Welcome to the Cardiff Oncology Clinical Development Update conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at that time, please press star followed by one, one on your touchtone phone. If anyone has difficulty hearing the conference call, please press star zero for operator assistance. As a reminder, this call is being recorded today, Tuesday, September 26, 2023. I would now like to turn the conference over to Kiki Patel of Gilmartin Group. Please go ahead. Thank you, operator. Slides for today's investor call can be found on the homepage in the Events and Presentations tab of the Cardiff Oncology website at www.cardiffoncology.com. Joining us on the call today from Cardiff Oncology are Chief Executive Officer, Mark Erlander, and Chief Medical Officer, Dr. Fairooz Kabbinavar. During this call, management 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. Our 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 our annual report on Form 10-K for the year ended December 31, 2022, filed with the SEC on March 2, 2023. 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 turn the call over to Chief Executive Officer, Mark Erlander. Well, thank you, Kiki, and good afternoon, everyone. We are pleased that you've joined us today for this clinical development update. As you know, on August 7th, we provided a comprehensive look at our lead program in first-line RAS mutated metastatic colorectal cancer, or mCRC. And today, we are providing an update on two earlier-stage programs as they compare to CRC in metastatic pancreatic ductal adenocarcinoma, which we will refer to as metastatic PDAC, and extensive stage relapsed small cell lung cancer. I would like to start on slide three by providing the highlights of the important data that we will be announcing today. For PDAC, we will be discussing three separate clinical trials. For the first trial, Cardiff 001, we will be providing an update to the data we released last September, showing efficacy and tolerability in second-line PDAC setting for the combination of onvansertib with standard of care. The second PDAC trial is a biomarker discovery trial that we have never discussed publicly before. This trial examines how a 10-day course of onvansertib monotherapy impacted well-known and validated response biomarkers. This trial was not designed to treat patients for traditional measures of efficacy response. As you will see, one of the two patients we have treated so far had a significant biomarker response for proliferative index and CA 19-9. And additionally, we are excited to see that extensive genomic transcriptome analysis for this responsive patient showed at baseline a high hypoxia-related signal, which was inhibited after 10 days of onvansertib monotherapy. These results are exciting because they are consistent with our preclinical colorectal cancer findings. Finally, we will provide clarity on our path forward, which consists of the third PDAC trial, which we will discuss today. Based on the totality of the clinical and preclinical data, our plan is to shift onvansertib's development in metastatic PDAC to the first-line setting through a new investigator-initiated trial. Next is the exciting data from the onvansertib monotherapy investigator-initiated trial in relapsed extensive-stage small cell lung cancer. Here, we are able to report today a confirmed partial response within the first seven patients. This is a very significant milestone because it demonstrates single-agent activity for onvansertib in a very challenging indication. On slide four, before we get into the new clinical data, I would like to briefly review the important attributes of our drug, onvansertib, that we believe will enable it to become the first-in-class, well-tolerated PLK1 inhibitor. Onvansertib is a small molecule, oral, and has a 24-hour half-life, allowing for flexible dosing schedules. Together with onvansertib's high specificity for PLK1 versus PLK2 and PLK3, we believe that these factors explain why we have observed in over 300 patients across four different clinical trials, that onvansertib is well-tolerated, even when combined with a variety of chemotherapies. On slide five, we show our development pipeline. During our last company call on August seventh, as you know, we announced a first-line clinical development path for our lead program in RAS mutated metastatic CRC. One of the additions to our pipeline that you can see on this slide is a new investigator-initiated trial in first-line metastatic PDAC, planned at the Oregon Health and Science University Knight Cancer Institute. In a moment, our Chief Medical Officer, Dr. Kabbinavar, will provide the rationale for this move.... Similar to our shift in to first line in metastatic CRC, our development strategy follows our data, both clinical and pre-clinical, to enable onvansertib to benefit the largest possible patient populations. These investigator-initiated trials are a highly capital efficient way to evaluate onvansertib in new indications. On slide six, we provide a sense for the scale of the opportunity for onvansertib. But before we look at the absolute numbers of patients, I want to address why onvansertib can target these large populations. Fundamentally, there are two ways to approach drug development in oncology. On the left-hand side, we have the