Hello, and welcome to the ALX Oncology's ASPEN-06 Phase II Interim Gastric Data Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a Q&A session. If you would like to ask a question during this time, simply press star one on your telephone keypad. If you would like to withdraw your question, again, press star one. I will now turn the conference over to Jason Lettmann, CEO. Please go ahead. Good morning, everyone, and thank you for joining today's conference call to discuss the ASPEN-06 interim randomized results. I'm Jason Lettmann, CEO of ALX Oncology, and I'm joined today by Dr. Sophia Randolph, our Chief Medical Officer. We are also thrilled to have Dr. Josep Tabernero, Head of Medical Oncology at Vall d'Hebron University Hospital and ASPEN-06 Principal Investigator. We're thrilled to be here with you today, and we're looking forward to sharing the data. Our goals are to provide a brief overview of our lead molecule, Evorpacept, and its development plan, then highlight the need in gastric cancer and share the interim results of the ASPEN-06 study, which we're very excited about. And then last, provide some guidance on future milestones and where we're headed from here. Next, on slide number two, we're gonna remind you all of our focus and how we are different. We are targeting the CD47 pathway or the "don't eat me" signal, which is a potent mechanism that cancer uses to evade destruction by the immune system. While CD47 is overexpressed on cancer cells across many tumor types, CD47 is also expressed on healthy cells, making it a very challenging area to target. As you can see on the left, macrophages require two events for maximal antibody-dependent cellular phagocytosis, or ADCP. First is the inhibition of CD47 binding to its SIRPα receptor to signal "don't eat me," and the second is a pro-phagocytic "eat me" signal that can be provided by a targeted anticancer antibody, which engages the Fc receptor on the macrophage. Given this dual, dual mechanism, the major question for the field for many years has been: Is it possible to separate the potent anticancer activity while sparing normal, healthy cells? We believe Evorpacept, or EVO, does this, as it is an engineered fusion protein and was uniquely designed to only block CD47. This is significantly different than others in development, as it has an inactive Fc that does not bind to the Fc receptor on macrophages. Turning to the next slide here, the two graphics highlight how EVO solves this challenge and takes a very different approach. EVO was designed to deliver a near-total block, blockade of the CD47 SIRP alpha signaling, while working in combination with a targeted anticancer antibody specific to cancer cells, which directs the cell killing to the tumor. In this way, and as depicted on the panel to the right, EVO spares normal cells, such as red blood cells, from destruction while directing the ADCP at the cancer cells. If you turn to the next slide, this approach is markedly different than conventional CD47 blockers, which provide both of these signals on the same molecule and use CD47 effectively as a tumor-targeting anti-antigen. Unfortunately, because CD47 is not specific to tumor cells, this also results in ADCP against normal cells like red blood cells or platelets, resulting in CD47-targeted destruction of normal cells and the associated toxicity because of that. Additionally, these toxicities can prevent the dosing needed for full CD47 blockade and, when combined with the sink effect created by directing macrophages to both healthy and cancer cells, limit its efficacy. Now we turn to slide number six, where we share how this mechanistic differentiation has now translated to the clinic most recently. On the top of this slide, you can see the competitive molecules in development and note that all have had hematologic toxicity signals due to the active Fc. Recent news in the field has also highlighted that several anti-CD47 programs have now been stopped or paused. This is in direct contrast to what we have observed to date in studies combining EVO with Keytruda, with Rituxan, with Herceptin, and even with chemotherapy, where we have no known safety concerns and better efficacy. This is also further reinforced by the randomized data we will report today in gastric cancer, which has demonstrated similar results. Next, on slide number seven, this is a quick reminder of our Evorpacept development plan, and I'm going to highlight this before we dive into the data. As a reminder, we are testing the drug across two mechanisms of action. First, by combining with targeted anticancer antibodies to activate macrophages. And second, by combining with checkpoint inhibitors to activate Dendritic cells and T cells. These combinations are being studied in gastric cancer, which again, we will focus on today, as well as multiple other indications, including bladder cancer, breast cancer, multiple myeloma, and others, as over 400 patients have received EVO to date. Next, Dr. Sophia Randolph, our Chief Medical Officer, will take us through the summary of the development plan, and then we're excited to have Dr. Tabernero walk us through the trial findings. Sophia? Thank you, Jason. As Jason noted, and on the next slide, today we will be presenting pre-specified interim data on 54 patients from our randomized phase II ASPEN-06 study of Evorpacept in gastric and gastroesophageal cancer. We will provide the first prospective randomized clinical data of any CD47 blocker that supports combining myeloid checkpoint inhibition with an anticancer-targeted antibody to improve clinical response in patients with advanced malignancy. Dr. Tabernero will present the interim data from the ASPEN-06 study, evaluating Evorpacept in combination with Trastuzumab, Ramucirumab, and Paclitaxel, referred to as evo-TRP, with Trastuzumab, Ramucirumab, and Paclitaxel, or TRP, in patients with advanced gastric