Welcome to Parabilis phase I/II study desmoid data update at ESMO. At this time, all participants are on listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Tom Kotarakos, Chief Financial Officer. Please go ahead.
Thank you, operator. Good afternoon and good evening to those of you here in Europe. Greetings from Madrid. Today, we will discuss updated phase I/II data for zolucatetide in desmoid tumors presented earlier today in an oral session at ESMO, along with an update from our recent FDA discussion supporting our planned advancement to a phase III registrational study. The ESMO presentation is posted on our corporate website, and you will find the press release and today's slides in the Investors section. Before we begin, please note that today's presentation and discussion will include forward-looking statements, including statements about the clinical data of our phase I/II trial, design and timing of our planned phase III PEDESTAL trial, our interactions with the FDA, the potential of zolucatetide in our pipeline, upcoming milestones, and our cash runway.
These statements are subject to risks and uncertainties that could cause actual results to differ materially, including those described in the Risk Factors section of our SEC filings. The clinical data we will discuss are interim and preliminary as of a June 22, 2026, data cutoff. Zolucatetide is investigational and not approved for any use. Except as required by law, we undertake no obligation to update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise. With me today are Dr. Mathai Mammen, our Chairman, CEO, and President, and Dr. Helen Ho, our Chief Business and Strategy Officer. Mathai will take you through the data and our path to phase III, and then the three of us will take your questions. Mathai?
Thank you, Tom, and thank you all for joining. We are really excited to be here in Madrid. It has been a big few months for our zolucatetide franchise, our company and its portfolio, and our team. Today, we are thrilled to share two important updates. Earlier today, Dr. Mrinal Gounder from Memorial Sloan Kettering, presented our updated desmoid data at ESMO. In a larger data set than at the February data cut shared in our S-1, zolucatetide continues to demonstrate compelling efficacy, favorable safety, and tolerability, reinforcing what we believe is its potential best-in-disease profile. Second, following our very recent and productive end-of phase II meeting with FDA, we now have a clear FDA-aligned path to phase III. Next slide. Before we dive into the data, I want to briefly remind everyone what makes zolucatetide unique.
Beta-catenin is a genetically validated driver of cancer, with mutations in APC or beta-catenin found in more than 10% of all cancers. Yet for more than three decades, this target was considered undruggable. The interaction between beta-catenin and TCF occurs across a large, flat surface inside cells that conventional small molecules just can't engage. This is precisely the kind of challenge our Helicon platform was designed to overcome. Zolucatetide directly binds beta-catenin, blocking its critical interaction with TCF and the downstream transcriptional program that drives disease, regardless of whether the underlying mutation is at APC or beta-catenin protein. To our knowledge, zolucatetide is the first and the only investigational beta-catenin TCF inhibitor in clinical development, uniquely positioning us to directly address the causal biology underlying a range of Wnt-driven diseases, including desmoid tumors, familial adenomatous polyposis, adamantinomatous craniopharyngioma, hepatocellular carcinoma, and many more cancers.
Today, our focus is gonna be desmoid tumors, where mutations in this pathway are found in nearly all patients, making it a compelling setting to evaluate the impact of directly targeting this causal driver of disease. Next slide. What does living with desmoid tumors look like for patients? Desmoid tumors are locally invasive. They can grow almost anywhere in the body, including the abdomen, the limbs, the chest wall, the head, the neck. Patients may be living with chronic and excruciating pain, limited mobility, disfigurement, breathing difficulty, organ dysfunction, and many tell us that the disease entirely controls their daily lives, and for many, for their entire lives. There are 30,000 people in the U.S. living with desmoid tumors, with about 11,000 currently actively managed, and only several thousand of these are started on systemic therapy today. A big reason for that is today's options are not optimal.
The sponsors creating gamma-secretase inhibitors, or GSI, have been pioneers. They brought this appreciative patient population the first-ever approved treatment for desmoid tumors, and that's really amazing and a true impact on health. But the GSI treatment experience leaves substantial room for improvement on efficacy, safety, and tolerability. Side effects like diarrhea, rash, ovarian toxicity are a very real burden, especially since many patients are young women who may be thinking about starting a family. As seen numerous times in medicine, the initial approved therapy opens the door, but it's the next generation of medicine, what brings most patients through that door. We've seen this before in hepatitis C, cystic fibrosis, myasthenia gravis, and obesity.
