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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 would need to press SAR11 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 Astro 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 unventurative clinical trials. These forward-looking statements are based on the company's current expectations and inherently involves 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 uncertainty. 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 Mohindra. Thank you, Hannah, and thank you all for joining this morning. Good morning. We are very excited to share the promising results from our CRDF004 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 unvancited 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-Joseph Lenz from USC, and we're hoping that Dr. Joseph Debonaro 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. Okay, following today's presentation, our CFO, Josh Munchner, will also be with me during the Q&A session. Before we get into Phase 2 data, let me quickly highlight the significant unmet need in first-line RAS-mutated metastatic colorectal cancer and the opportunity we believe Unvancitib is uniquely positioned to address. The slides should be up there. If they're not, I will move to slide 5, which the slides should on our website as well. Side 5 provides a high-level interview of Unvancitib, our PLK1 inhibitor, that has practice-changing potential in first-line RAS-mutated MCRC. Polo-like kinase 1, or PLK-1, is an important target that plays an important role in cell division and tumor-sick survival. Our strong confidence in Unvanceitib's potential is built on three key pillars. First, strong efficacy. The 30-milligram dose of unbancitib combined with folsiri and bevacizumab, which I will refer to as folsirib-bev, demonstrated 30% improvement in objective response rate, or ORR, with median progression-free survival of BFS that has not been reached in the treatment arm as of the March 18th data cut. Of note, the CRDS-004 trial is still ongoing, with patients being treated on different treatment arms. These data are aligned with our prior Phase 1B-2 trial in second-line web-naive patients. We will go through our Phase 2 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 band RAS-mutated MCRC except for KRAS-G12C subtypes. On Bansitib to PLK1 inhibition has the potential to address MCRC on all RAS mutations. And 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 MCR-C. The phase 3 trial, CRDF-005, is being designed to support both accelerated approval via ORR and durability and full approval via PFS. Slide 6, 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 United States 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, FOLFERI, or FOL FOXERI 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-grass-mutated MCRC, we believe Unvancitin 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 7 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 TRI trial of whole-pox injury BEV, a less tolerable regimen, shows a 66% ORR 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 CRDF-004 Phase 2 data compares favorably to these established outcomes. Next slide. With that With that context in mind, let's turn over to CRDF-004 results and the data that underpin our confidence in UNVANSA-DISC. I'll highlight the promising updated interim results from the Phase 2 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 18, 2026 data cutoff. Slide 9 shows the trial design of CRDF004, a dose-finding randomized control phase 2 trial. Enrollment criteria required first-line MCRC with KRAS or NRAF mutation. Key exclusion criteria were BRAF V600 mutations, MSI-high or deficient mismatch repair tumors, resectable disease, and prior BEV treatment. The trial was designed to enroll 110 patients, the IIT population, across six arms in equal randomization. The six arms tested two doses of Invantatib 20 and 30 milligrams, 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 Onvancitib plus standard of chemo BEV arm, and nine of these patients are Onvacitib plus Folfiri Bev arms, the chemo combination we intend to take forward in the phase three 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 end point. As you can see on the right side of the slide, in the 30 milligram Onvancitib plus Fofiri Bev arm, confirmed ORR by PICR was 72.2%, and the 4-3-D-BET control arm showed an ORR of 42.1%. That is very encouraging 30-percentage-point improvement of a standard of care in this randomized study. In the middle, you can see that the 20-milligram arm showed an Orr of 44.4%, with some deeper responses versus the control arm, indicating some dose-dependent effects and confirming that 30-milligram 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 and 30 million vans plus SITRIP-4-FERIBEV is 58.3%. Importantly, nine patients remain on treatment in the vans SITREP plus 4-FEREBEV arm, and only one patient in the 4-FEB control arm, as showed by dark arrowhead. And the depth of response in the 30-milligram 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-milligram Folferi BEV arm, four patients have been on treatment for more than 15 months as of March 18th data cut, with two on greater than 18 months of treatment. Slide 14, this Pride of Plot slide, shows individual patient tumor burden trajectory. In the 13-milligram Onvancidib plus Folferib BEV arms, the majority of patients showed sustained, progressive tumor shrinkage over time. In our view, this promising profile is consistent with the therapy producing durable, clinically meaningful benefits. Next slide, slide 15, shows progression-free survival, including Kaplan-Meier curve for PFS. When comparing both Invantatab doses together plus Polfiri BEV against