approach where a drug targets a specific oncogenic driver mutation, such as ROS1 or RET. However, if you look to the right, you can see that this focus on a specific mutation significantly narrows the targeted patient population. The second approach to oncology drug development is to inhibit a target that does not have an oncogenic alteration. As a PLK1 inhibitor, onvansertib is in this category, along with other large oncology drugs like PARP inhibitors, immunotherapy checkpoint inhibitors, and anti-angiogenics, which are some of the most widely used cancer therapies ever developed. PLK1 is not mutated in cancer cells, but rather is overexpressed by tumors and plays an integral role in tumor cell proliferation and survival. If you look to the right, you can see that with this approach, the number of patients that can be positively impacted by onvansertib is much larger than for some of the oncogenic mutation-targeted therapies. So while our development efforts are highly focused on our lead mCRC program, we are also evaluating onvansertib's potential in other large cancer indications. With this, I would like to turn the call over to Dr. Fairooz Kabbinavar, who is our Chief Medical Officer, to walk you through the exciting results from our metastatic PDAC and small cell lung cancer programs. Not only do these data demonstrate onvansertib has efficacy against both of these difficult-to-treat diseases, but in PDAC and small cell lung cancer, we have efficacy signals from onvansertib monotherapy. Fairooz? Thank you, Mark. It's a pleasure to speak with all of you today. Let's start on slide 8, highlighting the 3 different trials in our PDAC program. The first is the Cardiff 001 metastatic PDAC phase 2 trial. We first announced data from this trial in September 2022, and we have an important update to provide today. After that, I'll present some early results from an investigator-initiated biomarker discovery trial that we have not discussed publicly before. Finally, I'll share our conclusions from examining the data from these two PDAC trials that shine the light on the path forward to advancing our PDAC program to the frontline setting. Specifically, we'll be sharing with you the plan for a new investigator-initiated trial in first-line metastatic PDAC. Slide 9. I'll start by focusing on Cardiff 001 phase II trial. Slide 10 shows the design of our Cardiff phase 001 phase II trial. Enrollment criteria includes patients with metastatic PDAC who have progressed on frontline gemcitabine combination chemotherapy. Patients have measurable disease according to RECIST 1.1, an ECOG performance status of 0 or 1, and normal organ function. This is a single arm trial, so all patients will receive chemotherapy regimen of fluorouracil, leucovorin, and nanoliposomal irinotecan every two weeks. For the first five days of each 14-day chemotherapy cycle, patients receive onvansertib at a 15 mg/m² dose on a daily basis. The primary endpoint is objective response rate according to RECIST 1.1, and disease control rate is the secondary endpoint. On slide 9, slide 11, you can see that patients on onvansertib plus chemotherapy appear to have a higher response rate compared to historical controls. In this trial, we have 21 patients available for radiographic response as of September 13, 2023, with 1 confirmed partial response and 3 partial responses that are waiting for confirmatory scan, giving us an objective response rate of 19%, 4 responders out of 21 patients. Compared to the historical benchmark, 19% objective response rate achieved in this trial is superior to the 7.7% response rate seen in the second-line setting. It also comes very close to the frontline historical 23% objective response rate of gemcitabine. We are very excited about the results observed to date in this trial. On slide 12, we see the survival plot showing the patient responses to continued therapy over time. Importantly, 2 of the 3 partial responses still awaiting a confirmatory scan occurred at 6-month scan for patients 27 and patient 31. On slide 13, you can see in the spider plot how the responses from these two late-responding patients deepened over time... and occurred well past the historical median progression-free survival of 3.1 months, is the dotted line that you see in the middle of the graph there. Slide 14. On slide 14, we see the Kaplan-Meier curve for the 23 evaluable patients for progression-free survival as of September 13th, 2023. You can see that patients on onvansertib plus chemotherapy appear to have an improved progression-free survival compared to the historical control. The median progression-free survival in Cardiff 001 trial is 5 months, and the historical control for second-line median progression-free survival is 3.1 months. Once again, our second-line data approaches the benchmark of, of first-line median PFS setting, which is 5.5 months. The probability of being progression-free at 16 weeks from our trial is 56%. That data is not available for second-line historical control patients. But for the first-line patients, the probability of being progression-free at 16 weeks is 48%. So all in all, the response rates and the median progression-free survival appear to demonstrate a higher signal of efficacy for onvansertib plus chemotherapy combination in this indication. I'd like to