Good day, and thank you for standing by. Welcome to the ALX Oncology R&D Day conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To explore your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker for today, Jason Lettmann, CEO of ALX Oncology. Please go ahead. Welcome, everyone. I'm Jason Lettmann, CEO of ALX, and thank you for joining us for our 2025 R&D Day. We very much appreciate your interest, your time today, and as many of you know, this is the culmination of many months of work, so we're really looking forward to sharing what we're excited about and lay out a clear vision and path forward for our programs. Next slide. Before we start our presentation as housekeeping, here is our forward-looking statement for your review. On the next slide, we have several goals for today. I'm looking forward to walking you through them. Specifically, we'd first like to summarize the clinical data that is driving our and the clinical community's enthusiasm for evorpacept. It's clear that the clinical data continues to support that we have an active IO agent. Number two, we'd like to lay out a clear and focused development strategy. We have several paths towards FDA registration, and we're going to focus on what those paths are today and how we get there. Number three, we'd like to share the results of aggressive prioritization and cost cutting. The result of this is an important one as we're now extending our runway into Q4 2026. Last, we'd like to provide new guidance on upcoming data catalysts over the next 12 to 18 months. Bottom line, we've demonstrated that combining Evo with anticancer antibodies is active, and we're now advancing several trials to take this program towards approvals. Next slide. Here are the speakers for our webcast today. First, from the ALX management team, we have myself and Jaume Pons, who is the CSO and co-founder of ALX. We have three relatively new folks to the team that will also be joining us. First, Alan Sandler, who is our Chief Medical Officer; Alli Dillon, who is our Chief Business Officer; and then our most recent addition is Harish Shantharam, who is our CFO. We're also thrilled to be joined by two KOLs. First, Dr. Paula Pohlmann, who is a KOL in the breast cancer field, and she is the Chief of Clinical Research at MD Anderson in the Department of Breast Medical Oncology. Second, we're going to have Dr. Eric Van Cutsem, who is a KOL in the colorectal cancer field and is a key author on several papers that have defined standard of care and is the head of Digestive Oncology at KU Leuven and University Hospitals Gasthuisberg and Leuven in Belgium. On the next slide, here is a quick review of today's agenda. First, we're going to start with a quick overview of our vision, key priorities, and the scientific rationale behind evorpacept. From there, our focus for today will be on our antibody combination programs, specifically focusing on our new trials, which we're very excited about in breast and colorectal, which will be presented along with the treatment landscape by our two KOLs who are joining us. From there, we will focus on ALX 2004, which is a new internally developed program, which we'll be unveiling for the first time today. After that, we will then review and reframe the commercial opportunity for evorpacept in light of the new indications and where we're headed. Last, we'll conclude by an update on our financials, cash runway, and our near-term milestones, and then we'll open it up for Q&A. On the next slide, just taking a quick look back at 2024 and what we achieved over the year. Again, we had three major focuses. First, we were focused on execution, and within that, we were most excited about delivering the first positive randomized study in the CD47 space with the Aspen-06 gastric data, which we shared as an oral presentation at ASCO GI. We also shared several data sets across Aspen-07, as well as San Antonio with the breast data and NHL. Second, we've been very focused on driving what's next, driving into new indications, as well as driving ALX 2004 into the clinic. Last, we've been building out the team. We've been focused on making several new additions, and with these recent additions, we now even have a stronger team to deliver the next phase of growth for ALX, and we're really going to be focusing on delivering its potential with antibody drugs and driving the program into later stages of development. On the next slide, now turning to what our priorities are going forward. 2025 will certainly be a big year for us. We're first and foremost focused on execution. We will execute on the current studies, including announcing top-line data from Aspen-03 and Aspen-04 in first-line head and neck cancer. We're also going to be focused on expanding to other tumor types and combinations that they've now been de-risked. In this case, really prioritizing antibody combinations for Evo with a focus on breast cancer as we launch new trials both in breast and in colorectal. We will also continue to advance our lead pipeline asset, ALX 2004, which is a differentiated EGFR-targeted ADC into clinical development. Last, in light of current market conditions, we are going to continue to be very cost-disciplined and deliver major data catalysts on our current extended cash runway, which gets us to Q4 2026, and Harish at the end of the call will walk through this in more detail. Next on slide nine is really the vision for evorpacept. As a reminder, we have three major shots on goal at ALX, all representing significant patient reach and market opportunity. First, we're combining with anti-cancer antibodies. Second, we're combining with checkpoint inhibitors. Last, we're combining with ADCs. Each involves a different MOA, and each has been tested in the clinic. Importantly, these combinations represent some of the larger drugs in oncology, as we've now tested Evo with Herceptin, Rituxan, Sarclisa, and HER2, Keytruda, among others. On the right, you can see the clinical studies that we've completed to date. All of these have clinical proof, with the antibody story now producing five positive clinical sets to date. This slide really highlights the commercial relevance of each of these three shots on goal. As you can see, across ADCs, anti-cancer antibodies, and checkpoint inhibitors, it represents nearly $90 billion in sales. There is no question that evorpacept is addressing a very large market in oncology with its broad combo potential with different biologic agents as a result of its synergistic MOA and the great safety profile. The next slide highlights the development plan. Here is a snapshot of where we're going. Our priority is to advance evorpacept in combination with anti-cancer antibodies, as that is the most de-risked of the three buckets. Given the consistent proof of concept we've now seen across five clinical studies, it really motivates us and drives us to launch two new clinical studies. One in breast cancer, as we'll go through quickly, and two in colorectal cancer, in combination with Herceptin and Erbitux, respectively. The strong efficacy and optimal safety profile that we saw with Evo, with two HER2-targeting agents in both breast and gastric cancer, makes us very excited about these two new studies, and we're looking forward to presenting more details here today. Importantly, we are also thrilled to be advancing our second pipeline asset, ALX 2004, which, as I mentioned, is a differentiated ADC targeting EGFR into clinical development. On the next slide, this quickly hits the non-ALX-sponsored clinical trials, and here you can see the three studies that are being run by partners. We are particularly excited here about the partnership with Sanofi. It's now enrolling patients, and we know they continue to share our enthusiasm for the program and its combination with Sarclisa. On the next slide, just to briefly touch on upcoming milestones with Aspen-03 and Aspen-04 reading out in the second quarter of this year. As a reminder, we're looking forward to top-line results from evorpacept in combination with Keytruda, plus or minus chemo in front-line head and neck. These trials are expected to read out shortly, and the primary endpoint here is ORR for both studies, with PFS, OS, and DOR as key secondary endpoints. Note that we've now updated the current statistical plan to ensure we're putting the emphasis on ORR to align with FDA feedback and to give us the best shot at a potential accelerated approval. We expect to present top-line results from both studies next quarter, with more detail to come at a medical meeting later this year. Next slide. This slide really captures what we're excited about with first-line head and neck. Certainly, a lot of focus on that area right now, and what we see is a need for a novel agent in first-line head and neck that brings a different mechanistic approach that has been demonstrated in a randomized setting, as single-arm trials in head and neck have not consistently translated, three that can address the entire continuum of care in the first line, which includes both pembro and pembro plus chemo, and then last, our IO agents that can enable the long tail and ultimately benefit survival. This is where we see evorpacept come in, and this is what we're excited about with 03 and 04. We know Evo drives a different MOA to cell keep killing via T-cell priming and activation, and with over 300 patients enrolled across 03 and 04, these studies will be the largest randomized trials to read out since the LEEP study. Three, we're really looking forward to testing evorpacept across the entire front-line in head and neck, so this includes patients that are on pembro mono as well as patients that are on pembro plus chemo. Last, Evo is the most advanced IO agent in development and has the potential to be the first IO drug approved since pembro's approval back in 2019. Excited about this readout and looking forward to it in Q2. On the next slide. For the rest of the day, what we're really going to focus on is combining evorpacept with anti-cancer antibodies. We know this is the most de-risked path forward, and we know that because of the clinical data that has been emerging. As I mentioned before, we now have five unique data sets here that