...Okay.
Greetings. Welcome to Incyte Investor Event at ESMO 2024. At this time, all participants are in a listen-only mode. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to Pablo Cagnoni, head of. I'm sorry.
It's all good. Let's go ahead.
President and Head of Research and Development. Thank you. You may begin.
Thank you. Thank you, everyone, for coming. Thank you, everyone, that's joining us online for the webcast. We're very excited about sharing with you data that part of which was shared earlier today on two of our programs, retifanlimab, one of them, and our new CDK2 inhibitor that you will see today data for the first time, so this is a great ESMO for us at Incyte.
I think most of you know who I am, and I will be making forward-looking statements. We have a terrific agenda for you today. I'm gonna make some short introductory comments. I'm joined by two of my colleagues from Incyte, Ekaterina Setiani, our Head of Early Development, who will talk about the data from our potential first-in-class, potential best-in-class CDK2 inhibitor.
We're gonna focus on two tumor types today, ovarian cancer and endometrial cancer, and then Steven Stein, our Chief Medical Officer, will talk about some of the development plans for our CDK2 inhibitor. We're very excited, however, to have two guest speakers invited for this purpose, Dr. Rebecca Kristeleit, who will speak about gynecologic cancers and some of the improvements that are needed to manage these patients,
and Dr. Sheela Rao, who will re-review the data with retifanlimab and squamous cell anal cancer that was presented earlier today at the Presidential Symposium. Before we go to the core of the presentation, I wanna remind everyone how the pipeline is being transformed at Incyte as we speak. On the left side of the slide, you have three - four, actually, very important near-term milestones for us.
We've disclosed, obviously, pivotal data with the retifanlimab in two tumor types, one of which was presented today. We also recently disclosed pivotal that the trial of tafasitamab in patients with follicular and marginal zone lymphoma met its primary endpoint.
That could potentially be a really important indication for tafasitamab as well. And as you all know, axatilimab was recently approved by FDA for patients with chronic graft-versus-host disease, and we're in the process of getting ready to launch that medicine. We're also on track to submit Opzelura for a new indication in pediatric patients with atopic dermatitis. So a lot of near-term events that are really starting to progress very, very well.
The rest of the pipeline, with a number of potential first-in-class programs that you have on the right side of the slide, also continues to progress very well, with a lot of potential milestones in 2025 that we think are gonna continue to transform the pipeline. Axatilimab, or Niktimvo, is now approved. We're very excited about bringing this new medicine to patients.
We think this is a very important advance for chronic graft-versus-host disease and a potentially important opportunity for the business as well. Particularly in patients that have chronic graft-versus-host disease in more fibrotic-dominated organs, we think that this data could be very compelling as a new treatment option, and we're delighted by the response rate that we saw in the study and the durability of those responses in patients with chronic graft-versus-host disease. We haven't reviewed this data yet publicly.
We will do so later this year. Tafasitamab, which is currently approved for patients with relapsed refractory DLBCL, and now has a positive pivotal trial in follicular lymphoma, follicular and marginal zone lymphoma. The most common form of indolent lymphoma, as you know, is follicular lymphoma. We really think these are very important data that could potentially help change the standard of care in patients with follicular lymphoma, with additional tafasitamab to standard of care.
And then the data we're gonna talk about today. Squamous cell anal cancer is an important medical need where very little has happened over the past 10, 15, 20 years. Chemotherapy is widely used, but for patients that recur after initial treatment or have metastatic disease at diagnosis, things haven't really changed much in a long time, and Dr. Rao will walk us through the data that we have generated. And finally, CDK2.
This is an important mechanism in patients with a variety of solid tumors. Our focus initially today will be ovarian cancer and endometrial cancer. We have done work in other solid tumors that we will review over time, but today we're gonna focus on those two tumor types. One important milestone that we're adding to 2025 is initiation of pivotal trials in patients with ovarian cancer and our CDK2 inhibitor, and Steven will talk about that a little bit more during his presentation.
Let me briefly introduce our two guest speakers, and then I'll hand it over to them to start their presentation. Dr. Sheela Rao, who's a medical oncologist who specializes in gastrointestinal cancers at the Royal Marsden Hospital in London.
She's also a reader at the Institute of Cancer Research and a member of the International Rare Cancers Initiative with a focus of anal cancer. She has been, without a doubt, the driver of the data you're gonna see today, this very, very important study for patients with SCAC. Later on, we're gonna hear from Dr. Rebecca Kristeleit.
Dr. Kristeleit is a clinical senior lecturer and consultant medical oncologist at University College London. She specializes in the treatment of gynecological cancers, including cervical, endometrial, and ovarian cancer. She's a member of the Target Ovarian Cancer Scientific Advisory Board, Oncology and Hematology Expert Advisory Group, and the ESMO faculty from 2021 to 2025, and an investigator in the ongoing study with our CDK2 inhibitor, and she'll talk a little bit about the current management of patients with ovarian cancer and endometrial cancer. Both, Dr.
Rao and Dr. Kristeleit will be available for the Q&A.
... So with that, let me hand it over to Dr. Rao for the presentation on SCAC. Dr. Rao?
Thank you very much. Oh, let me choose this. This would work. Okay. Can I have my slides? Thank you. So thank you very much, everyone. I'm gonna talk to you about some data we presented today. So a bit of background. Anal cancer is a relatively rare disease, but its incidence has been increasing about 3% each year.
And this is largely due to human papillomavirus, so HPV. HIV is strongly associated with anal cancer, and there is a greater risk of this disease associated with HIV-positive patients. For many years now, the standard of care in the localized setting has been chemoradiation, but despite this, you'll get about 30% of patients who will progress. They will develop advanced disease, and another 10-12% who will develop metastatic disease. So about 40% of these patients will have advanced disease.
As previously mentioned, there has been very few developments in this disease. Chemotherapy as a backbone was established a few years ago by our group, with good response rate, durable response, but still modest progression-free survival and overall survival, at eight months and 20 months.
And HPV-driven malignancies provide a strong and attractive target for immunotherapy due to the depleted T cell microenvironment, and we've seen this both in head and neck and cervical cancer. So just to give you a bit of background, this is about 10,000 new cases per year in the U.S. and the E.U. And as I said, about 40% of these will present with advanced disease, so that's the group we're thinking about here.
In terms of the current treatment landscape, in the primary setting, it's chemoradiation, and this, as I said, has been a standard of care for a long time now. And in the metastatic setting, mainly chemotherapy regimens, so combination chemotherapy regimens that are given up there. In terms of on progression in the metastatic setting, there are a number of immunotherapy regimens, nivolumab, pembrolizumab or retifanlimab, as well as other chemotherapy regimens, but of note, none of these immunotherapy regimens in the second line setting are actually licensed currently.