We believe the same can happen here in desmoid. What patients need is therapy that works faster and deeper and more reliably and can be reasonably tolerated as a chronic therapy in exchange for the benefit offered. With that background in mind, here's what I want you to take away from our update today, which all reflects data from our June 22nd data cut. First, we continue to see really compelling and uniform efficacy, reinforcing the potential of directly targeting the causal biology disease. We observed 72.2% objective response rate at the 32 week landmark among response-evaluable patients who started at 450 mg or higher. We also observed 100% disease control rate across all 46 response-evaluable patients at those doses with no disease progressions at all.
Notably, we saw strong efficacy both in patients previously treated with GSI and in GSI-naive patients, pointing to the broad potential of our therapy across patients, regardless of past treatment history. Second, safety and tolerability remain favorable and entirely consistent with data we have reported earlier, despite a much larger data set. Side effects continue to be largely low grade. There have been no treatment discontinuations due to TRAEs. We have had no disease progression to date on treatment, and zolucatetide has not been associated with ovarian toxicity or with any high-grade diarrhea, high-grade rash, all three of which are commonly associated with GSIs. Third, we have a clear FDA-aligned path to registration. As a new update, we just had a really productive end-of-phase II meeting with FDA, where we have aligned on key components of our phase III design.
Hot off the press, we just received minutes from this meeting yesterday evening. Based on our FDA interactions, we anticipate initiating PEDESTAL in the first half of 2027 and can now share that we expect top-line phase III data in 2029. We are also continuing to recruit patients ahead of phase III and estimate that we will treat and follow about 100 patients in our phase I/II through approval, which will provide us with longer-term data as we progress through blinded phase III trial. Next slide. Let me walk you through the highlights of what Dr. Gounder presented earlier today, along with a few additional slides for context. The full ESMO presentation is on our website. Next slide. Since February, we roughly doubled the number of patients in our trial, with much of that enrollment occurring in just the last few months.
This includes patients in both dose escalation and our randomized dose optimization study, where we evaluated three different induction and maintenance regimens. The thinking behind this approach is rooted in something I believe in strongly, patient-centric drug development. Develop drugs in a way that matches the patient experience. When a desmoid patient comes into a physician, they are often in acute distress, be it excruciating pain, inability to walk or breathe, and so on. They need their tumors to shrink, and they need that relief as quickly as possible, and they also need a treatment they can stay on over the long term. That is the rationale for our induction maintenance approach. Start with a higher dose to drive rapid tumor shrinkage and symptom relief, then transition to a lower, less frequent maintenance dose that sustains and potentially deepens that response with a tolerability profile appropriate for chronic treatment.
That brings us to the regimen we have now selected for phase III, 450 mg weekly for four months, followed by 300 mg every two weeks for maintenance. This regimen is informed by arm B of our dose optimization study, which evaluated 450 mg weekly induction for four months, followed by 150 mg weekly maintenance. By moving to 300 mg every two weeks, we match drug exposure with half as many maintenance infusions, which is more convenient for patients participating in the multi-year phase III study.
Before we transition to a self-administered commercial product, which is the plan right now, we are very pleased to have reached full alignment with FDA on this regimen for phase III. Next slide. A couple of points on the patients in this trial. They are representative of desmoid tumor patients. The median age is 37, about 70% are women, consistent with the real-world desmoid population.
We've included both treatment-experienced and treatment-naive patients. 71% had already received nirogacestat and failed that therapy. Some failed because they simply couldn't tolerate the drug, others because their tumors actively grew on that therapy. This gives us a fairly large number of patients who have failed the GSI, a population where there's been no clinical data to date. We're also seeing treatment-naive patients choosing our trial over any approved GSI, demonstrating strong demand for a new therapy. Over a fifth of our patients have never taken a systemic therapy before. Next slide. Let's start with safety, because in desmoid, tolerability matters. At our phase III induction dose of 450 mg weekly, side effects have been predominantly low grade, and nobody has dropped from the study due to side effects. The most common AEs during this induction phase were fatigue, alopecia, and nausea.
