Cardiff Oncology, Inc. (CRDF) Earnings Call Transcript & Summary

All right. Good afternoon, everyone. Welcome to B. Riley Securities Oncology Conference and listening to our fireside chat. I'm Yuan Zhi, a Healthcare Equity Research Analyst at B. Riley Securities. Today, it's my great pleasure to have Mark Erlander, CEO of Cardiff Oncology. Thank you for joining us today. I want to focus today's discussion on your clinical trial of colorectal cancer and pancreatic cancer. But first, Mark, can you give us a quick overview of Cardiff Oncology and your pipeline?

Thank you, Yuan. And first of all, thank you for inviting Cardiff Oncology to be able to talk to you today at B. Riley Securities Oncology Day. We're very excited to be able to share the latest updates here at Cardiff Oncology. I'm going to use some props today. I'm going to be using some slides, and so hopefully that will allow us to even give more information than just the verbal. To answer your question, first of all, to level set everyone, Cardiff Oncology is a clinical stage oncology company and we are based in San Diego, California. And we have a molecule, a drug called onvansertib, and it's a very highly selective, well-tolerated PLK1 inhibitor. You can see here on the screen, it's a small molecule, it's oral, 24-hour half-life, great for flexibility of dosing, and also a very key feature of it is that it is highly selective for PLK1. You can see on the right that it's got about a 5,000 fold greater selectivity than any of the other PLK evolutionary related PLKs, which we would not want to hit. So that really gives you -- kind of level sets you. And then really, to answer your question, Yuan, we have a pipeline -- our lead program is in KRAS-mutated metastatic colorectal cancer. We are currently enrolling in our randomized trial, which we will talk about later together. But we have just come off the heels of some really great data in our single-arm trial within the same indication of metastatic CRC. We have other programs though that are -- we would call them more signal finding trials, and those include the pancreatic trial as well as 2 really exciting investigator-initiated trials in triple-negative breast cancer in combination with paclitaxel and also small cell lung cancer. So this is really sort of a high overview of what we are doing here at Cardiff.

Got it. Can you quickly remind investors of the rationale of targeting PLK1 and then combining PLK1 inhibitors with chemotherapy.

Yes. PLK1 is a serine/threonine kinase, and it is essential within the cell cycle, the tumor cell cycle. And there's been no question in the literature for the last 10 years that PLK1 is a great cancer therapy target. It's been really more about the fact that some of the earlier generation PLK inhibitors had some toxicity, which has been overcome with onvansertib. Now to get to your question of the underlying mechanism, we put together a little cartoon of 4 slides that I think really hones in on why we are in colorectal cancer. And specifically, in colorectal cancer, the standard of care is chemo agents, specifically irinotecan. And irinotecan, the way it works is it breaks up DNA in the cell cycle, specifically in the S phase. And when it does that -- when the irinotecan does that, this is a way that it can kill the tumor cell. However, tumor cells have hijacked PLK1, our target. And by hijacking it, they allow the DNA to be repaired and for the tumor cell to continue to replicate and to divide. If we can inhibit PLK1s with onvansertib, what happens is that you stall and stop the tumor cell from dividing and they go into cell death. So that's a very high level overview of why onvansertib and PLK1 actually is a great target in combination with chemo agents such as irinotecan.

Got it. I think it will be great for investors if you could give us a quick review of the key clinical data you have seen so far with PLK1 inhibitor, onvansertib, in colorectal cancer. Understand it was a single-arm trial, but it would be helpful to the audience if you discuss the data in the context of standard of care.

Yes. More than happy to do that. Really to start that conversation, we are targeting the metastatic colorectal cancer. Specifically, more than 50% of patients who have the very deleterious RAS mutations, they have the worst outcome. And for those patients, there is no targeted agents available and really it's a chemo cocktail. For that, we are looking at second line. And in second line, we're looking to add onvansertib on top of FOLFIRI plus bev. And the reason for that is what I was talking about earlier, that synergy between DNA damaging agents such as irinotecan, which is part of FOLFIRI and onvansertib. Now to get to your question, the actual trial, it was a single-arm trial and the enrollment is on the left-hand side, it's KRAS-mutated second-line metastatic CRC, and importantly, also unresectable tumors. On the right-hand side, you can see the question we asked, can we get a signal that complements and improves over current standard of care. And you can see in the middle of the actual dosing schedule. Now what we have reported out over the last 1.5 years has been very consistent data showing that we have response rates that are well above that of historical ORRs or objective response rates. You can see on the left-hand side, those range from 5% to 13%. And you can see on the right that when we started reporting up this trial at ASCO GI in January '21, we had only 14 evaluable patients, and we had a 36% response rate. Fast forward to ASCO GI of 2022, and we had 48 evaluable with a 35% response rate. So we are seeing consistency across the actual doses. I would say one other thing that we don't have enough time today to really discuss a lot, but one of the very exciting things that came out of this data was the fact that there was a subset of patients that came in that had not received bev in first line, but they had received it when they combined it with onvansertib. And this is a very busy slide. But what we're showing you here is that patients who came into our trial that were bev-naive, normally would have about a 25% response rate, and we were seeing a 69% response rate. And normally they'd have a median PFS around 6.9 months, and we were seeing 13.5 months. So this also has been very exciting for us because it is another potential window of identifying a subset of patients who would do extremely well with this combination.

