Good morning, ladies and gentlemen, and welcome to the Immunome top-line results conference call for the Ringside Phase 3 study of varegacestat in desmoid tumors. All participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. As a reminder, this conference is being recorded. I would now like to introduce Max Rosett, Immunome's CFO. Please go ahead, sir.
Thank you, Operator, and good morning, everyone. We appreciate you joining us for our conference call to discuss the positive top-line results from the varegacestat Ringside Phase 3 clinical trial. Before we begin, I would like to remind everyone that this conference call will include forward-looking statements. Please refer to our SEC filings for more information. With me today are Dr. Clay Siegall, President and Chief Executive Officer, Dr. Bob Lechleider, Chief Medical Officer, and Roee Shahar, Executive Vice President, Chief Commercial Officer. Also joining on the call is Dr. Mrinal Gounder, Associate Professor and Medical Oncologist, Memorial Sloan Kettering Cancer Center. Dr. Gounder is an internationally recognized leader in desmoid tumors and has led numerous clinical trials, including serving as the primary investigator of the Ringside trial. Dr.
Gounder also serves as the Scientific Director of the Desmoid Tumor Research Foundation, where he is a member of the Medical and Scientific Advisory Boards. The agenda for the call is as follows. Clay will make some brief introductory remarks. Bob will review the key top-line results from the Ringside trial, and Dr. Gounder will provide background on the treatment landscape and unmet need for patients with desmoid tumors. Roee will share some information related to our commercial preparations, and Clay will return to cover our next steps and closing remarks. Following that, the Immunome team will stay on and will open the line for your questions. Now, I'll turn the call over to Clay.
Thank you, Max, and good morning, everyone. Today is an important day for Immunome, but more importantly, for patients living with desmoid tumors. The top-line results of the Phase 3 Ringside trial evaluating varegacestat for the treatment of patients with progressing desmoid tumors represent a best-case scenario and reflect the potential for a best-in-class treatment. We are excited by the results of our Phase 3 Ringside trial evaluating varegacestat for the treatment of patients with progressing desmoid tumors. As a reminder, varegacestat is an oral gamma secretase inhibitor, or GSI, that is administered once daily. The Phase 3 Ringside trial met all primary and secondary endpoints. Today, we will discuss three of those endpoints, with full details on the others reserved for a major medical conference.
The top-line results reported today are the primary endpoints of progression-free survival, or PFS, the secondary endpoint of objective response rate, or ORR, and the analysis of median tumor volume reduction. We will also discuss a summary of safety. We achieved an exceptional PFS hazard ratio of 0.16. Our confirmed ORR of 56% is the best that has been demonstrated in a randomized trial in patients with desmoid tumors. The median best percentage reduction of tumor volume of 83% is also the best reported in this patient population. In addition to these meaningful results, varegacestat was generally well tolerated, with a manageable safety profile consistent with the GSI class. This is an important outcome for the desmoid tumor patient community, many of whom need better treatment options to address the impact of this disease on their lives.
I want to thank everyone from the desmoid tumor community: the patients, the investigators, and trial site personnel who participated in the Ringside study. I also want to thank the superb Immunome team for their passion and tireless efforts that brought varegacestat to this point. We look forward to meeting with FDA in early 2026 to review the results of the Ringside trial and to continue our work towards submitting a New Drug Application in the second quarter of 2026. Our manufacturing and commercial preparations are also on track to support the launch of this important medicine. I will now turn the call over to Bob.
Thank you, Clay. It is a privilege to be here today to report the top-line results from the Ringside trial. Before I discuss the study results, I would like to remind everyone that desmoid tumors are locally aggressive, non-metastatic tumors that can lead to significant pain and disability. Desmoid growth is driven by activation of the Notch signaling pathway, and GSIs block this pathway, preventing growth of the tumors. Varegacestat has superior pharmacokinetic properties that likely contribute to its market activity in the treatment of desmoid tumors, as demonstrated in the Ringside studies. Varegacestat has a half-life in circulation of approximately 41 hours, which is 78% longer than that of nirogacestat. It maintains a concentration above that required for inhibition of gamma secretase throughout the dosing interval. That, combined with once-daily dosing, makes varegacestat a potential best-in-class treatment for desmoid tumors.
Today, we report the top-line results of Ringside, the largest Phase 3 randomized study in desmoid tumors. This trial was a randomized, double-blind, placebo-controlled study of varegacestat versus placebo for the treatment of desmoid tumors. Eligible participants had desmoid tumors that progressed within 12 months of randomization and required systemic treatment. Other eligibility criteria closely mirrored similar large recent studies in this population. In this global study, participants were randomized one-to-one to receive varegacestat or placebo until progression. Participants who progressed on study were able to cross over to the open-label extension. The primary endpoint was progression-free survival, measured as the time from randomization until radiographic progression, as determined by blinded independent central review using RECIST version 1.1.
We demonstrated significance of the three statistically controlled secondary endpoints, which were objective response rate, a landmark analysis of change in tumor volume at week 24, and a landmark analysis of change in pain intensity at week 12. We're reporting the results for ORR today and will discuss the landmark results at a major medical conference. Another important endpoint to be discussed today is median best change in tumor volume. Varegacestat achieved the primary endpoint of the Ringside trial, delivering an 84% reduction in the risk of disease progression compared to placebo. The hazard ratio for PFS was 0.16, which was highly statistically significant at a p-value of less than 0.0001. Shown here is the Kaplan-Meier curve for PFS, demonstrating marked separation of the two arms as soon as the first tumor assessment at 12 weeks. The separation between the curves continues throughout the course of treatment.
