Welcome to the Cardiff Oncology onvansertib Data Update Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to turn the conference over to Candace Massey of Ashbury Partners. Please go ahead.
Thank you, operator. This is Mani Mohindru from Cardiff. Given the technical difficulties, I'm going to take over. Joining the call today with me from the Cardiff Oncology team will be me, myself, the Interim CEO. In addition, I'm joined with my Chief Medical Officer, Dr. Roger Sidhu, our Chief Scientific Officer, Dr. Todd Smeal, and our newly promoted Chief Accounting Officer, Ms. Nukhet Lindsay, and they'll also be available during the Q&A session. During this conference call, we will be making forward-looking statements, including, without limitation, statements related to guidance, results, and the timing of data readouts for advancing clinical studies. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. Our actual results and the timing of the events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties.
Factors that could cause results to be different from these statements include factors that the companies describe in the section titled "Risk Factors" in its annual report on Form 10-K, filed with the SEC for the year ended December 31st, 2024. Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. With that, I am going to take over the conference call and proceed further with my prepared remarks. Once again, good morning to all, and I would like to thank you for, for joining our conference call. Before we begin, I want to take a brief moment to introduce myself. As you may have read in our press releases, I've been appointed Interim Chief Executive Officer by the Cardiff Board of Directors.
Since 2021, I have had the honor of serving on Cardiff's board, where I have become intimately familiar with the company's development programs for onvansertib. In addition to serving on Cardiff's board, I have significant experience at both the operational and executive levels. I've been a biotech company founder, CEO, CFO, and board member. I'm a scientist by training with a PhD from Northwestern, and prior to my roles at biotech companies, I served as an equity research analyst on Wall Street, covering the sector, biotech sector. You can read more details about my background in today's release. Today, Cardiff issued two press releases that can be found on our website. The first one announces a management transition aimed at positioning the company optimally for late-stage development to fully leverage the value we believe onvansertib represents.
The second announcement provides an update on onvansertib's very promising phase II data from our ongoing clinical trial in first-line RAS-mutated metastatic colorectal or mCRC patients. I'll begin today's call with a discussion of the management transition first. Given that our management and financial needs have evolved, Cardiff's board decided that this was the appropriate time to transition the company's leadership to ensure it is best positioned to fully leverage the opportunity that onvansertib represents. This reflects a forward-looking business decision to position Cardiff for its next phase of growth as we look to finalize and execute on our registrational plan, starting with our program in first-line RAS-mutated CRC patients. This population represents about 50% of all of metastatic CRC patient population, with a significant need for new and improved therapies.
Before proceeding further, I do want to take a moment to thank both Mark and Jamie for their dedication and many contributions to Cardiff through the years. Their efforts led to the progress of onvansertib from early stage to phase two development, positioning it well for further advancement into late-stage clinical program. I do want to emphasize one very important point. This transition is by no means related to any issues with onvansertib's colorectal cancer program. In fact, this transition is a direct result of the promising data we are seeing with onvansertib. The CRDF-004 program remains fully on track and continues to demonstrate promising clinical benefit, as well as safety data in cancers such as RAS-mutated mCRC, as we reported today. I've been intimately aware of Cardiff's pipeline and operations over the past several years as a board member.
In my interim CEO role, I'm surrounded by experienced operational, scientific, and clinical development teams. Hence, we do not anticipate any operational interruptions during this transition. We will continue to lead this program forward and also explore the potential for indication expansion, driven by evidence. We remain extremely excited about the potential of onvansertib and its promise to be a paradigm-shifting therapy for patients with RAS-mutated metastatic CRC. I will now spend some time on the updated promising phase II data we reported today. Just as a reminder, onvansertib is a highly specific oral PLK1 inhibitor, currently in mid-stage clinical development for RAS-mutated metastatic CRC. It is being evaluated in multiple other cancers through investigator-initiated studies. Recently, very promising single-agent activity data showed hematological responses in chronic myelomonocytic leukemia, or CMML. These encouraging data were presented at the American Society of Hematology's annual meeting in December of 2025.
Today's data update is centered around CRDF-004 trial, a company-sponsored phase II dose-finding study, evaluating onvansertib in combination with first-line standard of care regimens in patients with colorectal cancer harboring the RAS mutations. Patients were randomized to receive either 20 mg or 30 mg of onvansertib in combination with either of the two standard of care regimens. That is, FOLFIRI plus bevacizumab, or FOLFOX plus Bev, or were given the standard of care therapy alone. The trial was designed to identify the lowest effective dose and to assess the safety, efficacy, and PK of our drug candidate in combination with FOLFIRI Bev or FOLFOX Bev in the first-line setting. In an intent- to- treat analysis, our updated data showed dose-dependent benefits across multiple efficacy measures, especially in patients who got onvansertib plus FOLFIRI Bev versus patients who either got FOLFIRI or FOLFOX-based standard of care regimens alone.