And at the current time, the practice guidelines from the NCCN recommend platinum-based chemotherapy as a first-line option and only recommend immunotherapy on progression. And that is also true for the European guidelines, the ESMO guidelines. So, this is just really telling you that again. So both guidelines will basically recommend chemotherapy only at the current time.
No immunotherapy in the first line is approved, and no immunotherapy in the second line is actually licensed, although it is being given. As I said, there's a really good rationale here for adding immunotherapy. These tumors are HPV. The HPV is tumor-initiating. It then shapes your microenvironment.
You get these exhausted T cells, and then clearly, when you add immunotherapy back in, what you can do is reactivate these T cells. We have seen this in a number of cancers that are HPV-driven, so cervical and head and neck are good proof of concept. This is a study we've designed. This is a phase three study, and basically what we did was add the retifanlimab and anti-PD-1 monoclonal antibody to carboplatin and paclitaxel.
We took patients who had inoperable, locally recurrent disease or metastatic squamous cell anal cancer, and they could not have had previous chemotherapy, so they could have had chemoradiation as primary treatment, but could not have systemic chemotherapy. Here is a study design. The planned enrollment was 300 patients, and we randomized 1 to 1.
Both arms got chemotherapy, and then the randomization was to the addition of retifanlimab or placebo for a total of 12 months, and patients in the placebo arm could cross over to retifanlimab after confirmed progression. The primary endpoint was progression-free survival, with a hazard ratio of 0.67, with an alpha of 0.25, with a key secondary endpoint of overall survival using alpha spending if PFS was positive, and a number of other endpoints are shown here. We stratified for PD-L1 expression, region, and extent of disease.
So this is the CONSORT diagram. In summary, we screened 376 patients and enrolled 308, 154 in each arm. The main reason for discontinuing treatment in both arms was progression, and you can see there's a full analysis set of 154 patients in both arms. 69 patients in the placebo arm crossed over to receive single agent retifanlimab. Demographics, very much as expected and very well-balanced between both arms.
A higher percentage of female patients, which one would expect. A significant proportion that had radiotherapy previously, and a high proportion of patients with metastatic disease, so over 80%. A third of patients with metastatic disease in the liver, a small proportion with HIV-positive disease, and PD-L1 expression was greater than 1, combined positive score in over 90% of patients.
So that's the primary endpoint, progression-free survival by blinded independent central review. We met our primary endpoint. The median PFS for the placebo group is 7.4 on the bottom, and the PFS for retifanlimab is 9.3 months, with a hazard ratio of 0.63 and a significant P value. And as you can see here, the curves actually separate pretty early on and continue to separate. This is overall survival. This is an interim analysis. These data are not yet mature. We've not yet reached our events, but as one can see here, another similar pattern. The curves are separating relatively early on.
We have retifanlimab on the top, the placebo on the bottom, and these curves are separating quite nicely, currently showing a trend towards improved overall survival of about six months, which in this disease is certainly meaningful, and obviously, we've not yet reached our events. So in terms of crossover, we did a rank preserving structure failure time model just to look at crossover, a fairly standard analysis, because clearly patients in the placebo group will have crossed over to retifanlimab
. So the bottom curve is that adjusted survival, overall survival, for patients who've crossed over. And what you do is you recalculate the survival as if they've not crossed over, to give you a true adjusted placebo. And what you can see there is that just enhances the benefit even more. So we're seeing definitely a strong trend towards improved survival compared to the adjusted group.
As I say, these data are not yet mature, but the curves are separating early, and these data look really promising. In terms of secondary endpoints, no big surprises. We see an improvement in overall response. We see a really significant improvement in duration of response and a significant improvement in disease control rate.
Oh, these data we compared to our original study just to confirm that the control group is basically performing as we would hope and expect. And actually, these data are really reassuring. So what we can see is that compared to the initial study that we conducted with the carb plus paclitaxel, the data are very consistent across the board, suggesting that these, you know, the control group is performing as one would expect. In terms of safety, no concerning readouts here.
Some adverse events that are greater with the addition of retifanlimab, as one would expect, slightly higher immune-related adverse events. But the data are consistent with data we already have in terms of safety. We have no loss of HIV control, and at the data cutoff, over 58% of patients in the retifanlimab arm still remained on study. When we break that data down further into drilling down on the clinical events, as I said, nothing concerning.
These safety events were manageable. There was some increased immune-related adverse events, as one would expect, but these were manageable and not out of keeping with previous data. So in conclusion, this is the first and largest phase 3 trial of a checkpoint inhibitor in advanced squamous cell cancer. We met our primary endpoint with a PFS of 9.3 versus 7.4 months with placebo.
We have a strong trend towards improved survival, with a meaningful improvement in survival, and we see this also with response, duration of response, and disease control. The treatment was well tolerated, and we're really seeing no concerning safety signals, and we didn't compromise the delivery of the chemotherapy with this administration. So essentially, this now represents a new standard of care for patients with advanced squamous cell anal cancer. And we have a very good presentation today, followed by a great discussant, who will also confirm that this is now a new standard of care.
Thank you. Hello. Just changing tack now, we will move to gynecological cancers. I'm just going to provide you with a brief background on mainly ovarian cancer. I think I'm sure you all know that most of these patients present in advanced stage. It's very difficult to pick these patients up early, even with all the new technology we have.
They're still presenting predominantly stage three, four disease, as you can see here in the new cases diagnosed in the lower diagram. The incidence of ovarian cancer is increasing in all these territories, so it's going to become a bigger problem over time, unfortunately. The clinical course of ovarian cancer, this also of advanced ovarian cancer, you have one chance of cure, currently, as we know it, with a combination of surgery, chemotherapy, and targeted agents.
In that first-line setting, we're giving PARP and BEP as maintenance, and we continue to do that. Even with the data presented today, there will be no change to that in terms of PARP's use, and BEP is used in most of our patients in the first-line setting. Once patients have relapsed, whilst there might be one or two that can be surgically cured, we don't have much evidence of that, and the general paradigm is that we keep on treating these patients as they need, mainly according to symptoms and disease burden, with various lines of therapy.
This is where we start talking about platinum sensitive or resistant patients, okay? Not in the first line. The treatment algorithm, this is ESMO, this is Europe. So I really, obviously, it's very busy, but what I want to draw your attention to is the two halves....
That's very much consistent with that treatment paradigm of newly diagnosed ovarian cancer, where we want to cure patients and stop them relapsing, stop them needing any more treatment. That's where we really need to invest all, you know, all our efforts to prevent those patients moving into a relapse setting. However, if we failed with that, the recurrent setting, the greatest need in these patients, they all have a need, but the greatest need is in early platinum resistance or patients that have progressed on their first-line treatment.