Notably, fatigue and nausea are associated with desmoid tumors, with high rates of both in the placebo arms for both GSIs phase III trials. We'll explore the extent to which there's a drug effect in a placebo-controlled setting. Also note that the rates of alopecia have been 20%-30% for nirogacestat and varegacestat in their phase III studies. At the chronic maintenance dose, side effects have been substantially less frequent, less severe than during induction, and generally low grade and quite manageable, which is important for longer-term treatment. We anticipate seeing significant improvements in TRAEs when patients drop from the induction to a lower maintenance dose. We also see the potential for clear differentiation from GSIs, where the recurring TRAEs reported are skin, GI, ovarian toxicity. Across all 76 patients treated, zolucatetide has shown no high-grade skin or GI toxicities, and it's not been associated with ovarian tox.
Notably, in the phase III clinical trials for GSIs, 20% patient discontinuation due to AEs was observed. To date, only two patients have left our study, and neither because of a side effect or progression. One moved away after a complete response and considered herself entirely well. The other withdrew for logistical factors entirely unrelated to the drug following a sustained partial response. Overall, these tolerability findings support our phase III dose and induction maintenance regimen and suggest potentially strong differentiation from other treatment options. Next slide. Compared to our February data cut with now 76 patients, we see no new safety signals and a very consistent picture. The table shows the detail by dose. At 450 mg starting dose, 13% of patients had a grade three event.
Across all 76 patients, there were two SAEs, one transient grade one fever and one grade two peripheral sensory neuropathy that we believe to be not treatment-associated and rather associated with the mass of the desmoid tumor compressing a nearby nerve. One grade three event is fatigue, and as mentioned, we need to see how fatigue looks like versus placebo, as fatigue is really common in this patient population. Another grade three event was a transient AST elevation not associated with any liver changes. The other is bilirubin, which we believe to be an asymptomatic and reversible lab abnormality and not associated with the liver. As a reminder, zolucatetide inhibits the OATP transporters that carry bilirubin into the liver. So bilirubin levels rise in the plasma without any damage to the liver and no clinical consequence.
The induction dose is well-tolerated with a very high dose intensity and no dropouts. At the 150 mg weekly dose, which is equivalent of our maintenance dose, there was one grade four TRAE attributed to a transient CPK increase, a high-grade asymptomatic lab abnormality that resolved within about a week and did not require any intervention. Any occurrence of alopecia was all grade one. All in all, we believe our maintenance dose will be very well tolerated for patients and suitable for long-term use. Our now large dataset demonstrate an increasingly robust understanding of the safety profile, and it supports the induction maintenance regimen we've chosen for phase III. Next slide. Turning now to efficacy, which we're very excited to share with you today.
This slide includes all patients who started treatment at 450 mg or higher, including two patients who started at 900 mg but averaged approximately 400 mg- 500 mg over their first four months after dose reductions, so approximately the same as our phase III induction regimen. The swim lane plot shows time on treatment for all 48 patients, while the waterfall shows the 46 patients who have at least one post-baseline scan. There are three things I'd highlight here. First, we've observed 100% disease control with responses across both GSI-pretreated and GSI-naïve patients. 100% of partial responses have been confirmed in patients who have had subsequent scans, and we've seen zero progressions demonstrating strong durability. Second, patients are staying on treatment. No patient has discontinued due to disease progression, and the longest-treated patient in this cohort has been on therapy for nearly two years.
Third, these responses are still maturing. We've enrolled a substantial number of patients in recent months, so many have only had one scan or two scans. As you can see from the waterfall plot, we're observing deep tumor shrinkage and responses generally continue to deepen over time. That is, the tumors tend to keep shrinking with time and with every scan. Next slide. As you can see, the results are extremely compelling. Among patients who start at 450 mg or higher, we observed an objective response rate of 61.9% at 24 weeks, increasing to 72.2% at 32 weeks. I'll explain why we're using landmark analyses to evaluate response rates in this dataset and likely going forward. As you saw in the previous slide, patients have been on treatment for very different lengths of time, from just a few weeks to nearly two years.