combined standard of care regimen, the hazard ratio by Bicker analysis is 0.44, with a median PFS that has not been reached in the unvantiative arm, versus 11.04 months in the control arm. The investigator-assessed hazard ratio is 0,53, with the median PFF, again, not reached in the unvantiative arm versus 10.11, 10.97 months in the control arm. With sample sizes of approximately 36 to 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 BFS, these are very promising trends. Moving to slide 16 and looking at the selected phase 3 dose specifically, the 30 milligram on vansetib plus folfiri bev regimen. Median PFS has not been reached in the treatment arm, and some patients continue to remain on treatment. Median BFS in the folfuri bev control arm was 18.8 mind months by bicker and 12.22 months by investigator assessment. The hazard ratio by Bicker and investigator assessments are very similar at 0.55 and 0.57, respectively. The slight discordance between Bicker an investigator-assessed median BFS in the control arm reflects the 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 bicker confirmation. Moving to slide 17, the ORR forest plot on this slide compares 30 mg Unvancitib plus Folfiri BEV versus Folfieri BEV control arm 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 Onvancitib plus Folfiri is seen even in difficult-to-treat subgroups, such as those with liver mets as well as multi-organ involvement. Slide 8 shows forest plots for subgroup analysis for PFS. The PFS forest plot shows the same pattern as the ORR forest plot. Hazard ratios favor the 30-milligram arm across all subgroup. 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 Unvancitib in this patient population. Slide 19 highlights the safety profile of Unvancitib and shows that it is quite tolerable. Adding Unvancitib 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 regimen. Grade 3 or higher events are comparable across arms, and no unusual or unexpected Unvansitib-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 Onvancitib as a tolerable agent that can be potentially added to other synergistic chemo combinations. Moving to slide 20, that shows whole box combination data. Similar to what we had reported in January of 2026, I want to mention again that adding on Vancitib at either dose to the Folfox-Bev regimen did not produce very meaningful improvement in ORR or PFS versus Folfax-Bevilone, although we do see some improvement in few patients. ORR in all Folfaux arms ranged from 44% to 56% with no consistent dose response trend and no PFS benefit observed with the on Vansitib sedition. While this combination did not show much additive benefit, it is not completely unexpected, and I will address the scientific rationale for unvancative synergy with fold theory versus fold forks in the next couple slides. Moving to slide 21, we have some data-driven mechanistic explanation and hypothesis as to why Unvancitib synergizes better with Folfiri and not Folfox. Both Unvansitib through PLK1 inhibition and Irenotecan, the active component of Folfuri, suppress HIF1-alpha, a critical driver of tumor vascularization and survival in the hypoxic tumor microenvironment. The result is a triple antigenic effect. unvancitib suppresses F1-alpha, irenotecan suppresses F1 alpha, and the BEV treatment blocks VEGET, which is vascular growth factor. Additionally, unvacitib likely also inhibits PLK dependent DNA repair downstream of irelotecan induced DNA damage, which highlights a second mechanism of synergy between unvansitib and irerotecan. In contrast, oxaliplatin in the backbone of FOLFOX does not suppress F1-alpha and uses a DNA repair mechanism with limited PLK1 dependence or no meaningful row. These mechanistic differences between irinotecan and oxaliplatin may explain the absence of synergy with FOLFOX and differential outcomes in the current study. But more importantly, CRDS-004 is the second trial where we see synergy of the unvancitve with folfuri-BEV. Our prior phase 1B-2 trial with unvanceitve plus folfiri-BEVR in second line in BEV-naive patients with KRAS-mutated MCRC also showed improved clinical outcomes with the schemo regimen, reiterating our confidence in taking this regimen forward in the phase 3. 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 milligrams of Invantacir plus 4-C-Rebest 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 milligrams 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 18, 2026 data cut, median PFS has not been reached in the 30-milligram arm, with 9 of 14 patients still on unvancitve plus porphyry bed treatment at the time of data cutoff. The strong Phase II data supports advancement of unvanceitve into registrational development, and I will discuss our plans in the next slide. Slide 24 shows the trial design of our proposed pivotal phase 3 trial, CRDF004. Sorry, CRDS, CRF005. CRDf005 is designed as a global registration phase 3 study. While we will continue to refine some elements of the trial, shown here is the design of a pivotal trial after feedback from the FDA at our end of Phase 2 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 onbansetib plus 4-feribet treatment versus 4-fereibet treatment alone. Enrollment criteria are consistent with the CRDF004 trial. First line MCRC, presence of KRAS or NRAS mutation, no BRAF V600 mutation, no MSI high or deficient mismatch repair, unresectable tumors with no prior treatment. The studies to all primary endpoints are ORR, which supports accelerated approval, and BFS, 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 BFF 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, a prior phase 1-2 study in second-line RAS mutated MCLC, and a current ongoing CRDF004 randomized controlled phase 2 trial in