cancer. He will show that Evorpacept was generally well-tolerated and that its activity compared favorably, not only to the internal control, but also to historical activity of Ramucirumab and Paclitaxel from the RAINBOW pivotal study, as well as Trastuzumab deruxtecan in the DESTINY-Gastric01 pivotal study. These initial interim data support the potential for a new standard of care in gastric cancer, and the ASPEN-06 final analysis is anticipated in the Q2 of 2024. As you can see on the next slide, Evorpacept's mechanisms of action and safety profile were explored initially in the ASPEN-01 first-in-human study. Specifically, in the HER2-positive gastric cancer 18-patient expansion cohort, Evorpacept was well-tolerated in combination with TRP, and the data supported its enhancement of antibody-dependent cellular phagocytosis, providing this mechanism of action's proof of principle with a strong signal of activity. Patients with HER2-positive gastric cancer demonstrated a 72% objective response rate in this single-arm cohort. This provided the clinical rationale to evaluate Evorpacept more rigorously in the randomized phase II setting, in combination with TRP. To understand the contribution of Evorpacept to the three-drug backbone, ASPEN-06 phase II patients have been randomized to receive Evorpacept-TRP versus TRP. Upon determination of proof of concept and contribution of Evorpacept's effect, this study will proceed to the pivotal phase III portion, where a similar patient population will be randomized to receive Evorpacept-TRP versus Ramucirumab Paclitaxel, the global regulatory standard of care. We are excited about the promise of Evorpacept as a novel therapeutic for patients, and I am pleased to introduce Dr. Josep Tabernero, a principal investigator on our ASPEN-06 study in gastric cancer, to discuss the current gastric cancer field and results from our interim analysis. Dr. Tabernero is recognized internationally as an expert in GI cancers. As Head of the Medical Oncology Department at Vall d'Hebron University Hospital in Barcelona, Spain, he is a true physician-scientist. He is also Director of the Vall d'Hebron Institute of Oncology, where his research interests include the development of novel and effective personalized cancer medicines. Dr. Tabernero recently served as ESMO President, and his expertise in GI cancer and novel therapeutics is well recognized and reflected by his more than 400 peer-reviewed articles and educational and scientific committee appointments for several practice-defining societies and journal editorial boards. We are honored to be working with Dr. Tabernero in Evorpacept's development in gastric cancer. Dr. Tabernero? Thank you, Sophia, and good morning to all. Advanced gastric cancer is a challenging disease to treat, and there is a global unmet need for novel and tolerable treatment options. While the age of the rising incidence is highest in Asia, it has a significant presence in Europe, the Americas, and other global regions. Patients' five-year survival is highest when the disease is treated in the locally localized setting. However, once distant metastases are identified, the five-year survival can be as low as 7%. There is a need for novel therapeutics for patients with gastric cancer, and given Evorpacept's proposed mechanism of action in combination with antitumor antibodies, the advanced HER2-positive gastric cancer setting was chosen to initially validate Evorpacept's mechanism of action. You can see the global standards of care for HER2-positive gastric cancer vary slightly by region. Available first-line standards in the advanced setting include Trastuzumab in combination with a fluoropyrimidine and a platinum-based chemotherapy, as well as the recent approval of Pembrolizumab in combination with this same regimen in patients with PD-L1-expressing tumors. For patients whose tumors have progressed on initial therapy, Ramucirumab plus Paclitaxel is a second-line global standard of care based on the RAINBOW study. The anti-HER2 antibody-drug conjugate, Trastuzumab deruxtecan, also known as ENHERTU, is currently also approved in the United States and Europe, based upon the results from the third-line DESTINY-Gastric01 study. In the third-line setting, Trastuzumab deruxtecan is approved in several countries in the Asia region. Single-agent or combination chemotherapy regimens are also used in the later-line settings, depending upon prior therapies and patient tolerability. Key activity from the practice-changing randomized pivotal studies, RAINBOW and DESTINY-Gastric01, are shown in the next slide. Although an advancement in the gastric cancer field, both studies reported modest improvements in response rates and survival benefits, highlighting this, the significant unmet medical need in these populations. The RAINBOW study enrolled a mix of patients with HER2 negative and positive second-line or greater gastric cancer. The overall response rate of Ramucirumab Paclitaxel was 28%, compared to that of the Paclitaxel control arm, of which was 60%. Duration of response in the Ramucirumab Paclitaxel arm was 4.4 months, and a significant improvement in overall survival to 9.6 months resulted in its regulatory approval. With no significant difference between the HER2 negative and positive populations enrolled, Ramucirumab Paclitaxel became a global standard of care for the broader gastric cancer second-line or greater setting, irrespective of the HER2 status. The DESTINY-Gastric01 study was conducted in patients from Japan and Korea, who had third-line or greater HER2-positive gastric cancer. In this randomized study, objective response rates of 41% were seen in the Trastuzumab deruxtecan arm, compared to 11% in the physician's choice arm of Paclitaxel or irinotecan. The duration of response in the Trastuzumab deruxtecan arm was 11.3 months, with an improved overall survival to 12.5 months compared