Merus N.V.

Today we will be taking you through the phase two interim clinical data of Pedosumptomab with Pembrolizumab and first-line recurrent metastatic head and neck scleromastinal carcinoma. This will include the data in the abstract published today on the American Society of Clinical Oncology, or ASCO's, website, as well as a summary of the data included in the poster presentation scheduled for Monday, June 2nd at the ASCO annual meeting in Chicago. This presentation is available on the investors and media page of our website. On this call, we will also make certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about our future expectations and plans, and events and circumstances, including about finances, intellectual property, projections about Maris' clinical development for 2025 and beyond, and the timing for plans and for meeting clinical and regulatory anticipated milestones related to Pedosumptomab and our other biconics candidates. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Maris' filings with the United States Securities and Exchange Commission, including its Form 10-Q for the ended March 31st, 2025, which we filed with the SEC on May 7th, 2025. Maris does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise in less required to do so by law. Leading us through the agenda will be Dr. Bill Lundberg, Chief Executive Officer, Dr. Fabian Zorin, Chief Medical Officer, Peter Silverman, Chief Operating Officer in General Counsel, and Shannon Campbell, Chief Commercial Officer.

Good afternoon from Boston. This

is an exciting time for Maris. Today's call will focus on the updated interim data for Pedosumptomab in combination with Pembrolizumab, or PEMBRO, as first-line therapy for -L1-positive recurrent metastatic head and neck cancer. We will discuss data which will also be presented at the ASCO 2025 Annual Meeting on June 2. Let me begin by providing a few remarks about our company and foundational technology platform that led to the generation of Pedosumptomab and our other clinical stage assets. Maris is an oncology-focused company with clinical assets of our own and multiple others we developed with our collaborators and licensees. We're also quite proud to have received our first approval by the U.S. FDA for Bizangri last year. We believe this not only validates our innovative technology platforms, it also demonstrates our strong capabilities in oncology drug development and execution. We've been innovators in the field of multi-specific antibodies for over a decade with our proprietary bi-clonics and triclonics antibody platforms that allow us to make multi-specific antibodies like monoclonal antibodies. A single cell produces essentially a single multi-specific antibody. This allows us to leverage the decades of experience making successful medicines from monoclonal antibodies, including high-throughput screens allowing biology to drive selection molecules, manufacturability, large-scale production from single producer cell lines, and the ability to rely upon tried and true CMC providers. And as fully human IgG1, our molecules are designed to have predictable in vivo behavior, low immunogenicity, and consistent half-life, and can involve the FC domain engineering like ADCC enhancement for stealth silencing for T-cell engagers. As well as compatibility for the generation of selective and potent antibody drug conjugates, or ADCs. These are powerful technology platforms, and while they don't guarantee success in the clinic, we believe by following tried and true approaches and reducing risk each step of the way, it can give us a better chance of being successful. Importantly, as the inventors of both our platform technologies and our clinical assets, we have an extensive and robust intellectual property patent estate covering our work. We used our Biconics platform to address both growth and survival signals of cancer cells. We generated a large and diverse library of approximately 500 bi-specific antibodies, where each antibody targeted an EGFR family member on one arm, and a Wnt pathway signaling molecule on the other arm. As shown in this cartoon, we evaluated this bi-specific antibody library for the ability to potently inhibit the growth of cancer derived as compared to normal tissue derived organoids, and more effectively than EGFR inhibition alone with cetustumab. From this work, we selected pedosemtumab, which binds with one arm to the well-established cancer target EGFR, and with the other arm, this new target called LGR5. We believe pedosemtumab acts through three distinct mechanisms. As shown on the left panel, pedosemtumab targets the well-established cancer antigen EGFR through the well-established cancer gene to prevent EGFR ligand binding and growth signaling. The other arm targets LGR5. LGR5 is a protein expressed on normal adult tissue stem cells and stem cell-like cells within a cancer, and is reported to be upregulated in a number of cancer types, including head and neck, colorectal, and other cancers. We have also observed an unexpected result shown in the middle panel. LGR5 acts by reducing the expression of certain proteins through internalization and degradation. In the presence of pedosemtumab, LGR5 also brings EGFR into the cell for degradation, essentially removing it from the cell. Finally, as shown on the panel on the right, pedosemtumab is ADCC-enhanced, designed to provide full engagement of the patient's own immune system against the cancer. This may be particularly relevant when combined with other immune-mediated mechanisms, for example, when blocking the PD-1 T cell checkpoint with PEMBRO. We've also observed that blocking EGFR itself with pedosemtumab leads to increased expression of LGR5, which in turn may result in an even greater effect. Targeting LGR5 along with EGFR is a wholly new approach to cancer therapy, with promise to become a robust and potent way to treat cancer. For those interested, I would refer you

to the publications cited on this slide. We continue to have high confidence in pedosemtumab.

We believe pedosemtumab is significantly de-risked with a high chance of success to become the standard of care in recurrent metastatic head and neck cancer for two important reasons. First is the compelling strength and consistency of the efficacy data and favorable safety, which we believe is the strongest clinical profile of any approved or experimental drug shown to date in this clinical setting across the clinically relevant patient populations, which Fabian will discuss with you shortly.

