I will now pass the conference call over to Doug Onsi, President and Chief Executive Officer of Leap Therapeutics. Doug? Thank you, Operator, and good morning. We're very excited to have you all joining us today for our presentation of the initial clinical data from Part B of the DeFianCe study and Part C of the DisTinGuish study. Our two randomized controlled clinical trials of sirexatamab, also known as DKN-01, are first-in-class monoclonal antibody targeting DKK1. I'm Doug Onsi, the CEO of Leap, and with me today are Cynthia Sirard, our Chief Medical Officer; Jay Baum, our Chief Scientific Officer; and other members of the Leap management team. As Cynthia will present to you today, sirexatamab is demonstrating a compelling 35% objective response rate in combination with bevacizumab and chemotherapy in our study of 188 patients with second-line colorectal cancer, compared to a 23% overall response rate in the control arm of bevacizumab and chemotherapy alone. This is a 12 percentage point improvement in ORR in the full ITT population and even improves upon the results seen in the single-arm Part A of the trial. This overall response rate benefit with sirexatamab was also observed across multiple large potential CRC patient populations, including a 13% improvement in patients with left-sided tumors, a 22% improvement in patients who are naive to VEGF therapy such as bevacizumab and its biosimilars, an 11% improvement in patients who are RAS wild- type, and a 27% improvement in patients who had prior EGFR therapy such as cetuximab and panitumumab. Sirexatamab also demonstrated activity in patients with right-sided tumors, RAS mutations, liver, and lung metastases. While we'll wait for the PFS data to mature over the coming months, it's a very exciting and positive initial analysis. Cynthia and Jay are also going to walk you through data demonstrating that a colorectal cancer patient's circulating DKK1 levels tie all of these outcomes and populations together and are highly correlated with clinical activity. This is a clear indicator of the novel mechanism of action and validation of the target. Seeing that patients with higher levels of DKK1 have increased activity with sirexatamab and decreased responsiveness to the bevacizumab and chemotherapy control arm gives us confidence that it is sirexatamab driving the treatment effect. As a result of this very strong response rate signal and the expectation that objective response rate could be an accelerated approval endpoint in colorectal cancer, Leap will now begin internal preparations, regulatory discussions, and commercial strategic analysis to support a registrational phase III study in second-line colorectal cancer patients. Today, we will also provide initial data from the randomized controlled Part C of the DisTinGuish study in first-line gastric cancer patients. While there is an improvement in the confirmed objective response rate by blinded central imaging review, and we believe that a blinded placebo-controlled trial adjudicated by blinded central imaging review would be successful in DKK1 -high and PD-L1- negative biomarker populations, the overall data set in gastric cancer patients does not provide the signal needed for us to advance to phase III given the competitive landscape and in comparison to the colorectal cancer market opportunity. As a result, Leap is making the strategic decision to focus our internal and financial resources on advancing sirexatamab in colorectal cancer patients. Leap will continue to seek strategic partnerships to advance sirexatamab and PD-1 combinations in gastric cancer and other indications where there is high DKK1 expression. We will continue to advance our preclinical program FL-501 targeting GDF-15 towards clinical trials with an upcoming preclinical presentation expected in early Q2. At the outset, we want to thank all of the 358 patients, the investigators, and clinical staff, and the Leap team for their commitment to these studies. We look forward to presenting more data as it matures and at medical conferences during the year. Following the formal presentation today, we will open the line to questions. This call is being accompanied by a slide deck, so I'll ask you to please turn to our forward-looking statements on slide two. I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factor section of the company's most recent annual report on Form 10-K, as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, January 28, 2025, only. A replay of this call will be available on the company's website, www.leaptx.com, following this call. Now I'll hand it off to Jay. Thank you, Doug. DKK1 is a protein known to play a critical role in the development of cancer, where it's often overexpressed, too, leading to worse outcomes for patients. It's able to promote cancer development through an induction of proliferation, metastasis, and angiogenesis. This occurs through a few different mechanisms illustrated here. First, DKK1 modulates immune cells in a tumor microenvironment, signaling directly to myeloid-derived suppressor cells to enhance their activity. It also promotes the presence of M2 macrophages while decreasing the activity of and the number of natural killer cells. This helps to create a more immunosuppressive tumor microenvironment. Importantly, DKK1 can also promote angiogenesis, resulting in an increased number and size of blood vessels, and finally, DKK1 can directly impact the cancer cells binding to the CKAP4 receptor to activate the PI3K/AKT pathway and drive cancer cell proliferation. It's important to note that DKK1 can be produced by multiple sources. In certain indications such as gastric cancer, high tumoral expression can drive tumor growth, and we're able to detect that with a very sensitive and specific assay that measures DKK1 at the level of the RNA in the tumor tissue using an RNAscope technology. In other cancers, like colorectal cancer, DKK1 is not expressed as highly by the tumor itself. However, patients still demonstrate elevated levels in their plasma, likely the result of bone-derived DKK1, which is then released into circulation, and Leap identified ways to measure this circulating DKK1 in plasma and implemented such assays into our studies as well, and we're excited to share those results with you today. Sirexatamab was designed to inhibit the function and reverse the harmful pro-tumorigenic effects of DKK1 regardless of the source of DKK1. Evidence suggests that sirexatamab is able to modulate the immune landscape, creating a more favorable tumor microenvironment, and this includes the reprogramming of macrophages to the M1 phenotype while reducing the activity of suppressive MDSCs and promoting the activation of NK cells. Importantly, evidence suggests that sirexatamab has a key impact on angiogenesis, resulting in fewer and smaller blood vessels. And preclinically, we've seen additive effects of combining sirexatamab and anti-VEGF antibodies such as bevacizumab, resulting in greater reductions in tumors than bevacizumab can do on its own. And finally, sirexatamab may have a different effect, may have a direct effect on killing the tumor cells through a blockade of the CKAP4 PI3K/AKT pathway. Now we'll turn to a bit about the colorectal cancer development. Colorectal cancer is a highly prevalent and impactful disease. All general oncologists see patients with colorectal cancer, and most individuals know someone who has dealt with this disease. It is the third most frequently occurring cancer globally and the second leading cause of cancer-related death. In 2020, there were nearly 2 million cases of colorectal cancer diagnosed and nearly 1 million deaths attributed to this disease worldwide. Specifically, in the United States, there are approximately 150,000 new cases per year with more than 50,000 deaths. Over the past decade, there have been a limited number of new therapies introduced as treatment options for