A simple overall response rate doesn't tell the story. It's much more telling to look at the data at consistent time points, taking time out of the analysis. Looking at the response versus time plot on the left, you can see that patients starting at 450 mg or higher experience rapid and deep tumor shrinkage with average tumor reduction crossing the 30% threshold for partial response at around 24 weeks and continue to deepen through 32 weeks. That's why we've chosen 24 and 32 weeks as our landmarks for this dataset. Based on our current understanding of the kinetics of our medicine, these are meaningful time points when responses are emerging and deepening. You'll notice there are 13 responders at both landmarks, but these aren't the same patients and weren't the same patients in our S-1 that responded.
These are patients who had responded at 24 weeks but had not reached their 32 week assessment. Additional patients converted from stable disease to a partial response at this time point. Importantly, even at 24 and 32 weeks, these are quite early time points. We expect to follow patients considerably longer in phase III, providing more opportunity for ORR to deepen over time. Next slide. Let me put these results into a broader context. First, our 72.2% response rate at 32 weeks is consistent with the 74% response rate from the February data cut reported earlier when patients had a median time of treatment of 36 weeks. Second, we have also included published phase III results for nirogacestat and varegacestat to help contextualize the magnitude of the responses we are observing.
At their primary analysis, after approximately 90 weeks of follow-up, the reported response rates were 41% for nirogacestat and 55.7% for varegacestat. After four years of follow-up, nirogacestat's response rate was 45.7%. Compare that with 72.2% we are seeing for zolucatetide at just 32 weeks. Of course, expect more responses with time and a deepening of the ORR. Importantly, these are not head-to-head comparisons with all the caveats associated with that. Even with those caveats, the magnitude of the early responses we are seeing with zolucatetide are striking and we believe strongly support its potential for a differentiated best in disease efficacy. Next slide. The GSI data on the previous slide reflects substantially longer follow-up than our current zolucatetide data set. I want to provide some more context here.
Here are the published swim lane plots from the phase III trials for nirogacestat and varegacestat from Mrinal Gounder et al., which show that when individual patients achieved responses. We use these plots to estimate response rates at earlier, more comparable time points, specifically 24 and 36 weeks, to allow a more apples-to-apples comparison to our data. At 24 weeks, the estimated response rates for nirogacestat is about 25% and about 22% for varegacestat. That is 25 and 22. At 36 weeks, nira is 35% and vara is 41%. Compare those numbers to 61.9% at 24 weeks and 72.2% at 32 weeks for zolucatetide. Of course, these estimates are derived from these published data shown on the slide, and all the limitations of cross-trial comparisons, of course, apply. This analysis provides further support for what we are seeing in our own study.
Zolucatetide has the potential to deliver faster, deeper responses by directly targeting the causal biology of desmoid tumors. Next slide. Behind these numbers are patients that speak to two different market segments. I want to share two of their stories, one pre-GSI, another post-GSI. The first is a 39 year-old woman with a tumor in her left leg who had never received systemic therapy. Concerned about ovarian toxicity, she declined nirogacestat. At enrollment, she was experiencing pain and numbness in her leg and foot, making it difficult to walk. She achieved a partial response at week 16, and her investigator reported significant improvement in pain even before her scan. She had been on treatment for 68 weeks on June 22nd and continues treatment at 150 mg every couple of weeks.
The second is a 32 year-old woman with a tumor in her left shoulder who had been through five prior therapies with disease progression on every one, including on nirogacestat. She has no treatment options left at this point. She came on our study and achieved a partial response at week 24, and as of June 22nd, she's been on treatment for 47 weeks. She's still on treatment at 300 mg every two weeks, which is the maintenance dose we'll use in phase III. Two very different patients, both responding and continue to see deepening of response with each additional scan. This represents an opportunity to reach the broad population of desmoid patients seeking care, both of those who have tried existing therapies and those who have been waiting for a better option. Next slide. This is a very big moment for Parabilis and for patients.