And the second

reason is our company's ability to execute time and time again. With our first FDA drug approval by Zangri late last year, our regulatory success with pedosemtumab, receiving two breakthrough therapy designations, completing the Project Optimist dose selection, aligning on Phase III trial designs, and the potential for accelerated approval for both trials under the Project Frontrunner framework. Our timely and consistent clinical presentations, most recently at ASCO 2024 and ESMO Asia 2024, and now the data to be presented at ASCO 2025. And most importantly, execution on both of our Phase III clinical trials, where we are continuing to accelerate startup and enrollment, giving us very high confidence that both trials will be substantially enrolled by the end of this year. I'm incredibly proud of our own Merit teams who continue to discover and develop outstanding bi-specific and multi-specific antibodies based on our innovative and proprietary multiclinic technology platforms. This continues to be a real story of innovation and success, and ultimately to execute on our mission of bringing new important medicines to patients with cancer. I'll now turn the call over to our CMO, Fabian Zorin, to discuss the prior clinical data for pedosemtumab, and then walk you through the very exciting new results, which will be presented

at ASCO 2025. Thank you,

Bill. Good afternoon to everyone on the call. It is an absolute pleasure to be with you today and share our latest exciting data. First, let me remind everyone of the pedosemtumab results we have previously presented. At ASMO Asia last year, we shared data on pedosemtumab monotherapy at 1,500 milligrams every two weeks in 75 efficacy-evaluated patients with second-line plus recurrent metastatic head and neck squamous bowel cancer. This presentation included approximately 30 more patients than we previously presented at ACR 2023. The confirmed overall response rate remained consistent with the larger sample size at 36%, and we continued to observe responses in patients with HPV-related cancer. The median duration of response was 6.2 months. Median progression-free survival was 4.9 months, and the median overall survival was 11.4 months. These monotherapy results are impressive. The efficacy seen with pedosemtumab as a single agent compares very favorably against available treatment in this setting. Pedosemtumab's proven monotherapy in head and neck cancer remains the foundation of our clinical development efforts. The safety profile of pedosemtumab monotherapy now in 82 patients and with extended follow-up continues to be favorable. Pedosemtumab has been well tolerated and observed thus far to have lower and less severe skin toxicity and gastrointestinal side effects compared to other EGFR-directed antibody therapies. Our updated infusion protocol resulted in significantly reduced incidence of treatment emerging at birth events associated with infusion-related reactions in the overall population. In summary, no new safety signals have been identified for pedosemtumab in the larger patient cohort and with extended follow-up, and the safety profile of pedosemtumab remains manageable and well tolerated. At ESCO 2024, we presented the first interim data on pedosemtumab in combination with pembrolizumab in the first line setting. The data cutoff date was March 6, 2024. At that time, a total of 45 patients had received at least one dose of pedosemtumab alongside pembrolizumab, making up the safety population. Conficiency data were reported for 24 patients. Overall, 67% or 16 of 24 patients responded, including one patient with a complete response. Responses were observed across HPV subgroups and across PDL-1 expression levels. This was an early look at the data with a median follow-up of 3.6 months, so -to-event endpoints were not estimated. The combination was well tolerated, and no significant overlapping toxicities with pembrolizumab were observed. Following this brief recap, I'm now excited to share the latest data from our ongoing Phase II trial of pedosemtumab plus pembrolizumab in first line, PDL-1 positive recurrent metastatic head and neck cancer. I encourage all of you to see the full presentation of these data that will be provided by Professor von Herpen on June 2nd

in the session on head and neck cancer. Illigible patients had PDL-1 positive head