those suffering from this significant unmet medical need. Of the new entrants into the treatment paradigm, most have focused on biomarker populations such as genetic alterations in BRAF, KRAS, or HER2, and microsatellite instability. Leap is encouraged by the data we're presenting today and excited to begin phase III preparations in colorectal cancer. Colorectal cancer is characterized by high activity of Wnt signaling, which is modulated by DKK1. Approximately 80%-90% of colorectal tumors contain alterations in the Wnt pathway genes, such as APC. Preclinically, DKN-01 or sirexatamab has shown activity across different CRC models, both alone and in combination. In terms of the treatment landscape, 5-FU based chemotherapies remain the backbone of first and second-line therapies in colorectal cancer. DKK1 has been associated with resistance to 5-FU in colorectal cancer. The DeFianCe study includes patients who are microsatellite stable, BRAF wild- type, who have advanced colorectal cancer and received one prior 5-FU based chemotherapy regimen. In Part A of this study, the safety run-in, we enrolled a total of 33 patients, and the results were reported last year at ASCO GI. Part A of the DeFianCe study demonstrated encouraging clinical activity as a second-line therapy for patients with previously treated colorectal cancer. A recent update from October, presented at J.P. Morgan earlier this month, provided more mature duration of response and survival outcomes. Briefly, the overall response rate was 33%, and the disease control rate was 93%. The response rate further improved in patients who had left-sided malignancies, as well as those patients who had not been exposed to prior VEGF treatment or bevacizumab. Further, these responses were durable, lasting nearly 10 months. As a result of the encouraging activity in Part A, we expanded the study to include a randomized component with Part B. Described on this slide, Part B is a phase II open-label global controlled trial in which patients are randomized in a one-to-one fashion to the experimental arm or sirexatamab in combination with chemotherapy and bevacizumab, or to the control arm consisting of the standard of care chemotherapy and bevacizumab, with similar eligibility criteria to that enrolled in Part A. The patients were stratified on the basis of tumor sidedness and prior bevacizumab exposure. This part of the study began enrollment in August of 2023 and completed enrollment of 188 subjects from the United States, Germany, and South Korea in September of 2024. The primary objective of this study is investigator-assessed progression-free survival in the overall population, as well as those patients with left-sided tumors based upon our early data from Part A. Some important key secondary objectives include investigator-assessed overall response and blinded independent central radiology review of progression-free survival and overall response. In addition, we will evaluate duration of response and overall survival. Some additional exploratory populations in this heterogeneous patient group include evaluation of clinical outcomes on the basis of DKK1 levels, genetics such as BRAF wild- type, or even prior therapies such as the VEGF- naive patients or EGFR experienced patients. The statistical analysis plans that the time final analysis of the primary endpoints for the ITT population on 145 progression-free survival events have been observed overall, and 105 events have been observed in the left-sided population. Looking specifically at benchmark studies in the second line, patient characteristics in prior therapy really drive the expected clinical outcomes. Features which impact the anticipated results include the prior use of anti-VEGF such as bevacizumab or biosimilars or anti-EGFR therapies such as cetuximab or panitumumab. Prior chemotherapy used in the front-line setting, of course, also plays a role, and given there are so many different factors that influence our treatment choices and outcomes, it's clear that this second-line population is a very heterogeneous group, and it follows that the historical efficacy for second-line treatments and phase III studies is quite varied. Response rates range from 5%-26%, with a lower range representing those patients who have been treated with prior anti-VEGF therapies and upper range representing those who are previously treated with anti-EGFR therapy or bevacizumab naive. Progression-free survival ranges from 5.5-7 months, and overall survival ranges from 11.2-16.2 months. Another important thing to note on second-line treatment is that in the past decade, we have really had no paradigm-changing treatment options. We have seen data on bevacizumab maintenance, and we have seen data on therapy in targeted patient populations, but still, for most of our patients, it's going to be standard FOLFOX to FOLFIRI as their progression from first to second-line treatment. It really highlights the fact that we need more treatment options in this area for these patients. We are also in sore need of novel therapies that will expand the treatment options for patients and, more importantly, expand the biomarker options for a personalized approach to targeted treatment considerations. This lends opportunities for new drug development in this space. As a result of our encouraging data from Part A relative to these historical benchmarks, we've expanded the DeFianCe study into Part B. At the time of this update, all patients had a minimum of three months' follow-up on study and a mean duration of the study of approximately six months. PFS is not yet mature. All subjects have had at least one post-baseline scan. Of the 188 randomized subjects, 91 patients began treatment on the experimental arm compared with 88 on the control arm. As of the recent data cut, 82 patients remain on therapy, with 10 more subjects continuing on the experimental arm compared to control, being 46 on the experimental arm compared to 36 on the control arm. This equates to roughly 49% of the experimental patients currently off therapy compared with nearly 60% or 59% of patients who are on the control arm. This slide depicts the patient population demographics from Part B. Of the patients who enrolled in Part B, the overall demographics were well-balanced, including by gender, age, and ECOG baseline performance status. 50% overall of patients were enrolled in South Korea. 77% of patients had primary left-sided tumors. The majority of the patients, or around 80% in total, had received oxaliplatin-based front-line therapy, either FOLFOX or CAPOX, while 50% had received prior anti-VEGF therapy and 27% had received prior anti-EGFR therapy. More subjects on the experimental arm had liver metastasis at baseline, 76% versus 69%, while more control subjects had BRAF mutations at 55% versus 46%. Overall, approximately half of the subjects enrolled had BRAF mutations. At present, more than 650 oncology patients across several tumor types have been exposed to sirexatamab either as a monotherapy or in various combinations, including 5FU-based chemotherapeutic regimens such as FOLFOX. Part A demonstrated a well-tolerated regimen when sirexatamab was combined with chemotherapy, that being either FOLFOX or FOLFIRI and bevacizumab. In Part B, once again, the overall treatment emergent adverse effect profile is similar between the experimental and control arms, suggesting that the addition of sirexatamab does not adversely impact the safety profile of the combinatorial agents. Specifically, sirexatamab does not increase the frequency of high-grade events such as those that are greater than or equal to grade 3, serious adverse events, deaths, discontinuations, or dose reductions. Overall, patients had expected adverse events given the chemotherapeutic backbone, and there was really nothing unexpected or unimaginable that arose for the subjects treated on study. Today, we will discuss the preliminary