Got it. In terms of clinical development plan, can you lay out where we are for onvansertib in colorectal cancer?

Yes, absolutely. So what we've been talking so far, Yuan, has, of course, been our single arm trial. And because of what we consider to be and our investigators consider to be such exciting data, really this was the impetus for us to go forward into a randomized trial. And we really had 4 objectives in this trial. First was really, of course, to demonstrate the contribution of onvansertib by doing a randomized trial, and I'll show you that design in the next slide, but also Project Optimus feedback from the FDA where they want us to identify the lowest, the maximal efficacy dose. And so that's also part of this. We have 2 different dose levels that really are equivalent to the lowest 2 doses of our original Phase Ib trial. Of course, it depends on the data, but we're also positioning ourselves for a potential accelerated approval opportunity. And then finally, we are a biotech company, we watch our pennies, and we really make sure that we use our capital with the greatest amount of efficiency. So that really gives you kind of an overview of where we're going in KRAS-mutated colorectal cancer. And the actual design is here, and you can see that what we've done is we've got a randomized trial of 3 different arms, the arm control arm with the FOLFIRI plus bev, and then 2 different dose levels of onvansertib in combination with standard of care. Now a couple of things about this. First of all, the enrollment criteria on the left is absolutely identical to what we did in our original Phase Ib/II trial. And secondly, you can see on the right that our dosing schedule is also the same. The couple of other things about this trial, like you've noticed it is randomized, but I did mention very quickly some data about patients whether they had bevacizumab or did not, so they're bev-naive or bev-exposed. In this trial, we will have a stratification prior to randomization, where 1/3 of the patients in each arm will be what we call bev-naive, that is to say they did not have bev or Avastin in first line. The second thing that's important is that this is the 80% power to detect a meaningful objective response rate over control. And so this is the other part of the design where that is our 80% power, and that meaningful difference is of 35% versus a 15% of response rate in the control arm. So that really gives you kind of an idea of where we're going. Now this trial -- we have now started the trial, and we've already activated 6 sites. The plan is to activate 40 sites and to really try to enroll this trial as quickly as possible.

Got it. Maybe we can quickly circle back to the Phase Ib trial, where you had 48 evaluable patients. I'm just curious will there be more clinical data released from those patients, or at one point you mentioned there would be a dose expansion cohort. Will there be an update from that as well?

Yes. First of all, last time we disclosed data on the trial. In the 48, we had 3 patients that were still on trial. We don't anticipate there being any big change in the data based on that. Secondly, the expansion, actually, we are still waiting to get more follow-up data on that to determine when that disclosure would happen. Those sites were really converted over into this randomized trial and were only kept activated for that expansion just to keep us, Cardiff Oncology, on their radar. So that was really -- and also we collected some PK data from that small number of patients. So we'll have to see where that goes as we wait for more follow-up. But that's where we are today.

So some investors were under the impression that right after this initial Phase I/II trial, you might initiate a pivotal trial of Phase III or a Phase III trial right after that. Can you maybe clarify that a bit? Investors would love to hear the behind the scene mechanism that led you to the current development plan.

Well, I think for us, our goal -- I mean, just to remind you, our goal was really these goals here. And so we were able to do that with the Phase II trial. And so that really was the -- the driving force here was that what kind of randomized trial would allow us to be able to check the box on these objectives, obviously, particularly the first 3. And so this trial did allow us to do that. And so that's why we're going forward with it.

And one last question on this topic. How should investors think about the timeline for the randomized trial to release top line data.

Yes. Right now we're projecting -- and I'll show that in a couple of seconds, but we are projecting a readout in the second half of 2024. That is the goal as we sit here today.

I want to spend the last few minutes to talk about your other ongoing programs, including the pancreatic cancers. Can you first talk about [indiscernible] to date on pancreatic cancer indication? And when can we hear an update from this program?