and neck sprain cell cancer that was treatment naive in the recurrent metastatic setting. An ECoC performance data of 0 or 1 and measurable disease per Rhesus 1.1 criteria. All patients received pedosemtumab at 1500 mg IV biweekly alongside pembrolizumab at 400 mg IV every six weeks. Treatment was continued until disease progression or unacceptable toxicity. Tumor assessments were conducted every eight weeks. The primary endpoint was overall response rate by investigator assessment and key secondary endpoints included duration of response, progression free survival and overall survival. For these new data presented at ESCO 2025, the data cutoff date is February 27, 2025. The median follow-up was 14.3 months. Out of the 45 patients enrolled in the trial, 43 were invaluable for efficacy. The baseline demographics and disease characteristics of patients involved in our Phase 2 trial were representative of recurrent metastatic head and neck cancer. The median age of participants was 64 years. Most patients were male, 78 percent, and had an ECoC performance data score of 1, 64 percent. There was a typical anatomical distribution of the primary tumor location among this cohort, and all patients had PDL1-positive disease. The proportion of patients with P16-positive disease was 18 percent, or eight out of 45 patients. The patient disposition shown in the right chart includes data from all 45 patients. At a median follow-up of 14.3 months, 31 patients, 69 percent, had discontinued treatment, while 14, 31 percent, continued therapy. The median duration of exposure to Peter's symptomat was 8.3 months, with a mean of 8.7 months, as of the data cutoff date. This slide shows the overall summary of safety for Peter's symptomat plus pembrolizumab. The table on the right provides the summary of treatment emerging adverse events, regardless of causality, for all grades, and grades greater or equal to three in all 45 patients treated with Peter's symptomat plus pembrolizumab. No significant overlapping toxicities were identified, and the combination continues to be well tolerated in this patient population. In particular, I believe EGFR antibody-associated adverse events, including skin toxicities such as acne form rash and gastrointestinal events, continued to look more favorable with lower rate and severity with Peter's symptomat plus pembrolizumab, then observed with approved monoclonal EGFR-directed antibody therapy. 38 percent of patients reported treatment emerging adverse events associated with infusion-related reactions, of which 7 percent were reported, were reported in grade 3, with no grade 4 or 5 events reported. Infusion-related reactions mainly occurred during the first infusion, all resolved, and our updated infusion protocol has continued to be effective. No related grade 5 treatment emerging adverse events were reported. In conclusion, no new safety signals have been identified for Peter's symptomat, and the safety profile of Peter's symptomat in combination with pembrolizumab remains manageable and well tolerated. The primary efficacy endpoint of this trial was overall response rate by investigator assessment using RISIS 1.1 criteria. I'm delighted to report that the confirmed overall response rate for Peter's symptomat plus pembrolizumab continues to be compelling with the addition of 19 more patients. Overall, 63 percent or 27 out of 43 patients responded. The 95 percent confidence interval indicates that the lower bound of the treatment effect of Peter's symptomat plus pembrolizumab is 49 percent. This is significantly higher than the historical response rate of 19 percent for pembrolizumab monotherapy, and even the 37 percent for pembrolizumab combined with standard of care chemotherapy in the CPS greater or equal to one population. With increased follow-up, we also observed evidence for a deepening of the responses with continued treatment with six of the 27 respondents now achieving a confirmed complete response. Responses were observed across HPV and PD-L1 subgroups. Among eight patients with HPV-related cancer, four responded. The median time to response remains fast with 1.9 months, and the median duration of response was not reached. At the time of the data cutoff, 14 respondents continued on therapy. Progression-free survival and overall survival were secondary efficacy endpoints in our trial. The Kaplan-Neyer estimate for median progression-free survival was nine months. A total of 15 patients remained censored without a PFS event. This is approximately three times longer than the median progression-free survival reported in historical studies of pembrolizumab alone in this patient population. The median overall survival was not reached at the time of the data cutoff. Only 13 OS events have been reported, and 30 patients were alive and in survival follow-up. The overall survival rate at 12 months was 79%. I believe the 12-month survival rate is an early predictor of long-term overall survival. While interpreting -to-event endpoints in single-arm trials and with cross-trial comparisons can be challenging, the addition of pitosemtumab to pembrolizumab resulted in an overall survival rate at 12 months of 79%, which is dramatically higher than the 12-month rate of 51% reported in the historical Keynote 48 registration trial for pembrolizumab monotherapy. I want to emphasize several key points regarding this data update, which greatly enhance our confidence that the observed clinical activity with pitosemtumab plus pembrolizumab is likely predicted of meaningful clinical benefits for patients. First, this update confirms the significant impact of pitosemtumab combined with pembrolizumab on the overall response rate in a larger population of 43 patients. Second, the absolute and relative magnitude of the ORR improvement remains significant with a confirmed response rate of 63% across the total population and a confirmed response rate of 66% in 35 HPV-negative patients. Importantly, because many of you have asked about smoking status, when we analyzed the responses seen with pitosemtumab across the program, including both first and second line treatment, we see that two-thirds of the responses with pitosemtumab in HPV-associated cancer actually occurred in never smokers, which we believe clearly refutes the smoking hypothesis and further underscores the differentiated activity of our drug. Third, there is a strong internal consistency of the treatment effect not just on one, but across multiple key efficacy endpoints in our data, including endpoints relevant for regulatory approval, such as overall response rate, duration of response, and overall survival. Median PFS was observed to be nine months, and the 12-month survival rate was 79%. In my opinion, adding pitosemtumab to pembrolizumab provides dramatically greater efficacy compared to the historical efficacy observed for pembrolizumab alone in this setting. And I believe these results greatly increase the probability of technical success for our Phase III registration trial. Fourth, pitosemtumab continues to demonstrate a favorable safety profile with no significant overlapping toxicities in combination with pembrolizumab, and no new safety signals have been observed. With such important results, we feel responsible for ensuring timely and effective clinical development to bring pitosemtumab to patients as quickly as possible. Our Chief Operating Officer, Peter Silverman, will now discuss our ongoing Phase III registration trial.