point out that the waterfall plot on the previous slide presented data from 21 patients, and the progression-free survival curve included 23 patients. This difference is because two patients who received two cycles of treatment did not receive a post-baseline scan before leaving the trial, and so did not have a radiographic evaluation to report. The fact that these two patients left before receiving a post-baseline scan underscores one of the important lessons from this trial. While the totality of the data I will discuss suggests that we are seeing a signal of efficacy from onvansertib, we believe that second-line patients on the trial may have a disease that has progressed too far for therapy to be optimally effective. Second-line patients seem to progress rapidly without giving an experimental drug time to work. After discussing this data with our investigators, we believe that a planned shift to the front-line setting will allow us to have a greater opportunity to fight this challenging disease at an earlier stage, when the chances of patients responding to treatment are the highest. As you can see on slide 15, I will now move on to the second metastatic PDAC trial, which is an investigator-initiated biomarker discovery trial. This trial is being conducted at OHSU Knight Cancer Institute. As I said earlier, this is the first time we are discussing this trial, and we are pleased by its early results, which support a planned shift to the front-line setting. On slide 16, we show the design for this trial, which aims to determine the biological action and the molecular activity of onvansertib monotherapy in patients with refractory metastatic PDAC. One of the aspects of this trial that made it intriguing for us is the fact that that it explores single agent activity for onvansertib. Patients receive 10 days of daily onvansertib as a monotherapy at a dose of 12 mg/m². These biopsies and blood samples will be subjected to extensive multiomic analyses. After the 10 days of onvansertib monotherapy, patients go on to receive standard of care only, regardless of their response to onvansertib. We are interested in participating in this unique trial because it would enable us, for the first time, to determine the sole biological action of onvansertib in tumors within a clinical setting. On slide 17, you can see the biomarker response data, including Ki-67 and CA 19-9, for the 2 patients evaluated to date on this trial. Intriguingly, one of the 2 patients, number 28, showed a robust biomarker response to the 10 days of onvansertib monotherapy. Ki-67 is a marker of rapid cell turnover and tumor proliferation, and for patient 28, this level responded well with an 86% reduction in Ki-67 when comparing the pretreatment levels to the levels immediately after 10 days of treatment with onvansertib alone. This result is consistent with onvansertib's mechanism of action established in preclinical models, where it inhibits tumor cell proliferation by cell cycle G2/M arrest. This is the first clinical demonstration of this mechanism of action. CA 19-9 is the most extensively studied and validated serum biomarker in PDAC, which provides a clinically meaningful surrogate for response to treatment. In other words, a downward movement in CA 19-9 reflects the tumor's response to treatment, versus an upward movement reflects a lack of response. We are encouraged by the ability of onvansertib to provide an approximately 30% reduction in this clinical biomarker with only 10 days of monotherapy. On the right hand of the slide, you will see the second patient who did not have a biomarker response. Ki-67 remained unchanged in the pre- and post-treatment periods, and the CA 19-9 increased at the 10-day mark. Thus far, we have had one biomarker responder and one non-responder to onvansertib monotherapy. Both these patients have liver metastases, and their biopsies were taken from these liver mets. When we compared the biomarker data from patients 28 and 23, we found an important and intriguing difference, which appears to validate one of the critical findings we discussed on the colorectal cancer program call in August 2023. On our mCRC call, we discussed the role of cellular hypoxia as a hallmark of cancer and provided extensive clinical data about onvansertib's role in inhibiting HIF-1α, which is hypoxia-inducible factor 1 alpha response pathway. Returning now to this PDAC biomarker trial, when we looked at the whole genome transcriptome from patient 28's pretreatment biopsy, we found that this patient had much higher level of hypoxia-related gene expression than patient 33. The post-treatment biopsy for patient 28 showed that the hypoxia-related gene expression was significantly reduced. This finding appears to once again validate onvansertib's role in anti-angiogenesis and potentially explain patient 28's strong biomarker response to onvansertib monotherapy treatment. Overall, we believe that the cellular hypoxia may be a biomarker for predicting response to onvansertib, and we plan to explore this in our future clinical trials. We do understand that two patients is a small number, but given the clear biomarker signal in the monotherapy trial, it gives us additional evidence of onvansertib's activity in the metastatic PDAC setting. When viewed together with the response rate and