to the physician choice arm. These data were the basis of its approval in the first-line setting in Asia and in the second-line setting in the United States and in Europe. On behalf of the ASPEN-06 investigators, I am very happy to present randomized data from the pre-specified interim analysis today. The next slide describes the randomized phase II portion of the ASPEN-06 study of Evorpacept in combination with Trastuzumab, Ramucirumab, and Paclitaxel, referred to as evo-TRP, in patients with advanced HER2-overexpressing gastric or gastroesophageal adenocarcinoma. Patients with second- or third-line HER2-positive gastric or gastroesophageal carcinoma were randomized to receive either the evo-TRP or the backbone of TRP regimens. The primary endpoints of the study are investigator-assessed overall confirmed objective response rate, with secondary endpoints of duration of response, progression-free survival, and overall survival. The objectives of this phase II study are to define the activity of Evorpacept plus TRP, compared with historical global standard of care, Ramucirumab plus Paclitaxel, as well as to understand the contribution of Evorpacept to the backbone therapy of Trastuzumab, Ramucirumab, and Paclitaxel. Key eligibility criteria include patients with advanced HER2-positive gastric or gastroesophageal junction cancer that have progressed on or after a prior HER2-directed agent and standard chemotherapy. Patients must have either second-line or third-line advanced disease and no prior treatment with an anti-CD47 agent, an anti-SIRPα agent, or Ramucirumab. Recognizing new standard therapies in the field, prior therapy with Trastuzumab deruxtecan, as well as immune checkpoint inhibitors, were allowed. For the prespecified interim analysis of 54 patients that we will be presenting today, futility would be met if the evo-TRP arm demonstrated no more than a 30% overall response rate, or if there were more responders on the control arm compared to the test arm. The final analysis has 80% power to see a 50% improvement in overall response rate compared to historical RP, and 68% power to see a 10% overall response rate delta between arms. As you can see on the next slide, as of August 29, 2023, 54 patients from 13 countries were randomized in a 1:1 fashion to receive either evo-TRP or TRP alone. The dose of Evorpacept in this study was 30 mg/kg, administered once every two weeks. Trastuzumab was administered with a 6 mg/kg loading dose, followed by 4 mg/kg once every two weeks. Ramucirumab and Paclitaxel were dosed according to their label in a 28-day cycle. The initial demographics of the 54 patients enrolled are shown. The majority of patients enrolled were male and Asian, with a performance status well balanced between ECOG 0 and ECOG 1. By arm, there was a slight increase in the median age and percentage of male patients on the evo-TRP arm, and slightly more patients with gastroesophageal junction cancer on the control arm, while other demographic characteristics were well balanced. The safety profile of evo-TRP versus TRP is presented on the next slide. evo-TRP was generally well tolerated, with a safety profile that was consistent with that of the backbone TRP therapy. Adverse events, including cytopenias, were balanced by arm, and there were no on-study treatment-related deaths. Evorpacept safety profile was consistent with the prior experience in over 400 patients previously dosed in clinical trials. On the next slide, the clinical activity of evo-TRP in the study pre-specified interim analysis of 54 enrolled patients is described in the table. The clinical activity of evo-TRP supports a substantial contribution of evobrutinib to the TRP backbone. The confirmed objective response rate in the evo-TRP arm of the study was 52%, compared with 22% in patients who received TRP. 4% of the patients from the evo-TRP arm had a complete response compared to none on the control, and 48% of the patients who received evo-TRP had a confirmed partial response compared to 22% on the control arm. At the time of this interim analysis, the median duration of response on the evo-TRP arm was not reached, and the median duration of response on the TRP arm was 7.4 months. evo-TRP's response activity compared to that of the TRP backbone supports individual contribution of evobrutinib to this regimen. The initial clinical activity of evo-TRP also compares favorably to the RAINBOW historical data, where Ramucirumab plus Paclitaxel demonstrated a 28% confirmed objective response rate and a 4.4-month median duration of response, as well as when compared to the DESTINY-Gastric01, where Trastuzumab deruxtecan reported a 41% confirmed objective response rate and a median duration of response of 11.3 months. On the next slide, we can see that almost all evaluable ASPEN-06 patients administered evo-TRP had some degree of tumor shrinkage, as measured by the best percentage change in the target lesion sum of the diameters. This broad antitumor effect compared to that of the TRP control arm and is consistent with improved best overall response rates reported by patients receiving evo-TRP. Similar to the ASPEN-06 Evorpacept experience, on the next slide, tumor shrinkage was also seen in most of the 11 HER2-positive patients enrolled in the ASPEN-01 first-in-human gastric cancer cohort who received Evorpacept. The consistency between the two waterfall plots is encouraging and supports the robustness of the Evorpacept antitumor activity. On the next slide, we see that confirmed objective response rates observed in patients receiving Ramucirumab Paclitaxel from the RAINBOW pivotal study on the left and the interim analysis data from ASPEN-06 on the right. Although the data set from ASPEN-06 pre-specified interim is preliminary and with 54 patients, this initial randomized data is encouraging, and the activity builds upon the activity demonstrated in the