The hazard ratio demonstrated in Ringside compares very favorably with results from other recent studies of patients with desmoid tumors, and to our knowledge, is the lowest hazard ratio reported for a pivotal study in this population. On slide 10, we see the effect of varegacestat on tumor size. This is some of the most compelling data we have generated with varegacestat to date. On the left is a waterfall plot of the best objective tumor responses determined by RECIST. The confirmed objective response rate was 56% in the varegacestat arm and 9% in the placebo arm, which yielded a statistically significant difference with a p-value of less than 0.0001. The placebo response rate of 9% is similar to that observed in other large studies of desmoid tumors, suggesting a similar population.
The waterfall plot shows that the vast majority of participants responded to treatment with shrinkage of their tumors, with no participants demonstrating progressive disease as the best response to treatment. On the right side of the slide, we see the results of an analysis of the median change in tumor volume. As you can see, study participants treated with varegacestat achieved a median 83% reduction in tumor volume. Participants on the placebo arm demonstrated a median 11% increase. The 56% response rate and median 83% reduction in tumor volume are important for patients. These data suggest the majority of the subjects treated with varegacestat will have a response and that many will achieve a large reduction in the size of their tumors. varegacestat was generally well tolerated, with a manageable safety profile consistent with the GSI class of drugs.
The most common adverse events were diarrhea, fatigue, rash, nausea, and cough. The vast majority of events observed were Grade 1 or 2, and no deaths were observed on study. Ovarian toxicity is a known side effect of gamma secretase inhibition. In Ringside, 55.6% of women of childbearing potential experienced ovarian toxicity, and most of these have been recovered at the time of data cutoff. A rate of ovarian toxicity of up to 75% has been reported in the GSI class in this population. The efficacy and safety results from Ringside are compelling, and we believe demonstrate its potential to deliver best-in-class results for patients with desmoid tumors. The statistically significant and clinically meaningful hazard ratio, as well as the demonstrated high response rate and reduction in tumor volume, can offer an alternative for patients in need of treatment. The overall safety profile is consistent with the GSI class.
We intend to submit a new drug application to the FDA during the second quarter of 2026. We further plan to present the complete results of the Ringside study at a major medical conference. Additional studies to characterize varegacestat in the treatment of desmoid and other tumors are currently under development. Generating data that can help clinicians understand and treat a broad population of desmoid tumor patients, including those with debilitating functional impairments, will be an important focus of our development efforts. I would like to thank the investigators in Ringside, the patients who participated, and their families and caregivers for their generosity and efforts in the study. Next, we will hear from Dr.
Mrinal Gounder, an attending physician at Memorial Sloan Kettering Cancer Center in New York, an expert in treating sarcoma and the first author of two major studies evaluating sorafenib and nirogacestat in the treatment of desmoid tumors that were previously published in the New England Journal of Medicine. Dr. Gounder.
Thank you, Bob, and good morning, everyone. Congratulations to the entire Immunome team on conducting this fantastic Phase 3 study. As you heard at the introduction, I'm a medical oncologist at Memorial Sloan Kettering, where I treat patients and lead clinical trials with a strong focus on desmoid tumors and sarcoma. I will briefly discuss insights on desmoid tumors, their impact on patients, and the treatment landscape. I will also provide my perspective on the Ringside results based on my review of the data. Next slide, please. I'll start with a brief overview of desmoid tumors. As you heard before, desmoid tumors are rare. They're non-metastatic. They're locally aggressive sarcomas of fibroblastic or myofibroblastic origin. They will often affect patients in young adulthood, typically patients in their 20s and 30s and 40s, and even younger adolescents and children as well.
This can be deeply debilitating, with potentially profound impact on morbidity. About 1,000 patients are diagnosed in the United States with desmoid tumors every year. This disease can have a significant impact on the quality of life due to debilitating pain and loss of function caused by the tumors. As I mentioned before, many of these patients are in their prime of their life, so this has a profound impact on education, employment, personal relationships, and such. Although this disease is generally non-fatal, in a small minority of patients, complications can be lethal. Next slide, please. Okay. The desmoid tumor treatment landscape has evolved significantly in recent years. Historically, surgery was often the primary treatment, but we have now understood that aggressive local interventions are usually not appropriate, particularly depending on the tumor location. Sometimes the trauma associated with surgery can actually increase the recurrence risk.
Increasingly and more recently in the last several years, active surveillance is now often recommended as the initial approach for patients, even those who are symptomatic. While spontaneous regression can occur, it is not common. As patients progress or become symptomatic, the need for active intervention increases. Systemic therapy is now the preferred option for the treatment of these patients. This shift reflects a broader recognition that desmoid tumors behave as a chronic condition rather than a surgically curable one. Patients often require treatment over extended periods, during which they may pause therapy and then reinitiate treatment when required. Historically, systemic options have been limited by tolerability challenges and modest efficacy, which limited their benefit. Now there is a growing excitement for therapies that can offer meaningful disease control with a more favorable balance of efficacy as well as safety. Next slide, please.