These harder to treat patients that present with early platinum resistance or even later platinum resistance after one or two lines of treatment in the recurrent cancers, recurrent ovarian cancer setting, they really stop responding to most, to most of our agents, and this is where most of the development is coming through.
So one other kind of truth to ovarian cancer is that all patients end up as platinum resistant. So, you know, it's a catch-all phrase, but the ones that begin with platinum resistance are, have a really, really high need. Highlighting here, the focus for Incyte with our CDK2 inhibitor and the needs of the patients is in the HR proficient or HRD negative first-line maintenance setting, where Bev is used, possibly in combination with Bev and in platinum-resistant disease, the two yellow boxes.
This is a really important slide, really important bit of data, mainly generated from within Incyte. What I really want you to focus on is in all ovarian cancer, they mainly split fifty/fifty into HRD negative and HRD positive.
You have expression of cyclin E1, overexpression in both HRD positive and HRD negative, but more of them. There's an increased percentage within HRD negative. Okay, so most HRD negative patients are CCNE1 amplifier, overexpressed. The other really important bit of information here is that there's some mutual exclusivity between fully receptor expression and CCNE1 overexpression. This is important with a lot of the new classes of drugs coming through.
You can see that there are many patients that will never be served by a folate receptor targeting drug. Okay? Talking about that maintenance development opportunity in the first-line setting, most patients receive bevacizumab in advanced ovarian cancer, and the HRD negative patients are around 52% of that newly diagnosed population. They have a massive need for improving their outcomes.
Their outcomes are much less good than the HRD positive and BRCA patients, and we need new drugs there to improve their survival. So we know that the cyclin E protein expression is enriched in this population, and bevacizumab is used in that population, so there seems a very strong rationale to try to augment bevacizumab and provide a benefit to these patients by the addition of a CDK2 inhibitor, knowing that there's a lot of CCNE1 expression in that population.
And this is the diagram on the left shows you the evidence that tells you that it's around 50% of CCNE1 increased expression in ovarian cancer. So these are the competitive parties, if you like, of other drugs that are coming through. I would highlight mainly the ADCs.
They're really pushing forward into earlier lines of treatment, and I wouldn't be surprised if we're seeing some of those approved really quite soon. I would also say that ADCs are whilst they're a class, they're a class of structure, not a class of target, so it's the way the drug is put together. Therefore, each individual ADC is gonna have a very different use or efficacy, and it's really chemotherapy still. You're targeting the chemotherapy, so you have those side effects potentially.
We know we get a lot of specific things like eye toxicity, pneumonitis, so they're not without their issues, and they're also being focused in relatively small biomarker-led groups, and giving these drugs intravenously as maintenance treatment is difficult. So those, I would say, are the main competitors in the ovarian cancer landscape at the moment.
And then, very briefly, endometrial cancer. First-line setting, as you know, we're getting immunotherapy in there with very good benefit in MMR deficient patients as a single agent maintenance. But, we're getting some benefit in MMR proficient, but that needs to be augmented. So the MMR proficient is a huge area of need in endometrial cancer, and post-IO is a huge area of need.
So in the second and third line settings, historically, people have said, "Oh, but endometrial cancer patients, they never get there because they're not well enough. They don't do well enough." That's changing. There's more of them getting into second and third line, but they really. We've got no proper standard of care post-IO, so there's huge opportunity in endometrial....
So the development here for CDK2, which will be taken, Ekaterina will move this forward much more clarity for you, but it's in a newly diagnosed ovarian cancer, first line, or platinum sensitive recurrent disease, or platinum resistant as monotherapy. Combinations here potentially with bevacizumab as maintenance and monotherapy and platinum resistant. Many options for combination, you know, as we move through, but just getting that activity for monotherapy first and endometrial cancer, really, I mean, pick your line. Thank you.
Thank you, Rebecca, for this overview, and I will remain on the same tack and continue with gynecologic cancers and CDK2 data we have so far. This slide you have seen this afternoon. One take home message I would like to repeat here is that using immunohistochemistry-based tools that we are currently developing as companion diagnostic, over 50% of patients with ovarian cancer have overexpression of cyclin E, and close to 70% of patients with endometrial cancer have overexpression of cyclin E.
The tumors that have overexpression of cyclin E have dependence on CDK2 inhibition, which is synthetically lethal. We have a lot of data on that, internal as well as published, and we have selective CDK2 inhibitor that have shown strong preclinical activity, and today we have disclosed clinical activity as well. Selectivity really matters.
I won't go into the details of those slides. I think numbers speak for themselves, but selectivity against other CDK inhibition of other CDKs is important, especially for CDK1, as it's pan cytotoxic. In this regard, we believe we might have first best-in-class molecule, and also we have most advanced data in ovarian cancer, and therefore, we could have first-in-class molecule as well.
Here are listed other CDK2 inhibitors, which are in clinic, and where we could gather data from published literature based on their biochemical cellular assays and selectivity. So this is the trial. Again, this was presented from different podium this afternoon. I won't go into the details. This trial has been going on for two years now, since 2022.
Today, we presented data this afternoon from dose escalation from 84 patients. I will be discussing a lot more expansive and also more mature data with later cutoff from over 200 patients. So we have actually safety database now for over 200 patients. And I will go in a bit more detail also for efficacy in two indications that we have treated in expansion cohort, and this is ovarian cancer and endometrial cancer. I must say that we are continuing.
We kind of finishing up those dose escalation-expansion part for monotherapy, but we continue with combinations. We just started this combination dose escalation, and it's quite broad spectrum of standards of care used in those indications that we are testing. So this slide, again, in different version with less patient numbers, was presented this afternoon.
We have 205 patients that have received at least one dose. Majority of those patients are gynecological malignancies that were treated in expansion cohorts. In those escalation patients were not preselected, however, we encouraged enrollment of CDK2 overexpressed or amplified patients, and a lot of them did have amplification as locally detected. In expansion, we select patients with those tumor types for either amplification or overexpression, which we do centrally.
So 89 patients with ovarian cancer, 14 with endometrial cancer. Please note that these are heavily pretreated patients. Heavily pretreated with chemotherapy, right? So the majority of those patients had multiple lines of chemotherapy, so pretty beaten up bone marrow. In this light, we should review the safety data that we have. So this is a busy slide.
I won't go through all the numbers, but again, 205 patients in safety database, a lot of them in the doses which we are moving forward in expansions. Eighty-eight patients treated with 15, 50 milligram BID, and 63 treated with 125 milligram QD, so pretty mature data here. Majority of toxicities are on target and as we expect, so a lot of hematological toxicities.