A similar dose-dependent and consistent clinical benefit has not been observed thus far with onvansertib in combination with the FOLFOX Bev regimen. I also want to highlight that today's onvansertib FOLFIRI Bev top-line data are actually aligned with positive results from a prior second-line mCRC phase II trial in Bev-naïve patients, where the chemo backbone was also FOLFIRI, FOLFIRI as well. Just want to remind that these results have been published in the Journal of Clinical Oncology, and in fact, were the basis of our decision, in consultation with the FDA, to move onvansertib to the first-line setting.
As you can see in the table included in today's press release, the onvansertib 40-mg dose, when combined with FOLFIRI Bev, provided a much higher confirmed overall objective response rate of 72.2%, versus 43.2% seen with FOLFOX, FOLFIRI standard of care regimens combined, or 42.1% seen with FOLFIRI plus Bev standard of care regimen alone. Additionally, median PFS has yet not been reached in either of the onvansertib FOLFIRI arms, which indicates extended benefit. In contrast, the standard of care regimens had a median PFS of about 11 months, which aligns with published data from other studies. Of note, the 30-mg onvansertib arm achieved statistical significance for PFS versus the standard of care, despite the relatively small number of patients.
These, these findings highlight both improved tumor responses and enhanced durability with the addition of onvansertib on top of standard of care regimen of FOLFIRI, Bev. Further, the PFS hazard ratio was 0.37 when comparing 30 mg onvansertib plus FOLFIRI Bev arm to the combined standard of care arms. This also achieves statistical significance, suggesting a notable reduction in the risk of disease progression. To be clear, this dose selection trial was not powered to assess the difference in the secondary endpoints of PFS or duration of response, and yet we saw consistent dose-dependent responses in the measures of durability with a higher dose of 30 mgs given with FOLFIRI plus Bev. The other important point here is that we expect our registrational study to also compare the onvansertib plus FOLFIRI regimen to the combined standard of care arms when measuring efficacy.
The safety and tolerability of onvansertib when added to standard of care remains favorable and similar to what we have reported previously. No unexpected toxicities or additive AEs were reported. Grade 3 or higher AEs were infrequent, with neutropenia being one of the most common treatment-emerging AE across onvansertib combinations, as well as the standard of care arms alone.... Together, we believe these data tell a very compelling and consistent story of onvansertib practice-changing potential. Based on the totality of the data thus far, we have selected the 30 mg dose of onvansertib in combination with FOLFIRI-Bev regimen to bring forward in a registrational study in patients with RAS-mutated metastatic CRC in the frontline setting. Cardiff expects to initiate a registrational program later this year.
The study protocol will likely include comparison of onvansertib plus FOLFIRI-Bev to both standard of care regimens, i.e., FOLFIRI-Bev and FOLFOX-Bev, in a prospective manner. This, of course, is subject to confirmation following a review of our study designed by FDA per usual guidelines. We expect to disclose details of the study design after our discussion with the regulatory authorities. Looking ahead, we expect to provide a more mature clinical data set from the CRDF-004 study before the end of first half of 2026, either at a medical meeting or a similar event. At that time, we also anticipate that we would have received feedback from FDA on our registration plan in metastatic colorectal cancer. It's a very exciting time for Cardiff as we make this transition to late-stage development.
I'm especially grateful for the opportunity to help guide the final stage of development for this potentially practice-changing drug candidate. I look forward to working closely with the outstanding team at Cardiff in realizing the full therapeutic potential and value of onvansertib. I also look forward to continuing the dialogue with you, our investor base, as we take steps towards our goal of regulatory clearance with an eye towards commercialization. Before we open the Q&A session, I would like to thank all employees and consultants of Cardiff who continue to work tirelessly to advance onvansertib further in clinical development. Most importantly, I would like to thank all the patients who have participated in our current and past clinical trials and contributed immensely to the advancement of our drug candidate.
With that, we will begin the Q&A portion of the call, where I will be joined by our CMO, Roger, CSO, Todd, and our Chief Accounting Officer, Nukhet. Lisa, you can open the call for questions.
Thank you. As a reminder, if you would like to ask a question, please press star one one on your telephone. You will then hear an automated message advising your hand is raised. If you would like to remove yourself from the queue, please press star one one again. We also ask that you please wait for your name and company to be announced before proceeding with your question. One moment while we compile the Q&A roster. The first question that we have for today will be coming from the line of Marc Frahm of TD Cowen. Your line is open.