We had a very productive end-of-phase II meeting with FDA, and we walked away with a clear path to registration. We're now moving fast to start PEDESTAL, our registrational phase III study, targeting the first half of 2027. We aligned on several key things here, including dose and regimen, a placebo-controlled design, a broad all-comer patient population including both pre-GSI and post-GSI patients, and PFS as a primary endpoint. Now, a word on PFS as a primary endpoint. FDA prefers PFS given the precedent from the registrational trials of both GSIs. As I mentioned earlier, with the data we've shown today, we think PFS sets us up for a very efficient study. Our new model from the recent robust data with still zero progressions points to an early and wide separation between zolucatetide and placebo, and a bigger effect shows up sooner than we even previously estimated.
That is, PFS is maturing at about the same rate as ORR. The once contemplated ORR PFS dual endpoint doesn't really offer any advantage. As mentioned earlier, we expect to be able to report top-line results now in 2029. Next slide. Let me bring it all together and step back to the bigger picture. Today's data reinforce our confidence in zolucatetide and its potential to redefine treatment for patients with desmoid tumors. We've demonstrated a 72.2% objective response rate at 32 weeks, 100% disease control, and a favorable safety and tolerability profile with no treatment discontinuations due to TRAEs among the 76 patients treated, and a consistent safety profile as our safety database gets a lot larger. And importantly, we now have a clear path forward.
We've aligned with FDA on key elements of our trial design and look forward to initiating PEDESTAL, a key step towards bringing this medicine to patients. And as you all know, desmoid is just the beginning. We see zolucatetide as a full pipeline and product, and we sit atop a mountain of opportunity for patients. We have the potential to address many diseases driven by aberrant Wnt/beta-catenin signaling. Our desmoid data provide important clinical validation of directly targeting beta-catenin TCF, along with a much deeper understanding of zolucatetide's safety, dosing, and exposure profile that we now carry into additional indications. Earlier this month, we initiated our dedicated dose-ranging study in FAP, building on the encouraging reductions in precancerous polyps we've already observed. We expect additional FAP data in the first quarter of 2027, as well as data in ACP and HCC in the first half of the year.
All areas of substantial unmet need. Beyond zolucatetide, we are advancing a broader pipeline of Helicon medicines against historically undruggable targets. We anticipate IND filings of our ERG and ARON degraders in prostate cancer, in the second half of 2027, alongside the IND-enabling work of our beta-catenin degrader. Our Regeneron collaboration is going well, which will extend Helicons into Antibody-Helicon Conjugates and into important diseases outside of oncology. We have the financial strength to execute with a cash runway into 2030. Next slide. We built Helicons to tackle disease-driving targets that have remained out of reach for decades. beta-catenin TCF is our first demonstration of what is possible, and we are working with rigor and discipline to extend that approach across multiple targets and multiple diseases. Today's results are an important step forward, and we believe we are just at the beginning of what Parabilis can achieve.
With that, Tom, Helen, and I are happy to take your questions. Operator?
Thank you, sir. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Tazeen Ahmad of Bank of America. Your line is open.
Okay, great. Thanks so much for taking my questions and congratulations on the updated data. Mathai, I did want to ask you, during the presentation today, I think there was a comment made about what the next trial should look like to the point of maybe this does not need to be a controlled trial, but a single-arm trial could potentially be sufficient. Can you just talk to us about what FDA has told you as part of the ongoing interactions that you have had with them? That being said, would there be potentially opportunity for, let us say, an interim read of your phase III program? That is the first question. Then second, thanks for giving us color on the commercial opportunity. We are aware of all of the potential safety advantages of your product versus the standard of care.
But some of the feedback that we have gotten from investors is questions about how do you still compete against an oral, even if there is a better safety profile, just given the perception that the oral is just a lot more convenient. Thanks.
Yeah. Thanks for the two questions, Tazeen. I'll take the first one and my colleague, Helen Ho, will take the second. We understand that we heard the conversation at the presentation today and calling for compelling data leading to single-arm approvals, and that is a really good point. Here the issue, as Dr. Gounder also pointed out, is there is regulatory precedent. We're in a situation where regardless of what we think, FDA does want a randomized, controlled study here. We've agreed fully on the design. We have minutes that are consistent with what I've presented here, which is a placebo-controlled two-arm study, with zolucatetide versus placebo with a PFS primary endpoint.