first-line graft-mutated MCRC that both confirm that Unvancitib synergizes with Polfiri 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 milligrams in vancative with Folfiri BEV shows an ORR of 72%, 30 percentage points of a standard of care with a median PFS not yet reached in the treatment arm and patients on treatment beyond 15 to 18 months. And no meaningful safety signals have been observed. Number four, we have FDA alignment on the phase three design with a path to both accelerated and full approval if successful. And 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 one of our two panelists. to both of our KOLs, but I'll start with Dr. Tabanero first. But I would first like to thank him for joining this call shortly after landing in Spain. Dr.Tabanero, I will provide... Thank you very much. Thank you, and I'm sorry for being a little bit late by my flight from Chicago to Barcelona. I was a little delayed. Well, you know, I think that the data speaks for Lance 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 ASCOM. 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. And one may raise whether, you know, with the number of RAS-specific, isospecific RAS inhibitors, pan-RAS inhibitors pan-K RAS inhibitor, actually there is some opportunity for a compound like 1,13. 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. is very happy about this situation for a difficult-to-treat population, but combinability of a PAN-RAS inhibitor with conventional chemotherapy plus veracizumab is something challenging, right? And in here, we have a compound that has demonstrated much very well with chemotherapy, especially with 430. And the results that have been presented are spectacular. So, I do fully support, you know, trying to evaluate the activity of Bansalotib combined with 440 and Bevacizumab in the first line setting of this patient population with KRAS and NRAS mutations. And actually, I think that design that has been presented, it's really very good to demonstrate the proposed dual primary points. And honestly, I think that this trial would recruit very, very well. But happy to answer any specific questions that you may have. Thank you. Thank You, Dr. Tavanero. 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 on-one-tether from the beginning. We did the first phase one trial, and I was particularly excited about the incredible inhibition of PLK1 and interfering with really the major signaling pathways. You heard about the IF-1-alpha-NG agendasis. It overcomes chemo-resistant by really interfered with the cell cycle arrest and it has actually an immunomodulatory and then with the preclinical data showing the significant synergism with ivanotecan because ivanotekin has double-stranded dna effects and oxalplantin more dna attacks it explains very well the differential in synergisms between onvancel-tip and ivanotican and bevacuzumab and we saw very early on clinical signals of efficacy. I think what we found is 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. So when I looked at the new data, and we had the phase 1b, and the patient with no prior beta-azuzumab treatment had 71%, that really was the basis to develop this randomized phase 2, which now really confirmed the significant synergism between folceriopaths and 1-benzalcate with no safety sickness. I think I'm very excited about the safety 2%. I'm also very excited at the hazard ratio of PFS, and I think Dr. Caponero is completely correct. I think there are pan-vascular inhibitors, which show some interesting efficacy, but the problem is really the toxicity-limiting combining these PANVAS inhibitors with any kind of chemotherapy or target agents. And this is one of the few trials which actually showed that we can combine easily on one side of the chemotherapy with no safety signals and no toxicity and high efficacy. So I think this is a very, very promising strategy, and I can only hope that this will go into registration as soon as possible, that we can have rotations to really advance that field. Thank you so much. Thanks a lot for your perspective. Operator, we can now open the line for Q&A. Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 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 and 30 milligram. How should we think about the durability across the two doses and are you seeing a meaningful change PFS separation between the two doses. And one question for Dr. Lenz and Dr. Sabanero. Among patients with RAS mutations, who do you think is most likely to benefit from adding on one circuit and to the full 40 plus their backbone? And are there specific clinical features you're focused on for patients who can benefit the most from this drug? So, probably I'll take the first question and then I'll let the two KOLs answer the second part. On the first questions of 20 versus 30 milligrams, if I understood correctly, the separation in ORR and how does it tie to durability? Is that right, Amin? That's correct. So, yes. So, the 20 milligrams showed an ORR of around 44 percent and the 30 milligrams approximately 72%, so you do see a dose trend, although the 44 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 exposure-response relationship as well. Secondly, the PFS benefit that you see with 20 milligram also shows the hazard ratios between 20 and 30 milligram by investigator assessment also show a dose-dependent trend in improvement. And this is not unusual. If you go back to the slide where I had shown initial addition of Bev on IFL and Bev on on post-COX Irene's decan, you can see that Bev did not add too much to the ORR, but had a significant improvement in PFS. So it may be these patients and the KOLs can, you know, talk to it more, but we do believe a 20 milligram is an active