So GSIs, or gamma secretase inhibitors, represent a meaningful inflection point in desmoid tumor treatment. As you heard before, the approach to therapy changed in 2018 with the first large-scale randomized studies of systemic therapies for desmoid tumors. Sorafenib, despite its safety and efficacy limitations, demonstrated the utility of this approach. Nirogacestat then established GSIs as a viable treatment option. Today, the results of nirogacestat further advance systemic treatments. What's important here is a progression of the field, both in terms of the innovation that has taken place and the benefit for patients. GSIs have advanced desmoid tumor treatment into an era of targeted, mechanism-based therapy. Varegacestat builds on that foundation as a next-generation GSI with a once-daily oral regimen and a clinical profile that I believe elevates the GSI class. While these are not head-to-head comparisons, the trajectory is clear.
GSIs are solidifying their role as the backbone of therapy in desmoid tumors, and varegacestat is positioned to become the standard of care in this setting. Next slide, please. All right. So this is a patient of mine. So it is important to understand how treatment with varegacestat can benefit patients. On the slide, you see the history of one of my patients. When he met me, he was a 25-year-old man who had initially been diagnosed in 2010, before he had met me, with a pelvic and left leg desmoid tumor. His initial treatment outside of Memorial was surgery, which was followed by recurrence. He then underwent a series of investigational systemic therapies, such as hydroxyurea, imatinib, and sorafenib. None of these led to lasting benefit. It was at this point that he came to my office to see me in my clinic.
He was 25 in the prime of his life, and he was in crutches. He was accompanied by his parents, who were both in tears. He himself appeared quite distressed and depressed. He had poor mobility. He was in significant pain, and he was unable to sleep at nighttime. This was 2021 when he initially enrolled in the open-label varegacestat Phase 2 trial. This patient had a profound response. He saw significant functional improvement with restored sleep and near complete reduction or resolution of his pain. Most importantly, he no longer now uses crutches, and beyond my greatest joy is that he's now an avid runner, and he comes into my office now once a year just to get a scan and to say hello, and he is living his life in full capacity.
What you see here in the MRI scans is you can see the dramatic reduction in the size of his tumor in these scans. And of course, I was delighted to provide such an effective, durable therapy that ultimately gave this patient a normal life after suffering from this disease for over a decade. Next slide, please. I want to conclude by saying that I want to summarize my thoughts and reaction to the Ringside Phase 3 top-line results. Overall, these data support the potential for varegacestat to become another standard of care in the treatment of desmoid tumors. First, the progression-free survival, objective response rate, and tumor volume reduction are best in class. Second, the progression-free survival hazard ratio of 0.16 and a p-value of less than 0.0001 is truly striking. Third, the safety profile is manageable and consistent with gamma secretase inhibitor class.
Clinicians like me have now increasingly become proficient in using these classes of medicines. I look forward to varegacestat approval. On behalf of Ringside investigators, it has been an honor to advance this important therapy. I will now turn the call over to Roee. Thank you.
Thank you, Dr. Gounder. There is clearly a need for better systemic options, and we are energized to bring forward a new treatment that offers a meaningful benefit for desmoid tumor patients. Our goal is to make varegacestat the standard of care, and we believe we have a pathway to achieving this through a focused commercial strategy. Our strategy is built around three pillars: start, support, and scale. These are designed to drive adoption upon approval and maximize opportunity for varegacestat. Our priority is to accelerate patient initiation through clinical differentiation and targeted provider education. Of the 11,000 actively managed desmoid tumor patients in the U.S., approximately 1,000 are on GSI therapy currently. Many of the others are managed through active surveillance. Of critical importance is providing physicians with evidence that varegacestat provides a better option for patients who are not well served by active surveillance.
Desmoid tumors follow a pattern of treatment, pauses, and retreatment. Strong patient services and drug access are essential to keep patients on treatment throughout their complex journey. There are approximately 85 specialty sarcoma centers in the U.S., allowing for an efficient-sized commercial team to drive rapid adoption. Now, the core elements that enable a successful launch are a differentiated clinical profile and a strong commercial plan. We are confident in our distribution and supply chain network. Manufacturing is scaled to support a high-demand product, and the timeline for launch preparation activities is anchored to potential priority review. We're building a team with an exceptional record of delivering for patients. They have deep experience in oncology and many have previously worked together on product launches. The U.S. and EMA orphan designations, which we have secured, provide favorable pricing and access dynamics.
Our initial focus will be on the roughly 85 sarcoma centers that treat the bulk of desmoid tumor patients, allowing for efficient engagement and quick uptake. Based on the analogs and early insights, we anticipate greater than 90% payer coverage at launch. KOL familiarity with varegacestat provides a strong starting point for launch. Many of the most respected desmoid specialists globally were Ringside investigators, giving them direct familiarity with varegacestat efficacy and safety profile. Our expectation is a superb commercial effort designed to translate varegacestat clinical differentiation into rapid and sustained market adoption. We have developed a strong partnership with the desmoid tumor community. The success of Ringside was enabled in part by advocacy organizations that have worked for years to raise awareness and push the science forward. The DTRF captured it perfectly in this quote.