point to evorpacept plus anti-cancer antibodies activity. On the next slide, really just highlights the mechanism. Again, back to the company's founding, this was what ALX was founded on back in 2015. It's a rather simple mechanism of using evorpacept to block CD47 with a dead Fc, and then when combining with an anti-cancer antibody, providing the EME signal to drive ADCP or drive phagocytosis against cancer. This is the core mechanism that we are chasing when we are applying it with an anti-cancer antibody, and John will shortly walk through our conviction in this from a scientific perspective. On the next slide, this just highlights the data sets that we've generated to date that support Evo's combination with anti-tumor antibodies. Again, across gastric, which is the randomized study on the left, breast, which is the middle panel, which was our combination with Zanny, as well as in heme malignancies, we have two very strong data sets in NHL, which support the drug's activity. When you take this all together, it really drives our conviction that the drug is very active in this combination. On the next slide, this specifically highlights why we are so excited about breast and why we feel it is a key area to go next. First, we've de-risked the program given the positive data now in two HER2 positive cancers. We have positive randomized data in 06, which is in gastric cancer with TRAS, and we also have positive data with Zanny in HER2 positive metastatic breast. Second, the changing landscape in breast really is driving our opportunity as patients who have progressed on HER2 and have progressed on other HER2-directed therapies are going to be in need of new agents. What we need to have are agents that are active in patients who progressed on TRAS, which we've demonstrated, as well as patients who have progressed on HER2, which we've also demonstrated in the Zanny study. Last, just to highlight the significant peak sales, the commercial opportunity, and the patient reach here. In second-line metastatic patients alone, there are 48,000 patients in need, and if you look at the first-line setting as well as the neoadjuvant setting, that totals about 120,000 patients. There is no question of evorpacept's potential to impact a broad swath of patients here in breast cancer. On the last slide here for my section, this highlights our path to registration. If you look at the evorpacept programs on the top, we first have Aspen-06 in gastric. Key next step there is interacting with FDA, and we now have a meeting planned for Q2 of 2025, and we plan to provide more guidance at that point. Next are Aspen Breast and Aspen Colorectal. Again, these are two new studies that we're launching. We've been actively working on getting these off the ground over the last many, many months, and we're now slated to have first patient in both of those studies in mid-2025. Last on this list is the Aspen-03 and -04. I've talked about the readouts with top-line data coming in Q2, potentially an FDA meeting to explore an accelerated approval next and a phase three initiation to follow. Last, but certainly not least, we're excited about launching ALX 2004 today, and we are very close to an IND submission, which we plan for this quarter, and we plan to then deliver safety data, which is very important in this class in the first half of next year. With that, I will turn it over to Jaume Pons, our CSO, who will walk through the history of Evo and some of the preclinical rationale. Jaume Pons. Thank you, Jason. Next slide, slide 21. Here you can see a cartoon of evorpacept. We paint it like an antibody, but it's not an antibody. It is comprised of the CD47 binding domain of SIRPα, the receptor of CD47, affinity mature for high affinity, fused to a totally inactivated FC domain that does not bind FC gamma receptors, but still binds FC RN to provide antibody-like decay. Evorpacept binds CD47 with peak combinatorial affinity. The dead Fc abolishes target-dependent cytopenias. The molecular weight is half of an antibody, providing higher effective dosing and better tumor penetration. Altogether, it makes evorpacept a very differentiated and potentially best-in-class CD47 blocker. Next slide. We started ALX Oncology to take advantage of the unique biology of CD47. On the left panel, you can see the expression of CD47 in tumor cells in red, and in black, the expression in adjacent normal tissue. It really stands out that CD47 is highly overexpressed in a large range of tumors, but that it is also highly expressed in normal cells. Therefore, if we design a molecule that uses CD47 as a tumor-associated antigen and targets for destruction all CD47-expressing cells, it will result in unacceptable toxicity. In fact, that has been the case for all the other CD47 blocking molecules that have been reported in the clinical data. What makes CD47 an interesting target is described in the right panel. CD47 interacts with SIRPα in immune cells, macrophages, and dendritic cells. After interacting with CD47, SIRPα sends an inhibitory signal that we call "do not eat me." What is very interesting is that blocking this interaction does not activate macrophages. Macrophages, to be activated and eat cancer cells, require a positive signal. This positive signal comes from the interaction of the active Fc of an antibody binding cancer cells with Fc gamma receptors in the macrophages. To maximally activate a macrophage, it is required to block the negative signal of CD47-SIRPα interaction and at the same time provide the positive signal of an active Fc with Fc gamma receptors in the macrophage site. Next slide. Conventional CD47 blockers like magrolimab were designed to do both things at the same time: block CD47 and try to thread the needle, providing the positive signal with a weak active Fc. CD47 blockers with a strong active Fc are too toxic and cannot be developed. The aim of these molecules was to have single-agent activity and try to minimize toxicity. The result was that this weak active Fc was not potent enough to have meaningful single-agent activity against cancer cells, but it was potent enough to destroy blood cells, limiting dosing and not totally blocking CD47 in the combination setting, therefore limiting efficacy. Next slide. We designed our molecule, evorpacept, to be used in combination. It has the highest CD47 blocking potency and a totally inactivated Fc. We can dose very high and get complete blockade of CD47. Despite it binding blood cells, it does not target them for destruction because evorpacept is not able to provide the required positive signal. When we combine evorpacept with an anti-cancer antibody like Herceptin that contains a potent active Fc, we specifically target cancer cells for destruction by antibody-dependent phagocytosis, a mechanism that Herceptin is not able to do by itself. Next slide. We proved this concept very early on in animal models, comparing evorpacept with a molecule containing the same CD47 binding site, but with an active Fc. You can see that the active Fc molecule in blue produces red blood cells, platelets, and white blood cells, while evorpacept with an inactive Fc in red has no effect in blood cell levels. Now, with about 700 patient doses, we have proven that evorpacept does not produce cytopenias like the other CD47 molecules do. Next slide. On the efficacy side in preclinical models, we have shown that in cells and animal models that evorpacept can enable the efficacy of all tested anti-cancer antibodies with an active Fc. Here you have a few examples with cetuximab, trastuzumab, daratumumab, and tomumab. Some of these combination data have been replicated in the clinic, as you will see later. Next slide. In the clinic, responders to evorpacept in different combinations have shown to have a higher number of T cells and macrophages in the tumor compared with non-responders, recapitulating in the clinic what we have seen in animal models. Now, our CMO, Alan Sandler, will show you more data from our patients. Thank you, John. In my section, what I'd like to do is provide some of the clinical results seen from several of our studies. I'll start by having the two HER2 antibody combinations in both gastric cancer as well as breast cancer. The next slide, which is slide 29. This is Aspen-06, our phase two study looking at evorpacept plus trastuzumab, ramucirumab, and paclitaxel in HER2-positive advanced metastatic gastric cancer adenocarcinoma subtype. Key eligibility criteria are shown here. The important aspect is patients had received prior HER2-directed therapy in the second and third-line setting. A total of 127 patients were treated, all of which had at least archival tissue demonstrating HER2 positivity. Forty-eight of the patients had recently acquired fresh biopsies demonstrating HER2 positivity. Primary endpoints were in both ITT as well as fresh biopsy populations are shown here, with the primary endpoint being improvement in overall response rate versus an assumed historical control of 30%, as well as an absolute improvement of 10% in response rate over the internal control. Secondary endpoints are noted. One other aspect is patients also had prospective collection of ctDNA for HER2 positivity, and will be discussed in the next couple of slides. Next slide, please. This slide shows the safety results for Aspen-06. In general, looking at this tornado plot, you see that the Evo-containing arm was generally well tolerated. Grade 3 plus TEAEs were balanced between the two arms. There were, however, 11 grade 5 treatment-emergent adverse events, however, only two of which were deemed to be treatment-related, one on each arm. Importantly, evorpacept's safety profile was consistent with its prior experience in over 700 patients treated to date, all primarily in combination. This next slide, it looks at the population of patients with either fresh or ctDNA HER2 positivity. You'll note the number of patients is 96 patients, approximately 80% of the overall population. This is a swim lane evaluation looking at the Evo-containing regimen on the left and the TRP control arm on the right. You can see both from a qualitative view the impact of the addition of Evo, resulting in an increased response rate of approximately 