ALX Oncology Holdings Inc. (ALXO) Earnings Call Transcript & Summary

Hello, and welcome to the ALX Oncology ASPEN-06 Phase I Interim Gastric Data Conference Call. [Operator Instructions] After the speaker's remarks, there will be a question-and-answer session. [Operator Instructions] 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 highlights 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. So next on Slide #2, we're going to 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. And as you can see on the left, macrophages require 2 events for maximal antibody-dependent cellular phagocytosis or ADCP. First is the inhibition of CD47 binding to a SIRP-alpha 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 macrophages given this 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 they have an inactive Fc that does not bind to the Fc receptor on macrophages. Turning to the next slide here, the 2 graphics highlight how EVO solves this challenge and takes a very different approach. EVO was designed to deliver a near total 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 wave, 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 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 #6. 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 a 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 #7. 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 2 mechanisms of action. First, by combining with targeted anti-cancer 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 prespecified 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 Evo-TRP 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-Gastric-01 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 Second Quarter 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 actions 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 3 drug backbone, ASPEN-06 Phase II patients have been randomized to receive EVO 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 EVO 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 durable treatment options. While the age standardized in this [indiscernible] is highest in Asia, it has a significant presence in Europe, the Americas and other rural regions. Patients 5-year survival is higher, when the disease is treated in the localized setting. However, once distant metastasis are identified, the 5-year survival can be as low as 7%. There is a need for novel therapeutics for patients with gastric cancer and even a [indiscernible] 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 the Fluropyrimidine and a platinum-based chemotherapy. As well as the recent approval of Pembrolizumab in combination with this same regimen in patients with PDL-1 expressing tumors. For patients whose tumors have progress 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 up on the results from the third line DESTINY-Gastric-01 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-Gastric-01 are shown in the next slide. Although on 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 enroll a midst of patients with HER2 negative and positive second line or third line 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 syndrome Ramucirumab/Paclitaxel became a global standard of care for the broader gastric cancer second line operator setting in respective of the HER2 status. The DESTINY-Gastric-01 study was conducted in patients from Japan and Korea, who have 3rd line or rather 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 third 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'm very happy to present randomized data from the prespecified interim analysis today. The next slide describes on the randomized [indiscernible] 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 adenocarcinoma were randomized to receive either the Evo-TRP or the backbone of TRP regimens. The primary endpoints of the study are investigator assess overall confirmed objective respond rate with secondary endpoint for 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 to understand the contribution of Evorpacept to the backbone therapy of Trastuzumab Ramucirumab and Paclitaxel. Key eligibility criteria includes patients with advanced HER2-positive gastric or gastroesophageal junction cancer that have progressed on or after a prior-HER2-detected patient 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-SIRP-alpha agent or Ramucirumab. Recognizing new standard therapies in the field prior therapy with Trastuzumab Deruxtecan as well as immune checkpoint inhibitors were alone. For the prespecified interim analysis of 54 patients that we will be presenting today, futility would be met is the Evo-TRP arm demonstrated no more than a 50% 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 respond 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, ASPEN-04 was 29 -- 2023, 54 patients from 15 countries were randomized in a one-to-one fashion to receive either Evo-TRP or TRP alone. The dose of Evorpacept in this study was [ 30 ] milligrams per kilogram administered once every 2 weeks. Trastuzumab was administered with a 6-milligram per kilo loading dose followed by 4 milligrams per kilo once every 2 weeks. Ramucirumab and Paclitaxel were dosed according to their level 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 the performance status well balanced between [ EcoCandICOX1]. By arm, there was a slight increase in the median age and percentage of male patients on the above TRP arm and a slightly more patients with gastroesophageal junction cancer on the control arm, while other demographic characteristics 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 previous experience in over 400 patients previous results in clinical trials. On the next slide, the clinical activity of Evo-TRP in the study prespecified interim analysis of 54 enrolled patients is described in the table. The clinical activity of Evo-TRP supports a substantial contribution of Evorpacept 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 on the Evo-TRP arm has a complete response compared to none on the control. And 48% of the patients who received Evo-TRP has 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 Evorpacept to [ zero rationale ]. The initial clinical activity of Evo-TRP also compares favorably to the RAINBOW historical data, where ramucirumab plus Paclitaxel demonstrated a 28% growth objective response rate and a 4.4-month median duration of response. As well as when compared to the DESTINY-Gastric-01, 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 available ASPEN-06 patients administered Evo-TRP had some degree of tumor [ synchrage ] as measured by the best percentage change in the target lesion sum of diameters. This brought antitumor effect compared to that of the TRP control arm and is consistent with the improved best overall response rates reported by patients receiving Evo-TRP. Similar to the ASPEN-06 Evo-TRP experience on the next slide, tumor [ synchrage ], was also seen in most of the 11 HER2-positive patients enrolled in the ASPEN-01 first-in-human gastric cancer cohort, who received Evo-TRP. The consistency between the 2 [ water ] 4 plots is encouraging and supports the robustness of the Evo-TRP antitumor activity. On the next slide, we see that confirmed objective response rates observed in patient 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 prespecified interim is preliminary and with 54 patients. This initial randomized data is encouraging, and the activity builds up on 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 second quarter of 2024, where we hope to confirm Evorpacept's activity in 122 globally randomized patients. In summary, as of this interim analysis, Evorpacept demonstrates as an initial confirmed objective response rate of 52%, with an enriched median duration of response in patients with HER2-positive gastric cancer in combination with Trastuzumab, Ramucirumab and Paclitaxcel in a rural second-line and third-line population. This is compared with the 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 ] 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 up on the activity previously reported in the ASPEN-01 first in human study. The final analysis of ASPEN-06 is anticipated to phase out in the second quarter of 2024. Thank you for your attention, and I'm happy to turning it back to Jason Lettmann. Jason?