The promising results with varegacestat from the Ringside trial drive forward the shared mission of finding effective, safe therapies and ultimately a cure for every person living with a desmoid tumor. I will now pass the call to Clay.
Thank you, Roee. Thank you, Bob, and thank you, Dr. Gounder, for taking the time to join our call today and provide your perspective. I've developed many drugs in my career, and the results presented today are truly outstanding. varegacestat is going to make a real difference in the lives of desmoid tumor patients. I also want to thank the entire Immunome team, many of whom I've worked with for years developing important medicines that are used daily to treat cancer patients around the world. I'm excited to build a company that's fiercely focused on developing therapies for oncology patients. The data we share today are only the beginning of what we plan to accomplish at Immunome. We have a robust pipeline of targeted cancer treatments, and I'm excited to implement our exceptional technology to develop ADCs directed against novel targets.
Our first ADC targeting ROR1 is in a Phase 1 dose escalation trial, and objective responses have been observed at multiple dose levels. We have three INDs planned for 2026 using our HC74 ADC technology. Additionally, we plan to dose the first patient cohort with our FAP, or FAP, targeted radioligand in early 2026. By this time next year, we plan to have six exciting programs in clinical development. I'm passionate about improving and extending the lives of cancer patients who need better therapies. The fantastic team at Immunome works tirelessly to enable successful patient outcomes like the one Dr. Gounder shared. We have an exciting 2026 planned with many catalysts, and I look forward to sharing our progress and accomplishments throughout the year. With that, I'll now open the call for questions. Operator?
Thank you. Ladies and gentlemen, if you would like to ask a question at this time, please press star 11 on your touch-tone telephone. To those dialed in, we'd like to ask you to limit yourself to one question each. One moment for our first question. Our first question will come from the line of Andrew Berens with Leerink Partners. Your line is open. Please go ahead.
Thanks, and congrats on the results. Clay and M ax. Definitely worth waiting for. Just a couple for me. Do you think that the numerical difference that you saw in the trial in the ovarian dysfunction rates versus Ogsiveo is that meaningful? And why would there be such a difference in the rates? I think previously you discouraged us from expecting a difference because it's thought to be an on-target effect of the GSIs as a class. And then a commercial question about launching the drug on your own. Can you give us some idea of the infrastructure you need, and will we be likely to see another BD deal for a late-stage asset that complements desmoid efforts?
Okay. Thank you, Andy. So first of all, on the difference in the ovarian toxicity, we saw in Phase 2 a similar lower ovarian toxicity than nirogacestat. And so we saw numbers that were very similar to what we saw in Phase 3. So I think that it's real, those numbers, because Phase 2 was small N, Phase 3, the much bigger N. And so we were very pleased that it was consistent, so we think it's real. There are a lot of potential reasons why this could happen. And the drug that we have has a very different pharmacokinetics than the other GSI, and it has used at a very different dose. It's different chemistry, very different Cmax. We use 1.2 milligrams per kilogram rather than 300 milligrams per kilogram per day, very different AUC. So it's not surprising that there are some differences in the safety profile.
Bob, do you want to add any color to that?
Yeah. No, thank you, Clay. I agree. I think that the numbers that we demonstrate are consistent across multiple studies, and I think the difference is real. And I think that, in my opinion, this will be potentially important both to patients and clinicians seeing a lower rate of ovarian toxicity.
Your second question is on commercial launch infrastructure. And it's a little bit of a strategic question and a little bit tactical. Strategically, Andy, as you know, I've launched many different drugs in my career. So I'm excited to launch drugs. I've launched drugs that Wall Street has predicted to be small market drugs like Adcetris until it became a large drug. And so I think there's a lot of approaches to doing this. And launching it in the U.S., Europe, Canada, I mean, this is well within our abilities easily and potentially more. One can consider distributors in various parts of the globe, like LATAM, as we call it, which is Mexico, Central and South America, Middle East, North Africa, which has some big markets like Turkey and other places. And then doing something in Asia potentially with partners.
But we've had outreach from companies that have said, "Hey, we'd love to talk to you about potential ways of working together." We're open ears to talk to folks, but our default is that we're going to launch this drug in major markets, and we're excited to. And on that front, we were able to recruit Roee Shahar, who you just heard from. Roee, heads up our commercial team. Roee and I have worked together for over a decade. He was in charge of Adcetris at Tivdak at Seagen, and he did a fantastic job at two relatively small market drugs and getting the maximum that was possible and really getting out the drugs to patients and making it work and connecting with doctors. Maybe, Roee, you could make a brief remark, a little color just on what you're thinking.
Sure. Like Roy, I've launched quite a few drugs, and I'm confident that we can have a strong launch just based on my experience in orphan tumors like Clay mentioned, Adcetris and Tivdak. The other thing you can see on the slide, we think we can have an efficient launch in these markets just given the market dynamics and the concentrated centers that treat desmoid tumors.
Okay. Thank you. Can I sneak one in for the doctor? Is that okay, Clay?
Andy, first of all, we need to move on and give other folks a chance, and Dr. Gounder has to step off and go back into, he had to go back to clinic.
Okay, well, thanks, and congrats again.
Thank you. One moment for our next question. Our next question comes from the line of Brian Cheng with J.P. Morgan. Your line is open. Please go ahead. Brian, your phone might be on mute. All right. We can move on to our next question. Just a moment. Our next question comes from the line of Tyler Van Buren with TD Cowen. Your line is open. Please go ahead.