49% as compared to the control arm of approximately 25%. What you also note from a qualitative perspective as well as quantitatively, the increase in the duration of response, with the median being 15.7 months in the Evo-containing arm versus 9.1 months in the control arm. This next slide shows the improved progression-free survival in patients with fresh biopsy or HER2 positivity via ctDNA. You'll note the hazard ratio is 0.64, favoring the Evo-containing arm. I'd also like you to look at the 12-month landmark analysis, which shows nearly a doubling of the number of patients alive disease-free on the Evo-containing arm. Let's move to the next slide. In summary, Aspen-06 shows a potential lead indication in a biomarker-selected patient population in gastric cancer. There's robust and durable clinical activity in HER2-positive patients, particularly those documented either by fresh or ctDNA, validated mechanism of action with a clear biomarker, a well-tolerated multidrug regimen, and it's active in patients who have progressed on conventional HER2-directed therapy. Evorpacept plus TRP compares favorably to benchmarks in the second-line plus setting. Also, I'd like to call out that there's an FDA meeting scheduled in Q2 of this year to discuss the ASPEN-06 results and possible path to accelerated approval, and an update was planned in Q2. Move to the next slide. Moving to breast cancer, this is a phase 1b/2 trial evaluating the safety and efficacy of evorpacept plus zanidatamab in patients who have progressed on prior HER2-directed therapy. Key eligibility is on the left. Patients were HER2 positive and had three or more prior regimens. Twenty-one patients were in expansion cohort 1, all documented to be HER2 positive. Again, the summary for the baseline characteristics in this cohort 1, heavily pretreated with a median of six prior therapies, all of whom had received prior HER2 therapy. Let's move to the next slide, please. This next slide summarizes safety for the combination of evorpacept and zanidatamab, showing that it is well tolerated with a manageable safety profile and again, consistent with the experience with each prior agent. Most treatment-related adverse events were grade 1 or grade 2. TRAEs of special interest included one patient with a grade 3 ejection fraction that had decreased and 12 patients with IRRs, all of which resolved. No non-infectious pulmonary toxicities occurred, and there were no treatment-related deaths. Let's move to the next slide. These are the efficacy results, showing activity of 56% response rate in the nine patients confirmed to be HER2 positive by central assessment. The median DOR for this group ranged from 5.5 to nearly 26 months, with the median not being reached. The median PFS was 7.4 months, and this compares favorably to the benchmark seen in the Sophia study with a response rate of 22%. Move to the next slide. We have now demonstrated with these two studies the power and potential of evorpacept in engaging the innate immune response, validating this mechanism with anti-cancer-directed antibodies in these two cases, HER2-positive tumors. There is robust and durable clinical activity in both gastric and breast cancer with a validated mechanism of action and a clear biomarker. These regimens have been well tolerated and active in patients progressing on conventional HER2-directed therapy. Next slide. It is now my distinct pleasure to introduce Dr. Paula Pohlmann, who's Associate Professor and Chief of the Section of Breast Cancer Clinical Research, the Department of Breast Medical Oncology, and the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center. She is well known for being a former fellow of mine at Vanderbilt University. With that, Dr. Pohlmann. My name is Paula Pohlmann, breast medical oncologist. I will discuss breast cancer and the treatment landscape in HER2-positive metastatic breast cancer. Next slide. Breast cancer continues to present significant challenges despite substantial advancements in the treatment of early metastatic disease. As shown in the graph on the left, we can observe the incidence represented by black bars and mortality represented by blue bars of various cancer types. Unfortunately, breast cancer remains one of the most incident cancers and contributes to a significant number of cancer-related deaths each year in this country. The graph on the upper right illustrates the trend in breast cancer incidence over the past 50 years. Currently, breast cancer accounts for approximately 15% of all new cancer cases in the US, with an upward trend in its incidence. While many patients do survive breast cancer, the five-year relative survival rate for those with distant metastasis is approximately 32%, underscoring the ongoing need for improved treatment and outcomes for advanced stages of the disease. Next slide. This slide outlines the current treatment options for patients with metastatic HER2-positive breast cancer. First-line therapy remains the Cleopatra regimen, which includes trastuzumab, pertuzumab, and a taxane. For second-line treatment, trastuzumab deruxtecan, or T-DXd, has now become the standard of care. Subsequent options include regimens such as tucatinib in combination with trastuzumab and capecitabine, as well as trastuzumab emtansine, or T-DM1. In addition, there are multiple combinations utilizing trastuzumab beyond progression, including with chemotherapy and with anti-HER2 tyrosine kinase inhibitors, as well as other targeted therapies like margetuximab. It's important to note that many of the regimens currently used beyond T-DXd were originally approved based on trials conducted before the T-DXd era. Furthermore, the ongoing DESTINY-Breast09 phase three trial, which is investigating T-DXd with or without pertuzumab versus THP in first line, may have the potential to reshape this treatment landscape. Next, the CLEOPATRA study was a phase three clinical trial that compared the efficacy and safety of pertuzumab, trastuzumab, and docetaxel to placebo, trastuzumab, docetaxel in patients with HER2-positive metastatic breast cancer. In the final analysis, with a median follow-up of approximately 100 months, the median overall survival was 57 months in the pertuzumab group compared to 40 months in the placebo group. The eight-year landmark overall survival rates were 37% in the Pertuzumab group and 23% in the placebo group. This trial established the combination of Trastuzumab, Pertuzumab, and Docetaxel, or THP, as the standard of care for first-line treatment in HER2-positive metastatic breast cancer. Next slide. The ongoing DESTINY-Breast09 phase three clinical trial is evaluating T-DXd with or without Pertuzumab compared to the Cleopatra regimen, a first-line therapy for patients with metastatic HER2-positive breast cancer. This study is a phase three trial with a three-arm randomization in which patients with advanced or metastatic HER2-positive breast cancer confirmed by central review and who have not received prior therapy for advanced or metastatic disease are randomly assigned in a one-to-one-to-one ratio to one of three treatment arms: T-DXd and placebo, T-DXd and Pertuzumab, or THP. The primary endpoint of this trial is PFS, or progression-free survival, as assessed by blinded independent central review. Next slide. As T-DXd moves to earlier lines of therapy, it becomes increasingly evident that there is a need to develop additional novel anti-HER2 treatment options. The DESTINY-Breast03 phase three trial compared T-DXd with T-DM1 in patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab and a taxane. This trial established T-DXd as the new standard of care for second-line therapy in HER2-positive metastatic breast cancer. Looking at the PFS curves from DESTINY-Breast03, we observe that approximately 25% of the patients experienced disease progression within one year of therapy, while 50% progressed within two years. This graph serves as a reminder that even with the introduction of T-DXd, patients with metastatic HER2-positive breast cancer will still require additional treatment options. Next slide. This slide outlines a range of treatment options, including various classes of drugs that are either approved or under development for the treatment of HER2-positive metastatic breast cancer. On the left, we see examples of antibodies and bispecifics. Currently approved agents include trastuzumab, pertuzumab, and margetuximab, with zanidatamab in development. For antibody-drug conjugates, two anti-HER2 ADCs are approved: T-DXd and T-DM1, while ARX788 represents an ADC currently under development. Approved tyrosine kinase inhibitors, or TKIs, include lapatinib, neratinib, and tucatinib, with AST1306 being an example of a TKI in development. In the field of immuno-oncology, while pembrolizumab and dostarlimab have tissue or site-agnostic indications based on mismatch repair deficiency and high microsatellite instability, they have shown limited efficacy as single-agent therapies in breast cancer. These agents have not been approved in combination with chemotherapy for HER2-positive breast cancer. Evorpacept, however, emerges as a candidate drug with a distinct mechanism of action. Next slide. What does the future hold? As T-DXd potentially becomes the first-line therapy following the results of DESTINY-Breast09, the treatment landscape for second-line and subsequent therapies will enter uncharted territory. No anti-HER2 targeted agent has been fully evaluated in the post-T-DXd population, resulting in a notable gap in our understanding of available treatment options. This underscores a growing unmet need for patients who have previously received T-DXd therapy. Combination therapy with evorpacept and zanidatamab has demonstrated promising anti-tumor activity in heavily pretreated patients with metastatic HER2-positive breast cancer, including those who have progressed after prior T-DXd treatment. Next slide. In a cohort of patients with heavily pretreated HER2-positive breast cancer, as confirmed by central review, the combination of evorpacept and zanidatamab yielded an overall response rate of 55.6%. These patients had a median of six prior lines of therapy, with all having received both T-DXd and