Ladies and gentlemen, thank you for standing by. Welcome to the Cardiff Oncology ASCO Data Presentation conference 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. To ask a question during this session, you will need to press star one one on your telephone, and you will then hear an automated message advising your hand is raised. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Hannah Ertman of Astra Partners. Please go ahead. Thank you, operator. During this conference call, the Cardiff management team will make forward-looking statements, including, without limitation, statements related to guidance, results, and the timing of data readouts for onvansertib clinical trials. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. Actual results and the timing of 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 the company describes in the section titled "Risk Factors" in its annual report on Form 10-K, filed with the SEC for the year ended December 31st, 2025. 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 will turn the call over to Cardiff's President and Chief Executive Officer, Mani Mohindru. Thank you, Hannah. Thank you all for joining this morning. Good morning. We are very excited to share the promising results from our CRDF-004 phase II study, first presented yesterday at ASCO by Dr. Heinz-Josef Lenz, who is fortunately also with us on our call today. Today's discussion will go beyond the ASCO presentation with additional data analysis and insights that further strengthen our confidence in onvansertib's potential in first-line RAS mutated metastatic colorectal cancer. We will also discuss our planned next steps for the program following a successful end of phase II meeting with the FDA this quarter. I'm very pleased that we have with us today not one, but hopefully two world-renowned GI oncologists. Dr. Heinz-Josef Lenz from USC, and we're hoping that Dr. Josep Tabernero from Barcelona, Spain, should also be joining us should his plane get there in time. Their clinical perspectives would be very critical in answering some of your questions. On the slide, the clinical positions and institutional affiliations can be seen on slide number three. I hope the slides are online. Okay. Following today's presentation, our CFO, Josh Muntner, will also be with me during the Q&A session. Going to slide four. You know what? I cannot see the slides. I'm not sure if the others can see it. Operator and Hannah, can you please make sure that the slides are online? Assuming the slides are there, if not, we'll move to slide four, which is a transition slide. Before we get into phase II data, let me quickly highlight the significant unmet need in first-line RAS mutated metastatic colorectal cancer and the opportunity we believe onvansertib is uniquely positioned to address. The slide should be up there. If they're not, I will move to slide five. The slide should be on our website as well. Slide five provides a high-level overview of onvansertib, our PLK1 inhibitor, that has practice-changing potential in first-line RAS mutated MCRC. Polo-like kinase 1 or PLK1 is an important target that plays an important role in cell division and tumor cell survival. Our strong confidence in onvansertib's potential is built on three key pillars. First, strong efficacy. The 30 mg dose of onvansertib combined with SoC and bevacizumab, which I will refer to as SoC/BEV, demonstrated 30% improvement in objective response rate or ORR with median progression-free survival or PFS that has not been reached in the treatment arm as of the March 18th data cut. Of note, the CRDF-004 trial is still ongoing with patients being treated on different treatment arms. These data are aligned with our prior phase I-B/II trial in second-line BEV-naive patients. We will go through our phase II data in more detail shortly. Second, the large commercial opportunity. First-line RAS-mutated MCRC represents an area of high unmet need with limited innovation over several years. There are no therapies approved specifically for pan-RAS-mutated MCRC except for KRAS G12C subtype. onvansertib, through PLK1 inhibition, has the potential to address MCRC with all RAS mutations. Number three, the clear registration path. We recently completed a successful end of phase II meeting with the FDA, where we aligned on the registrational path in first-line RAS mutated MCRC. The Phase III trial, CRDF-005, is being designed to support both accelerated approval via ORR and durability, and full approval via PFS. Slide six. The next slide shows why our data matter and the patients we aim to treat. Approximately 150,000 new patients are diagnosed with colon cancer in the U.S. each year, with 20% presenting with metastatic disease. Of this MCRC population, approximately 50% have cancers with RAS mutations, and only a small portion of these have G12C mutations, with the option to be treated with allele-specific inhibitors. First-line standard of care for most patients with RAS mutations have remained unchanged for 20 years. That is, chemotherapy backbone of FOLFOX, FOLFOXIRI, or FOLFOXIRI combined with BEV. Unfortunately, the median five-year overall survival is still only 15%, with median PFS of less than 12 months. Importantly, with no approved therapies available for pan-RAS mutated MCRC, we believe onvansertib has the potential to address a major unmet need and become a first-in-class treatment of these patients if successful in phase III. Slide seven shows data from two historic phase III trials that define the current standard of