Thank you, Dr. Tabernero. 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. 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 combined to potently block CD47, while being more targeted and more tolerable without the cytopenias and 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 2 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 4 Phase Ib studies already completed. And 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, 2 with ADCs and 2 Phase II randomized studies with KEYTRUDA, which we believe will be the first randomized study to read out in the CD47 space and 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 our Phase Ib 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 2 studies with ADCs. The first is ASPEN-07 in combination with [ PADCEV ] in urothelial cancer, and the second is the ISV study investigating EVO in combination within 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, and to 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.

[Operator Instructions] Your first question comes from the line of Chris Raymond of Piper Sandler.

Congrats on the data. Just 2 questions maybe if I can. Just on durability. I know you gave us the data you gave us in terms of the ORR in the control arm and not reaching it in the quad therapy. Any sort of color, I guess, that you can give on PFS, 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, you've caveats, you had a pretty decent sort of snapshot of historical data in your slides. But we get a ton of questions on this [indiscernible] of study. Just -- which 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 and third-line patients between cohorts and also as the study progresses. And I guess the way to ask that question is your confidence level in this ORR difference sort of holding up on final data?

Great. Thanks, Chris. I appreciate the question, both excellent questions. We'll take the first one, first, I think, obviously, thrilled with this data, again, first randomized data to read out and sell it in the space. But it 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. I'll just -- I'll ask it if 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. And on the second one, probably 3 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 2 arms. Also, we believe, I think as Dr. Tabernero mentioned, the first study to enroll patients that also had -- that had in HER2 and/or checkpoint exposure. And so this is truly I think, a first in that space as well. And so I think against that context and what is a very high bar. I think the second point I'd make is the fact that we showed a 30% delta versus control. We believe and have spoken to many of you about what we see as relevant and the big clinicians certainly felt that a 10% delta versus control and this rigorous setting would be a win. So obviously, very excited to see essentially triple that. And then last, then I'll have Sophia weigh in on this as well. But I think if you look at the RAINBOW study, which is the regulatory benchmark at 28%, 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 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?

Yes. No. I think what you're saying is absolutely right. And I think what ASPEN-06 brings here is the rigor of randomization, which is really important and is something that is expected by the field, by us, by the regulators to really be able to characterize the contribution of effect and then also just proof of concept with historical activity. I think the HER [ RAM ] study, 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 5 sites. Again, slightly different population, as Jason mentioned, in terms of some of the current standards that are available for patients such as in HER2. So I think 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 ASPEN-06 what you have is the key elements of a well-conducted study, meeting the randomization, the global patient population and the size. Hopefully, that helps.