the survival data from the ongoing Cardiff-001 trial, they support a broader, broader conclusion about the future of metastatic PDAC program, that we have a signal of efficacy that is worth exploring in a new trial in the first-line setting. Slide 18. As you can see on this slide, I'll be discussing this path forward in the first-line metastatic PDAC setting in the next slide. Slide 19 shows the proposed design of the new phase 2 trial that will combine onvansertib with the standard of care Gemzar and Abraxane. This investigator-initiated trial will be conducted at OHSU Knight Cancer Institute, which is the same institution that is conducting the current biomarker discovery trial. The enrollment criteria will include patients who are treatment-naïve, with an ECOG performance of 0 or 1. They will have unresectable or locally advanced or metastatic pancreatic cancer with measurable disease according to RECIST 1.1. Patients will be divided into 2 cohorts on a non-randomized basis. The first cohort of patients will receive 10 days of monotherapy as a lead-in, and they will get biopsies and research blood draws before and after treatment, similar to the biomarker discovery trial I just discussed. After the lead-in period, the patients will then move on to receive a combination of standard of care chemotherapy and onvansertib. The second cohort of patients will not receive onvansertib monotherapy lead-in, but will move straight to the combination regimen, as shown on the right-hand side of the slide 19. Importantly, we have preclinical data demonstrating synergy of onvansertib with Abraxane, which adds to our rationale for evaluating this, evaluating this combination in this trial. This combination regimen consists of gemcitabine or Gemzar and Abraxane on days 1, 8, and 15 of a four week cycle. Patients will receive daily onvansertib with chemotherapy on days 1 through 5, 8 through 12, and days 15 through 19. Patients will be monitored with blood work on a weekly basis. The rationale for this two-cohort approach is to allow us to further explore biomarkers that may predict a response to onvansertib, while in the second cohort, we'll determine the safety and efficacy of onvansertib, plus the standard of care gem and Abraxane, which could be informative for the planning of a future registration trial. Shifting our program to the frontline setting is an important and exciting move for Cardiff Oncology and follows our internal assessment and investigative recommendations based on the clinical and preclinical data. We anticipate the trial will begin enrollment in the first half of 2024. As you can see on slide 20, I'll now move on to the next item on our agenda, where we will share results from the investigator-initiated trial in extensive-stage small cell lung cancer. Slide 21. I'll start by sharing with you preclinical data in small cell lung cancer xenografts on this, on this slide. On the right-hand side of the slide, you'll see that treatment with onvansertib monotherapy results in reduction in tumor volume that is superior to cisplatin in both cisplatin-sensitive and cisplatin-resistant cell lines. Our goal then, was to see if these encouraging results in the preclinical models showing similar gen activity with onvansertib could be translated to the clinical setting. Slide 22 shows the design of the ongoing extensive-stage small cell lung cancer clinical trial. Importantly, like the PDAC biomarker trial, this is another example of exploring treatment with onvansertib as a monotherapy. However, in this trial, the treatment follows a more traditional clinical program, clinical regimen. The enrollment criteria are relatively simple. The trial includes patients who have relapsed after receiving 1 or 2 line, prior lines of therapy and have extensive stage disease. This is a single arm trial with two-stage design. In the first stage, 15 patients will be enrolled. If 2 or more responses are seen, we will move to the second stage, where an additional 20 patients will be added. The primary endpoint is objective response rate according to RECIST 1.1. The secondary objective is progression-free survival and overall survival. The treatment schema is as follows: patients will receive 15 mg/m² of onvansertib monotherapy on a daily basis for the first two weeks of a three week cycle, from day one to day 14 in a 21-day cycle. And then patients will have treatment-free days, period from day 15 to day 21. On slide 23, we have the preliminary safety and efficacy results from this trial. Preliminary data shows that safety of the first 6 patients reviewed by the University of Pittsburgh Medical Center Institutional Review Board, the IRB, has allowed the investigator to continue to enroll patients with no conditions attached. On the efficacy side, 7 patients have been enrolled, of which 1 had a confirmed partial response, 3 have had stable disease, and 3 have had progressive disease. The disease control rate, which includes partial responses and stable disease, is 57%. That is 4 of the 7 patients, as you can see on the slide. The single partial response observed is very exciting to medical oncologists like me, who treat small cell lung cancer, even in a small subset of 7 patients. It is particularly important that such an early signal of efficacy is coming from an oral small