overall response rates between the experimental and control arms. We will begin with the intent-to-treat population for all 188 subjects enrolled. As illustrated on this waterfall plot, the experimental arm had a 12% improvement in the overall response rate over the control arm, representing a response rate of 35% on the experimental arm compared to 23% on the control arm. As described earlier, the response rate of the control arm appears to be representative of the benchmark study, where the response rate ranged anywhere from 5% to 26% in this heterogeneous population. Importantly, the response in the experimental arm from Part B mirrors, if not slightly improved, upon that from Part A of the same study. This slide provides the Kaplan-Meier or KM curve for progression-free survival of the intent to treat population. Please recall that the progression-free survival data is not mature, as the pre-specified number of events for study completion is 145, and the mean time on study is approximately six months. To date, we've only had 75 PFS events, 37 occurring in the experimental arm and 38 in the control arm. Many patients continue to be censored, typically reflected on the graph at the time points of the required imaging per protocol, which occurs at eight-week intervals. Regardless, 82 patients remain on therapy, 46 on experimental, and 36 on control. The data will continue to mature over the coming year. As I mentioned earlier, we've developed plasma-based assays to measure DKK1 in circulation, which we believe to be the primary source of DKK1 in colorectal cancer. Our initial analysis has focused on plasma DKK levels using two cutoffs: one at or greater than the median, which represents 50% of patients in the study, and another at or greater than the upper quartile, representing 25% of the patients. Using these thresholds, we've observed a clear enhancement of clinical activity with increasing pretreatment DKK1. In the ITT population, this includes an increase in ORR from 22% in the control arm to 39% in the experimental arm based on a median cutoff. As DKK further increases to the upper quartile protein levels, the improvement for the experimental arm over the control arm becomes enhanced more than fourfold, with a response rate of 11% in the control versus 48% in the experimental arm. Importantly, the differences in response rate have begun to translate into PFS signals. We observe an initial separation of the curves with an advantage to the experimental arm using the median cut and a more pronounced advantage in separation throughout the curves with the upper quartile of DKK1 expression. This enhanced efficacy in sirexatamab-treated patients with high circulating DKK1 is further illustrated by this dot plot. This figure illustrates the range of baseline DKK1 levels and color codes of responding patients, represented by the red dot compared to the non-responding patients in black. The enrichment of responders is clearly observed in the top 50% of patients. And as you move into the upper quartile, this is further strengthened with only two responses in the control arm as compared to 12 in the experimental arm. As you'll see later, the correlation of DKK1 baseline values to improved response is not only observed in the overall population in this study, but consistent across each of the different subpopulations we analyzed based on sidedness, mutation status, or prior treatment. We will now review the clinical activity in patients based upon the location of the primary tumor, either left or right-sided. Our early hypothesis and one of the reasons that we stratified Part B on tumor sidedness was that we anticipated patients with left-sided tumors would have a higher proportion of patients with Consensus Molecular Subtype, or CMS2, tumors. CMS2 is predominantly found in left-sided tumors and is characterized by high activity of the Wnt signaling pathway, including APC mutations. It is hypothesized that sirexatamab may be more effective in these tumors by controlling the Wnt activity, driving left-sided tumors through a non-canonical Wnt signaling pathway. However, this study has demonstrated improved response rates regardless of tumor sidedness. And as you can see here, the overall response rate is favored in the experimental arm over the control arm in left-sided tumors with an overall 13% improvement, or specifically 38% compared with 25%. In right-sided tumors, with a 7% advantage for the experimental arm, demonstrating a response rate of 26% in the experimental arm compared to 19% in the control arm. Therefore, it is possible that the additive benefit of sirexatamab is observed due to factors beyond tumor sidedness and perhaps more relevant to the underlying genetic alterations, prior therapy administered, or even baseline DKK1 levels. This slide specifically compares the patients who have left-sided tumors and demonstrates the enhanced response in the experimental arm, whereby the overall response rate was once again improved by 13%, with 38% versus 25%. Once again, the progression-free data is not mature, as the mean time on study is only six months. Many patients remain censored, and we have only observed 59 of the required 105 progression-free progression events in patients with left-sided tumors. Now let's evaluate the impact of DKK1 levels and the therapeutic benefit in patients with left-sided cancers. DKK1 levels once again correlate with the clinical activity of the experimental arm and is enhanced as the DKK1 value increases. For example, at the median level of DKK1 expression, the experimental arm has a response rate of 43% and a disease control rate of 92%, compared with a response rate of only 25% and a disease control rate of 86% in the control arm. As you evaluate higher thresholds of DKK1 values, specifically in the upper quartile, the advantage of the experimental arm is further enhanced, which now improves to a response rate of 52% on the experimental arm versus only 8% on the control arm. Next, we'll move into some subgroup analyses of key patient populations that we would like to analyze. We will now turn our attention to subgroups that are related to the type of prior therapy. First, we will look at the bevacizumab-naive patients, meaning that these patients have not received prior bevacizumab or biosimilars. In our study, this population represented approximately half of all subjects enrolled. Included within this group are patients who received anti-EGFR as their front-line biologic agent or patients who received only 5-FU based chemotherapeutic regimens as their initial line of therapy. For the latter group, these patients include those who have progressed rapidly after adjuvant chemotherapy where anti-VEGF therapy is not warranted or in patients in whom anti-VEGF therapy may have been previously contraindicated. These rapid progressors after adjuvant therapy represent a particularly aggressive cohort of patients. In the anti-VEGF-naive subgroup, the experimental arm outperforms the control arm in overall response with a response rate 22% improvement over the control arm. The experimental response rate was 51% compared to a 29% response rate for those subjects on the control arm. The disease control rate is 10 percentage points higher in the experimental arm at 94% versus 84% for the control arm. I will also note that the overall response rate was equivalent in the patients who had seen prior VEGF or the VEGF-exposed population at 18% per arm. This is particularly important as we begin to see a differential based upon DKK1 values in the subsequent slide. This slide now further exemplifies the difference in response rates between the experimental and control arm in VEGF-naive patients. Additionally, there is a notable difference in primary progressive patients for the control arm, whereby 9% experienced primary PD compared to 0% for patients on the experimental arm. Visually, this can be seen when one looks