Hey, guys. Good morning and congratulations on the tremendous results across the board. I believe you said the KM curve separated at the first tumor assessment. So can you elaborate on the time to response and how meaningful that is for patients? And as a follow-up, based upon the data, it seems obvious that most, if not all, new patients would choose to go on varegacestat. But since Dr. Gounder had to step away, can you just talk about what you've heard from the KOLs in terms of switches? Could they see a significant number of current Ogsiveo or nirogacestat patients switching to varegacestat given this profile?
Thanks, Tyler. So first of all, we're very proud of the Kaplan-Meier curves. I mean, it's got a lot of white space, and I've developed a lot of drugs, as you know, and seeing a lot of white space always makes me proud of the work we've done to really help patients. And as Bob said in his remarks, even at the first tumor assessment, you could see a separation. And I think that—and I'm going to ask Bob to make some comments here—but I also want to say to your second part of it was we haven't yet outlined exactly what we're going to do out in the real world. But I want to point out that I think that this will be great for patients and great for the incidence patients and the prevalence patients and all that.
But if patients are on a different therapy and they're doing really, really well, patients should always stay on those therapies. We want the best for patients. We're a patient-focused company, and you don't just take a patient on a drug, and if they're doing well, even if it's a minority of patients, if they're doing well, we want the best for patients. Of course, when they progress, you could consider things or new patients or prevalence goal. But I just want to make sure that the world out there knows that we're a patient-focused company. So Bob, do you want to give a little color on the Kaplan-Meier plot?
Sure. Thanks, Clay. So I think what's important to remember is that for patients on varegacestat, none of them had the best response of progressive disease. So every patient who was treated with varegacestat had a best response that was either a partial response or stable disease, which I think is really important to patients. You asked about the time to progression. We'll report that at a future conference when we talk about the complete results. But those curves separate early, and they stay separated throughout the course of treatment.
Thank you. And one moment as we move on to our next question. And our next question comes from the line of Brian Cheng with J.P. Morgan. Your line is open. Please go ahead.
Hey, guys. Can you hear me now?
Can.
All right. Great. Well, thanks for taking our questions, and truly congrats on the data. Maybe just first on pill burden. Roee, I believe that you talk about the plan to reduce the pill burden for varegacestat. Can you give us some color on where you're on that front, and when can we start to think about the reduced pill burden formulation that will be on the market? And then I have a quick follow-up. Thank you.
Sure. So Brian, thanks very much. We have a small grouping of pills that are taken now by patients. We're certainly working really hard, and I think there will be a time where we switch that to a single pill for sure. So we're working really hard on that now. But to me, it's only once a day. I don't think there's a real burden here. I think it's very approachable commercially, especially only at the beginning of the product launch before we hopefully switch to a single pill. Roee, do you want to make any comment on previous launches you've done and things like this and switching to reduced pill burden?
Yeah. Hey, Brian, thanks for the question. And we're confident based on feedback we've received that there will be minimal pill burden initially. And as Clay mentioned, we're working on making this into one capsule that will be very soon after launch. So we're excited for that, but that's kind of the end of that.
Okay, and then just on your preparation towards the NDA filing, what's the gating factor here now that you have your clinical package in place? Can you talk about specifically the manufacturing preparation and also the toxicology work behind the scenes?
Yeah. So briefly, on manufacturing, if you asked me a year, year and a half ago, "What are you concerned with, Clay? What keeps you up at night with this?" it wasn't really going to be the drug. I mean, I felt our phase two data were strong. We heard a lot from doctors. The phase three data was coming along really well, and the sites were putting a lot of patients on, and we heard good things from doctors, even though we hadn't unblinded and stuff. So I felt really good about that. But if you look back a year ago, I was worried about the CMC because when we acquired this program a couple of years ago, there was no CMC work done. None. Zero. So we had to really do it and jump-start it.
And while Wall Street doesn't ask too much about CMC, I'm glad you're hearing it. What I would say the secret weapon and the arsenal of Immunome is our head of manufacturing, Philippe Tsai. I worked with Phil for, I think it was like 18 years or something at CGEN. And Philippe Tsai, he's a superstar in the world of technical operations and manufacturing. And he had a massive staff. I think his staff reporting to him at CGEN is much bigger than the entire Immunome company. And he knows everything about manufacturing and putting together packages for FDA and going through inspections and you name it. So Phil is a superstar in that regard. And while he's not here this morning, he's probably hard at work already. I feel really good with him there. And me and the executive team get reports from Phil all the time and updates.
We have multi-source manufacturing going on. It's just fantastic. I feel not only are we going to be good for launch, but I feel that the transitioning to a lower pill burden is going to happen and going to happen in a timely fashion. I'm really excited about it. You asked a little bit about toxicology. I want to give some other analysts a chance to ask questions, and we only have a limited amount of time. Maybe we'll move forward. We've already talked a lot about the tox profile, and we think it's very consistent with the GSI class. Operator, can we go to the next analyst?
One moment. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open. Please go ahead.
Good morning. Congratulations on the data. I was just wondering if you could comment on the strategy here to encourage more patients to be actively managed. And if you could compare your data or give us any color on discontinuations due to AEs and dose reductions where I believe Ogsiveo had about a 20% discontinuation rate on that front and 42% dose reductions. Thank you.