Thanks, Avian. And yet, with the combination of excellent activity we're observing, broad key opinion leader enthusiasm, strong support from the academic community, high degree of investigator engagement, and our effective execution, we've been very successful across each of our geographies and site activations. As you know, registration trial enrollment is limited by the number of active sites. A key performance indicator of success is site and country activation. Once sites reach a critical number, then one can expect enrollment to accelerate dramatically. And here, we're firing on all cylinders. Each of our Phase III trials now has more than 120 sites open, and we're within striking distance of having all the sites we believe we need to timely complete enrollment of both clinical studies. We remain confident in our view that we should be substantially enrolled in both of our Phase III registration trials by the end of 2025. With this execution, we're rapidly advancing from a late-stage clinical company to now having a line of sites becoming a potential commercial-stage company, and we couldn't be more excited. At Marist, we have a strong patent estate covering our platform technology, pedosensimab composition of matter, and related intellectual property. Pedosensimab is a highly innovative multi-clonic antibody, the first of its kind targeting the novel combination of EGFR and LGR5. It was generated by Marist based on our own proprietary platform technology. Incorporating our patented heterodimerization technology, novel format with binding domains produced by our patented common light chain transgenic animal we call NEMO, which stands for Marist mouse. We also have filed additional patent applications well beyond the composition of matter to protect our franchise assets. We have applications directed to methods of treatment, combination therapy, formulation, and administration of pedosensimab, among other subject matter, with any future patents that may issue from these potentially extending exclusivity well beyond 2040. We are quite proud of our history of innovation at Marist. Our Chief Commercial Officer Shannon will now discuss the opportunity of pedosensimab in head and neck cancer and beyond.

The head and neck cancer market is a large and growing opportunity. It's the sixth most common cancer. In the first line setting, around 55,000 patients are treated globally, with 17,000 in the U.S. In later line settings, we estimate approximately 22,000 patients are treated globally each year. As the commercial lead at Marist, I regularly speak with clinicians to understand their needs and perspectives on the diseases we target. What I'm hearing again and again is that head and neck cancer is still a devastating disease in an area of significant unmet medical need, including the first line setting, where median survival based on the keynote 048 study is still only about a year for pembrolizumab alone or in combination with chemotherapy. For clinicians, for patients and their families, this simply isn't good enough. Doctors are looking for innovative new treatments that provide the opportunity for more patients to achieve meaningful clinical responses and longer survival. We believe the compelling clinical activity of pitosensimab and recurrent metastatic head and neck cancer we've now shown across multiple data sets confirms pitosensimab's blockbuster potential and offers the opportunity for a new first and best in class chemo free standard of care that could very well be practice changing. The head and neck cancer market is estimated to be around $4 billion in 2024, and we believe this opportunity may be further expanded by a medicine offering far higher response rates and more durable responses with longer time on therapy. We are incredibly excited about the opportunity for pitosensimab for patients with recurrent metastatic head and neck cancer. We also believe there may be important additional opportunities in earlier stages of head and neck and metastatic colorectal and in other cancer types. I'll now turn the call back to Bill.

For those of you who know me, I'm

a medical oncologist at heart. My ambition is to bring truly meaningful medicines to patients with cancer, and that's our mission here at Marist, floating in on cancer. Now today with pitosensimab, we have that opportunity. By combining EGFR and LGR5 targeting, pitosensimab may represent a wholly new way to treat cancer. Our lead indication, recurrent metastatic head and neck cancer, is a large and growing opportunity with high unmet needs, and we believe there are meaningful opportunities in metastatic colorectal cancer and other indications. We now view pitosensimab as substantially derisked with a high probability of technical and regulatory success and a high probability of meeting the needs of the entire recurrent metastatic PDL1 positive first-line market. We're full speed ahead, executing well, accelerating site activation and enrollment, and are increasingly confident that both Phase III registration trials will be substantially enrolled by year end. And based on our remarkable progress today, I can share with you that we expect to provide top-line readout of one or both Phase III registration trials in 2026. We believe that among all approved or experimental therapies for first-line recurrent metastatic head and neck cancer, our Phase II interim data of pitosensimab with pembrolizumab demonstrates the strongest efficacy, safety, patient convenience, and commercial attractiveness, and is substantially far along in terms of the timeline to potential approval. I think you can hear our excitement that pitosensimab has the opportunity to become both best in class and first to market as the new chemo-free standard of care for patients with recurrent metastatic head and neck cancer and beyond. Thank you for joining us this afternoon. For MIRAS, creating novel, multi-specific antibody medicines is our core competency. I'm proud of the progress we're making towards our ambition to close in on cancer. I'll

now turn the call back to the operator for questions.

Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. And again, please note that each participant will only be

allowed one question. The first question comes from Tazin Aman from Bank of America. Please go ahead. Can you hear me now? I think I was muted.

Yes, Tazin.

Sorry about that. Congrats on your update and on the strong data. I maybe wanted to follow up on the HPV positive status patients. In this latest update, you have four out of eight responding. Can you just talk about that response compared to what you showed last year with a few more patients this year versus last year, and how you're thinking about what to expect in terms of response rates in your pivotal study, where you've indicated that HPV positive patients should be enrolled? Thanks.