care in RAS-mutated disease. ORR in the 40% range with IFL plus BEV, with PFS of 9.3 months versus 5.5 months with chemo alone. The trial of FOLFOXIRI/BEV, a less tolerable regimen, shows a 66% ORR in RAS-mutated subgroup and a PFS of 12 months with less than three months of improvement over chemo. These are some of the benchmarks the field has been working against, and we believe CRDF004 phase II data compares favorably to these established outcomes. Next slide. With that context in mind, let's turn over to CRDF-004 results and the data that underpin our confidence in onvansertib. I'll highlight the promising updated interim results from the phase II trial that were presented by Dr. Lenz at ASCO yesterday, along with additional analysis and data not included in the ASCO presentation. All results are based on March 18th, 2026, data cutoff. Slide nine shows the trial design of CRDF-004, a dose-finding, randomized control, phase II trial. Enrollment criteria required first-line MCRC with KRAS or NRAS mutation. Key exclusion criteria were BRAF V600 mutation, MSI high or deficient mismatch repair tumors, resectable disease, and prior BEV treatment. The trial was designed to enroll 110 patients, the ITT population, across six arms in equal randomization. The six arms tested two doses of onvansertib, 20 mg and 30 mg, combined with either FOLFIRI-BEV or FOLFOX-BEV, the two standard of care regimens, compared to each backbone alone as control. The goal of this trial was to determine a dose and regimen to bring forward into further development. The primary endpoint is ORR, assessed by Blinded Independent Central Review or BICR, and secondary endpoints were duration of response and PFS. Slide 10 shows the demographics and baseline characteristics that were largely balanced across all six arms for a trial of this size and this stage in development. Of note, the trial did enroll patients with liver mets and multi-organ involvement, two patient populations with worse outcomes on the current standard of care. Slide 11 shows the current status of the study as of the March 18th, 2026, data cutoff. Importantly, the trial is still ongoing with 13 of the 14 patients still in the study are from the onvansertib plus Standard of Care chemo BEV arms. Nine of these patients are onvansertib plus FOLFIRI-BEV arms, the chemo combination we intend to take forward in the phase III trial. Next slide. Slide 12 shows the primary endpoint of ORR. I just want to walk through it a little carefully, given that it's the primary endpoint. As you can see on the right side of the slide, in the 30 mg onvansertib plus FOLFIRI-BEV arm, confirmed ORR by BICR was 72.2%, and the FOLFIRI-BEV control arm showed an ORR of 42.1%. That is very encouraging, 30 percentage point improvement over Standard of Care in this randomized study. In the middle, you can see that the 20 mg arm showed an ORR of 44.4%, with some deeper responses versus the control arm, indicating some dose-dependent effect and confirming that 30 mg is the more active dose. This is also supported by PK exposure response analysis, data of which are not included here. The combined ORR for both 20 mg and 30 mg onvansertib FOLFIRI-BEV is 58.3%. Importantly, nine patients remain on treatment in the onvansertib plus FOLFIRI-BEV arm, and only one patient in the FOLFIRI-BEV control arm, as shown by dark arrowheads. The depth of response in the 30 mg arm is also quite notable. This waterfall plot analysis shows that the majority of patients achieving substantial tumor shrinkage, including several with near-complete or complete responses. Moving on to the swimmer plots on slide 13. This slide also tells an equally important story about durability. In the 30 mg FOLFIRI-BEV arm, four patients have been on treatment for more than 15 months as of March 18 data cut, with two on greater than 18 months of treatment. Slide 14, the spider plot slide, shows individual patient tumor burden trajectories. In the 30 mg onvansertib plus FOLFIRI-BEV arm, the majority of patients showed sustained progressive tumor shrinkage over time. In our view, this promising profile is consistent with a therapy producing durable, clinically meaningful benefit. Next slide, Slide 15, shows progression-free survival, including Kaplan-Meier curve for PFS. When comparing both onvansertib doses together, plus FOLFIRI-BEV against combined Standard of Care regimens, the hazard ratio by BICR analysis is 0.44, with a median PFS that has not been reached in the onvansertib arm versus 11.04 months in the control arm. The investigator-assessed hazard ratio is 0.53 with a median PFS again, not reached in the onvansertib arm versus 10.97 months in the control arm. With sample sizes of approximately 36-37 patients per comparison, the directional signal is very encouraging and consistent across both assessment methods. For a study of this size that is not powered for PFS, these are very promising trends. Moving to slide 16 and looking at the selected phase III dose, specifically the 30 mg onvansertib plus FOLFIRI-BEV regimen. Median PFS has not been reached in the treatment arm and some patients continue to remain on treatment. Median PFS in the FOLFIRI-BEV control arm was 18.89 months by BICR and 12.22 months by investigator assessment. The hazard ratio by BICR and investigator assessment are very similar at 0.55 and 0.57 respectively. The slight discordance between BICR and investigator-assessed median PFS in the control arm reflects a phenomenon seen in early stage or even some phase III studies. In certain of