Hey, thanks for taking my questions, and welcome aboard, Mani. Maybe just to start off with it, I know the focus is very much on the FOLFIRI combination, since that's the one that you plan to move forward. But maybe if you can just kind of address what trends or signals of efficacy may have also been seen within the FOLFOX subset of patients. And then looking forward to the phase III, can you maybe speak to some of the preliminary powering assumptions you have there in terms of how large the trial may need to be? Maybe some of the rationale for using both chemo backbones in the control arm versus maybe making a slightly simpler trial design by just focusing on FOLFIRI on both arms.
Sure. Nice to meet you, Marc, as well. Let me address what happened in the FOLFOX arm and why we haven't included that data in the release. We did see activity with FOLFOX in combination with onvansertib as well. However, the results were not as robust or consistent across all of, all the different measures of efficacy, and specifically in PFS, which is one of the durability measures. We didn't quite see the consistency and the robustness that we saw with the FOLFIRI arm. So we definitely, taking all of the trial results into consideration, and the trial is still ongoing, by the way, so we will continue to get some more mature data. We believe FOLFIRI is the right regimen to take forward, with onvansertib in the frontline setting for our next trial.
And now, to address your question about the phase III trial design, I know you asked a bunch of things. I am not in a position to comment on the size of the trial right now because we would need to work with the agency, taking into account the robustness of the data in doing the powering assessment, and that would lead to the 500 N or the total size of the trial. So stay tuned for that. But your question about, you know, making a simplified FOLFIRI plus onvansertib versus FOLFIRI alone or standard of care. I think I can tell you that most physicians want to see how did your drug do in combination with one chemo versus standard of care.
I think most people would like to see how did it perform, not only versus FOLFIRI, but also FOLFOX, because both of these regimens are used in front line. And given the robustness of the data, despite small N, I do, do want to make it clear, we are able to show that onvansertib, when combined with FOLFIRI-Bev, is better. It appears to be better than both FOLFOX and FOLFIRI-based standard of care regimen. So it makes sense to go with them. It is a more aggressive design, something I know that some of the regulators prefer, and certainly I think physicians' decision-making would become much more easier if we are able to replicate the results of our phase II study in a bigger registrational trial. Does that answer the question?
Yep. Thank you. All very helpful. Thanks.
One moment for the next question. Our next question will come from the line of Maury Raycroft of Jefferies. Your line is open.
Hi, good morning. Congrats on the update, and thanks for taking my questions. Maybe just one on, just we're not seeing a meaningful difference in response rate between the 20 mg dose and the standard of care, yet the PFS hazard ratio is 0.56. How do you explain the notable improvement in durability despite the similar response rates?
I think that's an excellent question, Maury. Nice to meet you. You know, if you study the literature or talk to the KOLs, especially in this disease setting in frontline, the focus is on durability. You know, it's great to see ORR, but there are limitations in this study. It's a small study, and it's a subgroup of the total onvansertib arm. It's FOLFIRI plus onvansertib 20 mgs. But the focus for this patient population is really trying to see whether you are able to have durable benefit, which also includes, by the way, stable disease, which is reflected in PFS. So, from our view, what we see is that the higher dose does much better than the lower dose in terms of ORR, but definitely we see a bigger benefit in PFS.
We do see benefit in both arms, but the bigger benefit, and I don't think this is unusual in this particular disease setting. That's why the focus is on ORR, but higher, bigger, bigger emphasis on trying to see the durability. If you can keep patients on a combination regimen for a longer time, stable diseases become effective as well.
Got it. Yeah, it's helpful perspective. And your analysis combines BICR and investigator-assessed data. Can you share insights on the standalone results for BICR and for the investigator-assessed separately on this call, or is this something that you'll share more details on later in the first half?
Again, a very astute observation. Yes, you know, the limitation is small numbers, and this trial is still ongoing. So the number of events, if you take either BICR or investigator alone, would become very small. So to make the data more meaningful, we had to combine, and that's what we've disclosed. I cannot predict what we'll be able to share, how many events later, but we will continue to collect the event-based data, and if BICR presents enough opportunity to do that, we'll present those updated results.
Got it. Okay, thanks for taking my questions.
One moment for the next question. Our next question will come from the line of Ted Tenthoff of Piper Sandler. Your line is open.
Great. Thank you very much. Hi, Mani, congratulations on the new position and on really stellar data. Can you hear me okay?
Yes, yes. Hi, Ted. Good to be reconnected.
Hi, how are you? Yeah.
Looking forward to your question.