dose, but certainly 30 milligram is a dose that provides the punch needed to take to phase three. Maybe I'll start with Dr. Lenz first and then go to Dr. Tabanero for the second part of the question. Dr. So, if I understand your question, what's really if it applies for all KVAS and N-VAS mutation, and if there are specific patients who benefit the most? Dr. That's correct, yes. Dr. Okay. So, from our data, we do not see that certain mutations have less or more benefit. It seems to really affect the PANVAS inhibitor, affecting all the K-MAS mutations as well as the N-VAS mutations. And the reason is very easy, because we are not binding to a very specific K-Vas mutation which limits the use and the development of allele-specific inhibitors. It's a downstream event of the downstream signaling interfering with all nature oncogenic signaling pathways. So we don't see a particular indication that some of the classes of the T-VAS or N-Vas mutations have differential benefit. What was the second part? I think that was it. That was it, okay. Okay, so I think this is a very unique target because it really interferes with the downstream oncogene-activated sickling with the KVAS and N-VAS mutations, and not depending on the binding affinity or characteristic of allele-specific or pan-Vas inhibitors. And Dr. Tabanero, if you have any specific opinions about what kind of patients with RAS mutations would benefit with a drug-like advantage? So, I fully concur on your answer and Professor Lange's answer, right? So, the important thing here is that the RAS signaling, independently of the K-RAS and N-Ras mutations that the tumor of the patient has, it's very constant, right, and the profound effect that it induces in the ERG pathway, it is 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, and they evaluated the different cells and different in vivo models with different RAS and RAS mutations. And the RAS signaling score was very similar in terms of activation of the ER pathway, right? So I don't foresee that there are going to be differences in the profile of patients depending on the RAs mutation that their tumors wear for the activity of ombarsity. And I wanted to follow up, and you also mentioned a very important point. So we obviously look for KVAS and N-VAS mutation, but in a large study we published a couple of years ago in Lancet showing the efficacy of cetuximab in wild-type RAS because the KVas mutation were excluded. And as Josep mentioned, there were wild-types RAS patients who had activated oncogenic signaling in the RAS pathway, which did not respond. So I think the online session would also work in this patient population based on the activation downstream pathway. So there is certainly very interesting aspects biologically which would expand that to certain biotype patients if we can identify the activated pathways downstream. Thank you so much. Operator, the next. Thank you. Thank you, and the next question will come from Mark. from with TD Coe, and your line's open. Thanks for taking my questions this morning. Maybe just to start on the trial design for the proposed phase three 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. So 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. So I will stop at that. So 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 involved by the time we take it to the FDA. Not fully read out, yeah, not fully read out, but fully. Yeah, yeah. Okay. And then 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, you know, is there any chance that some relative differences in tolerance of the chemo may be contributing at least some of the impairment treatment effect. So let me begin by talking about safety first. The safety profile is very similar across both chemo regimens, FOLFOX and FOLSERI. In terms of tolerability and if there were any kind of dose reductions or dose discontinuations of chemo, there are differentials. In the irenotecan arm, we hardly saw any reduction in or discontinuation in irenotecan. However, in oxaliplatin or full FOX regimen, there were discontinuations of the oxaliplatin regimen. But that is not unusual. That is similar to what has been reported in, you know, everyday practice. And I would let Dr. Lentz and Dr. Tabanero comment on that as well. Like, you Know, do you actually discontinue oxalipletin in few patients based on tolerability? Because that's what we saw in the study as well? Yes. So usually, when you have an effective chemo-savvy that's such for fear, you don't have really accumulative toxicities as you have with oxaloplatin. As you probably know, with Polfox, many of the investigators hold or stop the oxalaplatin after four months of treatment because of the anticipated neurotoxicity. You have also a little bit more differential hematological toxicity with oxalaplatin with more thrombocytopenia and a particular anemia, in the Folfiri regimen, you see actually usually very well tolerated. And in our clinical trials, we did not really have significant holding of treatment or dose modification. So it's a very safe, very effective treatment regimen. And the reason I think Folfuri is not only biologically a great partner, because you can actually treat till progression with no accumulative toxicities over time. Thank you, Dr. Lenz. Dr. Tabanero, do you want to add anything to it? Yeah, well, you know, if the drug has, so if the experimental drug does not have any interaction with none of the components of Folfiri, and this is Ayurvedica, but also the first metabolite, N38, 5-fluorosilocoborin, usually the combinations are really very tolerable. And the advantage of Fofiri compared to Folfor is you can really keep 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 iodine treatment on the midterm or