As we expected, some GI toxicity, majority are grade 1, 2, very few grade 3 and higher grade, or very few grade 4, just a couple of cases. I should note that majority of patients actually tolerated treatment at a given dose. We had very few dose treatment-related adverse event discontinuations, and only 11 patients needed dose reduction. I think it's pretty remarkable in phase I trial, actually.
We had some DLT, so the higher dose is 75 milligram BID, exceeded MTD. 150 milligram also had some toxicities, and we did not pursue that dose level, although it's not declared as above MTD. These doses, these higher doses, separate very well in terms of expansion from the doses that we move forward in expansion. This is what I would like to show here, that these two higher doses where we had DLTs. In terms of exposure, in terms of PK, they're actually much higher. They do cross in CDK1 target into the IC50 for CDK1.
But the dose is below that we moved forward and they're bolded here, so 50 mg BID and 125 mg BID. They remain well below IC50 for CDK1, but they do cover the majority of treatment period CDK2. So potent and selective, that's basically what I want to say here. Now, all those levels do have reduction in ctDNA, which we think matters.
Deep reductions in ctDNA do correlate with tumor shrinkage, and that's what we show on the next slide. So there is a reduction in tumor size in those patients. This is both from escalation and expansion, and here denominator is 78. So 78 patients that have post-baseline scan. There were some patients that discontinued without scan, only 3 of them.
There are some patients that just enrolled, and we don't have scans on them. So that's where numbers are coming from. Now, with the asterisks or star, we have patients which are ongoing, and this is data from ongoing patients, basically. So those numbers will obviously change. On the bottom here, there are prior lines of therapy, and except few patients, most of those patients are pretreated heavily.
Now, when we looked at the patients treated at expansion doses, and again, we expanded three dose levels, there are 37 in denominator. The denominator is selected very conservatively, so those are all patients that discontinued from treatment or had at least one post-treatment scan. And among those patients, we have response rate of 24%.
Now, 50 milligram BID was expanded a little bit earlier, so data is a bit more mature, and there the response rate is 31%. On top of it, I should say that there are a lot of patients with stable disease, as you saw on the previous scan, and this really matters. I mean, in this setting where patients are heavily pretreated, delaying progression does matter.
The disease control rate is 75%. So we just show here a spider plot of the patients that have response, and there are actually two which strangely overlap. So this, there are two patients that were scanned the same time and had the same tumor reduction. This is basically the lines don't do not correspond to the previous slide, but there are PRs and CRs that you can see here.
And the reason I would like to show is that these responses are actually durable. The majority of those patients are still ongoing, and I do not have duration of response, but that's because those patients are still ongoing. Here is data in endometrial cancer. We have not discussed this at all this afternoon, but this is a preliminary data. We have treated less endometrial cancer patients. Only 14 patients were enrolled because we're focusing on ovarian cancer, and in this early set, we have 4 PRs, and majority of patients have tumor shrinkage. I mean, this is quite exciting for us as well.
Just to summarize, we are working hard to finish up the monotherapy dose escalation, dose selection, and just to bring this drug to patients in the next phase of trial, and this is what Stephen's gonna discuss in a minute. Thank you.
Thank you, Eka. Just to pause for a second, you know, I think in two years, the team has done an excellent job, both in terms of enrolling patients and then getting us adequate data in terms of both dose and schedule to be, you know, in a very comfortable place in terms of meeting regulatory requirements on declaring the dose we'll use in the registration study.
Currently, as you saw from Eka, we're expanding both the 50 BID and the 125 QD, just pending regulatory discussion on that, but we're, again, in a comfortable place on dose. The second thing just to pause on is we think we've demonstrated very clear proof of concept in platinum-resistant ovarian cancer that is CCNE1 overexpressed, and one could argue, albeit the numbers are much smaller in endometrial cancer as well.
So just to be somewhat repetitive to the prior speakers, but just to show you real-world data from the United States in terms of what's actually used, and it's actually largely in keeping with guidelines. So this is the first-line maintenance setting, and you have to be careful of terminology. As Dr. Kristeleit pointed out, the platinum sensitive and resistant definitions only come out later.
But in terms of real-world setting, in terms of maintenance, if you focus on the left side here, on the BRCA wild type HRD negative population, you can see 50% of those patients are getting Bev maintenance. Another 28% are getting PARP in the form of niraparib. As Dr. Kristeleit told you, HRD negative represents about half, 52% of first-line maintenance.
That opportunity there is 22,000 patients in the U.S., EU5, and Japan before you do the CCNE1 enrichment part, that we do obviously with this program. The unmet need part Dr. Kristeleit pointed to, the HRD negatives have the poorest progression-free survival. So number there for you of 10 to 12 months, in contrast with HRD positive patients where the PFS is 39 months, and BRCA mutants,
where it could be upwards of 60 months or 56 months. Our use of cyclin E protein overexpression, and we're not declaring our cutoff yet, because we need to have the right regulatory discussions, about 60% of those patients who HR proficient or HRD negative are cyclin E high. So there's the opportunity.
The only PARP-approved there, although not used as much as Bev maintenance, is niraparib, but the majority of patients receive Bev maintenance. So huge setting of interest to us and need in terms of trying to improve, potentially cure rates here, and a very important study that we'd like to do. Just to focus again, real world data, again, in the United States, from this year.
This is the platinum-resistant population, and you'll see it's highly heterogeneous. So if you look across the board, those are all single agent chemotherapies, topotecan, Doxil, gemcitabine, docetaxel, paclitaxel, et cetera, et cetera. The unmet need remains high in this population of platinum-resistant ovarian cancer, with average of about a one-year survival. And you saw from Dr. Kristeleit, with each therapy, you know, shorter and shorter progression-free survival.
Chemotherapy, single agent use, remains the dominant use here, with Bev maintenance in settings where it hasn't been used prior, which not contraindicated. That may be another population that may be of interest to us. The ADCs have their role. The WEE1 inhibitor remains on clinical hold at the moment. Where are we with regulatory thinking?
The major caveat here is, we still need to have the regulatory interactions on both sides of the ocean. Let me just walk you through this somewhat carefully. The study listed first there is single-arm monotherapy study in platinum-resistant ovarian cancer and potentially in endometrial as well, given the data we've seen.
That would be a regulatory strategy that would be dominant for the United States, 'cause it'll be single-arm, looking at accelerated approval, with demonstrating a response rate that's durable to get across the finish line. You saw in the one population that Eka highlighted, with the most experience thus far, that we're hitting a 30% response rate, but we can't even calculate a median duration, 'cause most of those responders are ongoing with long durations thus far.