Yes, great. So, again, congrats on data, looks really exciting. I'm trying to think a little bit broader here and wondering whether, you know, with this strong data set, it makes sense to entertain partnerships, even potentially overseas, to help pay for the phase III trial, and/or to broaden development beyond the initial indication as you were sort of mentioning in your prepared remarks. Thank you.
Excellent question. Something that we continue to work on. I think, up until this point, we had single agent, sorry, single arm data that was published. But, you know, with this study, we are well-positioned to start both strategic discussions and some of which have already been started by, by the previous leadership, and we will continue to work on that. Yes, absolutely. I think the potential of this drug is even in CRC, is pretty broad, but beyond, it's even bigger.
Yeah.
So certainly something that would certainly be well-served by bringing a partnership in place.
Great.
We are actively working for that, yeah.
Yep, makes sense. Great. Looking forward to more details on the data presentation later this year.
Thank you.
One moment for the next question. The next question will be coming from the line of Andy Hsieh of William Blair. Your line is open.
Thanks for taking our question, and, Mani, I look forward to working with you. So in terms of baseline characteristics, since that's important, in terms of contextualizing what you're seeing comparing across arms, maybe, Roger, I'm curious if you can share your view on some of the baseline characteristic differences? Obviously, that's an artifact of just small N. But some, I guess, I would interpret as favoring the control arm, and some are favoring the experimental arm. So maybe just kind of overall, what you see in the baseline characteristics and how that could potentially impact the, you know, cross-arm comparison? Thanks.
So, I'll let Roger take over, but you know, we have shared, obviously, the baseline characteristics previously, so you should have that data as well. It's probably on the website as well in our presentation out there, but I'll let Roger give his views on the baseline characteristics then.
Yes, as you know, randomization has already been sort of completed in the first quarter of last year, and we have already kind of shared the baseline characteristics. We are seeing consistent benefit for the 30 mg onvansertib combination across key subgroups, which contributes to the robustness of the data moving forward. And we look forward to sharing more as Mani mentioned in upcoming medical meeting or such interaction.
Yeah, but at least based on our preliminary assessment, and Roger, you can correct me if it's wrong, like, we really didn't see anything jump out that could have skewed the results one way or the other.
That's, that's true.
Okay.
We haven't seen any significant outlier outcomes that could skew the data in terms of interpreting the objective response data we've shared or the PFS data that we've shared today.
The two standard of care regimens, the FOLFIRI standard of care, and the FOLFOX standard of care actually behaved very similarly to what has been previously reported, which gives us confidence in the overall data.
Got it. And I guess one of the things that were striking from the from last year's release was kind of the dose and depth of response. And I'm curious if you could maybe, you know, kind of characterize what you've seen with longer follow-up. Is that depth of response with higher, with the 30 mg versus standard care or 20? Was that trend also preserved? Thank you.
Yes. So we'll certainly share a lot more details around the data in an upcoming event, but I'll let Roger chime in as well. But I think the depth of response gets captured in durability to a certain extent. I think it's the combination of depth of response, stability, which is, you know, captured in durability measures of PFS and beyond. But I'll let Roger add his perspective as well.
Yeah. To address your question, we continue to see impressive depth of response in particular with the 30-mg dose in combination with bevacizumab in a dose-dependent manner.
Great. Thank you so much.
One moment for the next question. The next question will be coming from the line of Albert Lowe of Craig-Hallum. Your line is open.
Hi, good morning. A few questions about the data. First, I was wondering, did you see any pronounced dose-dependent effects from onvansertib in the FOLFOX combination arms?
So, what we did say that we did see activity of the drug in the FOLFOX combination arm, but they weren't consistent trends across all efficacy measurements, with the FOLFOX combination.
Okay, I see. I was wondering if you could share perhaps how many more patients remain on trial and perhaps what guided the decision around taking the data cut here versus giving the PFS data some more time to mature?
I cannot go into the specifics of how many patients are on the trial at this time. But I think, you know, we were at a critical point where we had seen efficacy with a certain dose, so we believe that we have the dose we want to take forward, we have the regimen, and with the transition, we thought this was appropriate time to provide the street some updated data, and more details to come as we continue to work on collecting the maturing data, and to present later at a medical meeting or an analyst event soon.
I see. Thank you. Maybe one last question, just to clarify, at the time of the next update that's coming here in the first half, do you expect to have already had the meeting with the FDA to potentially share the finalized trial details?
That is the plan, that we can get all the data together and have at least some discussion or have some connection with the regulators by within this half.
Okay, great. Thanks for taking my questions, and nice to meet you here.
Thanks.
One moment for the next question. The next question will be coming from the line of Kevin DeGeeter from Oppenheimer & Co. Your line is open.
