delta of three months or greater, in the PFS. So that’s kind of what they’re looking for.

Mark Fran, TD Cowen Biotech Team, TD Cowen: So like low low to mid double digits. Okay. Yeah. I mean, obviously, it depends a little bit on the control.

Mark Erlander, CEO, Cardiff Oncology: Yeah. Right. Okay.

Mark Fran, TD Cowen Biotech Team, TD Cowen: And I guess, what do you think this update in the first half, is that enough maturity to kind of pull the trigger on starting to start the process of opening five? Or do you need some of that PFS data before you Yes.

Mark Erlander, CEO, Cardiff Oncology: I mean, it’s a great question, Mark. I think as we sit here today, what we’re thinking is that as we’ve promised, we will put out an update in first half of this year, so really essentially Q2. But, you know, we also then, really, the gate to the registrational trial is the meeting with the FDA. And so the question there comes down to is, how much data do they want to see as far as confirmation of the dose? When we met with them, they said run a 90 patient trial.

Now, we would like to go sooner than that if we can, obviously. I think though that realistically, as far as an update on what the we we plan to have an update on the, in the first half with with efficacy and safety of zero zero four. But these next update is would be in the second half of this year. That we think is the time that we would have we’d be able to communicate our FDA feedback. Okay.

And I so because we wanna be able to put that out there, to the the community and say, look, this is what we we learned from the FDA. This is the final, trial design. This is the powering. This is the all the assumptions. We want to lay all that out.

And we don’t think that we’ll have that until in the second half is when we think we’ll have that data.

Mark Fran, TD Cowen Biotech Team, TD Cowen: Okay. And for that FDA meeting, you mentioned just, you know, confirming with them which of the two doses they’re going to go forward. But what are the other kind of key topics that you want to Yeah.

Mark Erlander, CEO, Cardiff Oncology: There’s really two objectives. Objective one is what you just said dose. Second objective is for them to, in essence, sign off on the protocol for the registrational trial. So those are really we we wanna get that those two things done and accomplished at that meeting.

Mark Fran, TD Cowen Biotech Team, TD Cowen: Okay. And I I think, you know, it is a the kind of seamless design that you’ve laid out with five of response rate followed by PFS is I mean, certainly things that we’ve heard from the FDA, but it is a little bit new But first, you want to discuss some of the regulatory pressures around there and some of the guidance I can

Mark Erlander, CEO, Cardiff Oncology: Right. I mean, on December twentieth of last year, it was announced that the breakwater trial, which was the, it was first line BRAF mutated tumors and first line CRC that they got accelerated approval. And they were running a seamless trial, which was really both ORR for the accelerated and then PFS and and OS, no showing no detriment for OS as as the full approval. We think that that’s a great template for us. I mean, obviously, we are in RAS mutated, which really do not are mutually exclusive of BRAF mutated, patients in general.

So we think it’s a great template for us. This is really, it was I mean, the FDA did suggest to us when we met with them in June of ’twenty three that, of doing this seamless trial where you had both accelerated in full in one trial. But it was great to see Pfizer’s BRAF inhibitor getting that approval and using that mechanism for accelerated. And then we just heard, I think it was in January, they press release that they were stat sig on their PFS endpoint and that they’d be reporting more details at a medical meeting.

Mark Fran, TD Cowen Biotech Team, TD Cowen: Okay. Maybe, I guess, that they’re run by IC, so you don’t have full control of them. But those other indications, just any sense where when we may see some updates there? Because I think a couple of those have reported some very early data history previously.

Mark Erlander, CEO, Cardiff Oncology: Yes. Small cell lung cancer, I mean, at this point, I can’t really give you any more guidance. I mean, we would like to with the small cell lung cancer, the PI moved to another institute that slowed that down. For small cell lung cancer, triple negative breast cancer, we may be able to report something out this year. We think we might be able to.

But I can’t tell you specifically until I have more details from the investigator. The third one is actually the first line PDAC, pancreatic. And we have started that trial with the investigator initiated trial on that. So but we’ll have to wait and see how that goes. And

Mark Fran, TD Cowen Biotech Team, TD Cowen: if O trials and other indications? Is it just off of four or is it waiting for five to read out for accelerated approval? Just how do you approach kind of expanding the program?

Mark Erlander, CEO, Cardiff Oncology: Right now, we’re open to going after another with a sponsor trial. We have not decided yet. We are exploring signal finding with these three investigator initiated trials. We are looking at you know, the RAS wild type group in colorectal cancer. We have reported AACR in 2024, activity there as well.

It’s a very interesting story, but we just have to wait and see. Okay. Our primary objective is this program that we have in RAS mutated CRC.

Mark Fran, TD Cowen Biotech Team, TD Cowen: Yeah. Okay. Unfortunately, it’s all the time we have, so we’re going to have to cut it off there. But thanks a lot, Mark.

Mark Erlander, CEO, Cardiff Oncology: Thank you, Mark. Really appreciate it. And thank you for your time.

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