So that's potentially of huge, huge interest and potentially a way we could go forward. In sort of, in the same theme below that, you could do that same population with a randomized control trial against physician's choice or you know best chemotherapy choice. There's different single agents in terms of your comparator.
Obviously, that'll give you a global study, 'cause, again, it's a randomized study. The endpoint here then would be a time to event endpoint, progression-free survival. We could, subject to regular discussion, do an interim on response rate there and then use that in the United States to get the accelerated approval, with the study ongoing to suffice for global approval as well as confirmation.
If we go that route, you could argue that you don't need the study above, the single arm study, 'cause you can get both with one study. So that's, again, an important population, as was highlighted, we want to address. In terms of trying to improve cure, is the study below. Again, it's maintenance after first-line chemotherapy. It's the HRD negative population.
Bev maintenance is the one in the guidelines as well as real-world data, dominant use here, and it would be a randomization of Bev plus minus CDK2 in this population. It's a progression-free survival endpoint. We still have to, you know, discuss the statistical assumptions here, but it's potentially a larger, bigger study that will take longer to get across the finish line.
Very important need to address. As Pablo said up front, we're ready to go in 2025 with this. We'll have the regulatory discussion soon, both on dose selection and the populations to go after. These are the ones of huge interest. I'll turn the podium back to Pablo for a Q&A. Thanks. Yeah.
We'll go to Q&A. Let me just make a couple of closing comments here. Earlier this year, we, we highlighted for all of you a number of important milestones that we promised to hit in the second half of 2024 and 2025. These milestones are critical as our pipeline continues to evolve and what medicines become more and more important, for patients and for continue to build the business.
Now, I think it's important to highlight that four of those milestones for the second half of 2024 have been met. Axatilimab is now approved. Retifanlimab has a positive study that we discussed today. Tafasitamab, the results that we announced, and just now we unveiled the results of what we consider proof of concept for our CDK2 inhibitor, and we give you an idea how we're going to develop this new medicine.
The submission for pediatric atopic dermatitis for Opzelura is on track for this half. For next year, we're adding milestones just to continue to build value here. The potential approval of retifanlimab in two new indications, anal cancer and non-small cell lung cancer, based on the data that we've disclosed.
The potential expansion of the label for Monjuvi, Minjuvi, for follicular and marginal zone lymphoma, and the initiation of pivotal studies or pivotal study, depending on what we decide for a CDK2 inhibitor in ovarian cancer, as Stephen summarized. So the portfolio continues to grow. If you consider current, there's milestones that we just hit.
Near term, we promise early next year the Jakafi XR data, with the initiation of our CDK2 inhibitor pivotal trials and the first pivotal study for povodacitinib in hidradenitis suppurativa, which is coming in early 2025. And then in the future, dominated by a number of novel medicines that will continue to advance and will continue to deliver data in the next year and beyond.
This will continue to progress to what we announced about a year ago, about nine, 10 months ago, which is that our pipeline is on track to deliver 10 or more potential high impact launches by 2030. I hope you would agree that based on the progress we're making over the past 12 months, this is becoming closer and closer to being a reality. So with that, I will stop my prepared remarks, and we'll be happy to take questions.
Thank you. Oh, okay. It's all right. Okay, we're gonna go from the front of the room to the back. There's one, two, three, four, five, six. I'll try to keep everybody. All right, go ahead.
Yeah. Stephen Willey from Stifel. Thanks for the presentation. Quick question on retifanlimab. Why was the duration of therapy limited to twelve months in the POD1UM trial? Do you think that you could have extracted additional clinical benefit by using longer maintenance therapy? And then maybe just another question-
Mm-hmm.
For the company. How are you thinking about resourcing retifanlimab commercial launch right now? You obviously have a little bit of GI infrastructure via Pemazyre. I know you've won in the POD1UM-304 study. You're not there commercially in lung. Is that something that you're aspiring to as well?
So let me have Dr. Rao first talk about the design of the study. I can take a first shot at the resources and Hervé can probably comment additionally. Dr. Rao?
Sure. I don't think my microphone... Oh, it is working. So HPV-driven cancer, advanced disease, that we had a lot of discussion about duration of treatment, but actually, if you look at those curves, they're separating very early on. So clearly we're getting that benefit with chemotherapy early on. So at this point, we believe that twelve months is adequate.
You can still see the curves separating now, and I don't really think there's evidence at this point to give longer. So that was the basis for our decision for twelve months. I don't think you're necessarily going to get an incremental benefit beyond that, given how early the curves are separating.
On the second part of your question, I think you answered it in the question, which is that the infrastructure it's in place because of pemigatinib. And so there's very minimal additional investment that should be required to launch squamous cell anal cancer in that population, based on the infrastructure we have in place from pemigatinib. I don't know if you want to add anything to that, Hervé.
So it's a very targeted group of physicians treating that disease. So I think there we will be very, it will be very easy, and it's not going to add very much to the, you know, sales and marketing budget. On the lung question that you asked, frankly, we don't have the answer yet.
So that's a completely separate subject. We don't think we would, should sort of invest heavily to compete in lung cancer based on the data we have, which is as good as Keytruda, but it's not very differentiated. So we are looking at a very different reason to go in lung cancer, is to have a reference, so that we can combine with our pipeline in the future, and that will be true in the U.S. only.
The lung cancer opportunity, commercially, I would put it on completely on the side and look at this squamous cell, where we have the team in place. Sorry, we can do the launch very quickly in 2025. There is a population waiting, and that population is treated by a fairly small number of physicians.
Okay, second, let's go back, and I apologize if I skip anyone. Over here, please. Ben, lighter jacket. Oh, anyway, I'm trying.
Thanks, Pablo. Evan Seigerman from BMO Capital Markets. So I want to touch on your trial design and kind of plan for ovarian cancer. You know, two questions. One, are you going to stratify for folate receptor positivity or cyclin positivity? I think that could be pretty important based on the slide that you presented. And then, as you think, kind of, bigger picture with a lot of ADCs, bispecifics, you know, how does this asset fit in five years from now, given, you know, how rapidly the space is developing? Thank you.
Yeah, great question. So let's first talk about CCNE1 overexpression. That's by IHC. As Steven mentioned, we need to discuss the cutoff with the agency. We're developing a companion diagnostic. We think based on the definition that we're using, it's a little bit over 50% of the patients. The overlap with the current definition of a folate receptor alpha positive patient, which is with the only approved one, which is mirvetuximab.
The overlap there is about a third overlap, and two-thirds don't overlap. So when we're starting to think about a study in the current environment with folate receptor anti-folate receptor ADCs approved, there's two ways to do it. Obviously, you can focus on the negatives, or you can include both negative patients and patients that have progressed on a folate receptor ADC.