our cases, investigators assessed and recorded progressive disease and discontinued these patients prior to their BICR confirmation. Moving to slide 17. The ORR forest plot on this slide compares 30 mg onvansertib plus FOLFIRI-BEV versus FOLFIRI-BEV control arms across various baseline characteristics as shown. The ORR benefit consistently favors treatment arm across all subgroups. This is highly encouraging and indicates that the efficacy signal is not driven by any single patient characteristics. Notably, benefit with onvansertib plus FOLFIRI is seen even in difficult to treat subgroups such as those with liver mets as well as multi-organ involvement. Slide eight shows forest plot for subgroup analysis for PFS. The PFS forest plot shows the same pattern as the ORR forest plot. Hazard ratios favor the 30 mg arm across all subgroups. Given the small patient numbers within individual subgroups, confidence intervals are appropriately wide, but the directional consistency across every subgroup strengthens our confidence in the overall signal and the meaningful clinical benefit of onvansertib in this patient population. Slide 19 highlights the safety profile of onvansertib and shows that it is quite tolerable. Adding onvansertib to FOLFIRI-BEV or FOLFOX-BEV does not introduce unexpected overlapping or new toxicities. The most common adverse events are consistent with the known profile of the background chemo and BEV regimens. Grade 3 or higher events are comparable across arms and no unusual or unexpected onvansertib-specific safety signals have been identified. This safety profile is supportive of the phase III program in the first line setting and also highlights the differentiation of onvansertib as a tolerable agent that can be potentially added to other synergistic chemo combinations. Moving to slide 20, that shows FOLFOX combination data. Similar to what we had reported in January of 2026, I want to mention again that adding onvansertib at either dose to the FOLFOX-BEV regimen did not produce very meaningful improvement in ORR or PFS versus FOLFOX-BEV alone. Although we do see some improvement in few patients. ORR in all FOLFOX arms ranged from 44%-56% with no consistent dose response trend and no PFS benefit observed with the onvansertib addition. While this combination did not show much additive benefit, it is not completely unexpected, and I will address the scientific rationale for onvansertib synergy with FOLFIRI versus FOLFOX in the next couple slides. Moving to slide 21. We have some data-driven mechanistic explanation and hypothesis as to why onvansertib synergizes better with FOLFIRI and not FOLFOX. Both onvansertib through PLK1 inhibition and irinotecan, the active component of FOLFIRI, suppress HIF-1α, a critical driver of tumor vascularization and survival in the hypoxic tumor microenvironment. The result is a triple anti-angiogenic effect. Onvansertib suppresses HIF-1α, irinotecan suppresses HIF-1α, and the BEV treatment blocks VEGF, which is vascular growth factor. Additionally, onvansertib likely also inhibits PLK-dependent DNA repair downstream of irinotecan-induced DNA damage, which highlights a second mechanism of synergy between onvansertib and irinotecan. In contrast, oxaliplatin in the backbone of FOLFOX does not suppress HIF-1α and uses a DNA repair mechanism with limited PLK1 dependence or no meaningful role. These mechanistic differences between irinotecan and oxaliplatin may explain the absence of synergy with FOLFOX and differential outcomes in the current study. More importantly, CRDF-004 is the second trial where we see synergy of the onvansertib with FOLFIRI-BEV. Our prior phase I-B/II trial with onvansertib plus FOLFIRI-BEV in second-line in BEV-naive patients with KRAS-mutated mCRC also showed improved clinical outcomes with this chemo regimen, reiterating our confidence in taking this regimen forward in the phase III. As shown in slide 22, we believe that CRDF-004 trial achieved all key goals and endpoints needed to move the program forward into a registrational trial. The primary goal, dose selection, is complete. 30 mg of onvansertib plus FOLFIRI-BEV is the dose and regimen we plan to advance into a phase III trial after discussions with the FDA during our end of phase II meeting. This dose and regimen demonstrated both superior efficacy and an acceptable safety profile. The primary efficacy endpoint of ORR was met. 30 mg demonstrated compelling ORR of 72%, a 30 percentage point improvement over standard of care. The secondary endpoint is also quite favorable and promising. As of the March 18th, 2026, data cut, median PFS has not been reached in the 30 mg arm, with nine of 14 patients still on onvansertib plus FOLFIRI-BEV treatment at the time of data cutoff. These strong phase II data support advancement of onvansertib into registrational development, and I will discuss our plans in the next slide. Slide 24 shows the trial design of our proposed pivotal phase III trial, CRDF-004. Sorry, CRDF-005. CRDF-005 is designed as a global registrational Phase III study. While we will continue to refine some elements of the trial, shown here is the design of our pivotal trial after feedback from the FDA at our end of Phase II meeting, completed in the second quarter of 2026. EMA feedback is pending. The trial, as designed, is a randomized control study with one-to-one randomization of patients to 30 mg of onvansertib plus FOLFIRI-BEV treatment versus FOLFIRI-BEV treatment alone. Enrollment criteria are consistent with the CRDF-004 trial. First-line