Sure. We feel that we have an excellent plan to really connect with doctors and patients, whether it's working with all the foundations and bodies that when you're diagnosed, someone tells you, a doctor tells you you have a desmoid tumor, you go home and you go to the internet and you find out as much as you can. You go to these foundation websites, and we're very connected with them. And they're very aware of this. Dr. Gounder is very connected, and he serves as a lead on the most important foundation. And so we're really connected there. We also put a huge emphasis on medical affairs. And medical affairs is going out and really connecting with doctors, listening to them, what they want to do. So we're not going to go where we are today and just go into radio silence until we get approval.
That's not going to happen. What we're doing is we already have been out there talking to doctors saying, "What kind of studies do you want to see? What else can we learn? What other things can we do to help you and help patients in considering how to use this drug, thinking about pain relief and temporal nature of it and pill reduction and dose reduction and all the different things that really matter to going from an approved drug to an actual well-used medicine?" And so we're already thinking that. We're going to be touching doctors in their office, doing other trials. And I think that we're. I've done this many times before, so has Roee, so has Bob Lechleider for the clinical standpoint.
This is not our first rodeo, so we really know how to connect with doctors, and we know how to get a really effective drug out there to patients, and so, Roee, you could maybe make a quick comment on what she was asking about active management.
Thanks so much for the question on that. When you showed a slide, we mentioned that there's about 11,000 patients who are actively managed that have desmoid tumors, and roughly 1,000 of them are on a GSI at the moment. What it will take to likely get the 10,000 or so of them to, if you will, come off the sidelines and get treatment is having an option like varegacestat that has really strong efficacy and safety profile that they can manage and hopefully in a one-daily format. We believe that that profile that we have with varegacestat will help them do that.
Thank you. And one moment for our next question. Our next question is going to come from the line of Michael Schmidt with Guggenheim. Your line is open. Please go ahead.
Hey, guys. Good morning. And congrats from me as well on this outstanding trial result. The efficacy of these speaks for itself, but maybe just going back to some of the tolerability, some of those side effects look meaningfully lower, numerically lower than what was seen in DeFi, especially some of the GI adverse events and rash. And we know that Ogsiveo is discontinued fairly frequently or dose-reduced. And yeah, just curious how you think about duration of therapy in clinical practice in that context. What is a good assumption there? And then the other question I had in your prepared remarks, you did note that there are additional trials planned. And I was just wondering, what are some of the other areas that you're considering for clinical studies with varegacestat? Thanks so much.
Thanks, Michael. So on the duration of therapy, in a clinical trial, it's not exactly the same as real life, but it does represent it in a sense. We have some patients that have been on for well in excess of a year. And so we're really excited to work with doctors to figure out the best way to help patients. And I think in some cases, patients will be on for a long time, years. And if you have a good drug and it's well tolerated, that's the kind of thing that is really important for doctors and patients. And so I think that we are well positioned to work with doctors on the duration and get a lot of patients onto this, have them benefit from that, have them stay on it, and have this to be an important part of having a better life.
So, I think that that would be really good. The tolerability, I think, is well within reason in this class. And we're excited about doing additional trials. Bob, can you comment a little bit about the duration, a little bit, and a little bit on maybe a few top thoughts? Because we haven't outlined it completely, but a few top thoughts on trials.
Yeah. So, I think, Clay, you're exactly right. Thank you. You're exactly right about the duration. We've seen some patients have been on for years, actually. And patients, once they get on the drug, have been able to tolerate it for quite a long time because they've received real benefit. So the safety profile is very similar to what's been demonstrated with other GSIs, and the efficacy profile clearly is differentiated.
As far as other studies go, one of the things that we're really interested in is understanding other populations within desmoid tumors. Are there patient populations where the primary problem is not necessarily growth of the tumor, but functional impairment? And so we're interested in understanding whether, not whether, but how varegacestat can improve those patients' lives. And then also looking at other tumor types where gamma secretase inhibition may be an important component of regulated tumor growth. Stay tuned for more to come.
Thank you.
One moment for our next question. Our next question comes from the line of Cory Kasimov with Evercore ISI. Your line is open. Please go ahead.
Hey, good morning, guys. I'd like to congratulate. Indeed a great result. So I wanted to follow up on the duration question. You mentioned in the slide this idea of pausing therapy on what's a potential chronic treatment journey for desmoid patients. When this does happen, how long do you expect drug holidays to be after the one-and-a-half to two years of treatment? Is this an evolving consensus view among doctors to pause, or is it really just patient-dependent, and you kind of go as you please as you go?
So hi, Cory. Thanks for the comment. So we don't see a lot of these patient holidays. It's not like it's a big thing. We think patients get on the drug, they stay on the drug. And what we're doing is working with doctors. And I think going to the comment on pill burden, what I'd like to see here is instead of a couple of pills one time a day, is one pill one time a day. And doctors also like to treat a patient that has a lot of tumor burden. And as you can see from our reduction in tumor burden, we're profound. I think it was 83% median. So once you start debulking tumors, and a doctor wants to keep a patient on for a long time, some of the doctors, they do a better job of actually really understanding a drug than companies do.
