Conference Transcript - CRDF 2026-01-27

Operator

Welcome to the Cardiff Oncology on Vaseber Data Update Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will 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 Candice Matthews of Aster Partners. Please go ahead.

Mani Mohindru, CEO

Thank you, operator. This is Mani Mohindra from Cardiff. Given the technical difficulties, I'm going to take over. Joining the call today with me from the oncology team will be me, myself, the entrant CEO. In addition, I'm joined with my chief medical officer, Dr. Roger Sisu, our chief scientific officer, Dr. Todd Smeal, and our newly promoted chief accounting officer, Mr. Geeta 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 a quantitative clinical study. 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 case filed with the SEC for the year ended December 31st, 2024. Call of 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 Once again, good morning to all, and I would like to thank you for joining our conference 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's 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 Unvancetive. 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 the Wall Street covering the sector,

Operator

biotech sector.

Mani Mohindru, CEO

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 OnVancetib represents. The second announcement provides an update on Unvancetib'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 Unvancetive 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 populations with a significant need for new and improved therapy. 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 Unvancitib from early stage to phase 2 development, positioning it well for further advancement into late stage clinical progress. I do want to emphasize one very important point. This transition is by no means related to any issues with Unvancitib's colorectal cancer progress. In fact, this transition is a direct result of the promising data we are seeing with Unvancetive. The Cardiff 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 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 Unvancetib, and it's promised 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, Unvancetib 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 CARDIF004 trials, a company-sponsored Phase II dose-finding study evaluating on Vansetip 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 unvancetib in combination with either of the two standard-of-care regimens, that is, Folfuri 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 Folfuri 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 Unvancetib plus Folfuri beds versus patients who either got Folfuri or Folfox-based standard of care regimens alone. A similar dose-dependent and consistent clinical benefit has not been observed thus far with onvansative in combination with the Folfox-BEP regimen. I also want to highlight that today's onvansative Folfary-BEP top-line data are actually aligned with positive results from a prior second-line MCRC phase 2 trial in BEP9 patients, where the chemo backbone was also failed for Folfuri 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 Onvansative to the first-line setting. As you can see in the table included in today's press release, the Onvansative 30 milligram dose, when combined with FOLFURY BEV, provided a much higher confirmed overall objective response rate of 72.2% versus 43.2% seen with FOLFURY standard of care regimens combined or 42.1% seen with FOLFURY plus BEV standard of care regimen alone. Additionally, median PFS has yet not been reached in either of the unvancitive porphyry 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-milligram Onvansitib arm achieved statistical significance for PFS versus the standard of care, despite the relatively small number of patients. These findings highlight both improved tumor responses and enhanced durability with the addition of Onvansitib on top of standard of care regimen of whole series of PEPs. Further, the PFS hazard ratio was 0.37 when comparing 30 mg on Vansative plus 4-3-BEV arms to the combined standard of care arms. This also achieved 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 BFS or duration of response, and yet we saw consistent dose-dependent responses in the measures of durability with a higher dose of 30 milligrams given with Folfiri plus BEPS. The other important point here is that we expect our registrational study to also compare the unvancative plus Folfiri regimen to the combined standard of care arms when measuring efficacy. The safety and tolerability of Unvancitib when added to standard of care remains favorable and similar to what we have reported previously. No unexpected toxicities or additive A's were reported. Grade 3 or higher A's were infrequent, with neutropenia being one of the most common treatment emerging A across Unvancitib combinations as well as the standard of care arms alone. Together, we believe these data tell a very compelling and consistent story of Unvancitib's practice-changing potential. Based on the totality of the data thus far, we have selected the 30 milligram dose of Unvancitib in combination with 4-3-BEV regimen to bring forward a registrational study in patients with RAS-mutated metastatic CRC in the frontline setting. CARDIS expects to initiate a registration program later this year. The study protocol will likely include comparison of Unvancetive plus Folferi BEV to both standard of care regimens, i.e., Folferi 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 CARDEP-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 a 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 Unvancative. 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. And 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 on Vansative further in clinical development. But 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 CA mod Roger, CSO Todd, and our Chief Accounting Officer, Brigitte. Lisa, you can open the call for questions.

Operator

Thank you. As a reminder, if you would like to ask a question, please press star 11 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 11 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 We'll be coming from the line of Mark Farman of TD Cohen. Your line is open.