mCRC, presence of KRAS or NRAS mutation, no BRAF V600 mutations, no MSI High or deficient mismatch repair, unresectable tumors with no prior BEV treatment. The study's dual primary endpoints are ORR, which supports accelerated approval, and PFS, which supports full approval. Secondary endpoints include duration of response and overall survival. The proposed sample size is approximately 640 patients, powered at greater than 90% to detect differences in both ORR and PFS endpoint. Moving to slide 25, let me close with few points. Number one, there have been no meaningful therapeutic advances in first-line RAS-mutated mCRC over many years. The unmet need is large, and the commercial opportunity is significant. Number two, we now have a clinical trial outcome from two studies, our prior phase I/II study in second-line RAS-mutated mCRC and the current ongoing CRDF-004 randomized controlled phase II trial in first-line RAS-mutated mCRC that both confirm that onvansertib synergizes with FOLFIRI-BEV in BEV-naive patients. This is a reproducible and promising signal supported by scientific data and mechanistic rationale. Number three, in the ongoing CRDF-004 trial, 30 mg onvansertib with FOLFIRI-BEV shows an ORR of 72%, 30 percentage points over standard of care, with a median PFS not yet reached in the treatment arm and patients on treatment beyond 15-18 months, and no meaningful safety signals have been observed. Number four, we have FDA alignment on the phase III design with a path to both accelerated and full approval if successful. Number five, going forward, our focus remains single-handedly on the execution of the pivotal program. Before opening the questions, I would like to turn the call over to both of our KOLs, but I'll start with Dr. Tabernero first. I would first like to thank him for joining this call shortly after landing in Spain. Dr. Tabernero will provide his- Yeah, thank you very much. Thank you. I'm sorry for being a little bit late, but my flight from Chicago to Barcelona was a little bit delayed. I think that the data speaks by itself, and Dr. Lenz, for sure, can provide more accurate messages as he did present all this data just one day ago, and there was a lot of interaction and questions because actually the data was really very exciting during the session that we had on Tuesday morning at ASCO. Perhaps just to complement on what has been mentioned before, and I completely agree that there are no new treatment options that we foresee for this difficult to treat population. One may raise whether, with the number of iso-specific RAS inhibitors, pan-RAS inhibitors, pan-KRAS inhibitors, actually, there is some opportunity for a compound like onvansertib. My answer is yes, basically because the data that we have seen at ASCO with a pan-RAS inhibitor for pancreatic cancer, it's very exciting. Everyone is very happy about this situation for a difficult to treat population. Combinability of a pan-RAS inhibitor with conventional chemotherapy, plus bevacizumab, is something challenging, right? In here, we have a compound that has demonstrated match very well with chemotherapy, especially with FOLFIRI, and the results that have been presented are spectacular. I do fully support trying to evaluate the activity of onvansertib combined with FOLFIRI and bevacizumab in the first line setting of this patient population with KRAS and NRAS mutations. Actually, I think that the sign that has been presented, it's really very good to illustrate the proposed dual primary endpoints, and honestly, I think that this trial would recruit very well. Happy to answer any specific question that you may have. Thank you, Dr. Tabernero. Dr. Lenz, I'd love to hear your perspective as well, and especially since you have experience treating patients with this drug. Sure. Good morning, everyone. Yeah, I have been involved with the onvansertib from the beginning. We did the first phase I trial, and I was particularly excited about the incredible inhibition of PLK1 and interfering with really the major cycling pathways. You heard about the HIF-1 alpha angiogenesis. It overcomes chemo resistance by really interfering with the cell cycle arrest, and it has actually immunomodulatory. Then with the preclinical data showing the significant synergism with irinotecan, because irinotecan established on the DNA effect and oxaliplatin, more DNA adduct. It explains very well the differential in synergism between onvansertib and irinotecan and bevacizumab. We saw very early on a clinical signal of efficacy. I think what really stands out that this drug is very well-tolerated. It's five days of oral medication out of a two-week cycle, and patients tolerate it very well. When I looked at the new data and we had the phase I-B and the patient with no prior bevacizumab treatment had 71%, that really was the basis to develop this randomized phase II, which now really confirmed the significant synergism between FOLFIRI-BEV and onvansertib with no safety signals. I think I'm very excited about the 72%. I'm very excited about the hazard ratio of PFS. I think Dr. Tabernero is completely correct. I think there are pan-RAS inhibitors which show some interesting efficacy, but the problem is really the toxicity limiting combining these pan-RAS inhibitors with any kind of chemotherapy or target agents. This is one of the few trials which actually showed that we can combine easily onvansertib with chemotherapy with no safety signals and no toxicity and high efficacy. I think this is a very promising strategy, and I can only hope that this will go into a registration as soon as possible that we can enroll patients to really advance that field. Thank you so much. Thanks a lot for your perspectives. Operator, we can now open the line for Q&A. Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question comes from Maury Raycroft with Jefferies. Your line is now open. Hi. Thank you for taking our questions. This is Amin on for Maury. Two from us. First, you've shown a clear ORR separation between the 20 mg and 30 mg. How should we think about the durability across the two doses, and are you seeing a meaningful PFS separation between the two doses? One question for Dr. Lenz and Dr. Tabernero. Among patients with RAS mutations, who do you think is most likely to benefit from adding onvansertib to the FOLFIRI-BEV backbone? Are there specific clinical features you're focused on for patients who can benefit the most from this drug? Probably I'll take the first question and then I'll let the two KOLs answer the second part. On the first question of 20 mg versus 30 mg, if I understood correctly, the separation in ORR and how does it tie to durability, is that right, Amin? That's correct. Yes. The 20 mg showed an ORR of around 44% and the 30 mg approximately 72%. You do see a dose trend although the 40 mg sounds closer to the standard of care. However, we do believe that 20 mg is an active dose. We have internal data which shows overlapping PK between the two doses, and there is dose exposure-response relationship as well. Secondly, the PFS benefit that you see with 20 mg also shows the hazard ratios between 20 mg and 30 mg by investigator assessment also show a dose-dependent trend in improvement. This is not unusual. If you go back to the slide where I had shown initial addition of BEV on IFL and BEV on FOLFOXIRI, you can see that BEV did not add too much to the ORR but had a significant improvement in PFS. It may be these patients and the KOLs can talk to it more, but we do believe a 20 mg is an active dose, but certainly 30 mg is a dose that provides the punch needed to take to phase III. Maybe I'll start with Dr. Lenz first and then go to Dr. Tabernero for the second part of the question. If I understand your question was really if it applies for all KRAS and NRAS mutation and if there are specific patients who benefit the most? That's correct, yes. Okay. From our data, we do not see that certain mutations have less or more benefit. It seems to really like the pan-RAS inhibitor affecting all the KRAS mutation as well as the NRAS mutations. The reason is very easy because we are not binding to a very specific KRAS mutation which limits the use and the development of allele-specific inhibitors. It's a downstream event of the downstream signaling interfering with all major oncogenic signaling pathways. We don't see a particular indication that some of the classes of the KRAS or NRAS mutations have differential benefit. What was the second part? I think that was it. That was it. Okay. I think this is a very unique target because it really interferes with the downstream oncogene activated signaling with the KRAS and NRAS mutations, and not depending on the binding affinity or characteristic of allele-specific or pan-RAS inhibitors. Dr. Tabernero, if you have any specific opinions about what kind of patients with RAS mutations would benefit with a drug like onvansertib? I fully concur on your answer and Professor Lenz answer. The important things here is that the RAS signaling, independently of the KRAS and NRAS mutations that the tumor of the patient has, it's very constant. The profound effect that it uses in the ERK pathway, it's very similar. This has been very well documented in several papers. I remember one published in Clinical Cancer Research where the authors look at what they call RAS signaling score. They evaluated the different cells and different in vivo models with different RAS and NRAS mutations. The RAS signaling score was very similar in terms of activation of the ERK pathway. I don't foresee that there are going to be differences in the profile of patients depending on the RAS mutation that their tumors bear, for the activity of onvansertib. Yeah. I wanted to follow up, and you also mentioned a very important point. We will obviously look for KRAS and NRAS mutation, in a large study we published a couple of years ago in The Lancet showing the efficacy of cetuximab in wild-type RAS because the KRAS mutation was excluded. As Josep mentioned, there were wild-type RAS patients who had activated oncogenic signaling in the RAS pathway, which did not respond. I think the onvansertib would also work in this patient population based on the activation downstream pathway. There is certainly very interesting aspects biologically which would expand that to certain wild-type patients if we can identify the activated pathways downstream. Thank you so much. Thank you. Thank you. The next question will come from Marc Frahm with TD Cowen, and your line's open. Hey. Thanks for taking my questions this morning. Maybe just to start on the trial design for the proposed phase III that came out of the FDA meeting. You've mentioned the potential for accelerated approval on response rate. Can you maybe discuss when that analysis would be able to be taken within the trial? Do you need the full enrollment of the entire trial? Do you need response rate on everyone, or could you take that on a much smaller sample than the full 640 that you'll need ultimately for PFS and full approval? Yes. Without going into every