the long-term basis. As you know, with oxaliplatin, although it's a very preferred chemotherapy backbone, there There are several aspects that limit the compliance and the dose intensity of oxaliplatin, but this is not only with this drug. It's with all experimental drugs, right? And 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, right. And this is the reason, on top of the efficacy and safety data that fulfills its well-accepted regimen, and very conminable. Just to put you, yeah, other examples, right, so also at ASCO, we have seen the data of another situation, and this is very rough, this is in mutant population metastatic colorectal cancer, and the data has been presented on this occasion, is a combination of fulvirin and chlorophenidazole tubsimab versus fulviribeth in the BRAF mutant population. I want to make clear that it's a different population. But the importance here is that, you know, the combination was very tolerable, and those patients could be treated for many, many months. And in this particular case, actually, even the results were slightly better than with Folfort. So, I do think that all these aspects fully support the Folfiri combination. And maybe it's also interesting that, particularly in Europe and Asia, Folfiribeth as a first line of fosfuria as a backbone is a preferred combination treatment. In the U.S., it's usually full FOXPATH, but with data showing like the CARDIV-004 study, the efficacy always trumps decisions what treatment we do because they're equally effective when you compare side by side. But if the combinations show significant synergism, I don't think there's any issue to use that also the U.S. I agree with Professor Lentz. So at the end, physicians and patients, of course, the final preference for the treatment options is the activity and the safety, right? And I do think that this trial is going to be recruiting very rapidly. Thank you, Dr. Lent and Dr. Debonero. Operator, the next question. Thank you. And the next questions is going come from Andy Shea with William Blair. Your line's open. Thanks for taking our question. So now we have full results, efficacy, you know, PFS, median, hazard ratio, the 004 study. And I'm curious for the 005 study, maybe just kind of an expansion from Mark's question earlier, in terms of PFS. I'm curious if you can kind of describe what level of risk reduction you expect from the 640 patient sample size. We also have a question for Dr. Lenz and Dr. Taber and Arnaud. In terms of the spider clot, we saw some dramatic reductions on the onvansertive arm, around six from the Forbiri 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 unanticipated specific phenomenon? Just curious about your thoughts on that. And lastly, for Mani, you know, maybe just in terms of Nerviano, what is the next step that we can expect, you, know, regarding potential resolution or, you know, how to go forward? Thanks. So, maybe – thank you, Andy. I'll start with the third first and put it to rest, and then we can focus on the scientific discussion. so regarding nerviano as you know we are in dispute and we tried to resolve the dispute uh outside of court 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 expedite manner and we thought of legal intervention you know the dispute was related to obviously um authorship or inventorship in our patents which we believe are still spotted patents based on the inventorship and they we will continue to defend that and regarding commercially reasonable efforts we have made a lot of efforts getting the program to this point and into phase three so 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 course so that with that done i will address the first question about the size whether the size of the phase three study can be reduced um it is too early and premature to comment on uh you know reduction in any size based on the current data the crdf004 style is still ongoing median bfs hasn't been reached but we have designed the study um the crdf005 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 bff and i will let dr tabernaro maybe start first on the spider plots you know the deeper spider plots that you see is it unusual is it 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, and for that actually, it's very good to see the activity in terms of not only tumor synchro, but also response rate that we have for, even for the control arm, right, that it's 42%. And this is what it's in the literature. So, both 440-BEV and 440SVEV, usually the response rate when it's independently reviewed by external radiologists is around 38-40%, right? and the data that we have in the control arm really fits what is expected for the control arm, right? But when you go to the experimental arms, I think that the data we have for an overall response rate for Folfilibref, especially at the dose of a marsatilda of 30 milligrams with an overall response rate confirmed 72%, this is amazing. And it's not only that, but when you look at the forest plot evaluating patient by patient, actually you see that, you know, it's about not only the overall response rate, but it's also about the patients that have disease control. So you can see that only one patient actually had, you know, a slight increase by 8%, you know, in the lesion, right? All the others had any kind of tumor shrinkage. But again, the impressive 72% overall response rate is really amazing for a combination of 430 deaths in this setting, right, so without any doubt, you know. the addition of the experimental drug on marsupial makes a difference. Dr. Linz, would you comment on your perspective on the depth of responses? So 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. And in many patients in this one, particular two one, it