single-arm ASPEN-01 first-in-human study in a similar population. We eagerly await the ASPEN-06 final analysis, anticipated in the Q2 of 2024, where we hope to confirm Evorpacept's activity in 122 globally randomized patients. In summary, as of this interim analysis, Evorpacept demonstrates an initial confirmed objective response rate of 52%, with an unreached median duration of response in patients with HER2-positive gastric cancer, in combination with Trastuzumab, Ramucirumab, and Paclitaxel in a 2L/3L second-line and third-line population. This is compared with a TRP control arm, where an overall response rate of 32% and a median duration of response of 7.4 months were seen. The interim data support that Evorpacept can be safely combined with TRP, and that is, has a positive contribution to this, that backbone therapy. These reported response rates compare favorably with historical pivotal studies in patients with advanced HER2-positive gastric carcinoma. The ASPEN-06 interim analysis provides the first randomized initial clinical evidence that blocking CD47 in combination with an anticancer antibody improves the innate immune response in patients with gastric cancer, building upon the activity previously reported in the ASPEN-01 first-in-human study. The final analysis of ASPEN-06 is anticipated to read out in the Q2 of 2024. Thank you for your attention, and I'm happy to turn it back to Jason Lettmann. Jason? Thank you, Dr. Tabanero. On behalf of ALX, we'd like to thank you again and all the investigators for their dedication to the ASPEN-06 program. We really, really appreciate it. So as we reflect on the data generated to date, we believe it is important to return to the mechanism to answer the key question: of why we are seeing such encouraging data and what is different here versus the other CD47 programs in development. On the left, you can see that we highlight how Evorpacept was designed. EVO is unique as it is a high-affinity CD47 binder with an inactive FC. It has a lower molecular weight with a PK profile similar to an antibody. Moving to the right, these attributes combine to potently block CD47 while being more targeted and more tolerable without the cytopenias, and is particularly well-suited for targeting solid cancers. EVO is also the ideal combination agent with a longer half-life that allows for improved dosing. And then on the right, this is what we believe is driving the encouraging efficacy, the best-in-class safety profile, and is also driving what we're seeing in today's randomized data in gastric. Last, I would like to conclude with our upcoming milestones and where ALX is headed from here as a company. As discussed, we're testing two mechanisms through a robust development plan to investigate both. With this positive interim data in the first randomized study to read out in the CD47 space in solid tumors, we have now added another data point to the four phase Ib studies already completed. Going forward, we're currently testing EVO across 10 clinical studies with new combinations and indications. We are running 5 studies in combination with anticancer antibodies, two with ADCs, and two phase II randomized studies with Keytruda, which we believe will be the first randomized study to read out in the CD47 space in combination with a checkpoint inhibitor. Last, this slide summarizes our future milestones and what to expect from us going forward. In Q2 2024, we will share the final data from the ASPEN-06 study in gastric cancer, as well as share data from a phase 1B study combining EVO with another anticancer antibody, Rituximab, in non-Hodgkin lymphoma. In the second half of 2024, we're planning to share top-line results from two studies with ADCs. The first is ASPEN-07, in combination with Padcev and urothelial cancer. The second is the I-SPY study, investigating EVO in combination with an HER2 in breast cancer. In the back half of the year, we will also share top-line results from the ASPEN-03 and ASPEN-04 randomized studies with Keytruda in head and neck cancer. Again, as a close, thank you again for your time today, for this opportunity to bring you all up to speed on the positive ASPEN-06 data. We think we have significant momentum heading into the year here and are absolutely thrilled about the many milestones and catalysts we have coming in 2024. Thanks again for the time, and we will now open the call for any questions. Appreciate it. Thank you. If you have a question, please press star one on your telephone keypad. If you wish to remove yourself from the queue, simply press star one again. One moment please, for your first question. Your first question comes from the line of Chris Raymond of Piper Sandler. Your line is open. Hey, thanks, guys, and congrats on the data. Just two questions, maybe if I can. Just on durability, I know you gave us the data you gave us in terms of DOR in the control arm and not reaching it in the quad therapy. Any sort of color, I guess, that you can give on PFS, you know, or what you're thinking about with respect to how this reads through to PFS? That's on the durability question. And then, maybe also just on the control arm. I understand obviously the caveats. You had a pretty decent sort of snapshot of historical data in your slides, but we get a ton of questions on this Rha et al. study, just which, you know, had the control or triplet therapy ORR at a higher rate. But just maybe remind us of the controls in place to sort of maintain balance between second-line and third-line patients, between cohorts, and also, you know, as the study progresses. And I guess the way to ask that question is, your confidence level, you know, in this ORR difference, sort of holding up upon final data? Thanks. Great. Thanks, Chris. I appreciate the question, both excellent questions. We'll take the first one, first. I think, you know, obviously thrilled with this data. Again, first