at the far left of the waterfall plot for the control arm, where you see the representative growth in target lesions on the control arm, that which is not seen in the comparable waterfall of the experimental arm. Further, there is an early separation in the KM curve despite the mean time on study of only being six months. Once again, despite the subgroup being presented, the theme remains constant, whereby DKK1 levels continue to correlate with clinical benefit for the experimental arm, both at the median and further enhanced at the upper quartile expression. This slide provides the context to the correlation of the experimental arm's activity in anti-VEGF-experienced patients. As I mentioned on the prior slide, the experimental arm and control arm had equivalent activity in the patients previously treated with anti-VEGF therapy with a response rate of 18% collectively. What is notable here, however, is the difference in the response rates according to the DKK1 levels. For increasing DKK1 values in the VEGF-experienced patients positively correlates for the experimental arm with a response rate at the median noting 18% overall response rate in the experimental arm compared to 7% in the control arm, and then increases to an improvement in response rate at 33% versus 0% favoring the experimental arm at the upper quartile, suggesting that the additivity of sirexatamab to standard of care in VEGF-experienced patients is driven by DKK1 values. Let's now explore the subgroup of patients who have been previously treated with anti-EGFR therapy, such as cetuximab or panitumumab. Global guidelines for the treatment of colorectal cancer recommend the use of anti-EGFR therapies for patients with left-sided tumors without RAS mutations or those who are RAS wild-type genetics. This subpopulation represents another targetable patient population. Recall that overall, 27% of the patients who enrolled on this study were treated with prior EGFR therapy in first line. Here, you can now see a doubling in the response rate favoring the experimental arm at 54% compared to 27% for patients who have seen prior anti-EGFR therapy. This is also a subgroup where you see an early separation of the KM/PFS curves despite the limited follow-up. Once again, in this subgroup, you notice a difference in number and percentage of primary progressors favoring the experimental arm over the control arm at 0% on experimental compared to 18% of subjects being primary progressors on the control arm. Although the data is not shown, this subgroup also has correlation with DKK1 values, whereby higher levels correspond to sirexatamab's clinical activity. Let's now evaluate the impact of the addition of sirexatamab to standard of care according to RAS mutational status. Patients who have RAS mutations are understood to have worse prognosis than those with RAS wild-type tumors. As you can see, regardless of RAS genetics, the experimental arm has improved response rates over the control arm. In patients who are RAS wild-type, the addition of sirexatamab to standard of care improved response rates over control by 11%. Notably, the overall response rate in the experimental arm was 43% compared to 32% in control. Additionally, in the RAS mutated patients, the experimental arm had an improvement in response rate from the control of 19% up to 26% for those treated with sirexatamab. Diving a little deeper into the patients with RAS wild-type tumors, in addition to improvement in the overall response rate, you once again see an early separation of the KM curves. Here as well, the only primary progressors are demonstrated in the control arm, representing 12% of the control population compared to 0% on the experimental population. As you just heard, across the full ITT in each of the subgroups explored, we've observed enhanced response rates in patients with increasing levels of circulating DKK1. In several of these subgroups with high DKK1, the control arm only showed zero to single-digit response rates, which may indicate a prognostic effect of circulating DKK1, while we saw 30%-60% response rates in the experimental arm of the same groups. We also saw early separation of PFS curves benefiting the experimental arm in most of these subgroups, indicating the role of DKK1 levels in driving outcomes of patients with colorectal cancer and the notable improvement of those treated with sirexatamab. So, in summary, in this 188-patient randomized controlled trial that we refer to as the DeFianCe trial, sirexatamab plus bevacizumab and chemotherapy is demonstrating higher overall response rates as second-line therapy for microsatellite stable colorectal cancer over the control arm of bevacizumab and chemotherapy alone. This benefit is further exemplified across a number of targetable patient populations, including by DKK1 levels, prior therapy such as those who are VEGF-naive or EGFR-experienced, and in patients with RAS wild-type genetics. Additionally, in the aforementioned subgroups, there was an early separation of the KM/PFS curve. Collectively, we believe this signal in CRC warrants advancing into planning for phase III studies. We believe the strong signal in colorectal cancer from this study supports us moving forward to plan a registrational phase III clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line microsatellite stable colorectal cancer patients, a group representing a high unmet medical need. This is subject to regulatory discussion. Potential phase III patient populations include DKK1 biomarker select, anti-VEGF-naive, anti-EGFR-experienced, or RAS wild-type patients. Further, the experience in anti-VEGF-naive patients warrants consideration for advancing into the first-line treatment paradigm given the demonstrated additivity of sirexatamab to standard of care. While the data matures, we've intended to conduct a global commercial and regulatory strategic analysis to select the optimal population. One such discussion would be for a potential accelerated regulatory path similar to recent pharmaceutical companies, in which we may be able to commit an early analysis based upon blinded independent central review response rates utilizing overall survival as a confirmatory endpoint. We will now transition our discussion to gastric cancer. I'll report data from Part C of the DisTinGuish study evaluating sirexatamab in combination with tislelizumab, an anti-PD-1 antibody, and chemotherapy in treatment-naive patients with advanced gastroesophageal junction adenocarcinoma in gastric cancer. Part C of the DisTinGuish study is a global phase II randomized open-label multicenter study of sirexatamab in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal junction adenocarcinoma in gastric cancer. Part C enrolled 170 first-line HER2-negative patients. Subjects were randomized in a one-to-one fashion to evaluate sirexatamab in combination with tislelizumab and chemotherapy as the experimental arm compared to tislelizumab and chemotherapy alone as the control arm. Patients were stratified using tumoral DKK1 as well as PD-L1 expression. The primary objective of this trial is progression-free survival by investigator assessment in all patients, as well as the biomarker-selected population of those patients with DKK1-high tumoral expression representing a TPS of greater than or equal to 20. Secondary objectives include overall response rate, duration of response, and overall survival as measured by both blinded independent central review as well as investigator assessment in all patients and in DKK1-high patients. Final results from the recent single-arm portion or Part A of the DisTinGuish study, which provided the results to permit the initiation of Part C, was recently published last week in the Journal of Clinical Oncology in January of 2025. This slide reflects the data for tislelizumab in their phase III trial RATIONALE- 305, which was the basis for the approval of the drug in patients