Thanks, Tazin, for the question. I think what we're seeing already in the overall population, including both in the HPV negative and HPV positive populations, is a dramatic and almost unprecedented high rate of responses. And again, this includes all the patients. And this proportion of HPV positive patients in this cohort is about what we would expect in or about what's been seen historically in Phase III randomized trials. And, you know, with that strong signal overall, continuing to be strong in an even larger population, we continue to have confidence in including and enrolling the entire population of patients, which is the strategy that registration trials and programs have had in head and neck cancer for at least the past five registration directed trials.

Next question.

Our next question comes from Andrew Burns from D-Ring Partners. Please go ahead.

Hi. Thanks, and congrats on the data. I guess we shouldn't have been nervous into the update, but congrats. I wanted to see if you could give us some color on the durability metrics and the time to event metrics broken out by HPV status, please.

Yeah, thanks for the question. So I can provide some comments, and David can provide a little bit of color as well. You know, one of the challenges we have in analyzing the data broken out by HPV plus minus is it really becomes an unplanned retrospective subset analysis. And we start to get down to very small numbers of patients, you know, where there are only eight patients in the HPV plus category making very wide confidence intervals for this unplanned retrospective analysis. So that's obviously a consideration. A second consideration is that we don't really have any good data to compare those different subsets to because we don't have a historical comparison data set with which to know what it might look like for Catruda alone. Having shared those two comments, I'll ask Fabian to provide a little bit of color on our experience. Yeah, thanks, Bill. The

additional comment that I can make that helps a little bit is probably we have shown obviously numerically higher ORR in the HPV negative population and also the median progression free survival was longer in the HPV negative population. However, the 12 months or S-rays very, very comparable, almost similar across the two subsets.

And with these types of analyses, you could imagine with smaller numbers, one might expect the confidence intervals to be overlapping. Next question.

Our next question comes from Charles from LifeSite Capital. Please go ahead.

Hello, good evening. Thank you for providing this update, for taking our questions and congratulations on the data. And also thank you for showing us what BTT looks like. As we know in head and neck cancer regimens containing PD-1, we often see a tail effect on these time to event endpoints. Just given the shape of your Kaplan-Meier curves, can you comment on whether or not you think we're starting to see that effect at minimum one year follow up and if we could expect that plateau to continue extending in potentially prolonged fashion? Thank you.

Thanks for your comments. And yes, we have been, had previously been intimating about the importance of very strong data to be able to receive breakthrough therapy designation from the FDA, especially in combination in what was an unprecedented granting of breakthrough therapy in this setting by the oncology division at the FDA. You're asking about, you know, we know with Pembrolizumab there's around 20 to 25% long-term response rate in those patients. And, you know, I think what we've shown you is the curves with the data that we have now. We know that we're seeing approximately triple the response, triple the median PFS and 30% more patients alive at the landmark 12 month OS response rate, all as compared to the previous one. And we've gone to the historical Pembrolizumab approval trial, fully acknowledging all the limitations of single arm cross trial comparisons. It's hard for us to try to make any firm comments further on because you can see where the patients are censored, but we would leave it to you to interpolate or evaluate further. We do believe we're clearly seeing a much higher response rate and a much more shallow sloping of the overall survival curve already, but we leave it to you to make further interpretations. Next question.

Our next question comes from Mario Raycroft, Jeffreys. Please go ahead.

Hi, congrats on the great data and thanks for taking my question. Fabian mentioned the predictive value of what you're saying. Can you just talk more about confidence intervals for your 12 month OS and where you think you're tracking toward on median OS? I'm just wondering if you can leverage these data to enhance enrollment even more than what you're at right now or do you think you're already at kind of the maximum enrollment rate?

Yeah, I can provide a little bit of color on the 79% OS rate at 12 months and Fabian perhaps can provide a little bit of color on the clinical trial progress, both state startup and enrollment. With respect to the 79% survival at 12 months, from our review of the literature and head and neck cancer, that's just unprecedented. We're not aware of any substantive data set in this setting that has both such a high survival rate at 12 months and such a high delta from where a historical control marker is. It really speaks to the potential that we believe that if these Phase III findings replicate the Phase II experience, the addition of -Semtimab-Tepembra is likely to be transformational in the frontline treatment of PD-L1 positive head and neck cancer. Given the continued high on-med need and potential magnitude of improvement versus currently available standard of care. Let me now invite Fabian to make some comments on clinical trial progress.

Yeah, we are very pleased with the progress in study startup. We have on both of our studies, you know, over 120 sites activated. And, you know, I think we keep very firm to our previous prediction that we look for substantially enrolled trials towards the end of this year.

Next question. Our next question comes

from Evan Sigerman from BMO Capital Markets. Please go ahead.

Hi, guys. Thank you so much for taking my question and congrats on the data. So what I see language that says substantially enrolled on Phase III trial by the end of the year, that says to me, you know, the potential for accelerated approval using this data set. Is that a fair interpretation that you may be able to use this very strong data to secure accelerated approval ahead of a pivotal trial readout in 2026?