That's the current landscape. Now, obviously, there's a number of ADCs being developed, and I would put them in two broad categories: follow on for folate receptor alpha ADCs, and I think what's been tried to do there is to increase or lower the percentage of cells necessary, but the percentage of positivity necessary for eligibility.
The way I read that data so far is those attempts are what they've shown efficacy in patients are lower expressors of folate receptor alpha. The toxicity of those ADCs seems to me prohibitive, particularly for organotherapy. We'll see how those evolves, but I've seen a lot of toxicity, particularly from the Sutro asset. The non-folate receptor alpha ADCs, that's certainly interesting. I would highlight the anti-cadherin-6 ADC, which has shown very impressive efficacy over 40%.
I think there are as few as, like, heavily pretreated patients than in our study, and good durability. So the way I see this evolving, which is why Steven talked about moving to early line therapy as quickly as possible. In the maintenance, after first line chemotherapy, which is long duration of therapy, we believe that's the key area where our CDK2 inhibitor needs to move towards as quickly as possible.
We will start with a rapid, hopefully a rapid approval, fast to market on platinum refractory patients, as we discussed, but moving to maintenance therapy, we think is the opportunity because of convenience, safety, and a better balance of safety and efficacy. And you saw the data. The percentage of patients, this is a phase 1 study, very heavily pretreated patients. The percentage of patients with discontinuations or dose reductions due to toxicity is extremely low.
That tells you that patients are going to tolerate this very well in the maintenance setting, and that's where we want to move to as fast as possible. Let's go here, and then we'll go back again.
All right, thank you. Matthew Phipps from William Blair. You know, first off, you I think you kind of hinted at this, but do you think a 30% response rate is almost like a bar to get single arm approval these days? The FDA, I think, has been a little bit hit or miss on where they're accepting that. And then, you know, of all the registrational paths listed, no chemo combo and no ADC combos, do you think the heme tox that you do see is limiting of going into some chemo or ADC combos?
Yeah. So maybe I'll start, and then Eka can address your second question. You know, obviously, it's somewhat tumor histology dependent, you know, given where things have been historically, response rate. But broadly speaking, in this population, we think around somewhere between 20%-30% response rate that's durable should be sufficient,
you know, indirect benefit of indication of clinical benefit to get across accelerated approval hurdle, and then you'll have to confirm it with a confirmatory study. In the study, and I think that's the number we're thinking, obviously, we're subject to discussion. And then in terms of the second question.
Regarding chemo combo, we are testing paclitaxel combination, so we'll see how it's tolerated. And we just thought that in maintenance setting, in combination with bevacizumab, we had a better rationale and better way to provide delay in the progression and recurrence for those patients, and that's, yeah, that's what we need to see.
I would complete the thought that Steven gave. So when you think about platinum-resistant ovarian cancer, if you look at the MIRASOL results, the control arm is a contemporary benchmark, right? It's contemporary. You know, 40% of the patients on weekly Taxol. There was three or four different chemotherapy regimens used.
The response rate was 16%. PFS was 4 months. So if we think about a single arm study, something that looks clearly better than that, which is somewhere between 25% and 30% with some good durability of responses, I think it should be potentially could be an approval package, and that's what we're going to discuss with the agency. Okay. So I'm probably leaving people out. Just pick one, Ben. I don't know.
The microphone.
Thank you, Andrew Berens, Leerink Partners. Guess there's a benefit to sitting at the front of the class. Just a couple on the CDK2. Is there any data that correlates replication stress and repair deficiencies? I can understand why you would certainly want to go into HRD negative patients, but just wondering how you would expect a CDK2 to work in that setting. And then I noticed, I didn't get a chance to look at it in too much detail, but there's no dose response so far. Just wondering about any comments there. And it looked, I know you tested intermittent dosing, so just any color on that you could give us would be great.
We can comment on the dose response. The first part of the question, I don't think there's data that we're aware of, correlating HRD status with CDK1 overexpression.
Yeah
and the importance of one over the other. At least we're not aware of it. You want to comment about.... Look, it's, it's tricky. It's a phase one study. Some of the cohorts are a lot smaller than the others.
Yeah.
Variability on patient population, including tumor type and prior therapy. So one has to be careful about making. And as Eka mentioned, the 50 BID cohort has longer follow-up. Those patients were entered earlier. So when you compare that with 125 QD, there's a different duration of follow-up. So I don't know if you want to comment any further.
We will perform exposure-response analyses once data matures from all three cohorts. 125 milligram QD are probably not separated that much in terms of the dose, but we will look at the exposure and differences in response rate and tumor volumes, et cetera. We'll put together as comprehensive a package as we can for our Project Optimus and just to defend the dose that we propose. I would not say that there is a very clear correlation of the dose and response right now. Again, once, as Pablo said, some of those cohorts are very small, so it's difficult to compare.
Michael.
Thanks. It's Michael Schmidt with Guggenheim. Similar question: Did you see any difference in activity in patients either with CCNE1 amplification versus the overexpression, and how finalized is your biomarker strategy? And then the other question was just about how you think about prioritizing other indications. I don't know if I saw breast cancer on your list, but I did notice in your table that selectivity over CDK4 was a little bit lower than the other-
CDKs, which could actually be a benefit in the breast cancer.
Thank you for noticing that.
Just curious how you think about that.
So why don't you take the first part of the question. I'll take the second part of the question on breast cancer.
...There's no difference. I mean, we have looked, and it's not obvious that amplified patients do better than overexpressed. And the way we are using expression kind of correlates with amplification. And I don't wanna go through the details of this, but we want to make sure that patients that we call overexpressed, they correlate with what protein level would be in amplified patients. And there's no like difference that you can eyeball. And the second part-
So the second part, I can take it.
Yeah.
Look, we have what we believe is potentially best-in-class CDK2 inhibitor. So for us, the priority was to move this as quickly as possible in ovarian cancer, try to get these pivotal trials going. The endometrial cancer was not a surprise, but it was certainly nice to see early responses in endometrial cancers are gonna push that fast as well. We are combining with appropriate therapies in breast cancer. We have already dose escalation data.
We're combining with hormonal therapy. It is a more challenging development plan for us. We don't have our own CDK4/6 inhibitor. We don't have our own CDK4 inhibitor. We are not abandoning breast cancer. We're gonna continue to do work. We'll make that decision probably at some point next year, and we'll communicate it at the time. For now, the focus is platinum-resistant, platinum-sensitive ovarian cancer and endometrial cancer.
So if I may add-
Yeah.
Pablo, the breast cancer will need combinations.
Mm-hmm.