I've been running companies for a long time, and companies do a clinical trial. They get approval. Doctors know better because they've worked with patients. They've worked with it over time, and they figure out how to use these drugs, and so some of the doctors that we've seen, they don't really necessarily do discontinuations, but what they might do is they give 1.2 milligrams per day, and then when the patient has a lot less tumor, they might go down to 0.9 milligrams per day and keep patients on for a long time or something like that, so as we go to single pills and in blister packs and trying to make this into a medicine that doctors want to use and it's easy for patients, we're going to have single pills at 1.2 on a day package in a blister pack.
We're going to have single pills at 0.9 so that if the doctor says, "Hey, we've already reduced a lot of tumor burden, and we just want to even have an easier tolerated drug, not that it's bad tolerated," we're going to have that available to them. We're going to make this into something that doctors really like to do and good for patients. So I'm not really thinking too much about the drug holidays, but more making this a great medicine for patients going forward.
Right. And then just to follow up on that, Clay, do you see most of your adverse events, like the ones you do have, are they usually early onset and then they get better tolerated with time, or are they throughout the treatment?
Yeah. Bob, can you comment on that?
Yeah. That's a really great question. Most of the things that we see occur relatively early during the course of treatment and then stabilize or get better with time. So we're not seeing an increase in adverse events with continued treatment.
Perfect. Thanks again. Super helpful.
Thank you. One moment for our next question. Our next question comes from the line of Biren Amin with Piper Sandler. Your line is open. Please go ahead.
Yeah. Hi, guys. Thanks for taking my questions. And congrats on the Phase 3 data. Given the data, how should we think about the price of varegacestat compared to nirogacestat? And then the second question, I know you talked about disclosing worst pain intensity data at a medical conference next year, but I was wondering if you saw trends on pain reduction to tumor volume reduction. Thank you.
Sure. Thanks for the question on price and stuff like that. It's not the right time yet to start talking about price and comparing this. As you know, nirogacestat price is out there in the world, and obviously, that's a data point for us. It's important for us. Roee and I have had a lot of experience pricing drugs. So this is not the first drug we're pricing. Hopefully, not the last. We're going to have other drugs here at Immunome too. And you look at different parameters. You talk to payers. We go out there and we pound the pavement. As you know, we don't leave a lot of stones unturned. And so we're going to talk to payers. We're going to talk to doctors. We're going to figure out what is the right and appropriate price for this drug. And then we'll put the price out there.
We're going to make this into a global drug. So it's not just the U.S. This is an important thing for patients. Patients don't know borders or boundaries or politics or anything. Patients know cancer. And it is important to me personally to get every drug that I've ever made to make them into global drugs, to make them available in different countries around the globe so that we can help suffering from tumors and different types of cancers that we're treating at Immunome with all our drugs. So we're going to be working really hard at that pricing, right. As far as pain reduction, we worked on that. That's a big important thing for us because it's important for patients. This is a disease that's really painful. And while you're not dying from this disease like pancreatic cancer, you don't die quickly. It's an awful disease.
This is not good, and you don't want anybody to have this type of disease, and it really changes lives. So pain reduction, which comes along with tumor burden reduction, is critically important. Bob, do you want to give a little color on what we've seen so far? Sure. Yeah. Biren, thanks for the question. The pain reduction is a very important secondary endpoint. As we pointed out, we met that in a statistically controlled manner, which is critical, and we also see tumor volume reduction. We haven't yet completed the analysis of how pain and tumor volume or response are related. That's obviously something we're going to do, but as part of top-line, it wasn't our initial analysis, so stay tuned for more information on that too.
Thank you. One moment for our next question. Our next question comes from the line of David Nierengarten with Wedbush Securities. Your line is open. Please go ahead.
Hey, thanks for taking my question. I was curious how many patients had been previously treated with either Niro or other agents and if there were differences in response rates and tumor shrinkage in patients depending on the prior treatment? Thanks.
Thanks. With that, I'll turn it over to Bob to answer that question.
Sure. Thanks, Clay. So prior treatment with a gamma secretase inhibitor was an exclusion criterion. So no subjects on the study were treated with prior GSI, but all of the patients on the study had some prior treatment of some kind, either systemic or local. Well, that obviously will be detailed when we publish the full results in the future.
Yeah, and we'll learn. While we executed it as a trial, which is a standard type of thing, we're certainly going to learn from what's going on in the world. For patients, patients are out there getting treated with nirogacestat, and there will be patients that aren't responding to that and switching to our drug, and we'll be working very closely with doctors to understand everything about this, but it's a different chemistry. It's a very different chemistry. It's a very different pharmacokinetic profile. You have a different CMAX and AUC, which can affect efficacy and safety, so it's not the same drug. It's the same class of drug, but it's a very different drug, and we look forward to learning even more about this. This is just the beginning. This isn't the end.
Got it. Thank you.
Thank you. And one moment for our next question. Our next question comes from the line of Charles Zhu with LifeSci Capital. Your line is open. Please go ahead.
Hey, good morning, everyone. Congratulations on these compelling data across the board, and thanks for taking our questions. I'll have one just asking you to expand some prior commentary around those patients that are being actively managed. What percentage of those 10,000 or so patients on active surveillance that are not currently taking GSIs, what percentage of them do you expect to be able to capture with varegacestat? And could you perhaps also expand on the reasons why they may not already be on something like nirogacestat, whether it's due to clinical profiling or maybe just where they are with respect to their current launch? Thank you.