trastuzumab. Next slide. It is essential to identify novel agents in the HER2-positive breast cancer space that offer a distinct mechanistic approach to targeting HER2 expression, demonstrate efficacy in post-HER2-directed therapy settings, including after treatment with ADCs like T-DXd, complement and enhance standard of care therapies rather than replacing the existing backbone treatments, provide a safer profile than ADCs, which are associated with off-target payload-driven toxicities, and include immuno-oncology agents that could trigger immune responses and potentially improve survival outcomes. Evorpacept emerges as a promising candidate because it utilizes a unique mechanism of action, enhancing antibody-dependent cellular phagocytosis, or ADCP, rather than relying on payload-based or kinase-driven approaches. It has demonstrated activity in both post-trastuzumab gastric cancer and heavily pretreated HER2-positive breast cancer patients. It is designed to work synergistically with established therapies in breast cancer, such as trastuzumab. It presents a favorable safety profile compared to ADCs, and it is an immuno-oncology option. Next slide. In terms of evorpacept clinical development in the metastatic breast cancer setting, this slide highlights the Aspen Breast phase two trial and the PRIOSPHI phase one B trial. On the left is the Aspen Breast trial, a phase two randomized clinical trial evaluating evorpacept in combination with trastuzumab and chemotherapy of physician's choice for patients with HER2-positive, locally advanced, or metastatic breast cancer following prior treatment with T-DXd. Additionally, we have the ongoing PRIOSPHI study, which is assessing the combination of evorpacept and T-DXd in patients with unresectable or metastatic HER2-positive or HER2-low breast cancer. In this trial, patients received evorpacept 30 or 45 milligrams per kilogram IV every three weeks in combination with standard doses of T-DXd. Initial results from this study are expected by the end of this year. Next slide. The proposed design for the Aspen Breast randomized phase two clinical trial is presented here. The key eligibility criteria include a diagnosis of HER2-positive metastatic breast cancer with measurable disease by RECIST 1.1 criteria, prior treatment with T-DXd, all approved treatments are allowed post-T-DXd therapy, no CNS metastasis or previously treated and stable CNS metastasis, fresh biopsy if feasible and safe, and performance status ECOG 0 to 1. There will be a one-to-one randomization into two groups of 60 patients. These patients will be treated with trastuzumab and chemotherapy of physician's choice, plus or minus evorpacept. The primary endpoint is overall response rate by blinded independent central review. The secondary endpoints are PFS, or progression-free survival, duration of response, and overall survival. Next slide. The Aspen Breast phase two trial is expected to dose its first patient mid-2025, with an interim analysis anticipated in the second half of 2026. Following the completion of the phase two trial, the plan is to proceed with the Aspen Breast phase three trial. This will have a similar design, but with approximately 600 patients in total, randomized one-to-one into the two treatment arms. The primary endpoint of the phase three trial will be progression-free survival. Thank you, Paula. It is now my pleasure to introduce Dr. Eric Van Cutsem, an internationally recognized expert in GI oncology, who has either been principal author or senior author of some of the more seminal papers in metastatic colorectal cancer. With that, Dr. Van Cutsem will now provide us with a background of the treatment landscape and epidemiology of colorectal cancer. Dr. Van Cutsem, please. Welcome. I'm Eric Van Cutsem. I'm a professor in gastrointestinal oncology at the University of Leuven in Belgium. It's a pleasure for me to explain to you some of the backgrounds around colorectal cancer and evorpacept. Just a couple of numbers and data around colorectal cancer. As you all know, colorectal cancer is a frequent disease. In the U.S., there are around 150,000 patients diagnosed every year. If you look at the global level worldwide, there are around 2 million patients. Around 1 million patients die worldwide of colorectal cancer. One of the problems with colorectal cancer is that many patients present with distant metastasis at the initial presentation, or they present with a more early localized or regional disease, but later on, they develop metastasis. As we know, metastatic colorectal cancer has a poor prognosis with five-year survival rates around 15%. We've seen some improvements in the treatments of colorectal cancer. Today, we are individualizing and personalizing according to clinical presentation, according to presentation of the metastasis, but also according to molecular characterization. This scheme gives an updated algorithm as it is based in the NCCN or ESMO guidelines, with even some newer data on the slides for BRAF mutant patients or KRAS G12C mutant patients, for instance. In general, if you look on the left side, patients with a RAS and BRAF wild-type tumor may be treated with chemotherapy plus an anti-EGFR antibody or plus bevacizumab. Right-sided and left-sided colon cancers may help also to individualize the treatment options in this setting. That means that also in second line, when patients progress on first line, and that happens quite often, patients are then treated with another chemotherapy, switching, for instance, from FOLFOX to FOLFIRI, and then changing also the antibody that is added to that. That means that in second line, there are quite a lot of patients who are candidates for anti-EGFR treatment. There are two anti-EGFR antibodies available, cetuximab and panitumumab, in the indication of metastatic colorectal cancer. Cetuximab's story is ongoing since some time, and we started and had the privilege to co-chair that study, that initial pivotal study leading to the first registration and approval of cetuximab in colorectal cancer together with David Cunningham. Around 20 years ago, we published these data of cetuximab monotherapy or cetuximab plus irinotecan in irinotecan refractory metastatic colorectal cancer, showing that there were some patients with an objective response in the combination treatment between 20-25% of the patients. Later on, we did further analysis and looking at the RAS wild-type patients because it was shown that KRAS and RAS mutant patients do not benefit from cetuximab. With this enrichment of the patient population, response rates were a bit higher, but that is still a basis for many patients, as I have indicated earlier on the slide, irinotecan plus cetuximab or FOLFIRI plus cetuximab. This study was done also in third line, but later on, it moved up to second line. Even some data in first-line treatment, these are the data from the CRISTAL study that we published several years ago in first-line treatments where patients were randomized in first line, FOLFIRI plus or minus cetuximab. Initially, this was done in all comers regardless of RAS status. Later, we did analysis in RAS mutant patients and RAS wild-type patients, showing that there was no benefit in RAS mutant patients, but that the benefit for cetuximab was limited to the patients with KRAS and later on a RAS wild-type tumor. That is the first-line treatment. That gives in two minutes a couple of important reasons and arguments in the background of the management of colorectal cancer and why we are in the need of new agents. There is a benefit with this anti-G4 antibody, but we need to do much better. We come in the field of the new agent that we are discussing today, which is targeting CD47. CD47, we know that this is overexpressed in colorectal cancer cells compared to healthy tissue. We know that there is a decreased CD47 expression or that the decreased CD47 expression is prognostic for survival in patients with metastatic colorectal cancer. Therefore, evorpacept interfering with CD47 and blocking CD47 may be a new agent that may be useful and that may lead to benefit in patients with metastatic colorectal cancer. There is a clear rationale. On top of that, another important argument is that macrophages are important. The classic checkpoint inhibitors about which we speak a lot targeted T cells. Many colorectal cancers are relatively cold tumors and lack T cells. Evorpacept targets, as you've heard already, the CD47, which is the checkpoint for macrophages, and that is overexpressed in colorectal cancer compared to healthy tissue, as is illustrated on the slides. Macrophages are generally the most abundant immune cell type in cancers and the most profuse leukocyte in the colon. Therefore, targeting CD47 with evorpacept may show activity also in what we call traditionally cold tumors due to the absence of T cells. Clear rationale also explains in a few words. This illustrates, again, as you've seen already, the interaction between the cancer cell and the macrophage with the EGFR receptor, with which cetuximab interferes, and then CD47, to which evorpacept is showing some potential ways of enhancing the activity of cetuximab when evorpacept is added to cetuximab and chemotherapy. Going back to colorectal cancer, as I've shown already, there is a need for new agents in the space of colorectal cancer, agents that may enhance the mechanism of action of EGFR antibodies with a different mechanism of action, agents also that leverage the importance of macrophages in colorectal cancer. They are important, as we know, as I've shown you briefly. With that, also the potential of agents that may improve the activity of the anti-CD47 antibody, cetuximab in this setting. Of course, we need agents with a favorable safety profile in this. If you link some of these needs in colorectal cancer, evorpacept has clearly potentials also in this setting. You've heard already on the interesting and promising data in the Aspen-06 gastric study that we presented recently at the ASCO GI meeting in San Francisco. Evorpacept was uniquely designed to activate macrophages that are highly abundant in colorectal cancer. It is designed towards synergistically and adds on the phagocytosis on top of