with PD-L1 expression greater than or equal to one. Published efficacy outcomes reported from the RATIONALE- 305 study provide the benchmark for the control arm of the DisTinGuish trial. In the intent-to-treat population, the progression-free survival on RATIONALE- 305 in the tislelizumab-treated patients was 6.9 months compared to 6.2 months in the control arm, representing a hazard ratio of 0.78 overall. Different subgroups on this study yielded different results, including the subjects enrolled in the United States or Europe who had little advantage with the addition of tislelizumab over the control arm relative to progression-free survival at 5.6 compared to 5.4 months. Additionally, in the PD-L1 negative or those who are CPS less than 1 group, the group which represents a population that's not approved for tislelizumab therapy, the progression-free survival was 7.9 months overall in the tisle treated arm compared to the control arm at 6.9 months, but only had a hazard ratio of 0.98 on overall survival. In general, on RATIONALE- 305, the overall response rate ranged from low- to mid-40% for the tislelizumab arm. The results from RATIONALE 305 were in line with other large contemporaneous phase III studies utilizing different anti-PD-1 molecules in frontline gastric cancer, such as the CheckMate 649 study with nivolumab and the KEYNOTE- 859 study with pembrolizumab. From a benchmark perspective, these three large randomized studies for PD-1 antibodies plus chemotherapy in the same HER2 negative first-line population are quite consistent in their outcomes. A recent ODAC meeting from September in 2024 noted that the addition of anti-PD-1 standard of care chemotherapy did not improve outcomes in patients with PD-L1 negative disease. As a result, there remains a very high unmet medical need in patients with low or negative PD-L1 expression. Overall, 170 patients were enrolled in Part C. They were equally distributed to the experimental and control arm. In terms of treatment, 84 of the 85 randomized to the experimental arm initiated therapy compared to all 85 in the control arm. At present, 34 patients continue on study therapy, 18 on control, and 16 on the experimental arm. More control patients overall discontinued for patient decision at 10 versus one on experimental or withdrew consent or lost to follow-up at 15 on the control arm compared to 4 on the experimental arm, potentially having an impact on the progression-free and overall survival outcomes. In terms of the demographics, the arms were well balanced for baseline demographics and tumor characteristics. Roughly 60% of all subjects were enrolled from South Korea, the remaining 40% from the United States and Germany. Only 26% of patients enrolled were DKK1- high, representing a TPS score of 20 or higher, unlike in Part A in which we had 50% who were DKK1- high. Over 70% were PD-L1 low with values of CPS of less than 5. 27% were GE junction adenocarcinomas in the control group, had 10 more patients with GEJ tumors than the experimental arm. Each arm had three patients who had MSI high disease. 59% overall had had one cycle of chemotherapy administered during the screening period. Unfortunately, when reviewed by the blinded independent central radiology review, over a quarter of the patients, or 27%, were identified as not having measurable disease at baseline with imbalance favoring the control arm of 25 compared to 20 patients with low volume disease. Once again, the addition of sirexatamab did not add toxicity to the standard of care arm as the overall treatment-emergent adverse events, high-grade events of those greater than or equal to grade three, serious adverse events, and deaths occur at similar rates across the treatment arms. In this open-label phase II study, investigator assessment was the primary endpoint and was not concordant with the blinded independent central review. Patient tumor scans were reviewed at each site in addition to the blinded independent central review. The BICR review involves two blinded readers reviewing each scan independently, and in the event of disagreement in the tumor assessment, it was adjudicated by a third independent reader. Many know that gastric cancer is a very difficult tumor to assess radiologically, and most large phase III studies rely on the blinded independent central review for primary endpoints. Across our ITT population, again, 170 subjects, patients treated with sirexatamab plus tislelizumab and chemotherapy had a confirmed response rate of 52% by both independent investigator assessments as well as blinded independent review. This compares to the control arm in which the investigators assessed a response rate of 56% compared to that of 42% by the blinded independent central review. Therefore, investigator assessment identified 12 additional confirmed responses in the control arm compared to zero in the experimental arm. BICR also identified non-measurable disease in the control arm at 20 subjects compared to 15. Again, DKK1- high patients were expected to represent roughly half of all enrolled in Part B, as we had seen in Part A. In this arm of the study, however, or overall, only 27% or 44 patients were enrolled with DKK1- high disease in Part C. Based upon the blinded independent central review assessment, patients in the experimental arm had a confirmed response rate of 59% compared to 36% in the control arm. When you look at the confirmed response rate by the investigator assessment, they are the same in both arms at 64% respectively. Investigator assessment once again identified six additional confirmed responders in the control arm compared to only one in the experimental arm. Now, if we look at the PD-L1 negative population, in the PD-L1 negative population of those with CPS less than 1, the investigators and the blinded independent central review both assessed the experimental arm to have a higher response rate than the control arm. Based upon the blinded independent review assessment, patients in the experimental arm had a confirmed response rate of 44% compared to only 32% in the control arm. Confirmed response by investigator assessment also favors the experimental arm at 50% compared to 37%. The statistical analysis plan states that the time for analysis of primary endpoint for the intent-to-treat population when 137 investigator-assessed progression events are observed in the DKK1-high population when 49 investigator-assessed events have been observed. The specified number of progression events has not been reached and may never be reached due to the patient withdrawals and discontinuations without progression or death events, primarily in the control group. In the intent-to-treat population, preliminary median progression-free survival in the experimental arm was 9.72 months by blinded independent central review and 7.66 months by investigator assessment compared to 11.99 months by blinded independent central review and 10.4 months by investigator assessment for the control arm. Progression-free survival hazard ratio by investigators favored the control arm at 1.4. However, note that 24 patients were censored prior to progressive disease, 17 of whom were on the control group compared to 7 on the experimental. Blinded independent central review disagreed with the assessment of progressive disease in 52% of the investigator assessed cases and only agreed with the same PD time point in 31% or less than a third of the subjects as assessed by the investigators. The median progression-free survival for tislelizumab plus chemotherapy in RATIONALE- 305, if you recall, was only 6.9 months. In the DKK1- high population, preliminary median progression-free survival in the experimental arm was 7.72 months by blinded independent central review and 7.43 months by investigator assessment compared to 7.79 months for the blinded independent central review and 11.14 months by investigator assessment in the control arm. The