detail of our discussions with the FDA, broadly, I will say that yes, the FDA did give us guidance as to what could lead to ORR-based accelerated approval. One of which I will say was that they expect the trial to be fully enrolled and also to make sure there's no detriment to survival. I will stop at that. While there is a path forward for accelerated approval with a certain number of patients and durability data, we believe that the trial has to at least be fully enrolled by the time we take it to the FDA. Okay. That's helpful. Not fully read out. Yeah. Not fully read out. Yeah. Okay. Just on the data that you presented, can you maybe speak to the relative dose intensity that you're able to achieve with the chemotherapies in the different dosing arms and is there any chance that some relative differences in tolerance of the chemo may be contributing at least some of the apparent treatment effect? Let me begin by talking about safety first. The safety profile is very similar across both chemo regimens, FOLFOX and FOLFIRI. In terms of tolerability and if there were any kind of dose reductions or dose discontinuations of chemo, there are differentials. In the irinotecan arm, we hardly saw any reduction or discontinuation in irinotecan. However, in oxaliplatin or FOLFOX regimen, there were discontinuations of the oxaliplatin regimen, but that is not unusual. That is similar to what has been reported in everyday practice. I would let Dr. Lenz and Dr. Tabernero comment on that as well, like, do you actually discontinue oxaliplatin in few patients based on tolerability? That's what we saw in the study as well. Yeah. Usually, when you have an effective chemo strategy such as FOLFIRI, you don't have really a cumulative toxicities as you have with oxaliplatin. As you probably know, with FOLFOX, many of the investigators hold or stop the oxaliplatin after four months of treatment because of the anticipated neurotoxicity. You have also a little bit more differential hematological toxicity with oxaliplatin, with more thrombocytopenia and particular anemia. In the FOLFIRI regimen, you see actually usually very well-tolerated. In our clinical trials, we did not really have significant holding of treatment or dose modification. It's a very safe, very effective treatment regimen. The reason I think FOLFIRI is a not only biologically great partner because you can actually treat till progression with no cumulative toxicities over time. Thank you, Dr. Lenz. Dr. Tabernero, do you want to add anything to it? Yeah. Well, if the experimental drug does not have any interaction with none of the components of FOLFIRI, and this is irinotecan, but also the first metabolite, SN-38, fluorouracil or capecitabine. Usually, the combinations are really very tolerable. The advantage of FOLFIRI compared to FOLFOX is you can really treat patients until progression of the disease or an acceptable toxicity. Because usually, you don't have any kind of toxicity that mandates reducing or omitting the irinotecan treatment on the midterm, on the long-term basis. As you know, with oxaliplatin, although it's a very preferred chemotherapy backbone, there are several aspects that limit the compliance and the dose intensity of oxaliplatin. This is not only with this drug, it's with all experimental drugs. On top of that, actually, everyone knows that after four months of treatment, because of the increasing sensitive polyneuropathy, oxaliplatin has to be dropped out. This is the reason, on top of the efficacy and safety data, that FOLFIRI, it's a well-accepted regimen and very combinable. Just to put you other examples. Also at ASCO, we have seen the data of another situation, and this is a BRAF, which is converting mutant population in metastatic colorectal cancer. The data has been presented on this occasion is a combination of FOLFIRI and encorafenib versus FOLFIRI-BEV in the BRAF mutant population. I want to make clear that is a different population. The important thing here is that the combination was very tolerable, and those patients could be treated for many, many months. In this particular case, actually, even the results were as slightly better than with FOLFOX. I do think that all these aspects fully support the FOLFIRI combination. Maybe it's also interesting that particular in Europe and Asia, FOLFIRI-BEV as a first-line, or FOLFIRI as a backbone, is a preferred combination treatment. In the U.S., it's usually FOLFOX-BEV, with data showing like the Cardiff 004 study, the efficacy always trumps decisions what treatment we do because they're equally effective when you compare side by side. If the combinations show significance in that system, I don't think there's any issue to use that also in the U.S. I agree with Professor Lenz. At the end, physicians and patients, of course, the final preference for the treatment options is the activity and the safety. I do think that this trial is going to be recruiting very rapidly. Thank you, Dr. Lenz and Dr. Tabernero. Operator, the next question. Thank you. The next question is going to come from Andy Hsieh with William Blair. Your line's open. Thanks for taking our question. Now we have full results, efficacy, PFS, median hazard ratio, the 004 study. I'm curious for the 005 study, maybe just kind of an expansion from Marc's question earlier. In terms of PFS, I'm curious if you can describe what level of risk reduction you expect from the 640-patient sample size. We also have a question for Dr. Lenz and Dr. Tabernero. In terms of the spider plot, we saw some dramatic