Maybe I'll answer, Tazeen, your second question, which is around the commercial opportunity for desmoid tumor. Maybe I'll just step back and say that we truly believe that the desmoid market currently is under-penetrated, and there's a lot of room to grow in terms of the opportunity. For the reason that, as Mathai mentioned, there are 30,000 desmoid tumor patients in the U.S., 11,000 of them under active management, only 1,000 of them on GSI right now. We believe that there's opportunity with a good therapy out there, like we've seen in our industry many times before, that when you have a really good drug, it has an opportunity to bring patients into therapy and benefit them.
The way that we're thinking about with the zolucatetide based on the data that we have, especially what we just shared today, are three different buckets of patient that we could target, and those include GSI-switch patient population, those includes the post-GSI patient, as Mathai said, there are many patients that come on our trial because they either have failed GSI and/or they're not well tolerated, and so they came off and come to our trial. I think the other big opportunity that we're really looking at is those watch and see patients, and these are patients who are going to the physician's office looking for care because they do need help, but they're hesitant to get on therapy right now.
And so we believe that when you have something that is efficacious, you have something that is well-tolerated for a long time, this is an opportunity for us to better serve the patients.
Thank you.
Thank you. Thank you. Our next question comes from the line of Jonathan Miller of Evercore ISI. Your line is now open.
Hi, guys. Thanks so much for taking my question, and congrats on all the progress. Mathai, I just wanted to make sure that I heard you correctly during the presentation and follow up a little bit on something I thought I heard you say, which was that the responses from the landmark analysis at ESMO aren't the same as the responses from the S-1. Can you clarify that a little bit? Are there additional responders between the two groups? It's 14 in the S-1 and 14 in this table. So I just want to make sure that I'm tracking how many responses
Yeah
you have in total. Secondly, I wanted to ask about Sub-Q formulation to your last point. How are we doing on formulating in a Sub-Q format, and where are we on the ability to get this out of an IV format?
Yeah, thank you for both those questions, Jonathan Miller. On the first, the responders, if you were to look back at the S-1, at these time points, it's about a half to two-thirds of the responses are at these 2 time points, at 24 and 32 weeks. These are not the same responders. This response rate excludes some of the late responders that were in the S-1. That's very important. If you were to calculate ORRs at week 24 and 32 from the S-1 data, you get about 60% and 73% at week 24 and 32. But we didn't do that because at that time point, we had so few patients. These landmark analyses don't make as much sense. Right now, we're starting to accumulate enough patients that a landmark analysis is the right way to do it. That takes time out of the equation.
If you don't do a landmark analysis, the problem is you include a lot of patients that just enrolled. They've had a scan or maybe two scans, so they haven't had a chance to respond. With our response rates, the appropriate time points to look are to look at 24 weeks and 32 weeks and ask how many responses are there among the response-evaluable population. That's exactly what we did. For the second question, it's on the self-administered formulation. Our plan is still to launch with such a drug product where the patients can use such a product at home, and the dosing schedule there would be the same, except in a self-administered format. We are on track for that.
We're doing a host of experiments right now pre-clinically on a very good-looking set of predictive data, which is that this compound is very stable and soluble, with low viscosity at these high concentrations. We expect this to be able to go forward and tested in humans for bioequivalence. As I think I've mentioned before, our plan right now is to seek that launch with bioequivalence data, and even if we need to enroll another 20 patients or so, if FDA requires that, we'll do that as well.
Maybe, Mathai, if I can go back to Tazeen's question earlier, commenting on oral therapy being a differentiator from the GSIs. Tazeen, maybe just go back to your question. As we talk to patients around their preferences and in this era of GLP-1s and where you have a good number of good and convenient therapy that are self-administered, the feedback that we got there is that the patients are obviously looking for convenience, which we believe that we can deliver with a self-administered auto-injector or what we decided to do on. But also, what is most important is that you want to be able to have efficacious and tolerated therapy, so that's what we believe that we're delivering here.