cetuximab's ADCC-driven tumor killing. The safety profile may be very favorable because of the intentional use of the silent Fc receptor on evorpacept that distinguishes evorpacept from other anti-CD47 agents. This therefore has the potential to be a novel IO in a second-line treatment of metastatic colorectal cancer, where there is a high unmet need for better treatments. This slide shows the design of the plans of the Aspen colorectal cancer study, in which the goal is to look at the combination of FOLFIRI, cetuximab plus evorpacept in second-line metastatic colorectal cancer, of course, in KRAS and RAS, so RAS wild-type and BRAF wild-type patients, microsatellite stable patients. The cold tumors were progressive on the first-line treatment. As you can see, there are two regimens. That goes back to the fact also that cetuximab can be used and is approved on a weekly regimen A or a biweekly regimen, regimen B. You can see that evorpacept is combined with this regimen of cetuximab plus FOLFIRI in regimen A in a weekly regimen, administration of evorpacept in regimen B on a biweekly regimen. Therefore, the doses are slightly different. This study is constructed in that way that around 40-60 patients will be included, the two different dose levels, with this primary objective to look at safety tolerance to determine a recommended phase two dose recommended regimen. Of course, in this study, the goal is also to look at a secondary objective at clearly hints and signs of anti-tumor activity with a classic evaluation, efficacy evaluation parameters. Finally, this may then lead if that study shows interesting data, what we do expect as clinicians and experienced clinicians and investigators knowing the field also and the needs and the mechanism of action of this agent. This may then lead to potential registration studies after this initial phase one-two study that I explained to you already. To later, large studies where standard of care of FOLFIRI, cetuximab is compared with FOLFIRI, cetuximab, evorpacept. The studies have to start. The plan is to start soon with the phase one-b-two study that I've shown on the previous slide. Of course, we do hope, and I think the cards are in the right direction, that this agent has the potential to show an improved activity and to be added to the armamentarium of the clinical oncologist, the GI oncologist who wants to treat and who needs better treatment options for patients with metastatic colorectal cancer. Thank you for listening to me. Thank you, Dr. Van Cutsem. Now I'll talk about three additional studies in the hematologic malignancies that are also based on the same concept of antibody-directed combinations. Let's move to the next slide. R2 is the standard of care for relapsed follicular lymphoma. What's been noted is that SIRPα positive macrophages increase at the time of progression after treatment with this particular regimen. This suggests a potential role for CD47 blockade in the lymphomas. Next slide. Aspen-01 is a phase 1b clinical trial of evorpacept plus the CD20 targeted antibody rituximab in both aggressive and indolent non-Hodgkin's lymphomas. The treatment identified two potential regimens for dosing schedules for evorpacept in combination with rituximab and showed significant activity in a small number of patients. Overall response rate of 8 out of 11 or 72%, and six of those patients achieving a complete remission. This compares quite favorably to the randomized data in the AUGMENT pivotal study. Next slide, please. Another study that I'd like to comment upon and building upon the results from Aspen-01 is the ongoing MD Anderson Cancer Center phase 1-2 IST that looks at the combination of evorpacept plus R2 in indolent and aggressive relapsed or refractory non-Hodgkin's lymphoma. Key eligibility criteria is shown there. All patients were previously treated as noted. The phase one arm looked at a 30 mg per kg dose every two weeks of evorpacept in combination with rituximab and lenalidomide. Built upon that with a 60 mg per kg dose every four weeks with the same combination of rituximab and lenalidomide. A total of 20 patients were treated, 18 of which were indolent lymphomas. Primary outcomes were safety and establishing the recommended phase two dose. Next slide. This slide shows the efficacy results. On the column on the far left, looking at the combination of evo plus R2, 18 patients as noted with an overall response rate of 94%, 83% achieved a complete remission. This compares again quite favorably to the AUGMENT regimen of R2, where the overall response rate was 78% and 34% complete responses. The rituximab alone arm in the same AUGMENT study with a response rate of 55%, 18% of patients achieving a complete remission. An update of this data will be coming at a major medical meeting in the second quarter of this year. Next slide, please. The last study I'd like to comment upon is an ongoing trial of evorpacept and the CD38 targeted antibody Sarclisa, sponsored by Sanofi in multiple myeloma. Key eligibility criteria are shown here on the left. Again, relapsed or refractory multiple myeloma with at least two prior therapies. The treatment consists of the experimental arm of adding evorpacept to Sarclisa, pomalidomide, and dexamethasone, with an active comparator arm of Sarclisa, pomalidomide, and dexamethasone alone. The study dosed the first patients in September of last year and is currently enrolling patients. With that, I would like to move to the next slide and introduce Alli Dillon, our Chief Business Officer. Thank you, Alan. You heard from our speakers a comprehensive review of evorpacept's clinical programs and opportunity to increase benefit for patients when combining with existing standards of care across multiple cancer indications. The combination drugs we are evaluating with evorpacept are flagship drugs serving many patients as established standards of care, including Herceptin, Erbitux, Rituxan, and Keytruda. Starting with our lead indications, first is second-line HER2-positive gastric cancer, where we have a biomarker patient population identified, and we are looking forward to an FDA meeting to discuss a possible path to accelerated approval based on the ASPEN-06 data. We are also currently awaiting data from our two head and neck trials in the first-line setting, regardless of PD-L1 status. Positive data in these settings would allow us to consider expanding into other pembrolizumab-based indications. Next. As you heard from Jason and Alan today, our priority in advancing evorpacept is by combining with antibody drug combinations. We have seen strong proof of concept with these evorpacept combinations based on results from multiple phase one and two trials. I join the team's excitement for launching our phase two trial in breast cancer this year. We believe that the results we saw with evorpacept in combination with Herceptin in confirmed HER2-positive patients in gastric cancer and in HER2-positive breast cancer in combination with zanidatamab significantly de-risks our BC program. This is an area of urgent unmet need for HER2-positive breast cancer patients who have progressed after treatment with Enhertu and represents a significant commercial opportunity for evorpacept. With the combination of evorpacept and Erbitux in colorectal cancer, evorpacept could have the potential to be the first new treatment for second-line wild-type colorectal cancer patients in years. With these two indications, evorpacept could target over 100,000 patients. This would also unlock the possibility of expanding into earlier or broader patient segments. Next. When we look at the future and evorpacept's development opportunity in hematologic indications, we have the opportunity to build on the phase one data in follicular lymphoma. Here, there is a significant opportunity to go into additional rituximab-based standards of care in B-cell lymphomas. Additionally, we look forward to seeing the results from the ongoing Sanofi-sponsored collaboration of evorpacept in combination with Sarclisa in multiple myeloma, another area of high unmet need. Next. For the longer-term future, successful results from clinical trials in the mentioned solid tumor and cancer indications could open further development opportunities for evorpacept, broadening its potential to expand into earlier lines of treatment. Next. We are excited about this very significant commercial opportunity for evorpacept thanks to its broad combineability with many blockbuster drugs while maintaining a manageable tolerability profile. With that, I'll pass it over to Jaume to introduce the very exciting new ALX 2004 program. Thank you, Alli. Next slide. Today, I want to introduce to you our first ADC coming from the platform we have been creating in-house for the last four years. Before founding ALX Oncology, I was CSO and site head of RINAT, the Center of Biologics of Pfizer in San Francisco. There, I developed the transglutaminase site-specific conjugation. I was co-leader of the global ADC effort, and I moved the first drug ADC into the clinic. From that experience, I think I learned the key principles to successfully develop a new platform, and I have applied them here. The first candidate that uses our technology is a unique anti-EGFR antibody that binds and inhibits EGFR but does not compete with cetuximab and neither with panitumumab. In addition to being designed to have a very strong single-agent activity, it can be combined with approved anti-EGFR antibodies. We have also optimized the affinity of the antibody to maximize therapeutic window. From our collection of proprietary payloads, we have selected one that has more bystander effect than DXd, the benchmark topoisomerase inhibitor of the ADC. We also improved the linker stability compared with T-DXd. In fact, we have not seen any ILD in non-human primate studies. The molecule has a uniform DAR 8, and it is very well behaved in terms of biophysical properties. Next slide. ALX 2004 produces tumor regression in many disease-relevant animal models, including patient-derived xenografts. As expected, our molecule can kill cancer cells by inhibiting EGFR, also delivering the toxic payload, and also for antibody-dependent ADCC and ADCP, resulting