Thanks for the question, Evan. Guys, as we've been pretty clear about over the past number of months, we do believe that there's a real opportunity both in the first line setting that we're talking about today and in the second line setting for there to be a potential accelerated approval based on an early endpoint such as ORR with confirmation coming from survival in the same setting. And as you know, the two efficacy endpoints are ORR and overall survival in both registration trials. I would say that we've also been clear about a couple of other things. The first is that ORR to the FDA means confirmed. And the second thing is that to the FDA, they've always referred to whether these responses are durable and historically the durability metric for accelerated approval data sets has been, you know, the FDA has never said, but we've looked at other approvals where six months has been around a number that the FDA has commented on previously. And then lastly, the FDA has commented on wanting to be able to take a quick look at overall survival and just get a sense or something like overall survival and get a sense of trending in the right direction. And so all three of these are important components on what a potential accelerated approval data set could provide in this context. Even with these three criteria, we're sufficiently pleased with the progress we've been making with the registration on trials that we're now guiding potential top line readout for one or both of the Phase 3 trials in 2026. Next question.

Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead.

Hey, thanks for taking my questions. And yeah, congrats on this great Phase 2 data update. I had a bigger picture question. So we've seen recently data at ACR from Merck's keynote 689 study and there's a similar trial with the DIVO at ASCO in the atuant setting and so of a PD-1 inhibitor. So my question is, you know, with this data today in hand and fairly high certainty on possible success in Phase 3 for pedosympathetic map in the metastatic setting, I guess how high is the bar for you to potentially committing to initiating an atuant head and neck cancer study with pedosympathetic map? Thanks so much.

Thanks, Michael, for the question. So the keynote 689 study that read out at ACR this year demonstrated a prolongation of event free survival or time prolongation of time before patients cancers recurred following surgery. If the patient's peri-surgical treatment also included Pembrolizumab or Catruda, there's similar data in a much smaller data set for Opdivo in the setting of combined modality treatment for local disease. It is an area we're particularly interested in, especially because we now know we can combine pedosympathetic map with Pembrolizumab quite safely and we do view the locally advanced commercial opportunity as substantial. We haven't provided any specific guidance on what it would take for us to trigger a specific clinical trial in this setting. And as you know, I've said many times, it's critically important for us to maintain focus and execution on our two Phase 3 registration trials. It's paramount importance for us as a small company, but it does represent, we believe, an increasingly attractive and promising opportunity to be able to address larger patient population, many of whom could benefit in this setting if Pedsimptomab continues to provide benefit to Pembrolizumab in the locally advanced setting as well. Next question.

Our next question comes from Tara VanProf from TD Cowan. Please go ahead.

Hi, good evening and thanks for taking the questions. So I was hoping you could tell us more about how you determine censoring of the pages for the 12-month OS rate, like who was excluded and why and how did this impact the outcome? Thanks so much.

Thank you, Tara. Probably the best person to comment on analysis of large data sets in this setting is Fabian, our chief medical officer who has thousands of experience in Phase 3 registration trials and solid tumor oncology. He can talk about the curves and the 79% overall survival at 12 months.

I would say the importance is that you have a follow-up that includes one year for each of the patients that you are reporting and that you have essentially a survival status close to the time of the data cutoff, which is called a survival sweep. That allows you to actually report true survival statuses of all of these patients. That allows you also to make a statement as we did that the 30 patients without an event are alive and ongoing at the time of the data cut.

And Tara, you can look at the curves that we have provided in the presentation and you can actually count and identify all the patients. There are nine patients who died prior to the 12-month mark and that leads us to the 79% mark. And then following the 12-month mark is where there are patients who may be censored because they're still alive and ongoing and many of them are actually still on treatment. So it's very clear from that graph that there are no patients censored prior to the 12-month mark. It is a mature 79% data point. Next question.

Our next question comes from Amy from Needham. Please go ahead.

Hi, good evening. Congratulations on the data and thanks for taking my question. Just on the smoking status, the comments that you made of the four responders that were HPV positive, can you clarify how many of those were never smokers? And just more broadly, as we think about the commercial setting, how do you see PETA compete in the HPV negative population, particularly with some of the competitor data that has emerged, particularly from Vicaro? Thank you.

So thank you for the question regarding smoking status. I just want to point out that one of the most negative prognostic factors for head and neck cancer is actually whether the patient smokes. It's not a good thing. And there has been some conjecture that paradoxically somehow smoking helped the HPV positive disease patients be more responsive to treatment like the HPV negative patients. And as I've been saying for a long time now, this is nonsense. It's just not true. It's a claim based on misinformation promulgated by others. But let me be clear, across our first line and our second line plus data sets that we've provided over the past five months, two thirds of the HPV positive responders were never smokers. Smoking didn't cause their responses to happen. Smoking doesn't cause responses to happen in HPV positive head and neck cancer, especially to EGFR agents. It's just not true, especially for PETA symptomab and pembrolizumab. Next question.

Our next question comes from Eva Fortina from Wells Fargo. Please go ahead.