I think that's a true differentiation there, and we don't believe that the convenience here is going to be a difference between ours and the oral therapies out there.
Great. Thank you so much. It makes a lot of sense.
Thank you. Our next question comes from the line of Michael Schmidt of Guggenheim. Your line is now open.
Yeah. Hey, guys. Thanks for taking my questions. I find it interesting that so many patients, I think it was over 70%, had already seen a gamma-secretase inhibitor in this study. I am just curious if you know for what reason they came off of a prior gamma-secretase inhibitor.
Yeah.
Was it tolerability mostly, or efficacy? Whether you have looked at activity of zolu in naive patients as well compared to the experienced patients. I had a follow-up.
Yeah. So right now, our efficacy data appear at the numbers we have right now entirely independent from any past medical history, whether they have seen any other systemic therapy, including a gamma-secretase inhibitor, or for what reason they would have come off or failed a gamma-secretase inhibitor in the past. We did not break it all out this time, but we may do that for CTOS in another month or so. Right now, all I can say is that about half of them came off because they just could not tolerate the drug. The other half came because they had progressive disease on nirogacestat. So independent of any of these past medical histories, they came on our drug, and every scan just keeps ticking down.
Okay. The other question I had related to your phase III design. The other thing that came up in the ESMO discussion today was whether a defined treatment duration is something that makes sense here. I am just curious if that is something that you have considered, especially thinking about the every other week maintenance schedule.
Yeah. We see the patients here requiring a chronic or approximately chronic kind of treatment. We see that the induction dose will quickly get them out of their acute distress, and then the chronic dosing after that depends on to what extent they need continued care. My expectation is they will require chronic or semi-chronic care here. These are very difficult to eliminate entirely. If we do, that's wonderful for the patient. If they don't and we leave it at a residue, they have the option of taking a little break and coming back to it. But these are chronic or subchronic kind of drugs as we envision it today.
Okay. Thank you.
Thank you. Our next question comes from the line of Charles Zhu of LifeSci Capital. Your line is now open.
Hey, good evening, and thanks for providing the data update as well as hosting this event. I have a couple of questions for you. One, I'm looking at your S-1 swim lane plots and seeing that perhaps just over half of your responders are coming at eight or 16 week timeframe. I'm kind of wondering if this is consistent with the experience that you're seeing now in this updated data cut for ESMO, given the data that's been put out in your current swim lane plots. That's one. Two is, given the importance of follow-up and seeing these responses develop and mature deepen over time, any qualitative color you can provide on what your patients may have been seeing since the June 22nd data cutoff date? Thank you.
Yeah. On the second question, Charles, we are not going to be able to comment on data that was after June 22nd because that is our data cut. But we can say that the patients are doing really well on study. Before, you see in the sort of the pseudo spider plot, the condensed spider plot that we presented here, that at 450 mg, we see approximately crossing of the 50% mark, at around 24 weeks, maybe a bit before, is when we see the strong responses. Then we can see that our average time response, if we were to calculate it here, is around four months. We still see a lot of responses coming in, consistent with what we have shown before.
We will have to wait till a longer period of time and greater maturity to look at the overall ORR even later, like at 40 weeks and a year and a half. As a reminder, the gamma-secretase inhibitors, they are in the low 20s% at 24 weeks. If you do the exact same methodology we took, our 62% would compare to 20%-25%. At 32 weeks, our 72% would compare apples to apples to about 35%-40%. We are trying really hard to be extremely transparent and fair with how we compare data.
Got it. Thanks.
Thank you. I would now like to turn it back to management for closing remarks.
Thank you very much for the time that you spent with us today. As I said, we're extremely excited by where we are as a company and on behalf of patients, we're working really hard every day to bring first zolucatetide over the line. Our next step is to head into our PEDESTAL phase III study, and we'll look forward to doing that, and report when that happens in the near future. We look forward to seeing many of you at upcoming medical and investor meetings. Thank you so much for participation today.
Thank you for your participation in today's conference. This concludes the program. You may now disconnect.