reductions on the onvansertib arm, around six from the FOLFIRI cohort. I'm curious if you can describe the nature of these patients. Do you see those dramatic reductions pretty common, or it's kind of a rare occasion or an onvansertib-specific phenomenon? Curious about your thoughts on that. Lastly, for Mani, maybe just in terms of Nerviano, what is the next step that we can expect regarding potential resolution or how to go forward? Thanks. Thank you, Andy. I'll start with the third first and put it to rest. We can focus on the scientific discussion. Regarding Nerviano, as you know, we are in dispute, and we tried to resolve the dispute outside of courts, but reached a point where we felt that it was quicker and more expedited. It was important for us to get this resolved in a more expedited manner, and we sought legal intervention. The dispute was related to, obviously, authorship or inventorship in our patents, which we believe are still awarded patents based on the inventorship, and we will continue to defend that. Regarding commercially reasonable efforts, we have made a lot of efforts getting the program to this point and into phase III. We will continue to defend our position, and we hope to reach a resolution very soon. We are open to resolution in and outside the courts. With that done, I will address the first question about the size, whether the size of the phase III study can be reduced. It is too early and premature to comment on reduction in any size based on the current data. The CRDF-004 trial is still ongoing. Median PFS hasn't been reached, but we have designed the study, the CRDF-005 study, to ensure that we have a higher probability of success. The powering and all has been made with keeping that in mind, that we power the study adequately for both accelerated and full approval with PFS. I will let Dr. Tabernero maybe start first on the spider plot. The deeper spider plots that you see, is it unusual? Do you see it with other therapies or not? Sorry, I was on mute. Thank you for the question. Actually, I think that the data with the forest plot is really amazing, right? I have to tell you, for that actually, it's very good to see the activity in terms of not only tumor shrinkage, but also response rate that we have even for the control arm, right? That it's 42%. This is what is in the literature. Both for FOLFIRI-BEV and for FOLFOX-BEV, usually the response rate, when it's independently reviewed by external radiologists, is around 38%-40%, right? The data that we have in the control arm really fits what it's expected for the control arm, right? When you go to the experimental arms, I think that the data that we have on overall response rate for FOLFIRI-BEV, especially at the dose of onvansertib of 30 mg with an overall response rate confirmed 72%, this is amazing. It's not only that, when you look at the forest plot evaluating patient by patient, actually you see that it's not only about the overall response rate, but it's also about the patients that have disease control. You can see that only one patient actually had a slight increase by 8% in the lesion, right? All the others had any kind of tumor shrinkage. Again, the impressive 72% overall response rate, it's really amazing for a combination of FOLFIRI-BEV in this setting, right? Without any doubt, the addition of the experimental drug, onvansertib, makes a difference. Dr. Lenz, would you comment? Sure from your perspective on the depth of responses from forest plot? Whoever asked is a very smart person, and I think this is really a standout observation because usually it takes four to five months to really have the full response. In many patients in this one particular tumor one, it was very fast. I think there is a very unique dynamic, and when you look at the waterfall plot, five patients had basically no detectable disease out of 18. I think this rapid response, as Dr. Tabernero mentioned, is very unique. There is basically not an innate resistance, and it seems the duration of response is very long. It almost looks like an immunotherapy efficacy profile. I don't think we have a very good understanding who these patients are. We had in the phase I-B, II, we looked for the circulating DNA with allele-specific measurements of the mutations of the patient and the ones who had more than 90% within four weeks, and it was a very rapid decline in that one. These patients did the best, but that was relative to a small patient population. I think highlighting this significant dynamic and fast response of these patients. Thank you, Dr. Lenz. Andy, I apologize if I have misunderstood your question. If you were trying to ask our statistical assumptions that led to the design and the size of the study based on PFS movements, again, without divulging all the details, we have been conservative in designing the study. It's not as aggressive as 0.5 hazard ratio that has been reported in phase II. We've been realistic and looked prior phase II to phase III results. We have taken that into account while designing the size of the phase III study. I hope that answers your question. Yeah. Thanks for clarifying that. Yes, I was asking about the sample size. Not about sample size, but about the risk reduction. Thank you. Yes. We have been conservative, is what I can say in our assumptions. Operator, the next question, please. Thank you. Our next question is going to come from Albert Lowe with Craig-Hallum. Your line's open. Hi. I think, Mani, you referenced it in your comments that the 20 mg dose with FOLFIRI-BEV is