Thanks for taking our question and congrats on the data. A quick one from us. So for the Phase 3 Registrational Studies and following up on a previous question, in terms of the data required for accelerated approval, can you remind us, do you need to provide data for all patients expected to enroll in the first line study, which if I recall correctly, it's around 500 or just a subset? And also, does the FDA require the same amount of data for like first line and second line studies? Or are there any differences there? Thanks.

I'll provide a little bit of color and I can ask maybe in the comment as well. The way we've answered the number of patients for an accelerated approval readout, we clearly have a statistical analysis plan, but we haven't provided the granular details of the statistical analysis plan. What I have said is in this context, overall response rate, if we were to include all the patients enrolled in the trial, the trial would be vastly, vastly overpowered. I've also pointed to the breakwater trial as a trial that recently received accelerated approval under the Project Frontrunner Format or guidance, which is the format that we are also, the construct that we are also following. And in that trial, the approval, accelerated approval was based on overall response rate from 110 patients per arm. And that's a similarly sized overall size trial. Regarding whether the, perhaps Fabian would be the better person to comment on, regarding whether the FDA would require both the first line trial data set and the second line trial data set in terms of contemplating accelerated approval for either one.

Yeah, I don't think that you need both studies at the same time, but what I would say is if you have one positive study, then there might be an opportunity for an acceleration to the approval actually on the second study, because once you have proven a survival essentially signal in an indication, that's the point in time where you can start asking for probably a more aggressive call from the FDA. Next question.

Our next question comes from Astika Gunnewarden from Tourist Securities. Please go ahead.

Hey guys, thanks for taking my question and congrats. I'll add my congratulations to this exceptional data here. Just wanted to double click on something. The survival benefit, the survival data here looks really encouraging. Can you really comment on whether the patients going on subsequent therapy on progression was similar to LEAP-10 and Keynote 48? Thanks guys.

So thanks for the question, Astika. What we've provided today is essentially the data and the information that's in the clinical presentation that will be at PASCO. And we want to be careful to focus on that presentation. In general, I can tell you that there hasn't really been any innovation in second and third line therapies in head and neck cancer since the Keynote 048 and the LEAP-10 trials. So one would imagine that the subsequent therapies would be generally quite similar. Your question does raise an interesting point that we've speculated about internally here, which is the experience of the LEAP-10 trial of LENVA showed us that a very toxic medicine that could provide responses early was also sufficiently toxic that it led to inferior survival. And whether there's an opportunity for a medicine like pedosyptomab with PEMBRO where the safety profile is substantially better and it seems to be based on the data so far to be a much more well tolerated medicine, whether that could even in the more favorable safety benefit in addition to the responses seen provide some benefit long term to patients in terms of being able to go on additional therapies. Next question.

Our next question comes from Yigal Machalovitz from CDGlobe. Please go ahead.

Hi, Bill and team. I just had a question on the complete responses and the swimmer's plot. Could you just comment with the six CRs, how many of those were new among the additional patients that you're showing and how many of those were incremental people that were PRs that converted to CRs?

I think I can ask saving the comment on what was new versus what was seen previously in the clinical data set.

So

in the previous

data set at ESCO 2024, we presented a single CR. Now we have six CRs. Of these six CRs, two occurred at the first disease assessment and four CRs essentially occurred after a PR or SD.

And I'll add that it's the nature of solid tumor oncology trials that patients don't hit their best mark on the very first scan. Patients tend to continue to develop benefit over time for most oncology solid tumor drugs. So we're not surprised with this. And again, this is a look with only a median of 14 months follow up. So, you know, we continue to follow the patients and continue to look for a deepening of response. But we believe that's a characteristic in solid tumor oncology trials in general. Next question.

Our next question comes from Rich Laws from Goldman Sachs. Please go ahead.

Hey guys, good evening and great to see you. Good day to head of ESCO. How would you compare the phase three patients being enrolled to the patient baseline in the phase two study? And also, is your goal to maintain a very consistent patient population between phase three to what you show in phase two on that 58% CPS grid in 20 and then the 36% ECOT zero and also the P16 status?

I can ask Fabian to comment on the focus of the phase three trial and similarity to this phase two population. But first, let me make a comment, a general comment, which is, you know, for those of us who've grown up on the R&D side and running clinical trials, the number of times that you learn again and again not to make changes between phase two and phase three just seems like we keep learning that lesson. And again and again, it's a paramount importance to try to keep things the same between phase two and phase three. Fabian can provide color on this.

Yeah, the additional importance for phase three is to essentially balance your prognostic factors. So P16, CPS greater 20 and the ECOT performance status, you know, to balance them across the treatment arms by stratified randomization.

Next question.

Our next question comes from David D from UBS. Please go ahead.

Great, thanks guys. And I also want to add my congratulations on this great data here. Just a couple from me. One is just how are you thinking about this data compared to some of the competitors like, you know, like the KERA data, which was presented today. And then secondly, how do you think this data can be through into your colorectal cancer data, which should be expected sometime later this year or next year?