Your next question comes from the line of Li Watsek of Cantor Fitzgerald.

Congrats on the data. Exciting day for CD47. Maybe just a couple from this. Just curious about the next steps with FDA. Can you offer any thoughts on a potentially accelerated approval pathway based on the strong interim data? Also, do you have any plan to apply for [ birth ] through definition?

Great. Thanks, Li. I appreciate the question. Certainly, something we've been talking about as a team. I think the beauty of this design here is it is a Phase II and Phase III design that we've discussed and I think have alignment with the agency on. And I think you pointed out the options here. I mean, obviously, it will be data dependent and dependent on the FDA review, but randomized data of this sort, given the unmet need, certainly, I think, is something that we would explore in terms of breakthrough designation with the agency. Again, yes, very excited about it. And I think it's a pretty clear signal. Sophia, anything you want to add there on the regulatory front?

Yes. Just that is 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 strength of the data, the final analysis definitely will be interacting with the health authority.

Okay. And maybe another one for the doctor. Can you just talk about how this regimen kind of fitting to the current treatment landscape? And how would you sequence on HER2 versus [ IPSA ]?

Dr. Tabernero, do you want to take that one?

Yes, absolutely. Thank you for the question because it's really very relevant. So obviously, this is an interim analysis, where the board overall response rate and the duration of response will favors this possible combination of Evorpacept TRP compared to TRP. And of course, in here, actually, as you know, for the time being, the continuation of trastuzumab on 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 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 granted the approval by the FDA and the positive consideration by CHMP at the European level. But remind that this is a study, where most of the patients having included in the third-line setting. So for the time being and looking at the rate we have seen in the preliminary data, we have seen ASPEN-06 study. I think that the continuation of this in the Phase III portion actually could define, whether the combination of Evorpacept plus TRP is superior to -- sorry, the combination of Evorpacept trastuzumab TRP is superior to Paclitaxel and Ramucirumub, 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 going to be administered in the first-line setting or the standard of care right now, the combination of cisplatin, [ V 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 mining antibody that shows superior activity, when add to the standard of care, #1. And actually, we don't see the slight effect that we have seen with previous CD47 directed antibodies.

Your next question comes from the line of Colin Bristow of UBS.

Congrats on the data. A few questions from our side. Maybe we'll start with just how do you view the profile of the Evorpacept combo in this setting versus what we've seen from in HER2. Secondly, could you tell us what the stratification that has worked with this study. And then finally, just on the AE side, there is a slight imbalance on grade 4A. So I just wondering if you could characterize those for us.

Sure. On the HER2 comparator, I think the DESTINY-Gastric-01 study, the randomized Phase II that they conducted, achieved an ORR of 41%. So again, 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 in HER2 world, so to speak, which just hasn't been studied as much. So that's how we're viewing in HER2. Sophia, do you want to add anything there?

Yes. And in terms of the -- if I caught the question as well in terms of the adverse event profile for in HER2's versus the profile that we're seeing in ASPEN-06. Certainly, 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 events slide, that we showed that the adverse events were very -- were 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 HER2 itself, obviously, there are serious side effects in terms of Interstitial lung disease. There's even been mortality associated with it. So, I think having a safe regimen like what -- or a tolerable regimen like what we've seen to date in the study is very advantageous.

And on the stratification factors?

Yes. 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.

I just want to add. 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 2 arms is that 1 received Evorpacept and the other didn't. So I think we feel good about that.

Your next question comes from the line of Michael Yee of Jefferies.

Let me be the first to congratulate you. I think it's worth -- congratulations. So congratulations to Sophia and Jason, nice to step into that as your first call. Maybe just 2 questions. One was a clarification on the balances of the 2 arms of the study. I know Jason, just sort of clarified he feels comfortable, but just to be clear. There are no answers today on necessarily the balance of second and third line and in HER2 prior failed in HER2 in either arm or you're just saying that you feel good that those 2 are balanced. That's question one. And then question 2 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 I just wanted to try and triangulate your thoughts about comparing this to RAINBOW.

Sure. So I think on the randomization front, I think just to highlight what was said in the presentation. Again, I think the demographics are fairly balanced, if anything, I think, slightly tilted against EVO in some ways. But I think 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 in HER2 or a check point. 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.