molecule monotherapy. On slide 28, 28, we have presented the baseline and post cycle 2 scans for the patient in the trial who had a confirmed partial response. But before discussing the images, I want to remind you that small cell lung cancer is an extremely difficult disease to treat. For 30 long years, cisplatin and etoposide were the only standard of care treatments available to the—for these patients. And then in 2019, in a study that I was involved in, atezolizumab was added to the chemotherapy with improvement in survival to little over one year, and this has become the new standard of care. Once patients fail in the front line setting, the options in second line and beyond are not very effective. The outcome for these second or third line refractory patients is extremely grim, with response rates that range between 18%-25% range, and the median progression-free survival ranges between two to three months, with an overall survival, again, a very dismal four to six months. At the end of the day, regardless of what chemotherapy agent we use, these numbers have remained unchanged, and hence, there's a significant and urgent unmet need to improve treatment options for these patients. Turning now to the scans, as you can see on the baseline scan on the left-hand side, there's a fairly large tumor in the front of the chest, in the anterior medial panel. If you look at the restaging scan done 6 weeks later, after patient had received 2 cycles of treatment on the right-hand side, the tumor has shrunk dramatically. The investigator assessed this as a 50% shrinkage of the tumor, qualifying this patient to have a partial response. On the subsequent six weeks scans later, the partial response was confirmed. I understand it is just one patient, but it is still very exciting, especially because this demonstrates a single agent activity for onvansertib. Our current plans are to continue enrolling in this trial by exploring, exploring the single-agent activity. But importantly, our expectation is that a future clinical path forward in small cell lung cancer is likely to include a combination of, combination regimen of onvansertib and paclitaxel. While the onvansertib single agent data activity would give us reason to be optimistic, our preclinical data suggests the combination of onvansertib and chemotherapy could be the most powerful approach to treating this difficult disease. Now I will hand things back over to Mark to close the call. Mark? Well, thank you, Fairooz. Turning to slide 25, we highlight our data readouts at Cardiff Oncology. Today, we have delivered on our guidance of sharing data on our metastatic PDAC and small cell lung cancer programs, with the exciting results that Fairooz has just shared with you. The next anticipated milestone will be our lead program in first-line metastatic colorectal cancer, where we anticipate an interim readout from our randomized trial in mid-2024. I would like to note that we have removed an estimated time of data release from the triple-negative breast cancer investigator-initiated trial, as we are still in a dose escalation phase of the trial. We will provide an update when possible. From a financial perspective, at the end of June, Cardiff Oncology had $89.4 million in cash. Our cash burn averages around $8 million per quarter, providing a cash runway into 2025. In conclusion, we at Cardiff Oncology are very excited about the data we have shared with you today in metastatic PDAC and small cell lung cancer, and also what we shared with you last month regarding metastatic CRC. Together, these achievements reflect the immense opportunity we see for onvansertib to provide a meaningful benefit to patients living with and fighting cancer. With this, we are ready to take your questions. Operator? Thank you. As a reminder, to ask a question, you will need to press star one one on your telephone. To remove yourself from the question queue, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Marc Frahm of Cowen. Hey, guys. Thanks for taking my questions. I guess, as moving forward with this first line PDAC trial, I guess, with these early cohorts of patients, what would you view as kind of proof of concept that would justify moving into larger first line trials? Can you repeat that, Mark? It was kind of garbled at the end. Oh, all right. Just as you start getting data in the first line trial, what would you view as kind of proof of concept to justify kind of expanding that program out from these initial running cohorts? Oh, yeah. Yeah, as you know, we're coming off some really exciting data in the second line, and there we're having a 19% response rate. When we look at first line, as we noted in that one slide, 23% is the response rate. The PFS is a little over 5 months. So we'd be looking for a 50% increase in those response rates in PFS. Okay, that's helpful. And then just in the, kind of, on the second line trial, is it... There's no more enrollment happening, is that correct? That these are all the patients that will ever be in that trial. And then, I guess, you, you mentioned the next update being from colorectal, but should we expect an update from this with longer follow-up and maybe, you know, an attempt to hopefully confirm some of these responses that are still unconfirmed but ongoing? Yes. Thanks, Mark. Yes, we will