median progression-free survival for the control arm by BICR is over three months shorter than that assessed by the investigators. Once again, the blinded independent central review disagreed with primary PD in 43% of the investigator-assessed cases and only agreed with the PD time point in 37% of patients, noting an earlier date of progressive disease by BICR on six patients in the control arm compared to two patients in the experimental arm. The hazard ratio overall for the progression-free survival by blinded independent central review favored the experimental arm at 0.68, representing a trend in favor of the experimental arm in the overall time to event analysis in the biomarker high population. Lastly, in a subgroup analysis of patients whose tumors were PD-L1 negative, progression-free survival hazard ratio by investigator assessment favored the experimental arm at 0.55, with a median progression-free survival on the experimental arm of 9.82 months compared to control of 7.46 months. Progression-free survival hazard ratio by blinded independent central review demonstrates no benefit and a hazard ratio of 0.96. The median progression-free survival for the control arm is over five months longer by BICR than the median progression-free survival for that was demonstrated in RATIONALE- 305 at 7.9 months. In summary, there was a high level of discordance between the investigator assessment and the blinded independent central review assessment. Due to complexities evaluating gastric cancer radiographically, most phase III studies utilized central review to standardize assessment and remove bias. According to the central review, sirexatamab in combination with standard of care demonstrated improved response in the intent-to-treat population, the DKK1- high population, and the PD-L1 negative biomarker subgroups. While demonstrating activity in biomarker populations, the study did not generate a clear positive signal and will be negative on the primary progression-free survival endpoint for both the ITT population as well as the DKK1- high population when the study completes. This has resulted in the decision to not move forward with phase III studies in gastric cancer at the current time. In conclusion, in 188 patients randomized with colorectal cancer who were enrolled in the DisTinGuish study, there was a clear overall response benefit observed for the sirexatamab treated arm in the intent-to-treat population, patients with left-sided tumors, and across multiple potential phase III populations. DKK1 levels highly correlate with sirexatamab clinical activity in second-line colorectal cancer. Preparations will begin for a registration of phase III study in second-line CRC patients while follow-up continues and data matures. Colorectal cancer will be prioritized over gastric cancer as there is a larger market opportunity with a clear path in phase III development, And now we'd like to turn it over to the operator to answer any questions. If you'd like to ask a question at this time, you will need to press star one on your telephone and wait for your name to be announced. If you'd like to withdraw your question, simply press star one one again. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Joe Catanzaro with Piper Sandler. Your Your line is now open. Great. Hey, everybody. Thanks for all the data. I have a couple of questions. Maybe first one, just sort of thinking about how we should think about some of the ORR deltas you're reporting and those translating to potential PFS benefits. You're seeing a 12% response rate delta in the ITT, and I appreciate it's early, but that doesn't seem to be translating to PFS benefit based on the early curve. So I guess my question is, what subgroup do you have the greatest confidence in at this point that the response rate benefit you're observing will, in fact, translate to benefits on other efficacy measures? Thanks, and I have a follow-up. Sure, Joe. Thanks. So we definitely believe that as you look at the number of patients who remain on study, that we continue to have the potential for the ITT population and the left side to show separation with further follow-up with the 10 additional patients in the experimental arm and the number of patients that are centered at two months and at four months because they haven't hit future time points. We certainly understand that as you move into phase III, it's not going to be an ITT heterogeneous population that you take to phase III. So I think for us, we're most excited by the opportunity to take the DKK1 biomarker into phase III. It is the consistent tying mechanism both for the drug and in every subpopulation. The data that Jay and Cindy walked you through were at the median, you see a strong treatment effect driven by the DKK1 biomarker. They get even larger as a treatment effect as you move to the upper quartile. It suggests to us that as we look across the data sets, that is the strongest signal and the one that is most across whether it was treatment naive, treatment experienced patients, the RAS wild- type prior therapy. I think that beyond the DKK1 biomarker, as you look at the VEGF- naive population, this is one where as you looked at both Part A of the study and Part B, you see a greater than 50% response rate. You are seeing early separation in those curves. It tells us mechanistically there is significant added value on top of VEGF therapy. It opens the line, the question of should first-line therapy be considered in the future. But I think the VEGF- naive is the next kind of broad, if we're following the current treatment, how patients are treated today, broadest phase III opportunity. And within that, you understand that's been composed of patients who've had prior EGFR. Those are VEGF- naive. They were half of the VEGF- naive population. Very strong separation on PFS in that much more homogeneous population because they're left-sided, originally KRAS wild- type, and have already had EGFR therapy. So they would normally get that in the second line. And I think as we look at the RAS wild- type patients, again, there's a lot of overlap there as well. It would put us clearly differentiated from the KRAS targeting agents looking at G12C. So I think we've looked to focus in on those four subpopulations as being more specific, both tied to the mechanism of drug and where we are already seeing and have the room for much more of a very targeted and exciting therapeutic opportunity. Great. That's helpful. And maybe you actually answered the follow-up I had, but maybe I'll still ask it in terms of current thinking around the potential move forward population. Is it maybe going to be based on one variable, meaning just DKK1- high patients, or will you cut it multiple ways, i.e., DKK1- high and anti-VEGF- naive? Just the thinking there. And then maybe relatedly, how much work is there needed to define DKK1 plasma positivity? Is this thought to just use this quartile separation, or is there a stricter cutoff that you're thinking about? And what percent of the CRC population would that capture? Thanks. Right. So I didn't attempt to answer it. I think as you look at the cleanest, most consistent, and most mechanism-directed patient population, we'll be looking at DKK1. That it did not need to be if that is your biomarker, you don't need to further segment it based on what they got in first-line therapy or what their genetics were. You had clear wins across the board. I think that from preparing it for phase III, I think Jay and his biomarker team know that there is quite a bit of work that you will need to do to be prepared to roll this out into phase III and to use it as a potential companion diagnostic. That is part of what the phase III planning activities are all about, making sure that you get good regulatory interaction around this biomarker and understand is that the right commercial opportunity, or is it better to take one of the known