in a very strong efficacy in models resistant to EGFR therapies, like the pancreatic model on the right bottom, where you can see that rituximab in blue does not slow down tumor growth, while ALX 2004 produces a durable tumor regression. Next slide. We believe that ALX 2004 is differentiated and has the potential to be a very relevant new drug for patients. When we were looking for our first target, we wanted something clinically validated where all the ADC approaches had failed. A target where our technology could make a big difference and we could be first. We think EGFR clicks all the boxes. Not only is there not approved EGFR ADC, there is only one other EGFR dopobase ADC in early clinical trials in China. We believe that our design is superior in many aspects. In the second quarter, we will have another R&D day to focus on ALX 2004 and our platform to disclose more details. Next slide. Now, I want to introduce Harish, our CFO, to talk about our financials. Thank you, Jaume. Turning to slide 79, everyone, let me quickly remind the key milestones that are ahead of us, most of which were alluded to during the course of our presentations today. In terms of anti-cancer antibody franchise, we have our discussions with FDA scheduled during the second quarter this year that should guide us on potential accelerated approval path for Evo in gastric cancer setting. Our newly planned breast and CRC studies are expected to have their incremental analysis and early safety bar efficacy readout during the second and first half of 2026, respectively. In the very near term, we expect to announce top-line results from our Aspen-03/04 phase two trial for Evo in combination with checkpoint inhibitor during the second quarter of 2025. We will also have data updates from phase one combination trials with ADC this year. As Jaume mentioned, we are very excited for our second pipeline asset, ALX 2004, and are planning to file for an IND by the end of this month and initiate our phase one study soon after. We anticipate early safety data readout from our phase one trial during the first half of 2026. Now, turning to finance and business update on slide 80, we ended the fiscal year 2024 with about $131 million in cash and cash equivalents. The full fiscal year 2024 financial results will be released on March 6. Our strategic prioritization and cost optimization efforts have enabled us to extend our cash runway guidance into the fourth quarter of 2026. As a part of this effort, we have substantially decreased our preclinical research investments and are announcing approximately a 30% reduction in force, primarily in our research function. We remain hyper-focused on executing the development strategy that we laid out today and remain very excited about many value-enhancing near-term milestones that we have ahead of us. Let me now turn the call back to Jason for closing comments before we open the line for Q&A. Jason. Thanks, Harish. Appreciate it. What you heard from the team today is several key messages. One, after coming off a big year last year with several data readouts, there's no question in our mind that evorpacept is an active IO agent, and we've now demonstrated activity in no less than six clinical studies to date. Two, we are now pursuing a focused development strategy. We now have several past FDA registrations across both evo and now with ALX 2004 that can drive this program forward. Three, as Harish just mentioned, we've extended runway now into Q4 of 2026 due to some aggressive prioritization and internal cost-cutting. We now have the runway to deliver on many milestones and catalysts over the next 12 to 18 months. With that, I will close. Again, very excited about what's ahead of us and look forward to your questions. Thanks again for joining. Thank you. As a reminder, if you would like to ask a question, please press star 11 on your telephone. You will then hear an automated message advising your hand is raised. If you would like to remove yourself from the queue, press star 11 again. We also ask that you please wait for your name and company to be announced before proceeding with your question. One moment while we compile the Q&A roster. Our first question today will be coming from the line of Michael Yee of Jefferies. Your line is open. Good morning. Thank you for all of the updates today. We had two questions. First is on the head and neck studies that are reading out very soon. You emphasized, or at least pointed out, that the primary endpoint has changed to overall response rate, and that is a change. I wondered if you believe that is due to statistics around the 12-month overall survival, or how do you think about hitting that? Because obviously, the mechanism of action is different than the anti-cancer approach, and therefore, I am a little concerned about how to think about ORR as a primary endpoint now for the PD-1 studies. The second question relates to the great idea that obviously, with the anti-cancer antibody combinations, it does appear to be a strong proof of concept from the gastric study, which is why you're doing the breast and the colorectal studies now. If you are going to get positive feedback from FDA in the second quarter, would you actually fund that? What is the messaging around the gastric? Thank you. Yeah, great. Thanks, Mike. Both good questions. Appreciate it. On the first one regarding the head and neck readouts, I think as is typical when you get closer to the data, again, we are blinded to the data, but we want to make sure we're aligning our statistical analysis plan to give us the best shot. I think, as you know, to drive and accelerate approval, again, that's what these studies were designed to support. FDA's view is that it's ORR-based. Therefore, we want to make sure that we put ourselves in the best position to support that. I think when you look back through the data, although you are absolutely right in our phase 1b, we certainly were encouraged by what we saw in terms of the survival. We also did show an ORR benefit. Our phase 1b in the pembrolimodel setting, we showed an almost 40% ORR versus the Keynote benchmark of 20%. Therefore, I think we are hopeful we will see an ORR benefit. I think from a powering perspective, just want to set us up in the best way possible in terms of the SAP to support that. On your second question, I think it's a good one. I think the way that we're looking at this, have made some tough decisions on priorities and resources to get there and enable our runway to Q4 of 2026. I'd say we are being very data-driven. What we know now is when we combine Evo with an anti-cancer antibody, we see very strong activity. What you see here today is our base case plan. Our plan to advance in breast and colorectal, I think, reflects our priorities. To your point, we have an important meeting with FDA coming up here next quarter. I think in the event that we get good news there and have a compelling path forward, then I view it as an and. I think that meeting is critical to understand not only the accelerated approval path, but also understand what the next phase could look like. That will, of course, impact our priorities. For us, Mike, this is really the base case plan. This is the plan we think makes the most sense given the data and one we're excited to go forward on. Alan, do you have anything to add on that front? No, thanks. I think you've covered it all, I think, quite well. Just going back to the head and neck, remember, Mike, this is a randomized phase two study, so one's limited with the power for survival. We will be able, in addition to have the change in the primary looking at response, to provide information on PFS. We also will at least have a look at and be able to evaluate survival for internal purposes as well, although it's certainly not powered for survival like any other phase two study due to the smaller numbers of patients. The first one makes sense. The first one makes sense because it was co-primary, and we want to focus on ORR. On the second one, it's more about potentially filing, which would be a huge upside if that was the case. I think I get it. Thank you. Yep. Thanks, Mike. Thank you. One moment for the next question. Our next question will be coming from the line of Li Watsek of Cantor Fitzgerald. Your line is open. Hey, good morning. Thank you for the comprehensive update. We had two questions as well. I guess one for the upcoming ASPEN-03 and 04 in head and neck, given the primary endpoint now is based on ORR and is compared to the historical control versus the actual arm. Can you just set the expectations for us in terms of the delta that you need to show to support AA? The second question is for the ASPEN Breast cancer trial. Just curious if you will be using fresh biopsy for the patient selection and what's the ORR delta that you need to show for you to move forward, given there are many modalities out there being investigated in this setting, as you alluded to on the call. Yeah, great. Thanks, Lee. Both good questions. I'll take the first one and then ask Alan to take the second one. I think on the first one, in terms of how the ORR or how FDA looks at an accelerated approval, a key metric is how we compare with standard of care and how do we compare with benchmark studies. Through FDA interactions, I think we know that is important. I think the bonus here is that we also have a control arm. I think that'll allow us to do additional analyses versus the control. I think in terms of the bar, Keynote 48 sets that bar for us, as well as others that are hopeful about developing new therapeutics in head and neck. If you look at the numbers for Keynote, it's about a 20% ORR is what they reported. We would want to see a 50% nominal gain. So 10% above that, we think, would be clinically meaningful. We think that's the bar. As Alan said, nothing has changed in terms of the design and the maturity of the study and are hopeful about seeing PFS and OS as well and will be an important part of what we look at here next quarter. On the second one, Alan, do you want to field that? Sure. Yeah, let's see. To refresh the breast cancer study, will we be using fresh biopsies? Yes, the intent is to use fresh biopsies. Certainly, whenever