be following up in this phase two trial in pancreatic. As you've noted, we'll be following up. We'll have some confirmatory scans, and we have a couple more patients, and then we're pretty much hitting what we had planned to do in this trial, in this phase two trial. So we are in essence wrapping up this particular trial. Okay, thanks. Very helpful. Thank you. Please stand by for our next question, which comes from the line of Joe Catanzaro of Piper Sandler. Hey, hey, guys. Thanks for taking my questions here. I have maybe two. First one, just wondering if you could speak a little bit more to the safety you're observing within the combination in pancreatic cancer. I guess I'm specifically interested in the rates of high-grade neutropenia that you may be seeing, and it looks like there were two discontinuations due to AE on the Swimmer's plot. Just wanted to see if maybe you could say what those were. Thanks, and I have one follow-up. Yeah, I think, you know, what we probably should do there is follow up with you because we don't have those specifics here in the slide deck. Joe, I know we have a call with you coming up later today, but Fairooz, would you want to speak a little bit to it in general? Yeah. So there's two patients that came up with toxicity. Again, this is, remember, this is a pancreatic cancer patients that have in the second and third line setting, and so it's a rapid decline in the functionality, and even with a little bit of toxicity, these patients have come off the study. As far as the severity of toxicity, I have not seen any grade three or four toxicity that required us to withhold treatment or decrease the dose of the patients, but we'll provide you with the details when we speak with you on one-on-one. Okay, again, then I guess my follow-up may be sort of along the lines of Mark's earlier question on establishing proof of concept. I think if I remember back to last year, you had said that in second line PDAC, you'd see proof of concept as a 20% OR and median PFS of six months or greater. So, you know, appreciate small numbers here, but I guess what gives you confidence to move forward, even if, you know, maybe you're coming up just short of that internal hurdle that you've previously stated? Thanks. Oh, thanks, Joe. Yeah, we're coming off of the trial results are, pretty much in line with what we are looking for. And I think also, with the other thing that we're looking at is what is currently, standard of care, which keep in, keep in mind, is, 7.7%, and, the median PFS is at 3.1 months. So we are looking at this. And then secondly, is the exciting work that, came out of the discovery trial, where we saw, this, really amazing, response, biomarker response, with single, monotherapy with onvansertib. So when we really look at that and totality, along with our preclinical data, that's really what made the decision to move to first line. Okay, got it. That's, that's helpful. Thanks for taking my question. Thank you. Our next question comes from the line of Alexandra Ramsey of William Blair. ... Hello, thanks so much for taking my questions, and congrats on the new data. So I had a couple quick questions. The first one was on historical control data for PDAC, the 7.7% response rate. I think that says that that's from the label for liposomal irinotecan. I was just wondering if you could kind of just illustrate for me the difference between that 7.7% response rate and then the, I believe, 17% response rate that was reported in the final overall survival analysis from NAPOLI- 1. I was just kind of curious what the difference there is. And then as my second question, I was just wondering if going forward, if outside of colorectal cancer, you're kind of planning for these other indications to be explored through investigator sponsored trials to kind of preserve capital, or if there's any indications that you think you might bring more into in-house development going forward? Thank you for taking the question. Sure. Thank you very much. You know, the 7.7% comes from, as you know, the FDA insert, which is looking at confirmed responses. So that's where that comes from. The Napoli publication had higher, but had many unconfirmed responses. So that's point number 1. And we're very confident with our trial results so far, with the 4 PRs that we've seen. Keep in mind, as you noticed, that 2 of those PRs actually occurred with deepening responses and occurred 6 months out, so versus a 3.1 median PFS. So we're very excited about that data. I think going forward, as I mentioned on the call, we do believe that it, it's very capital efficient to be able to explore these other indications initially through these investigator-initiated trials, and we would continue to do that. Very helpful. Thanks so much for answering the questions. Thank you. Please stand by for our next question, which comes from the line of Raghuram Selvaraju of HC Wainwright. Thanks so much for taking my question. I was wondering if you could comment on the broader regulatory environment at this time, particularly in regard to the use of partial responses, confirmed or unconfirmed, from single arm non-randomized studies. And if in a general sense, your strategy focusing on earlier line settings is partly in keeping with what you see as the ongoing evolution of the regulatory