treatment paradigms and work within that? Okay. Great. Thanks for taking my questions here. Thanks. Thank you. Our next question coming from the line of Joel Beatty with Baird. Your line is now open. Hi. Thanks for taking my questions and sharing the data today. First question I have is in the press release, it mentioned how there's more patients still on study in the experimental arm. I think it shows 46-36 in talking about the CRC data, which seems to be favorable for how the survival data can mature over time. I guess my question is, are there certain subgroups where you're seeing maybe even more of an imbalance in favor of the experimental arm and how many patients are still on study compared to control? That's a great question. We'll have to get back to you on the specifics within each subgroup as the team in terms of patients still on. I think it's a very good question and one that we're continuing to look at as we think about how this data might mature and be presented in the future. I think it was important for us as we looked at these very large advantages on overall response rate that in an initial look, you know that every patient contributes to your best overall response table and that patient censoring and follow-up can be at different stages of duration on each of the subgroups. We definitely expect to be presenting additional updates on this data over the course of this year, not just at one time late in the year. Got it. Thanks for that. And then a question on potential phase III trial design. You gave a little bit on potential ideas here today, and I know there's more work to do, but are there any other phase III trials you could point to as potential examples that you might learn from for your phase III trial? I think we certainly are aware of other companies and the FDA white paper demonstrating that overall response rate is an accelerated approval endpoint in colorectal cancer. That was really the driving factor behind getting an early look at the colorectal cancer data to be able to have for ourselves those regulatory conversations. While we looked at single-arm data and saw what we thought were impressive overall response rate results, we knew we needed to see for sure what a control arm would look like and would we continue to see a greater than 50% ORR in VEGF-naive patients, a 33+% ORR in the overall ITT population, and have a contemporaneous control arm. So I think that as we think about phase III design, we are looking for strategic input as well as regulatory input to make sure that we are optimizing where the opportunity is in second-line. And certainly, as you look at the VEGF-naïve outcomes, a larger company would certainly be interested in that as a first-line add-on to VEGF chemo. Great. That makes sense. Thank you. Thank you. Our next question coming from the line of Tony Butler with Rodman & Renshaw. Your line is now open. Thanks very much. Two brief questions, if I may. Is it known yet in left-sided tumors only, what was the% that had liver mets versus those in non-liver mets with respect to ORR? And then the second question, if I may, is around prior VEGF use. Could you just maybe allude to the notion of what might have been the mechanism for differences between prior versus non-prior VEGF use with respect to the utility of DKK in the population? Thank you. Sure. So those are both great questions, and I'll let Cindy and Jay add in. We'll have to get back to you on the percentage of liver mets with respect to the left-sided population. And I think you saw overall there were 136 of the patients with liver metastasis. So the majority of the patients in the trial had liver mets. I think it was very important that we saw a treatment effect in patients that had liver mets. Typically, you do not see a treatment effect for immuno-oncology agents in patients once they have liver metastasis. I think we noted the lung metastasis data as well, while there is probably a fair amount of overlap where people might have both liver and lung metastases. But as you see a very striking response rate benefit in those patients with lung metastasis and causes us to think back to DKK1 being high in non-small cell lung cancer, the fact that we had single-agent activity in non-small cell lung cancer. So one of the things we want to look into is in those patients who are seeing benefits, what is the mix of where the tumor reductions come from in target lesions with respect to the metastatic lesions or potentially the primary? So we'll have to get back to you on the percentage, but I think it is an important characteristic to see a drug with an overall 9 percentage point improvement in patients with liver mets and really a 25% improvement, over a tripling in those that had lung metastasis. respect to the prior VEGF population, when we think about the mechanisms for DKK1, a local anti-angiogenic effect has been part of the equation for us from the beginning, from the earliest work at Lilly. As we think about patients who've had prior VEGF, is there already a reduction in blood vessels that affect potentially the ability of DKK1 to be in the tumor microenvironment and the extra impact you would get from further anti-angiogenic effect? And so I think that it was not surprising to see a lower response rate in those patients who had prior VEGF if you're bringing an additional VEGF mechanism and if some of your strongest data is that you can improve upon VEGF activity. The time to do that is the first time a patient is exposed to a VEGF anti-angiogenic agent. But it was very encouraging us to see that when there was high DKK1 in the patients, that those patients did have benefit, that there was striking benefit at the median and upper quartile. And so as we think about that as patient populations, that will be something we study more of, how do you think about drawing a point going forward? But very instructive to us to see even those patient populations where on the whole, we haven't yet shown an overall response rate benefit across the full population. As you look to DKK1, as DKK1 gets higher, the treatment effect and the activity of the drug increases, and the treatment of the control arm decreases. Thanks, Doug. Thank you. Our next question coming from the line of Swayampakula Ramakanth with H.C. Wainwright. Thank you. Good morning, Doug and team. Thanks for this. Just trying to understand a little bit more about the expression of DKK1 and the sidedness of the tumor. So is it clear that DKK1- high is normally seen only in left-sided colorectal cancer patients, or can it be seen independent of what side the tumor is? Yeah. So thanks for the question, RK. Absolutely. DKK1 is present in the circulation. It is, in our work, equally identifying of treatment effect both on the right side and left side. We focus on the left side because the consensus molecular subtype 2 related to Wnt activation, consensus molecular subtype 4 related to angiogenesis are known to be higher in patients on the left side, and patients on the left side represent 75% overall of the colorectal cancer marketplace. So I think that it's something that is a valid DKK1, a valid potential diagnostic test covering both left and right-sided patients and consistently identifying patients that have a stronger treatment effect for sirexatamab treatment. Okay. Thanks for that. And then I believe the DeFianCe study was selecting patients for HER2 marker. Is that right? No, so in the gastric study, they're HER2 negative. In the DeFianCe study in CRC, the patients excluded were microsatellite instability high. They would normally get a PD-1 antibody, and those that had a BRAF mutation who would normally get targeted therapy, but it was all comers otherwise, and so from a design perspective, we knew going in this is a heterogeneous patient population, and the mission is to identify how would you move into phase III. What were the populations where there was the highest activity