randomized data to read out and sell it in the space. You know, but you know, is an interim analysis. Therefore, in terms of looking at PFS and OS, the data is just not mature enough to be able to do so yet. So that's where that stands. And just- I'll ask Sophia if she has anything to add on that front. No. No, that's correct. So we'll have more mature data at the time of the final analysis. But with the interim, this is the data that we have. Great, thanks. And on the second one, you know, I probably three points to make there in terms of what we're seeing and maybe how does it compare. I think the first is that this is a randomized study. Again, a rigorous randomized study that we ran across 13 countries with very well-balanced demographics across the two arms. Also, we believe, I think as Dr. Tabernero mentioned, the first study to enroll patients that also had, you know, that had ENHERTU and or checkpoint exposure. And so this is truly, you know, I think a first in that space as well. And so I think against that context and what is a very high bar, you know, I think the second point I'd make is, you know, the fact that we showed a 30% delta versus control. You know, we believe, and I've spoken to many of you about what we see as relevant, and the clinicians certainly felt that a 10% delta versus control in this rigorous setting would be a win. So obviously, very excited to see essentially triple that. And then last, and I'll have Sophia weigh in on this as well, but I think, you know, if you look at the RAINBOW study, which is the regulatory benchmark at 28%, you know, I think we feel that what we're seeing here is reflective of this patient population, which again, is a second and third line patient set that, you know, just doesn't have many good options. So again, I think we feel that this is in line with what we'd expect. But Sophia, do you want to expand on that a little more? Yeah, no, I think what you're saying is absolutely right. And you know, I think what ASPEN-6 brings here is the rigor of randomization, which is really important and is something that is expected by, you know, by the field, by us, by the regulators, to really be able to characterize the contribution of effect and, and then also just proof of concept with historical activity. I think the HER-RAM study, you know, just for reference for others as well, it is an encouraging study, but it's a single-arm, single country, phase I study, conducted across five sites. Again, slightly different population, as Jason mentioned, in terms of some of the current standards that are available for patients, such as, such as ENHERTU. So I think, you know, the results in their study are encouraging, but really, without the randomization and a global population, it's challenging to characterize the activity of that regimen. And again, I think with ASPEN-06, what you have is the, you know, the key elements of a well-conducted study, meaning the randomization, the global patient population, and the size. So hopefully that helps. Thank you very much. Yep, thank you. Your next question comes from the line of Li Watsek of Cantor Fitzgerald. Your line is open. Good morning, and congrats on the data. Exciting day for CD47. Maybe just a couple from us. You know, just curious about the next steps with FDA. Can you offer any thoughts on a, you know, potentially accelerated approval pathway based on the strong interim data? Also, do you have any plans to apply for breakthrough designation? Yeah, great. Thanks, Li. Appreciate the question. Certainly, something we've been talking about as a team. You know, I think the beauty of this design here is it is a phase II and phase III design that we've discussed and, you know, I think have alignment with the agency on. And I think you pointed out the options here. I mean, obviously, it'll be data dependent and dependent on the FDA review, but randomized data of this sort, given the unmet need, you know, certainly I think it is something that we would explore in terms of breakthrough designation with the agency. Again, yeah, very excited about it, and I think that it's a pretty clear signal. Sophia, anything you want to add there on the regulatory front? Yeah, just you know that, you know, as with standard with any phase II, we would interact with the agency, at the time, after the final analysis and discuss paths forward. So again, depending on the, the strength of the data, the final analysis, definitely we'll be interacting with the health authorities. Okay, and maybe another one for the doctor. Can you just talk about, you know, how this regimen can fit into the current treatment landscape, and how would you sequence on HER2 versus ipataslimab? Dr. Tabernero, you want to take that one? Yeah, absolutely. Thank you for the question because it's really very relevant. So, obviously, this is an interim analysis, but the both, o verall response rate and the duration of response favors this quadruple combination of Evorpacept TRP compared to TRP. And of course, in here, actually, as you know, for the time being, the continuation of Trastuzumab and progression of Trastuzumab in the first line setting is not a recognized treatment. So the second line setting is open, and as mentioned before, the only study that has evaluated or has included patients HER2 positive in a phase III study is a RAINBOW study, and there were no difference between the HER2 positive and the HER2 negative. So the standard of care in most of the countries right now is the combination of Paclitaxel Ramucirumab. Of course, we are aware of exciting data with Trastuzumab deruxtecan, especially coming from the randomized study in the third-line setting in the Asia Pacific population and some phase II confirmatory studies that actually have prompted the approval by the FDA and the positive consideration by CHMP at the European level. But remind that this is, you know, a study where