Hey, yeah, thanks for taking our questions. Yeah, just one from me. Thanks for including the PFS rate at six months. You know, particularly in what's pretty small cohorts, they're numerically, you know, quite similar. So is it reasonable to conclude a lot of the PFS benefit kind of captured in the hazard ratio? You know, is really kind of separation of the curves kind of beyond six months, or is there something that's kind of more nuanced that we should be considering when trying to parse out sort of depth of response based on what was disclosed today.
Thank you. That's an excellent question as well. I think what we wanted to share was a few different things, but in a nuanced way. The 6-month PFS is a little bit early, you know, but it's an important landmark to see if the drug's benefit is in the right direction. You can see actually within that analysis that there is a dose response there as well. You know, you don't expect too many differences between the control and the test arms, but there's certainly a trend towards improvement with onvansertib, and that too, in a dose-dependent manner, which gives us confidence in these data. You know, these are small n's, so we have to look at the data every which way.
Curves are definitely when we are ready to share with you, you can see, like, you know, based on the hazard ratio, the curves are much more separated with the FOLFIRI arm, and we've just not disclosed the full FOLFOX hazard ratio. But we feel quite comfortable, and not just with FOLFIRI alone arm, but even looking at the standard of care regimens combined arm. But the six-month.
Sure.
Landmark analysis is just to get more confident about what we are looking at, dose trends and the right direction the efficacy is heading.
That's really helpful perspective. Thanks for taking our questions.
One moment for the next question. The next question will be coming from the line of Christopher Liu of Lucid Capital Markets. Your line is open.
Hey, guys. Thanks for the question, and it's good to speak to you again, Dr. Mohindru. Congrats on the data so far. Maybe a question about efficacy and then a question about tolerability. For the question about efficacy, what's kind of the median time to response that we see in the 30-mg arm? And are we continuing to see some deepening of responses as time goes on, including, you know, now? And then for the tolerability question, what was the dose discontinuation rate looking like?
So you, you have asked quite, quite specific details. You know, unfortunately, I will not be able to provide full data on, on, you know, the depth of response over time. But I think the way from our perspective to look at the data is to look at PFS hazard ratio and the totality there. Because, in this patient population, stable disease matters as well. You know, we, we do believe, and we've shared this with you previously, that the depth of response is certainly much better with, with onvansertib combinations. But, but we should not take stable disease patients lightly, and, and I think that's important to be captured. And remind me what your second question was. Sorry, I.
Oh, no worries. I was just wondering what the treatment discontinuation might have looked like?
Oh, yes. Treatment.
In the 30 mg.
I would say stay tuned for the full dataset, but there was, there were differences in treatment discontinuations, I can tell you, between different arms. You know, but stay tuned for that, so we can share, you know, the reasons of discontinuations, as well in the next data cut. There were differences between FOLFOX and FOLFIRI. Like, let me put it this way, which obviously is reflected in the data, but we'll give the full details, at a later time.
Got it. Thank you very much.
One moment for the next question. Our last question of the day will come from the line of John Vandermosten of Zacks Small Cap Research. Your line is open.
Thank you, and good morning. I think that, Pfizer had the right, first, look for, the data from the trial. Did they... Was there any response from them or any sign of interest from them at all that you've seen?
This is too early to comment on that. You know, certainly Pfizer has. You know, we have shared the data, and we will continue to share for that with them and others. But too early to say anything beyond this at this point in time.
Okay. And since you're looking for a new executive team, will you be focused at all on deal experience or commercialization experience? It might be too soon for that, but, you know, perhaps it's never too early. What are some of the features you're looking for in the full-time CEO?
Yes. I think certainly, you know, not just the CEO, you know, we are increasing and expanding our clinical team as well, and bringing people in with a focus towards taking the drug to late-stage development, regulatory interactions, and commercialization as well. So all of these things, and not just in metastatic CRC, but, as I mentioned in my prepared remarks, even looking beyond that, because we are seeing signals of activity, clinical benefit, and other indications. So certainly, we'll keep all that in mind as we build, not just the leadership team, but the company at large.
Great. Thank you, Dr. Mohindru. Appreciate it.
Thank you.
Thank you. This does conclude today's Q&A session. I would like to turn the call back over to Mani Mohindru, Interim Chief Executive Officer. Please go ahead.
Thank you, Lisa. We're incredibly excited about the potential opportunities with onvansertib and look forward to keeping you updated as we advance this program. Thank you again, everyone, for joining us this morning, and please reach out for any additional questions. Thank you.
This does conclude today's program. Thank you so much for joining. You may now disconnect.