so that over time, you could do multiple phase III studies and build a market, a larger market opportunity, but you take your first shots at the patient populations where you see the greatest treatment effect and market opportunity? Okay, and then the last question for me is, when do you think the next update would be, and will you be able to tell us a little bit more on the response rates and especially if there are going to be any CRs that we could be seeing in that update? Yep. So we expect to be doing updates throughout the year. So this isn't one where we plan to be kind of silent till late in the year. We know that as this data matures, every month you add really meaningful information. Every two months, patients get a new scan. So while this is very hot off the presses, so it's too soon to commit to exactly when the next update might be, we're committed to consistently updating the markets and being able to watch these trends so that we can make good decisions as well as draw external validation and support. Okay. And the last question for me is probably this question I already asked, and if it has been, I apologize for that. What percentage of patients in the overall population really fit the phase III population? So I'm just trying to understand what's your target population? Sure. Yeah. So if you would take the DKK1 median, it would be 50%. If you choose the upper quartile, that would be 25% of the second-line population across the board. Based on our study, if you chose VEGF- naive, it would be roughly 50% of second-line patients. That's what we saw in Part A as well as Part B. And the EGFR experienced patients are about half of the VEGF- naives. It was 27% in this study. So it's a subgroup within the VEGF- naive, but still a very large one, particularly internationally, where the guidance is very clear about using EGFR in the first line for left-sided KRAS wild-type patients. And then broadly, a little over half of the patients are KRAS wild-type or sorry, RAS wild-type. And so I think it's a much larger market opportunity than any of the KRAS targeting agents, dramatically larger than BRAF or KRAS G12C. And certainly much larger than MSI high in this patient population. So each and every one of these potential indications is a very large and high-end medical need. They currently have no targeted therapies and no new mechanisms that have been brought to bear since the approvals of Avastin, Erbitux, and Vectibix. Thank you. Thank you, Doug, for answering all the questions. I appreciate that. Thank you. Our next question coming from the line of Matthew Phipps with William Blair. Hi, Doug. Thanks for taking my questions. I appreciate the look at the median and upper quartiles of DKK1 here, but are you all going to perform a receiver operating characteristic analysis to determine what that optimal cutoff could be for DKK1 levels? And would that be based off of response rate, or could you do it based off of time to progression? I'll let Jay handle that. I think it would be too easy for me to just say yes, but let Jay give you a little more detail. Yeah. So as I mentioned, we've utilized actually multiple DKK1 assays that show high concordance with each other. So right now, those assays are largely ready for selecting patients to phase III, but we're now having conversations with diagnostic companies to determine really which one would provide the best regulatory pathway, ensure which one's most ready for phase III, and the greatest access to patients globally. So I think once we have the data a little bit more mature and we determine what the final assay would be to take forward as a companion diagnostic, if we go that route, I think at that point, yes, absolutely, we would conduct those analyses to determine the optimal cutpoint based both on response rates and survival, largely dependent on our regulatory conversations and the agreement with regulators. But I think we would like to do both. Thanks. With the CRC data that you presented today, was that all investigator assessments, or do you have the blinded independent review for the CRC data? Yeah. No, that's a great point. So this was all investigator assessment. We are also doing blinded central imaging review. We've done that in Part A, and it was highly concordant. I think we found that overall, blinded central imaging review is much more concordant in colorectal cancer than, unfortunately, we saw in gastric cancer. We will, based on early looks at the BICR data, it looks very concordant in Part B as well. So I think we feel very confident that one of the next updates will be to be able to present that. But all of the trends and subgroups and activity that we're seeing here are just as strong as we're seeing so far by BICR, just with the timeframe we had. We put together investigator assessment. It came together more quickly because BICR tends to lag by a couple of months due to the process of the blinded readers reviewing it, going back over prior scans, and then the need to adjudicate if the two reviewers don't agree with each other before they come up with an outcome, so it's a little lagged to the investigator assessment, and we wanted to, given a very clear signal from the investigator assessment, to be able to have that data for ourselves as well as for the community. Yep. Okay. Doug, I was wondering, just how much time do you think would be saved on a development path if there was an accelerated approval based on ORR that the FDA obviously likes to have some follow-up for duration versus just a PFS endpoint, given especially if you're looking at the upper quartile DKK1? I mean, it seems like your median PFS might come in below seven months, especially for the control arm. Just always curious how much time is really saved from that accelerated approval path versus just a full approval off of PFS. So certainly, we'll have to have the conversations with regulatory agencies to determine that. Initial inclinations are it is shorter. It is a much cleaner from the objectivity. Certainly, when you have blinded central imaging of each patient contributing to that response, and it's generally a subset of all of the patients to enroll in the study is what we've been hearing because you need to size the study for overall survival for full approval, and you can get agreement around a smaller number of patients who are on ORR for accelerated approval. But until we have those conversations with regulatory agencies for ourselves versus what we hear from consultants and read in the literature, it'll be too early for me to say specifically. Yep. Sure. Last question. Doug, going forward, how do you think about balancing your investments between sirexatamab and your GDF-15 antibody FL-501? Yeah, so the team is incredibly, I think, still incredibly excited about GDF-15 as well and moving it into development. The goal for us is to build a company that can do both programs, advance CRC phase III, and then be in a path to move FL-501 into the clinic, and that's our mission: to find the strategic or financial support to do so. Okay. Thanks. Same question. Thank you, and there are no further questions from the queue at this time. I will now turn the call back over to Doug Onsi for any closing remarks. So thank you all for your support, your time this morning. We're happy to answer additional questions in follow-up. And in the meantime, just really want to thank the lead team, the patients, the clinicians, clinical staff. These are two very large randomized controlled trials. The team did an excellent job executing them. And I think we're in position with very exciting data in colorectal cancer, and everyone here is motivated and enthusiastic to move on to the next steps. So thank you all for your listening and participation today, and we'll be in touch with more data as the year progresses. This concludes today's conference. Thank you for your participation, and you may now disconnect.