Yeah. Thanks, Charles. So when we say around 10,000 or 11,000 patients actively managed, keep in mind there's over 30,000 prevalence pool just in the U.S. of desmoid tumor patients. So the prevalence pool is big, but not all of them come into being treated each year. So that's a big pool. And you look at Europe, and if you combine the whole EU, it's pretty similar to the U.S. And then you look at the rest of the world, there's a lot of patients with desmoid tumors around the globe. And so to us, that's the opportunity, the global desmoid tumor population. And some of the patients, they're just early stage or whatever reason, and doctors are just watching them, as you heard from Dr. Gounder, this surveillance, if you will. But the active managed patients, these are the ones that need things.
They're suffering in a lot of different ways: pain and debilitation and having a huge tumor on their shoulder, and their arm is now paralyzed, literally. It can't even move, and they can't move their neck or legs, and they're on crutches, so there's a lot of patients that really need therapy. Our goal is to do best by the patients, and you have to make a simple-to-use drug. Once a day is about as simple as possible. We've looked out in the world. We've talked to doctors, and doctors have all told us that they prefer a once a day because of compliance by patients, and so we've heard that from doctors, and so we want to make this as simple to use for patients as possible and as effective as possible.
So if you can get both simple and effective, which is what we have here, we think we have something that could really help patients. And I think we'll get a lot of the patients on active surveillance to really consider this. And we'll be connecting very strongly with doctors, with our medical affairs team, and ultimately our commercial team when we get approved. Roee, do you want to make any quick comments on active surveillance and touching base with docs?
Yeah. Thanks, Charles. Thanks for that question. We're confident. In my experience, we've been able to do exactly what you're saying of getting patients off the sideline because of what Clay stated, is that benefit between efficacy and safety. 56% response rate means that more than half of patients will have a response and will be able to get treatment. And I think that will be encouraging for them to come off the actively managed, meaning they're probably getting MRIs or scans and choose to get active treatment. And that's what we believe we'll do. And we'll be preparing for kind of the campaign to educate physicians and patients on that.
Yeah. And one more comment. When you look at our waterfall plot and you see things, almost every patient benefits from this drug. This isn't just 56% of patients and the other patients aren't doing well. That's 56% by this strict FDA criteria, which is not necessarily done in clinic every day. So it's too cumbersome. That's a trial. So what this drug represents is a doctor can talk to a patient and be on the level with a patient and say, "Hey, you have a very high chance of having a real response here." And that's really meaningful out in the real world and not necessarily in a trial.
Okay. I think we have time for maybe one or two very quick questions.
All right. One moment for our next question. Our next question comes from the line of Karina Rabayeva with Truist. Your line is open. Please go ahead.
Hi. Congrats on the stellar data. Can you guys comment on what percentage of patients with an ovarian dysfunction discontinued treatment and then how many patients the condition resolved? And the second question is, given that the study involved patients who were 12 years and older compared to nirogacestat 18 years and older, what percentage of patients could potentially be added from this younger age group? Thank you.
Sure. Bob, do you want to comment on that?
Sure. So, the first question. Thank you very much for the question. The first question about ovarian dysfunction, patients remained on study. And the majority, although we will report the exact number, but the majority of those patients with ovarian dysfunction did, in fact, recover function either while they were taking drugs or after they discontinued for other reasons. And then, as far as the younger population goes, we enrolled adults in this study only, although we were able to enroll younger subjects. We will be conducting a study in the future to look at the pediatric population, but that's still in the planning phase. We haven't started that study yet.
Okay. Maybe we have to do one more question. We're near the bottom of the hour. So maybe one quick question.
All right. And our last question will come from the line of Adam Vogel with Craig-Hallum. Your line is open. Please go ahead.
Thank you. And congrats team on the great data set. So just maybe just quickly on the time course of benefits. Do you continue to see new responses or deepening responses beyond the first year, similar to late responders described for Ogsiveo?
We have seen late responders. We've seen some quick responders, and we've seen late responders that have stayed on drug for a long period of time. We're going to continue studying this, but the benefit of this drug, when you have a well-tolerated once-a-day drug and you continue to see benefit, when you see responses, we're talking about the FDA type of responses. So let's say you're doing multiple measurements to get a RECIST response. It's looking really at a full volume, not just a linear measurement. So we follow this. We look at this. So patients can be doing really, really well, and when they are not in a clinical trial, they'll be on this drug, and doctors will be going, "Hey, your tumor's getting smaller.
Your tumor's getting smaller." And they're not going to necessarily be measuring it by every single tool to they get a RECIST FDA-mediated type of response, which a company does. We have to. We have to have a certain box that we have to look into. So I think that what we've seen in our trial, which is the most critical, is that patients can get early responses, mid-level, or later responses, which would encourage doctors, as the patients are doing well, to keep them on drug. I think we need to move on now. We're done. We're at the bottom of the hour, and it's important that we step off now. Thank you all, and operator, can you close the call?
This concludes today's question and answer session. Ladies and gentlemen, thank you for participating in today's conference call. This does conclude the program, and you may now disconnect. Everyone, have a great day.