most of the patients have been included in the third-line setting. So for the time being, I'm looking at the preliminary data that we have seen in the ASPEN-06 study. I think that the continuation of this in the phase III portion actually could define whether the combination of Evorpacept plus RP is superior to Sorry, the combination of Evorpacept, Trastuzumab deruxtecan is superior to Paclitaxel Ramucirumab, and that could well define a standard of care in this second-line setting. More and more, we are assisting in a situation, attending a situation where, of course, immune checkpoint inhibitors in the HER2 population are gonna be administered in the first-line setting or the standard of care right now, the combination of Cisplatin, Fluorouracil, Trastuzumab and Pembrolizumab. So the second-line setting is absolutely open, and especially for a well-designed study like this that only targets the HER2-positive population. And again, I think that the beauty here is that for the first time, we have seen a CD47 binding antibody that shows superior activity when add to the standard of care, number one, and actually, we don't see the side effects that we have seen with previous CD47-directed antibodies. Thank you. Your next question comes from the line of Colin Bristow of UBS. Your line is open. Hey, good morning, and congrats on the data. A few questions from our side. Maybe we start with just how do you view the profile of the Evorpacept combo in this setting versus what we've seen from ENHERTU? Secondly, could you tell us what the stratification factors were for this study? And then finally, just on the AE side, I noticed a slight imbalance in grade 4 AEs. I just wondered if you could characterize those for us. Thank you. Sure. On the, on the ENHERTU comparator, you know, I think the DESTINY-Gastric01 study, the randomized phase II that they conducted, achieved an ORR of 41%. So again, you know, we believe that we compare favorably. Again, I'd remind the group here that this is also a very different population and is done in a post- ENHERTU world, so to speak, which just hasn't been studied as much. So that's how we're viewing ENHERTU. Sophia, do you want to add anything there? Yeah, and in terms of the, if I caught the question as well, in terms of the adverse event profile for ENHERTU versus the profile that we're seeing in ASPEN-06. Certainly, you know, the side effect profile that we're seeing in ASPEN-06, we do not see any sort of exacerbations of anything beyond the backbone. So and I think that's reflected in the adverse event slide that we showed, that the adverse events were very well-balanced and is consistent with the safety profile of over 400 patients for Evorpacept that's been presented in the past. So with in ENHERTU itself, obviously there are serious side effects in terms of interstitial lung disease. There's even been mortality associated with it. I think having a safe regimen or a tolerable regimen, like what we've seen to date in this study, is very advantageous. Thank you. And on the stratification factors? Yeah. At this point, because the study is still accruing, we don't want to engender any kind of bias until we get to the final. So, the details of that will be disclosed at the final analysis. Okay, thanks very much. Yeah, I just would add, you know, I think we feel really comfortable with the randomization here, and comfortable with, I think, saying that we feel that the only significant difference between the two arms is that one received Evorpacept and the other didn't. So, I think we feel good about that. Thank you. Your next question comes from the line of Michael Yee of Jefferies. Your line is open. Hey, guys. Let me be the first to congratulate you. I think it's worth a congratulations. So congratulations, Sophia and Jason. Nice to step into that as your first call. Maybe just two questions. One was a clarification on the balances of the two arms of the study. I know Jason just sort of clarified it if feels comfortable, but just to be clear, there are no answers today on necessarily the balance of second and third line, and ENHERTU, prior failed ENHERTU in either arm, or you're just saying you feel good that those two are balanced? That's question one. And then question two was maybe for you or for the doctors. It seems I think that these patients would be sicker than what's in Rainbow, I think, right? And so I'm just trying to understand. There was a lower response rate, but yet the median duration of response was much higher. So just wanted to try and triangulate your thoughts about comparing this to RAINBOW. Thank you. Sure. So, you know, I think on the randomization front, I think just to highlight what was said in the presentation, again, you know, I think the demographics are fairly balanced. If anything, I think slightly tilted, you know, against evo in some ways. But I think, you know, the other thing we've said, which is important, is that the study is second and third line and did enroll a substantial number of patients that received ENHERTU or a checkpoint. And again, I think that makes this study fairly unique. And then on the Rainbow comparison, again, Rainbow had a 28% ORR, but I'll let maybe Sophia expand on how to contextualize that for us. Yeah. I think within the RAINBOW, and again, as Dr. Tabernero mentioned earlier, there it is a mix of patients. It included both, predominantly HER2-negative as well as, HER2-positive patients. But as there was no statistical difference in terms of activity between the two populations, it remains a standard of care for gastric cancers, irrespective of HER2 status. So you know, there it was predominantly a second-line population in ASPEN-06. Of course, we're looking at both second- and third-line patients. And again, with the notes that Jason mentioned about additional therapies that this population had access to, compared to those in the time of