feasible, we'll also be looking at ctDNA as an exploratory opportunity as well for patients. The second half of your question, I believe, related to the delta we'd like to see for OR. This is a very interesting area right now in the post-Enhertu space where there's not a lot of data for third line and beyond in that post, and certainly not second line either in the post-Enhertu setting. We certainly don't think that historical response rates are going to be higher than what we've seen in this setting of third line plus, probably in the mid-20% range or so. That's, I think, one of the advantages of the approach that we have with a randomized phase two study where we'll have a control arm that will be there. All the patients will be post-Enhertu. That will give us an opportunity to compare both to historical control and also see how the controls do in a more contemporary setting post-inheritance. Let's see. Hopefully, I think I answered your questions. Let me know if that's sure. Yep. Thank you. Very helpful. All right. Great. Thanks. Thank you. One moment for the next question, please. Our next question will be coming from the line of Brad Canino at Stifel. Your line is open. Hi. This is Dara on for Brad. Thanks for the development path clarity here. Can you walk us through your reasoning to not allow prior setups in irinotecan for pretreated second line CRC? What's your confidence level in the ability to enroll a representative left-sided second line patient population when they can ideally demonstrate ivermectin added combinatory efficacy clearly? I have a follow-up after this. Yeah. Thanks, Dara. Good question. I may ask Dr. Van Cutsem to weigh in as well since he's one of the key leaders on part of your question, which is just reflecting on the benchmarks. I think for us in colorectal, the bar is pretty clear with what cetuximab can do in a naive setting. The unfortunate part for those patients is that largely hasn't changed over many years. Interestingly, I think if cetux is used in the second line, it also can be used in the first line, depending on how clinicians feel about BEV for those patients. I think here we know "know" in quotes, but know the bar. I think that's what gives us conviction in running the single-arm study because I think the signal should be there. Maybe I'll pause here and let the true expert, Dr. Van Cutsem, add some color. Yeah. I think it's a good question. Indeed, in left-sided, based on irinotecan guidelines in Europe more than in the U.S., still to recommend to start in first line with EGFR antibodies. However, what we see is that still some patients are treated with VEGF antibodies. In the U.S., most patients, also left-sided, in community practice and in the field are treated with bevacizumab. On top of that, in right-sided, of course, all patients are treated with bevacizumab based on guidelines. Looking for a study like this is really feasible. There are enough patients that can be treated, and it is still relevant. If I understood your question well, it is why there is no study, let's say, cetuximab or EGFR refractory patients? That's a completely different design. If you would do that type of study, that goes a little bit back to what was done in the past, the bone study that I cited 20 years ago. We looked at irinotecan refractory patients and then to show that the continuation of irinotecan plus cetuximab, that was also based on the fact that there were preclinical data showing that cetuximab could reverse resistance to each of our antibody. That's a different question, I think. I think I'm pretty sure that if first an initial study that is being done like this one here, that later on somebody may do a study, but in cetuximab refractory patients to add an EVO on that. That's a strategy, and that's a different strategy. The bar is different, and the setting is completely different, and there is an extra condition in this type of design. Yeah. It sounds like enough patients fall through the cracks of the front line that is supposedly responsive to EGFR, but they could be naive to EGFR. I hear on that point. Maybe for Dr. Van Cutsem, what kind of responsiveness then would you expect from cetux plus FOLFIRI chemo alone? Will that leave enough room for improvement there for another agent to come on top and clearly show that there is an added benefit, a developable signal moving forward? That's it for us. Thanks. Yeah. Your question is, if it's in the cetuximab naive patients, what would be the response rate of all three? That's right. That's pretty much it. Yeah. If that's wild-type patients, I think the response rate in this setting would be rather as what we've seen in the BOND study. In the bone study, I've shown that it was between 20% and 25% response rate in this group of patients in this first line. This was all commercial. It's a bit higher. In second-line treatment, maybe around 30%-35%. There's still a lot of room for improvement in this situation to add on with EVO and to further improve that. Cool. Thanks. Thank you. One moment for the next question. Our next question will be coming from the line of Sam Slutsky of LifeSci Capital. Please go ahead. Hey. Good morning, everyone. Thanks for taking the question. Just two for me. I guess one with the upcoming head and neck data, just depending on those results, how might that impact your kind of plans for EVO going forward in one way or another as relates to the breadth of indications and studies you're thinking of? Then secondly, just on the EGFR ADC, could you just remind us kind of what's been shown in the field before? And then just kind of key points of differentiation with your EGFR or ADC versus others? Yeah. Sure. Thanks, Sam. Great question. Appreciate it. On the first one, just remind me what the first one again. I got the second one. Remind me. Yeah. Just on the head and neck readout, depending on the results, how that might impact the breadth of kind of studies that you plan to run with EVO going forward. Yeah. No, I think as Harish commented on, we are gating future spend, but in no way does that reflect our belief in either the path of gastric or head and neck. I think we're being prudent with our capital in terms of budget, but I think we're still very optimistic. I think we are trying to let the data guide us, right? We know what the data has shown in combination with anticancer antibody. That is what gives us conviction to run these studies with breast and colorectal. Frankly, there is nothing coming that would either be positive or negative in the short run on the antibody front that would change our conviction. On head and neck, I think a positive readout on O3 or O4, of course, unlocks that for us. I think it would be big news. Obviously, this is two large randomized studies, as we highlighted in our slides. This is the biggest data to read out in the field since LEAP. Frankly, the field has lacked randomized data since LEAP. That is going to be very exciting. Once we get that data, I think that'll then put us in a very great spot to both talk to FDA about accelerated path, but also move forward on a phase three. I think importantly, we have, through this exercise, laid out priorities as to where we would go with Pembroke beyond that. That's what we would do. That's the plan. Does that answer your question on the first one? Yeah. That's great. Thanks. Yeah. The second one, I'll make a few intro comments, but I'll let Jaume weigh in on some of the specifics. I think, of course, there are many ADCs in development. I think we recognize that. I do think the bar for us in terms of target selection and why focus on EGFR was very high. One of the things that we're particularly intrigued about is the history, which is what you mentioned. It is very challenging to find a known target in ADCs that has not been completely trampled and where you're not going to be one of many. I think EGFR is unique in that way. There have been early failures due to safety. We know from how we've designed the scaffold and the payload here and all the great work Jaume and team have done from the NHP data that we feel we have a safe molecule. We are in a position, which is, again, unique to be both first and potentially best in class against a known target. Importantly, as we think about capital allocation in this environment, getting safety data really matters because, again, that is what has been the stumbling block for those who have come before us. Excited about that. I think it's relatively minimal capital to turn over that card. Jaume, anything else you want to add on the differentiation front? Yeah. Most of the EGFR approaches in the past were early-starting base. They had skin toxins that are dose limiting and that were discontinued. At this moment, there is one study advanced, early-starting base. It's looking good. It actually gives us a good proof of principle for EGFR and ADC. Of course, we all know that topoisomerase inhibitors tend to outperform tubulin inhibitors both in therapy and efficacy. If you look at them compared to, compare with carcilla, for example. Our molecule, we have worked very closely, each one of the pieces. Despite it looks that it doesn't look that different for each one of the pieces, altogether makes a very different molecule. For example, Depitop is not cetuximab. All the other ones are cetuximab-based and compete with cetuximab. The affinity has been also very well tuned to have a very good safety profile that we have proven in non-human primate studies. In terms of payload, we're still very close to DXD, but improving some of the aspects that we think are important specifically for this target. We have not seen ILD, for example, in any of our GLP tox studies in monkeys. Altogether, I think that we can be the first in a pure topo summary-based ADC and probably the best as well. Thank you. One moment for the next question. The next question will come from the line of Trang Han of UBS. Your line is open. Hi guys. Thanks for holding the event. Very informative. I have three questions, if that's okay. Just quickly on financials, how are we going to view OpEx changing going forward? We've got some new programs introduced, some rolling off with 06, 03, and 04. You announced this 