I'm going to leave the harder question of read through to colorectal for Fabian who can comment on that second. I'll comment on just how we view this data. I mean, I think, you know, it's exceptionally hard to make comparisons between our results and a retrospectively highly selected subset in a different population of patients where we really have only been talking about one efficacy endpoint while ignoring all the others. I'm not sure what that would tell you. I think the better comparison is to compare our results to the overall population of competitors and look at all the endpoints in the broader phase two populations, not simply to one post-hoc retrospectively selected data point. And again, you know, we think these data for Peta-Semtumab are compelling. They're consistently strong across patient populations and endpoints and importantly show internal inconsistency. And when we make these comparisons to other programs, we believe Peta-Semtumab clearly has the strongest efficacy and safety data as compared to all approved or experimental regimens in this setting. And perhaps Fabian can just add a little bit of color on how we think about colorectal cancers. Yeah,

for me, they're the most important aspect is, you know, we keep forgetting we have also confirmed single agent activity and that single agent activity looks favorable against, you know, EGFR targeting monoclonal antibodies, at least in this indication. So further exploring Peta-Semtumab in an indication where EGFR targeting monoclonal antibodies are established center of care makes great sense and we're looking forward to the readout. Next question.

Our next question comes from John Newman from Canna Cora, Jenningsburg. Please go ahead.

Thanks for taking my question. I just had a follow up on the accelerated approval strategy. Just curious if we should be assuming that you would wait until the phase three study is completely enrolled, of course, depending for accelerated approval. So just in light of the FDA's history here and some of the changes at the agency or I don't think you would wait until the phase two is completed, but just wanted to confirm if you could comment a little bit more on the detail on timing. Thanks.

Yeah, thanks for your question. Clearly, if the study is completed, we'd have all the data and wouldn't need to worry about an accelerated endpoint. In terms of the accelerated approval endpoints, I think the FDA has been more clear recently about their concern, which is that if a trial reads out before enrollment is finished, if there's sort of public declaring of the data and results, that could impede subsequent enrollment on the trial and confound the ultimate enrollment of the overall trial. Now that's different than requiring full enrollment before even looking at anything or other aspects. But the FDA hasn't officially formally weighed in publicly here, but they've been quite clear about their concerns about making sure that you don't screw up your trial by reading out the first part publicly before the second part is complete. Next question.

Our next question comes from Matt Phillips from William Blair. Please go ahead.

Hi Bill. Let me offer Mike and Gats as well. Great update here. Back to the CRs and CR rate. You know, there's two patients with not 100% resist reduction. Did they add maybe some kind of fibrotic remnants or anything there? And then kind of touched on this, but do you have a time to CR so far? Just wondering if maybe we could hope for some other CRs with more follow up. Thank you.

Fabian had made an initial comment on time to CR. I'll let Fabian take this question both on the why is a patient with only 75% or approximately shrinkage declared a CR and also just color on the CRs that we've seen.

Yeah, the lack of 100% tumor shrinkage in a CR is based on recent criteria where you essentially include lymphatic nodes as part of the target lesion. And since those cannot fully regress even in the context of a CR, you are supposed to indicate what was essentially the diameter of the lymphatic tissue as part of the target lesion. That's the reason for it. I don't have a specific time to, you know, CR rate, just the summary that I just gave.

Next question.

Our next question comes from Sebastian Pandeshu from Kempen. Please go ahead.

Hey, good evening everyone and congratulations on this very strong update. I was wondering regarding the duration of treatment for the patients who do respond to treatments. Can you say anything about when patients get into complete remission, when you will take them off of treatment and do you have any insights on the treatment duration of Pembroluzumab Monotherapy in responders?

Fabian can clarify if I get this wrong, but I believe that the original keynote 048 protocol that led to the Pembroluzumab or Catruda approval contemplated two years of treatment in that study. And that was the protocol mandated duration. And we have just feedback from clinicians. If you have a patient who's doing well, who's tolerating the medicine well, and they may have a partial response, but their tumor isn't growing and you reach the two year mark, some physicians are nervous about taking their patients off. I think in our monotherapy experience, what we've seen is that we do seem to have these kind of surprising long-term responders just to Pedosemtomab alone. And that's data that Fabian went over in a previous slide in our investor presentation, just reminding everyone of what the ASCO, sorry, the ESMO Asia presentation was last week. So I think we're going to be faced with a question as well of, or our clinicians, our physicians, which are running the trial for these patients who do seem to have long-term responses. Some due to the Pembroluzumab alone perhaps, some clearly could be contributions of Pedosemtomab. Just want to check, did I get that right, Fabian?

No, that's right. And that's an excellent problem to have. Yeah, thank you.

Next question.

There are no further questions at this time, so I'll turn back to call over to Dr. Bill Lumberg, CEO.

Thank you everyone for joining us this afternoon. For Miros, creating novel multi-specific antibody medicines is our core competency. I'm proud of the progress we're making with Pedosemtomab and proud of the progress we're making towards our ambition to close in on cancer. Thank you.

This concludes today's conference call. You may now disconnect.