Probably with CDK4/6 and fulvestrant, and that's what we are just starting now. So this data will come as well.
Thanks. Imogen from Cantor and Eric Schmidt's team. So you talked about the CCNE amp and overexpression, not necessarily correlating, but did you see a correlation between the level of overexpression of cyclin E and response? We saw a kind of binary high expression or-
Mm-hmm.
or low expression. And then second question, will all of the responses in resistant confirmed resistant responses?
Go ahead.
Whether they're confirmed or not. So the first question, so the way we defined overexpression, it correlates at what you would expect in amplified patient at protein level. So there is a correlation because of that.
So, the level of expression correlated with response. That's the question.
Yeah, yes. We have not looked at it. I don't want to answer this question.
We have not looked at it.
Using the cutoff, yeah, you saw the data, but I don't know if, like, higher overexpression would correlate with deeper response, et cetera, because numbers are small. I mean, I would not go there for it.
You wanna take the second one, which the answer is yes, which is they're all RECIST confirmed. Go ahead.
It's confirmed based on local assessment. We don't have central radiological assessment of those tumors.
Responses are confirmed, and denominators are conservative. I just wanna make sure everybody-
Yeah.
There's a lot of noise in this business. Responses are confirmed, and denominators are conservative. Okay, the only patients excluded from denominators are patients that have not had an assessment or in the waterfall, patients that failed before the first assessment, so you have no measurable disease. But when you calculate the response rate, those patients are included. Kelly?
Hi, Alex Kelly, TD Cowen. Thanks for taking my question. Yeah, so I was just curious if you could maybe briefly expand on why you see your CDK2 program as differentiated from maybe some of the other competitor programs, other than the fact that, you know, some of those programs may be targeting breast initially versus ovarian.
So we can only speak from public data, and what I see, what we've seen is, you know, I can summarize the preclinical data. I think that taking data that other competitors present at face value, we think we have the best balance of potency and selectivity. And the selectivity that really matters here is CDK1.
They all do, but the CDK1 is the one that lets you push the dose to really be above IC fifty, IC ninety of CDK2 for as continuously as possible, which is the PK data that I can show. So that's point number one. The single-agent activity has been reported by our competitors is pretty modest at best. There's some more interesting combination data, and there today was a presentation about CDK2 with CDK4, again, in breast cancer. The data has been presented in ovarian cancer.
We find it inferior to the data we presented today, and the third point I would make is at least one of our competitors has, what I would consider, a problematic off-target toxicity, which was ocular toxicity, which resulted in a clinical hold. Just to put it all together, I think we have the best balance of potency, selectivity, and the best balance of efficacy and safety that I've seen for single-agent CDK2 inhibitor in the clinic.
Kelly Shi from Jefferies. I have three questions. Hope you don't mind, like, too many.
No.
The first one is, you got two complete responses out of 37 patients, and it's not a very easy to end up POC settings. Curious, any particular patient characteristics you noticed from those two CRs? And the second one is, we also notice a very promising disease control rate. So curious whether you have the spider plot for those patients who achieve the SDR, are they, like, durable? And then lastly, do you have information on the mutual exclusivity between CDH6 and CCNE1, as you have showed for FRα? Thank you.
Great. So let me take the last two, and Eka can talk about those two CRs and were there any patient characteristics. I commented not that long ago that I thought disease control was important in this setting, particularly for a well-tolerated drug in the maintenance setting, because it should lead to prolonged progression-free survival. I think that's really important.
I mean, 75% disease control rate in a population of patients with three, four prior lines of therapy, I think it's a substantial number, and I think we, we need to, you need to keep an eye on that. We don't know what are the parameters of the CDH6 test. So we can't tell. We're trying to generate some in-house data, but none of that has been made public.
Allegedly, they can cover 65%-85% of the patients. We recognize that that's the way it's been communicated. For now, we're starting to do some work to understand the potential overlap. But I would go back to the way I answered your question earlier, which is, this is why we wanna move earlier. We wanna move to early lines. We think maintenance is the place for this medicine. It's a pill, easy to take, very limited toxicity. If we can drive the efficacy in those patients, that's where the most patient benefit will be and the longer duration of therapy. Eka, I don't know, you want to talk about the CRs and whether they had any?
Yeah, so the CRs, I mean, I didn't wanna go into the details of this, but responses deepen with time, which is a good thing, 'cause we might have more responses in stable disease patients as well. One of the CRs is patient that is longest on treatment, and it was actually PR and converted into CR. Should I say this or not? We have another.
You shouldn't, but you did, so go ahead.
Okay, I didn't say anything. But basically, responses deepen, so the one of the two CRs has converted as a CR gradually. The other one is patients with lymph nodes, and that. I mean, that's all I can say about that, so that patient had a lymph node. Like, majority of disease was in a lymph node, and that was also CR.
We're gonna go to the phones now, to see if there are any questions. Greg? Five. Okay.
Thank you. If you would like to ask a question over the phone, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your headset before pressing the star keys. Our first question is from Kripa Devarakonda with Truist Securities. Please proceed.
Hey, guys. Congrats on all the data, and thank you so much for taking my question. I have a question for Dr. Kristeleit. I wanna make sure she's online still. Okay, so the retifanlimab data looks really strong, and you gave us a little bit of an idea of the market opportunity. I was just wondering, first, are you already using the drug in the current SCAC? And if approved, where do you expect it to be most used? You know, you talked about 40% of advanced patients. And if the drug were to be approved, what % of your patients would you prescribe the drug to? Thank you.
Thank you for that question. Let me just paraphrase it just to summarize. So the question here is, for Dr. Rao, is: What do you see as the biggest opportunity for retifanlimab in squamous cell anal cancer? And if approved, what percentage of your patients would you offer it to? That's the gist of it.
Okay. Thank you. In terms of what this offers, well, clearly for any patient with advanced squamous cell anal cancer, this would be the treatment of choice. Patients with inoperable disease or advanced metastatic disease, this would certainly be a standard of care, and this would be a standard of care globally. In terms of the proportion of patients, it's usually about 40% of patients with anal cancer. You saw that incidence earlier, about 10,000 new cases a year in the EU and America. That, it's the ballpark there is about 40%. Most of those patients would be eligible, so nearly 40%.
Thank you.
Thank you.
Second question.
Thank you.
Yeah. Sorry, go ahead.
Our next question-
I was just gonna ask-
Oh, go ahead.
I was gonna ask about the strategy. So I know you haven't talked about the other indications, where CDK2 might be relevant. If you can't talk today, can you give us an idea of when you can talk about the potential broader opportunity for CDK2?
Yeah, yes. So beyond ovarian cancer and endometrial cancer, I think my comments were, next year, we'll provide an update on our approach to other tumor types. At some point in the next six to nine months, we'll refine that guidance, but for now, we're not going to give any more details.