Yes, absolutely. So we do have a single-arm trial ongoing in PDAC or pancreatic cancer. And these are patients that have failed the Gem/Abraxane, which is standard of care in first line, and then they've moved on to receiving FOLFIRI in second line, which is standard of care. So what we've done here is we've used the same rationale that we use in the colorectal to combine onvansertib in that second line. So you can see here the actual dosing schedule 5 days on for onvansertib as an oral drug in a 14-day cycle. Now really the bar though, and what we're trying to achieve here is that these patients, it's a huge unmet need, and the historical response rates for these patients is exceedingly low in single-digit territory. And also the historical median PFSs are only around 3 months. So we are trying to see what kind of signal we have in this trial in this indication in second line. What we have reported out so far as of last year was that we had 5 evaluable patients with 1 with a partial response, 3 with stable disease, and 1 with a progressive disease. And you can see the Spire plot on the right-hand side showing that actually, 4 patients, they all had some sort of tumor shrinkage 4 out of 5. So this was encouraging data. As we publicly said, we plan to, sometime in mid this year '23, give an update on this trial. The other thing that I thought I would just take the liberty to talk to you about is we do have also some really exciting investigator-initiated trials. And one of them in particular that's quite interesting is the triple-negative breast cancer trial in which we are combining onvansertib with a taxane, paclitaxel. Paclitaxel is a standard of care for these patients. And what's exciting about this is just as we talked about the mechanism underneath the combination of onvansertib with DNA damaging agents in the S-phase of the tumor cycle, the cell cycle and the whole concept of DNA damage and PLK1, we're trying to -- repairing that and inhibiting that. So therefore, the tumor cell dies. The other place where PLK1 plays a big role is in the M-phase of the cell cycle or when cells divide. And there, the PLK1 interacts with microtubules. And these microtubules then are disrupted by taxanes. And so we also see really great synergy with onvansertib with paclitaxel. And we see it actually across multiple different tumor types. Now the one that we're going for here and for a signal finding is with the triple-negative breast cancer. And we plan to put data out on this towards the end of this year. This trial just started a couple of months ago. Patients have enrolled, already have been dosed, but we'll have to see how it goes. But we're very excited about this trial as well to see what kind of signal we see.

Well, maybe circle back to the pancreatic cancer trial for a moment. How was the enrollment for that trial so far? And in a rough estimation, how many patients worth of data will be shared or evaluable when you share the data with investors.

I mean, the enrollment has been going okay, but it is a little slower than we anticipated. And the reason for that mainly is that these patients are extremely sick. By the time they get into a second line situation, they are very sick patients. I think -- at this point, I don't want to estimate numbers of patients, because I don't want to say one number and then they have a different number later in the year. But patients are being enrolled and patients are being dosed as we speak.

Got it. So I think at one point in the colorectal cancer trial, you shared biomarker data of ctDNA. For the pancreatic cancer as well as the TNBC trials, will you share that data as well? How investors should read into those biomarker data?

Yes. Our plan would be to do that. I mean, we're all looking at the conventional biomarker, the CA19-9, which is used in pancreatic cancer to monitor, and also we're looking at KRAS changes. One thing about pancreatic cancer that is interesting from a scientific point of view is that you sometimes have multiple RAS mutations simultaneously in the pancreatic cancer in these patients. And sometimes, one will go down, one will go up. So there is interesting interplay that we don't quite understand in pancreatic cancer, whereas in colorectal cancer it's really the tumor is a little bit more homogeneous as far as having only a single RAS mutant subtype. So I would just say that's a prelude of what you might see later this year, but it is scientifically interesting if that might mean that the complexity and heterogeneity in the pancreatic tumor, it may be more complex than in colorectal, but we have to wait and see.

Got it. So lastly, can you provide us with your current cash balance as well as guidance on of the cash runway to support your upcoming catalysts?

Yes, absolutely. So as I mentioned earlier, Yuan, we'll have some information about these trials this year. The PDAC, I've already talked about that. You can see it here midyear. Small cell lung cancer, haven't talked about that, but that's another investigator-initiated trial that we are really interested to see what happens there. This is a trial with onvansertib being a single agent. In the triple-negative breast cancer, we have already talked about. And then, of course, our lead program, the randomized trial in second half of '24. As we said here the last time of disclosure of cash, we had about $114 million in cash at September 30 of last year. If we look down below that, we show $14 million. That's for 2 quarters of cash. We try to give a little more accurate assessment of our cash burn. So we're clocking in at about $7 million burn per quarter. As we sit here today, we have cash with all these programs into 2025. And so that's where we are today.

Got it. That's very helpful. And I think we can end this session a little bit early. Thank you for your time. Thank you for the investors' interest.

Thank you, Yuan, and thank you for all of you that have been listening. One thing I will say, since I have a couple of seconds, is that you can find us at www.cardiffoncology.com. If you're interested in hearing more about what we're doing, you can always reach out to us and set up a call and we can have a much more detailed conversation with you if that's something of interest to you. But thank you for your time, all of you, and Yuan, greatly appreciate the opportunity to once again share Cardiff's story with potential and current investors. Thank you.