Mark Farman, Analyst — TD Cowen

Thanks for taking my questions and welcome aboard, Manny. Maybe just to start off with it, I know the focus is very much on the full theory 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 full box subset of patients? And then looking forward to the phase three, 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

Mani Mohindru, CEO

on full fury on both arms sure um nice to meet you mark as well um let me address what happened in the full fox um and why we haven't included that data in the release we did see activity with full fox in combination with unvancative 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 FOL-FERI arm. So we're 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 FOL-FERI is the right regimen to take forward with Unvancetive in the frontline setting for our next trial. And now to address your question about the phase three trial design, And 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 final end or the total size of the trial. So stay tuned for that. But your question about, you know, making a simplified 4-3-plus advance versus 4-3 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 frontline. And given the robustness of the data, despite small ends, I do want to make it clear, we are able to show that Unvancetive, when combined with Folferi PEV, is better, it appears to be better than both Folferi and Folferi-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 two study in a bigger registration trial. Does that answer the question?

Roger Sidhu MD

Yep. All very helpful.

Operator

One moment for the next question. And our next question will come from the line of Murray Rankoff of Jefferies. Your line is open.

Maury Raycroft, Analyst — Jefferies

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-mig dose in 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

Mani Mohindru, CEO

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 and 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 on it's both 30 plus on 20 milligrams. 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 BFS. 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 BFFs. We do see benefit in both arms, but a 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 If you can keep patients on a combination regimen for a longer time, stable diseases become effective as well.

Maury Raycroft, Analyst — Jefferies

Got it. That'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?

Mani Mohindru, CEO

Again, a very astute observation. Yes, you know, the limitation is small numbers, and the 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 bigger presents enough opportunity to do that we'll present those updated

Maury Raycroft, Analyst — Jefferies

results got it okay thanks for taking my questions one moment for the next

Operator

question. And our next question will come from the line of Ted Tendoff of Piper. Your line is

Ed Tenthoff, Analyst — Piper

open. Great. Thank you very much. Hi, Manny. Congratulations on the new position and on

Mani Mohindru, CEO

really stellar data. Can you hear me okay? Yes. Yes. Hi, Ted. Good to be reconnected.

Ed Tenthoff, Analyst — Piper

Yes. Yes. Great. So, again, congrats on data. That's 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 three trial and or to broaden development beyond the initial indication, as you were sort of mentioning in

Mani Mohindru, CEO

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 um 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 is even So certainly something that would certainly be well-served by bringing a partnership in

Ed Tenthoff, Analyst — Piper

Great. We are working for that, yeah. That makes sense. Looking forward to more details in the data presentation later this year.

Operator

Thank you. one moment for the next question and the next question will be coming from the line of Andy of William Blair your line is open

Andy, Analyst — William Blair

thanks for taking our question and Moni 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 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.

Mani Mohindru, CEO

So, I'll take Roger to take over, but, you know, we have shared, obviously, the baseline characteristics previously, so you should have that data as well, and 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.

Roger Sidhu MD

Yes, you know, randomization has already been sort of completed in the first quarter last year, and we have already shared the baseline characteristics, we are seeing consistent benefit for the 30 milligram co-period combination, key subgroups, which contributes to the robustness of the data moving forward, and we have something to mention.

Mani Mohindru, CEO

Yeah, but at least based on our preliminary assessment, and Roger, you can correct me if I'm wrong, like we really didn't see anything jump out that could have skewed the results one way or the other.

Roger Sidhu MD

That's true. 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 TFS data that we've shared today.

Mani Mohindru, CEO

And the two standard of care regimens, the FOLD-FERI standard of care and the FOLD-FOX standard of care actually behaved very similarly to what has been previously reported, which gives us confidence in the overall data.

Andy, Analyst — William Blair

got it um and and i guess one of the things that were uh striking from the from last year's release was kind of the dose and definite 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 um with higher with the 30 milligram versus serum care or 20 was that also was that trend also

Mani Mohindru, CEO

preserved thank you yes uh so we'll certainly share a lot more details around uh the data in a upcoming event but i'll draw your let chime in as well but i think the depth of response gets uh captured in durability to a certain extent i think it's the combination of depth of response stability which is uh you know captured in in durability measures of bfs and beyond but i'll Roger, to add his perspective as well.

Roger Sidhu MD

Yeah, to address your question, we continue to see an impressive definite response, in particular with the theory of the 9x.

Operator

One moment for the next question.

Operator

And the next question will be coming from the line of Albert Lowe of Craig Hallam. Your line is open.