Great. Thank you so much, guys.
Okay, let's go to the next online question, please.
Our next question is from Jessica Fye with J.P. Morgan. Please proceed.
Hey, this is Nick on for Jess. I was hoping... I know you mentioned that you don't have duration of response yet in ovarian, but, any based on the data you have on hand, is there any color you can provide around that and what the duration of response could shake out to be, as well as any insights into PFS?
Yeah. So, so thank you. So obviously, it's gonna be a key point to use in potentially regulatory discussions and very important based on our accelerated approval discussions. The problem, you know, is one, is limited numbers, and two, is most of the responders in the curves Eka showed you are ongoing, so you can't really calculate. But the point she was making is that many of those are already beyond 24 weeks.
So we think we're in a very good place in terms of duration of response, and then potentially, obviously, PFS as well. But it's hard to put precision on the number, but it's looking healthy, is the best way I can describe it. Yeah. Stay there for now.
Yeah. Yeah.
We need more follow-up in a lot of these patients. Next question online?
Okay.
I was hoping I could ask another one on the safety profile of CDK2. Just looking at that, I know there's discussion of it being consistent with the CDK2 targeting agent and hitting it on target, but it looks good so far. But at any of the higher doses, or even at the 50 milligram BID or the 125 milligram QD, are you seeing any evidence of off-target or potentially any CDK1-related tox, or any potential ocular tox in some of those TREAs?
So let me, let me take a shot, and you can complete it if you think I'm off base. So when you look at the PK data, at 50 BID and at 125, maybe there's a little bit of CDK1 effect based on what we know about the selectivity of this molecule. Now, to tell you for sure that some of the hem tox is CDK1, CDK2, I mean, that's, that's impossible.
What we know is that what we've seen in terms of hem toxicity has been limited to grade three. I don't even know if there's an occasional grade four. Some of the grade fours are non-hem. And they're rare, they're below 10% of the two dose levels that we're talking about. And they... When you look at patient discontinuation and dose reductions, those were very, very rare events.
So for me, that's usually the measure. And, I mean, you know, either one of our doctors can comment on how they use these medicines. If you can keep patients on drug without reducing the dose, that tells you that the drug is tolerated. Dr. Kristeleit, you've used the drug. You want to comment?
I mean, it's a really easy drug to give. I mean, I've been involved in a lot of PARP inhibitor phase ones. This is a really easy drug to give in the phase one setting to both endometrial and ovarian cancer.
Thank you.
Great. Thank you.
Our next question is from Brian Abrahams with RBC. Please proceed.
Oh, hey, thanks so much for taking my questions, and really appreciate the very detailed presentation. Just a couple from me. First, can you confirm that you haven't observed any ocular tox across the arms? Secondly, what's the right way to think about your expression threshold and internal diagnostic?
Any potential FDA back and forth or possible pushback around it, and then lastly, just curious on your dose selection plan for the registrational studies and whether, you know, fifty BID we should think about as the most likely go-forward dose, or whether it might actually depend on whether you do monotherapy or combo. Thanks.
We have not seen any ocular toxicity. We are not ready to discuss expression threshold. We think we have. We spent a lot of time in the past year working with companion diagnostics for this program, this is not something that started last week. So we think we're gonna be in very good shape when we go talk to FDA. We'll have that conversation.
We'll explain why the cutoff that we selected and the methodology we selected. So is there gonna be a back and forth? We certainly hope there won't be. And we believe we're gonna have a very productive, a very constructive conversation with the FDA. When it comes to the selection, I'm not gonna start picking favorites. We have 50 BID and 125 QD. You saw the data.
The follow-up for fifty BID is longer, so I would caution about not putting your money on that dose yet. Once we have longer follow-up and a few more patients, then we're gonna sit down. First, we're gonna do an exposure-response analysis, which the team is already working on, and that will be followed, again, not first an internal conversation and then a conversation with FDA once we have the dose selected. All this should lead, will lead to a pivotal study start next year. Two more questions online.
Thank you.
Let's go ahead.
Our next question is from Gavin Clark-Gartner with Evercore ISI. Please proceed.
Hey, guys. Thanks for taking the questions, and also thanks for putting on the event, so I had two. First, on the CDK2 and ovarian, what was the response rate at the 50 mg BID dose if you pooled the expansion and escalation portions?
We'll look at the number, and we'll let you know. I mean, they're small numbers. We can add them up, but we never looked at them that way.
Okay, got it. Secondly, what was the average time on drug until a lot of the responses have been seen? And what's your expectation for how much the QD expansion arms, the response rate may improve over time? Thanks.
Yeah. I'm not gonna speculate how much better the data is gonna get. We'll do the experiment, and we'll communicate it externally when we're ready. You wanna talk in general terms about the speed of response, Eka?
Since with sequential scans, majority of... I was actually looking at it now. So majority of responses happened on a first or a second scan, but then tumor shrinkage continues, basically.
Our next-
Yeah, go ahead.
Our last question is from Salveen Richter with Goldman Sachs. Please proceed.
Hey, thanks. This is Matt on for Salveen. Congrats on the updates. Just three quick ones, if I may. I know it's still early, but do you think the 50 mg BID might be best based on just what you know about the PK profile? Second, will you share PFS data from the study in the near term? And then lastly, on the companion diagnostic for Cyclin E, will this be something that's straightforward to incorporate into a potential launch, or would it be more of a lift? Thank you.
So the companion diagnostic should be straightforward. I think it was mentioned today, I think, by one of the speakers, IHC is a pretty straightforward test. It's widely available, no special equipment. I don't think that's going to be a problem, and I think, as I mentioned, we are on track to have that ready at the right time. I can't give a timeline for PFS.
We'll disclose PFS data when we consider the data mature enough to be disclosed. That's what we try to do. That's why we waited until we had 200 patients plus worth of safety data and the efficacy data you saw to disclose this for the first time. Once we have mature PFS, we'll disclose that. And the 50 BID, I'll answer the same way. The 50 BID cohort right now has longer follow-up.
Does it look better because it's better, or because, as Eka explained, the responses deepen over time, and the fifty BID has had a little bit longer follow-up? It's unclear at this point. That's all the questions online. Let me come back to the room, see if there are any burning questions. We have time for one, maybe two more.
One, two, three. Thank you, everyone, for attending. I hope this was helpful. It was terrific for us to update you both on the results of an amazing pivotal trial, as well as what we believe is now a program that puts us on the lead for CDK2 inhibitors at a minimum in ovarian and endometrial cancer. Thank you, everybody, for attending and enjoy Barcelona.
Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.