was very fast. So 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. So, I think this rapid response, as Dr. Tapanera mentioned, is very unique. There 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. So I don't think we have a very good understanding who these patients are. We had in the phase 1b, 2, we looked for the circulating DNA with a little 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, but I think highlighting the significant dynamic and fast response of these patients. Thank you, Dr. Lenz. And Andy, if I understood your, I apologize, I have misunderstood your question. So if you were trying to ask statistical assumptions that, you know, 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. So, it's not as aggressive as 0.5 hazard ratio that has been reported in Phase 2, and the prior Phase 2 to Phase 3 results, you know, we have taken that into account while designing the size of the Phase 3 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. And our next question is going to come from Albert Lowe with Craig Harlem. Your line is open. Hi. I think, Rani, you referenced it in your comments that the 20 milligram dose with FulfuriBed is active. But could you share what the PFS and hazard ratio was for the specific dose arm? Yes. So, the median BFS hasn't been reached, but we did not share the details of it. You know, I'm happy to share, but it is – 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-milligram arm with the investigator-assessed, you know, metric, but I don�t have it up the top my head. It is directionally, you know, if you look at investigator assessment-based analysis, it is directionality. The hazard ratio is a little bit higher than what has been reported, it's higher than 0.5. Okay, thank you. And just to follow up… For the phase 30 milligram, it is higher than 30 milligrams, yeah. I was wondering, you now, what's the timeline for potentially starting this phase 3 trial and could it begin while this license agreement dispute is still outstanding? So pending funding, we expect to start the phase three initiation-related activities late this year, early next year. You know, 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. perspective, it is business as usual. Great. Thank you. Thank you, and the next question is going to come from Christopher Liu with Lucid Capital Markets. Your line's open. Hey, guys. Thanks for the questions, and congrats on the data. So two for 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 milligram and 30 milligram? Any additional analyses? And then for the second question, quite a few patients in the 30 milligram arm were able to get 100% tumor aggression in the target tumor. Just wondering what kind of made those patients go off treatment? So, maybe I'll start on the 20 versus 30 milligrams. You know, they do have overlapping PKs. So, there is, but there is a, you know, a dose exposure versus response relationship there, both in terms of ORR and BFS. While there wasn't as much of a difference in BFS, the ORRs were definitely different. And as I said, you know, with Avastin, you have seen similar phenomenon where you don't see too much of an impact on ORR, but much more and benefit with BFS. So we similarly see that in 20 versus 30 milligrams. The trial is still ongoing. We will continue to do more exposure-based analysis. But from our perspective, we have the right dose to take forward in the phase three. And we also believe that 20 milligram dose is active, maybe not as high as 30 milligram dose. And remind me what was... Yes. So on the second question, with the 30-milligram dose, you said that the patients had very deep responses. There was a lot of reduction in target lesions. And they continue to be, most of them continue to be on treatment for a long time. We will continue to assess and come up with the median PFS there. There were discontinuations leading to, due to various reasons, but very few due to progressive disease. I can tell you that in the 30 milligram arm, there were very few to progressive diseases. There could be other reasons, whether related to patient decisions. Actually, five patients went on curative surgery as well in the 30 milligram arms. The highest numbers of patients who went on curative surging was with the 30 milligrams arm. So 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 cured resections. And 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 metastasis sites in really well-controlled metastasic cancer patients, you have a very good chance of cure. And these patients, obviously, depending on whether 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. Lin. And yes, and hopefully we'll be able to publish the full results of the study in the coming month where you can see, but I can tell you that, yes, the most number of curative surgeries were in the 30-milligrams on vansetib plus porphyry. Next question. I think we're coming at the top of the hour. Operator, do you have any more questions? No, I am showing no further questions at this time. So I'd like to turn it back over to Manny for closing remarks. Thank you, Operator. Before I conclude, I would like to thank the patients and their families who place their trust in our clinical trials. Their participation makes this work possible, and it is the foundation of the data we share today. I also want to recognize our investigators, especially Dr. Lentz, our advisors, consultants, Dr. Tabanero 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 advances in RAS mutated NCRC 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 and trial. Thank you, everyone. Have a good day. Thank you. Thank you all. This concludes the conference call. Thank you so much for participating, and you may now disconnect.