active. Could you share what the PFS and hazard ratio was for the specific dose arm? Yes. The median PFS hasn't been reached, but we did not share the details of it. I'm happy to share, but I don't have it at the top of my mind, but it is a little bit higher. The hazard ratio is higher than what has been reported with the 30 mg arm with the investigator-assessed metric. I don't have it at the top of my head, but it is directionally, if you look at investigator assessment-based analysis, it is directionally, the hazard ratio is a little bit higher than what has been reported. It's higher than 0.5. Okay. Thank you. What we have reported for the phase II, 30 mg. It's higher than 30 mg. Yeah. Okay. I was wondering what the timeline for potentially starting this phase III trial is. Could it begin while this license agreement dispute is still outstanding? Pending funding, we expect to start the phase III initiation-related activities late this year or early next year. This litigation or this dispute is ongoing, and I don't think it impacts any of our activities because, for us, the license agreement is still active and the patents are ours. From our perspective, it is business as usual. Great. Thank you. Thank you. The next question is going to come from Christopher Lui with Lucid Capital Markets. Your line's open. Hey, guys. Thanks for the questions and congrats on the data. Two from me. I guess for the first question, have you guys done any kind of analysis to discern why there's such a stark difference in efficacy between the 20 mg and 30 mg? Any additional analyses? For the second question, quite a few patients in the 30 mg arm were able to get 100% tumor regression in the target tumor. Just wondering what made those patients go off treatment. Maybe I'll start on the 20 mg versus 30 mg. They do have overlapping PKs. There is a dose exposure versus response relationship there, both in terms of ORR and PFS. While there wasn't as much of a difference in PFS, the ORRs were definitely different. As I said, with Avastin, you have seen similar phenomenon where you don't see too much of an impact on ORR, but much more benefit with PFS. We similarly see that in 20 mg versus 30 mg. The trial is still ongoing. We will continue to do more exposure-based analysis. From our perspective, we have the right dose to take forward in the phase III, and we also believe that 20 mg dose is active, maybe not as high as 30 mg dose. Remind me what was The patients discontinued. The tumor reduction. Yeah. On the second question, with a 30 mg dose, you said that patients had very deep responses. There was a lot of reduction in target lesions. Most of them continued to be on treatment for a long time. We will continue to assess and come up with the median PFS there. There were discontinuations due to various reasons, but very few due to progressive disease. I can tell you that in the 30 mg arm, there were very few due to progressive disease. There could be other reasons, whether related to patient decisions. Actually, five patients went on curative surgery as well in the 30 mg arm. The highest numbers of patients who went on curative surgery was with the 30 mg arm. Hopefully that answers your question. That's a very important point because I think with higher efficacy, with response rate over 70%, we will see more and more patients who will become eligible for curative resections. I think it's very important to know colon cancer is a very unique cancer. If you shrink it and you can resect it and remove the metastatic disease, these patients have a good chance of cure. That's not true for many other solid tumors. In breast cancer, you can never cure a metastatic disease. In colon cancer, because of the biology, if you can remove these metastatic sites in really well-controlled metastatic cancer patients, you have a very good chance of cure. These patients, obviously, depending when they had a really good pathological response and how much treatment they got, may not continue or may not need further chemotherapy. Thank you, Dr. Lenz. Yes, and hopefully we'll be able to publish the full results of the study in the coming months where you can see. I can tell you that, yes, the most number of curative surgeries were in the 30 mg onvansertib plus FOLFIRI arm. Next question. I think we're coming at the top of the hour. Operator, do you have any more questions? I am showing no further questions at this time. I'd like to turn it back over to Mani for closing remarks. Thank you, operator. Before I conclude, I would like to thank the patients and their families who placed their trust in our clinical trials. Their participation makes this work possible, and it is the foundation of the data we shared today. I also want to recognize our investigators, especially Dr. Lenz, our advisors, consultants, Dr. Tabernero for stepping onto this call right after landing in Spain, our investors, and importantly, Cardiff employees for their dedication and commitment. We believe today's results represent an important step forward and further strengthen our confidence in the potential of onvansertib in RAS-mutated mCRC and beyond. While there is still work ahead, we remain focused on advancing this therapy for patients and creating value for stakeholders. Thank you for joining us today, and we look forward to updating you on our continued progress to the registration trial. Thank you, everyone. Have a good day. Thank you. Thank you. Thank you. This concludes the conference call. Thank you for participating, and you may now disconnect.