Roger Sidhu MD

Hi, good morning. A few questions about the data. First, I was wondering, did you see any pronounced dose-dependent effects from Lundvancertib in the full-cloth combination arms?

Mani Mohindru, CEO

So, what we did say that we did see activity of the drug in the Folfox combination arm, but there weren't consistent trends across all efficacy measurements with the Folfox combination.

Andy, Analyst — William Blair

Okay, I see.

Roger Sidhu MD

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 PFF data some more time to mature?

Mani Mohindru, CEO

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. I see. Thank you. Maybe one last

Roger Sidhu MD

question, just to clarify, at the time of the next update that's coming here in the first half, you expect to have already had the means with the FDA to potentially share the finalized trial

Mani Mohindru, CEO

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 within this path. Great. Thanks for taking my

Roger Sidhu MD

questions and nice to meet you here. One moment for the next question. The next question will be

Operator

coming from the line of Kevin Jeter from Lindenburg. Your line is open. Hey, thanks for taking our

Kevin Jeter, Analyst — Ladenburg-Thalman

questions um yeah just one for me um thanks for including the pfs rate at six months um you know particularly in uh what's pretty small cohorts um you know they're numerically you know you know quite similar so is it reasonable to include a lot of the pfs benefit kind of captured in the hazard ratio um it was really kind of separation of the curves kind of 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?

Mani Mohindru, CEO

Thank you. That's an excellent question as well. I think what we wanted to share was a few different things, but in nuanced way. The six-month BFS 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 trends towards improvement with Onvancetib, and that too in a dose-dependent manner, which gives us the confidence of these data. You know, these are small ends, so we have to look at the data every which way, and 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 FOLFURY arm, and we've not disclosed the FOLFURY hazard ratio, but we feel quite comfortable, and not just with FOLFURY alone arm, but even looking at the standard of care regimens combined arm. But the six-month landmark analysis is just to get more confident about what we are looking at, those trends, and the right direction the efficacy is heading.

Kevin Jeter, Analyst — Ladenburg-Thalman

That's a really helpful perspective. Thanks for taking our questions.

Operator

One moment for the next question. And the next question will be coming from the line of Christopher Liu of Lucid Capital Markets. Your line is open.

Christopher Liu, Analyst — Lucid Capital Markets

Hey, guys. Thanks for the question. And it's good to speak to you again, Dr. Mohindra. um congrats on the data so far maybe a question about efficacy and then a question about tolerability for the question about efficacy um what's kind of the median time to response that we see in the 30 milligram 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?

Mani Mohindru, CEO

So you have asked quite specific details. You know, unfortunately, I will not be able to provide full data 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 BFS hazard ratio and the totality there, because in this patient population, stable disease matters as well. You know, we do believe, and we've shared this with you previously, that the depth of response is certainly much better with unvancative combinations, but we should not take stable disease patients lightly. And I think that's important to be captured. And remind me what

Christopher Liu, Analyst — Lucid Capital Markets

your second question was. Sorry. No worries. I was just wondering what the treatment discontinuation

Mani Mohindru, CEO

might have looked like in the 30 milligrams. I would say stay tuned for the full data set, but nothing very... 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 card. There were differences between full FOX and full fee, 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.

Operator

Got it. Thank you very much. One moment for the next question.

Operator

And our last question of the day will come from the line of John Vandermalsen of VAX. Your line is open.

John Vandermalsen, Analyst — VAX

Thank you, and good morning. I think that Pfizer had the right first look for the data from the trial. Was there any response from them or any sign of interest from them at all that you've seen?

Mani Mohindru, CEO

This is too early to comment on that. You know, certainly Pfizer has. we have shared the data and we will continue to share with them and others but too early to say anything beyond this at this point in time.

John Vandermalsen, Analyst — VAX

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 perhaps it's never too early. What are some of the features you're looking for in the full-time CEO?

Mani Mohindru, CEO

Yes, I think certainly, you know, not just the CEO, you know, we're 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.

John Vandermalsen, Analyst — VAX

Great. Thank you, Dr. Andrew. Appreciate it.

Operator

Thank you. Thank you. This does conclude today's Q&A session. I would like to turn the call back over to Mani Mohandru, Interim Chief Executive Officer. Please go ahead.

Mani Mohindru, CEO

Thank you, Lisa. We're incredibly excited about the potential opportunities within Vansative 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.

Operator

Thank you. This does conclude today's program. Thank you so much for joining. You may now disconnect.