RAINBOW. So, you know, I think overall, you know, you can always pick a particular demographic to look at, but I think again, the rigor that is needed because of that is the randomization and the globalization, and that's what ASPEN-06, I think brings to the discussion today. Between that and the consistency seen with the results from the ASPEN-01 expansion cohort and gastric, I think that really is the most important thing, and to be able to see that in a contemporary population that has access to these new standards in the field. So I think we both, you know, we all really feel very good about the data, the consistency, and look forward to seeing the final analysis. Okay. Thanks, Sophia. Thanks for the question, Mike. Yeah, go ahead. May I just have a follow-up just to clarify? I would say you can see the questions, including myself and some others. I think it's a question of some of the assurances of the balance, particularly ENHERTU. So there might have been a lot of HER2 patients, but they may or may not be balanced, and so I think that's where the questions derive from. Thank you, guys. Your next question comes from the line of Swayampakula Ramakanth of H.C. Wainwright. Your line is open. Thank you. Good morning, Jason and Sophia. Congratulations. A quick question on... I believe there was one CR in the treatment group that you reported today. So trying to see if there is any possibility of you characterizing that CR, and also, within that treatment group, do you see any PRs which are, you know, getting close to become a CR? And the second question is, what's the longest exposure that this current treatment group has seen? Thanks, RK. I think I'll have Sophia take both those for us here. Mm-hmm. Yeah. So in terms of the, obviously, in terms of, RK, thanks for the question. In terms of the details of the patients and, sort of, you know, the characterization of the nature of the PRs, that will have to wait until into the final analysis in this ongoing study. But we have seen the CR in the patient, and I think that's very encouraging, and I think it's, you know, exciting. I mean, as we said, once this disease, you know, progresses from either initial therapy or is diagnosed in the advanced metastatic setting, you know, the five-year survival of these patients is just so poor. So to see something like a CR in this population, I think is really. is really exciting, not only for the patient, but, you know, also for the development of the drug, and we hope to see more. You know, as of the final analysis, we'll be able to provide much more color in terms of, you know, durability of response, which again is, you know, for now has not reached at this interim. So we'll have more information on that at the final analysis. And then the second question, I forgot. What's the longest exposure? Ah. Just in general, at the time of this interim, patients must have been sixteen weeks on study, and that's to confirm the ability to have two rounds of imaging for these patients for the primary endpoint, which is confirmed overall response rate. At the interim, median time on follow-up time is about that. It's about a little over eight months. At the time of- Thank the final analysis, we'll obviously have a longer duration that we can comment on. Thank you. Thank you very much, Sophia. Talk to you soon. Mm-hmm. Your next question comes from the line of Brad Canino of Stifel. Your line is open. Hey, good morning, and congrats on the data from me as well. So you've got a lot of questions on the balance of prior and HER2 between the two arms, but did you see any differential response in the evo arm, whether or not prior and HER2 was administered in these patients? I'm wondering the same for prior PD-1 too. Yeah, thanks, Brad. Appreciate, appreciate the question. I think, you know, as I think you can appreciate, we're still enrolling this study. So, you know, trying to look at subgroups here and disclosing subgroups would potentially bias the study. So you know, obviously, that's not something that we wanna do here. But again, I just would point back to what we've said in terms of this population being different, this population having substantial exposure to both ENHERTU or a checkpoint. And again, I think feel really good about, you know, the split, if you will, among the two arms. And I think confident in that and confident that this isn't leading us astray. So I think. Okay. Yeah, I think we've covered that. But, yeah, again, you know, I think that's where we are, given this study's ongoing and, yeah, again, I think feel good about the randomization here. Okay. Maybe one more on the DOR. Can you say anything about the median duration of follow-up for the evo arm, whether or not it was comparable to the duration of follow-up for the responders on the control arm? Thank you. Um. Go ahead, Sophia. Yeah. So just, you know, just like I said before, overall, the median follow-up was approximately eight months, a little bit over eight months, and that would be for both arms. Thank you. Your next question comes from Sam Slutsky of LifeSci Capital. Your line is open. Hey, good morning, everyone. Congrats on the update. Thanks for the question. Couple for me. Just first, could you remind us on the regulatory discussions around the two parts of the ASPEN-06 study and the FDA stance on how part 1 suffices the agency to see cornerstone showing contribution of evo to allow for Trastuzumab to be dropped for phase III? So basically, what I'm asking is, could you give background on how the FDA's okay with phase III being four drugs versus two, instead of four versus three? Sure. I mean, I'll let Sophia add some color, but, you know, I think we've covered that in the presentation at a high level. But the RamPac doublet is the regulatory standard of care, I think, in running the phase II. As you rightly pointed out, the important thing for us, certainly as a company, but