environment within oncology? Well, thank you, Ram, for that question. As you know, our plan right now in metastatic colorectal cancer in first line is a randomized trial, where we combine with standard of care, versus standard care alone, and we will continue to go down that road, with the FDA agreeing to our plan. One thing I'll note there that's very exciting for us is that the FDA has agreed to us using the objective response rate in first line setting for accelerated approval in a randomized trial. So, I think as we look forward in these other trials, as we did mention on the call, we are looking at them in combination therapy. Having said that, we're very excited about the single agent activity we've seen, both in the pancreatic trial as well as in the monotherapy in small cell. But our clinical development path is really using the combination, which then would require a randomized trial for accelerated approval. Okay, and then, another general question on the biomarker front is: Do you feel that at this juncture, you have sufficient information from a biomarker perspective to have elucidated mechanistically what you feel is most important to elucidate about the MOA of onvansertib? And would you characterize, you know, the positioning at this point in your biomarker strategy to effectively be shifting more towards, personalized medicine and identifying those patient subpopulations most likely to respond? Just give us a sense of where you feel you are in that process of the evolution of your biomarker strategy. Yeah. Thanks, Ram. You know, first of all, we are seeing really great response rates in combination therapy. As you know, in second line, metastatic CRC, we had a 73% response rate without any kind of biomarker play per se, and, and that's why we moved into first line. Having said all that, we continue to explore biomarkers as part of our programs because we do believe that understanding how and why patients are responding can only help future patients and future, targeting of identifying those most likely to respond. But in high level, it's an ongoing, process, and we will continue to see, and report out what we find. Okay, and then just very quickly, I'm assuming that nothing so far in your clinical experience with onvansertib would indicate that onvansertib is particularly effective in a specific subset of KRAS mutant cancers. In other words, regardless of what the mutant KRAS phenotype, what the mutant KRAS background is, you would expect a roughly similar likelihood of responsiveness to onvansertib. Is that correct? ... That is correct, and thank you for bringing forward that question because it's a very important one. We have reported already, as you know, within that phase II or the second-line trial, that we have activity across the board, across all mutant subtypes. This is really important because it differentiates us from the G12C-targeted therapies that really only address a very small sliver of metastatic colorectal cancer. Thank you. Thank you. Thank you. Please stand by for our next question, which comes from the line of Joel Beatty of Baird. Hi, thanks for taking the question, and congrats on the data. The first one is, could you discuss the likelihood of all three of the unconfirmed partial responses to confirm? You know, and related to that, there's also appears to be a few patients with stable disease that they got close to responses. Are there any potential for any of those patients to confirm later on? Thanks. Thanks, Joel, for that question. You know, first of all, we're coming off of some pretty exciting data in our second-line trial. And as you know, and we really, on purpose, showed that slide of the swimmer plot, showing that you can see that we had. And also the spider plot, where you see for these patients who did have a PR, they continue to have scan after scan, a more deepening and deepening of response. We feel very confident about those kinds of responses because they're all the way out to six months, which is, you know, double what the median PFS is. Now, you know, as far as going forward in the first-line, we obviously will follow these patients, and we will, as I mentioned earlier, subsequently report that data. We believe we have enough strong data now, to be able to move into first-line with this investigator-initiated trial that we described. Great. And then I guess another question on the historical controls that showed a 7.7 response rate in second line, could you discuss how your baseline characteristics in your study compared to the baseline characteristics of those patients? Yes, they're similar. It's, in essence, it's relapsed, refractory second line that have progressed on first line. Specifically, they exactly match that because these are patients that also progressed on Gem-Abraxane in first line. Great, thank you. Sure. Thank you. At this time, I would now like to turn the conference back over to Mark Erlander for closing remarks. Sir? Well, thank you, operator, and the slides of the investor call we can found in our homepage, and really you can look at it at www.cardiffoncology.com. I would like to say thank you all for your attention, and we are really excited to share this data with you all, and we look forward to sharing data in the future. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.