30% reduction in R&D. Any help directionally on OpEx spend over the next few years, that would be helpful. Then just two on EVO. Going back to the 2Q meeting for accelerated approval in GC. We have the 006 study. It looks like ctDNA was an exploratory endpoint. How much emphasis can you place on that data with FDA? Given the patient numbers with events, I think it was around 30. Do you think that's big enough given a few patients performing either way here could impact the curve? Just trying to gauge some of your compliments here on accelerated approval. Then on Aspen-03/04, if that fails on the primary ORR in the ITT population, what's your path forward in head and neck? Is there any point you would consider terminating EVO overall development and prioritize use of R&D in other things like the new ADC? Thanks. Sure. Thanks, Trang. I think I got those questions. Maybe just we'll start with the last because I want to very much make sure we all understand that there's three different mechanisms here, right? The antibody mechanism, the checkpoint mechanism, and the ADC mechanism. We've talked a lot about the antibody story today. Separate and distinct from that is what we're doing with Aspen-03 and -04 with Pembroke. I think the good news here is we will have clarity. We're running two large randomized studies. Again, I think we're hopeful about that. We're hopeful that we'll be able to add another mechanism to the story, which would unlock a whole lot of other plans from there. In the event that this mechanism doesn't hold and we don't see the T cell activation and priming that we hoped, and we don't see it translate, I think we are essentially back to the base case that we rolled out here today, as it does nothing to our conviction around the antibody story. I think to answer the other part of your question, ALX 2004 is super exciting. I think it's differentiated and comes from a group that has delivered a lot of drugs to patients. We're excited about it. I think right now we are allocating cash appropriately. We want to put cash on 2004 to get to safety. From there, we're going to let the data speak across all of these different readouts. We have several catalysts coming. Once we see the data, we'll make decisions based off that. That's the last answer to your question. Maybe I'll go back to the first one on OpEx, and I'll let Harish weigh in. Needless to say, through these rather painful efforts on headcount and prioritization, we're a much tighter organization, and we've reduced OpEx, which is going to allow us to extend runway, of course, but also minimize our burn in the future, which I think can affect how much we would need to raise if and when we get to that point. Harish, do you want to add to that? Jason, I think you alluded to the main points there. I think at this point, we're focusing our capital on these new antibody in anti-cancer trials and in breast and CRC as well as ALX 2004. We believe we have the capital we need to get to meaningful interim analysis and through these multiple what we see as catalyst points between now and Q4 of 2026. That has been a priority. Depending on what we see on head and neck and our accelerated approval pathway discussions on gastric, I mean, we may make some prioritizations and adjustments, but what we're focusing is on the base case that Jason alluded to. Yeah. On your second question, Trang, I think the key thing to note in terms of the number of patients in Aspen-06 where we have confirmed HER2 positivity is that we now have looked at it two different ways, right? First with FRESH, second with ctDNA. When you look at the ORR population, meaning positive via FRESH or positive via ctDNA, we're talking about nearly 100 patients, which is about 75% of the study. We think that is significant in terms of showing the FDA that, in fact, we had several patients that were HER2 negative. I think the inverse is very important too because, frankly, we know in a HER2 negative patient that our mechanism will not work. I think that's the case for the drug. Again, that's the case we'll make with FDA. From there, it'll be their decision as to how they look at it. Did that answer the question, Trang? Very clear. Thanks very much. Okay. Thanks. Appreciate it. Thank you. One moment for the next question. Our next question will be coming from the line of Li Chen of H.C. Wainwright. Your line is open. Hello. This is Li. Thanks for the update. I have three questions, quick ones. First of all, maybe a question for management and also Dr. Pohlmann, if she's still online. My question is, do the phase two and phase three study in breast cancer require HER2 positivity confirmed by central assessment? Why and why not? Second question is about the CRC, the new CRC study. We internally think that in order to be successful in MSS CRC, you need to have EGFR and VEGF inhibition. What's your confidence of your combination regimen in the second line? Third question is about the multiple myeloma. We know that the BCMA ADC has achieved very positive data in the second line setting. Maybe talk about the potential of EVO in AVO, sorry, in navigating this evolving landscape in third line, multiple myeloma. Thank you. Sure. Thanks. To break those down, maybe on the breast front, I'll have Alan as well as Dr. Pohlmann and Wayne. Alan, do you want to kick that off? Yes. The question related to central evaluation in breast cancer. I think what we're going to be looking at in there is that's sort of an emerging role to have sort of recommended in many studies now look at central evaluation as a component for breast cancer studies to deal with the variability and heterogeneity associated with. We're also looking at those post-in-HER2 biopsies that we've historically called FRESH biopsies to evaluate to ensure. The key element for our program is to ensure that the target, in this case, HER2, is present for the antibody in combination with EVO. We will look at providing that evidence for that. Both of those means are there. Also, as I mentioned earlier, the exploratory ctDNA approach as well. This is Dr. Pohlmann. I think this is a very important point. There is always a lot of discussion about the confirmation of the HER2. Usually, what we see is that for early-stage developments such as phase one, you may even have a local assessment of the HER2, but you want to collect that tissue so that you can confirm centrally and then describe the results accordingly. For phase two, and especially for phase three, you definitely want to have the central confirmation. With regards to the HER2 expression after TDXD, I think this is also a very important point. We have just published a paper, Clinical Cancer Research by Golda. Our team has looked at approximately 40 patients that received anti-HER2 therapy after TDXD. We biopsied them. We got the fresh biopsies. We had about a third of the patients that lost the HER2 expression. You really want to check if you really need to have that HER2 expression. You want to make sure HER2 is still there. Great. Thanks, Dr. Pohlmann. On the second question, just around the role of EGFR and VEGF in colorectal, I think you're absolutely right. Those are the two really backbone therapies in the segment we're looking at, which again is left-sided RAS wild-type patients. Those patients either get BEV in the front line and then an EGFR or vice versa. For us in the second line setting here, our patients will largely have seen BEV in the first line. They will have seen a VEGF and then come into our study. We are not changing standard of care in terms of having to take on BEV or take on an EGFR. We are going to combine with an EGFR and seek to be additive to it. I think Dr. Van Cutsem in the prior answer to Dar's question laid out what the bar is for us there. The third question is just around multiple myeloma. I think there is a lot of activity in that field. I think it represents still a very significant patient population and a large market. I mean, there's no question commercially. I think it's been proven how big of an opportunity it is. For us to combine with Sarclisa here, I think is a big opportunity for us. Certainly, Sanofi is also excited about this and looking forward to the readout. We have yet to see other studies that have truly redefined standard of care there in combination. We are excited about what we'll share there. As we mentioned, we're now actively enrolling patients in the midst of that study. Great. Thanks, Britt Olsen. Thank you. That does conclude today's Q&A session. I would like to go ahead and turn the call back over to Jason Lettmann for closing remarks. Please go ahead. Great. Thanks. I appreciate all the engagement, good questions, and you all spending some time this morning. Just one last announcement, I think with the reductions to research that we're going through in order to extend runway and better prioritize. As many of you have surmised, this also means that Jaume Pons, who is our founder and CSO, will be transitioning. As many of you know, Jaume was our CEO for many years. He led the company from its inception and then stepped into a CSO role after some arm twisting when I joined. He agreed to help me through the transition and lead the research group, which he's done a fantastic job of. Jaume has been a great partner for me. He's a friend. Frankly, his insights are why we're here. He's not leaving today, but is planning to transition in Q2 of this year. We very much plan to keep him heavily involved as he moves into a newly defined role of senior scientific advisor. He'll continue to provide good guidance for us. As one of the best drug hunters I know, with, I think, four approved drugs to his name, he leaves us now with two fantastic programs, one in the clinic, as you know, with EVO, and one now just within weeks of entering the clinic. Very enthusiastic about what we have, grateful for his leadership and partnership. We're going to drive this forward and looking forward to a big year. Thank you all for joining. Looking forward to talking soon as we have many catalysts coming. Again, appreciate all the interest in our program. Thanks. Thank you all for joining today's conference call. This is the end of today's program. You may all disconnect.