also from an agency's perspective, is to understand the contribution of evo, which again, you know, I think we're very, very encouraged by. And I think as we've discussed before, the combination phase II to III design here is in line with the feedback we've got from FDA. But Sophia, do you wanna comment on that? Yeah, no, everything you just said. And, again, there's sort of two things that we're looking for: One, out of this phase II. One is proof of concept, with the, historical regulatory comparator. The other is contribution of components, because it is a 4-drug regimen, and we wanna know what is our drug bringing, to that backbone. So, the phase II addresses both of those. And then, and then the phase III, because as was noted, Traz Rampac, or TRP, is not a regulatory comparator. So the regulatory comparator is Ramucirumab Paclitaxel. So that is what the phase III, comparator arm, needs to be. Got it. Okay, and just, two more for me. So you have combination studies ongoing with, antibody-drug conjugates. How important is the effector function of the antibody in an ADC relative to a naked antibody? And do you think you could achieve similar improvements in activity with an ADC partner, as seen in the ASPEN-06 trial? Yeah, I think we do is the short answer. And you know, I think the overall strategy here has been to plant some seeds, if you will, in other areas that we think make sense mechanistically. And I think the combination is with ADCs, as you pointed out, makes sense. So we're, I'd say, particularly excited about the I-SPY study that is essentially a basket study that's exploring evo in combination with HER2, for example. But I think mechanistically it makes sense. Sophia, anything you wanna add on that one as well? Yeah, no, exactly. As we're building for the future, it's looking both at combinations with naked antibodies as well as ADCs for that, for that, you know, mechanistic rationale. So the other study we have is our bladder cancer study, ASPEN-07, where we're combining with Enfortumab ADC as well. So they're really, you know, looking at this mechanism of combining with a cancer-targeted antibody, it should also cross over to combining with an antibody that has a chemo load such as an ADC. So definitely excited to see both safety results as well as activity from combining with that group of therapeutics. Okay. And just, last question. Just, you touched on it a bit during the call, but can you discuss just the failures of magrolimab in MDS and AML, how that is or isn't relevant to your program, given that, Gilead did not combine with an antibody that induced an ADCP signal? And then to that end, too, is there anything to learn from the non-Hodgkin lymphoma experience with the class, given that their studies were combined with an appropriate antibody, being rituximab? Yeah, I think on the first one, you know, we, I think what we tried to hit on at the beginning here of our remarks is just the differentiated nature of Evorpacept. And again, that's been since the early days with Jaume and team really recognizing that a dead Fc is important. And of course, you know, I think in the early days, you know, a lot of that is good science and theory, but until you get to the clinic, you don't fully know. And I think the space evolved in a way they typically do, where you have a lot of single-arm data and signal finding. And I think, you know, just really proud of this team and putting randomized data as the bar. And, you know, that's what we think is playing out. I think the dead Fc is fundamentally very, very different than the conventional approaches with an active Fc. And again, that's by design. So, you know, we still believe in these two mechanisms and are gonna pursue both aggressively from here. And then the second part of your question I missed. So maybe you could just repeat that for us. Apologies. Yeah, just, I guess anything to glean from the non-Hodgkin's lymphoma experience, given that the class did use an appropriate antibody, being Rituxan, in those studies and had pretty good response rates? Yeah, I think, you know, the good news there is, you know, in terms of the guidance we provided for first half of next year, we are running a study in combination with rituximab, that's being done as an IST at MD Anderson. That's gonna read out Q1, Q2. So we'll have more data there soon. But, you know, I don't have other comments on that specific study, unless you do, Sophia. No, just that it's a combination of rituximab and lenalidomide or Revlimid in a relapse refractory population. But absolutely. I mean, it's building upon this mechanism of action. And I think, you know, I would characterize it as a mechanism that we have almost the most data to support the combination with an anticancer-targeted antibody. And even that's across the field, right? So that's from, you know, our expansion cohorts looking at ALX in combination with Ritux within our first-in-human study. And even other CD47s that looked at combinations with Rituximab in the early days. I think the safety profile could be limiting for other CD47 agents, and I think that has impacted development. Whereas for Evorpacept, and again, as we've, you know, been hammering home by design, we are not limited by those safety constraints, and we're able to dose very effectively in combination with an anticancer targeted antibody. I think that shows, and that's why we're able to continue development in some of these areas, such as lymphoma and gastric cancer that we're presenting now. Excellent. Thank you. There are no further questions at this time. I will now turn the call over to Jason for closing remarks. Great. Just again, would like to thank, Dr. Tabanero, and all the clinicians involved in the study. Exciting data here and excited about where we're going, so appreciate all the support. Thank you. This concludes today's conference call. You may all disconnect.