We're going to get started. Thank you everyone for joining us here in Berlin and there are many more of you that are online. Welcome to the small tumor update that we're having at ESMO 2025. We're very excited about two programs that we're going to talk about today. We're going to focus on two solid tumor programs, our TGFβ receptor 2 by PD-1 bispecific and our KRAS G12D inhibitor. Data for both programs was presented here at ESMO. One of them was presented on Friday, the other one was presented earlier today. We will be making forward-looking statements and let me walk you through the agenda that we have for today. We have three members of our team that will walk you through the biology rationale for a bispecific. Patrick Mayes, our Chief Scientific Officer, will do that.
Then Eka Asatiana, Head of Early Development, will talk about the two programs, the two data sets for TGFβ and for G12D. Steven Stein, our Chief Medical Officer, will work on the future plans for these two programs, we'll have plenty of time for questions and we'll be happy to address as many of those as you have. We're going to focus on two programs but equally important is we're going to focus on two tumor types today for the purpose of this update. For our TGFβ receptor 2 by PD-1, we're going to focus on microsatellite colorectal cancer. As you know, this is 80%, 85%, maybe sometimes 90% of the patients. Colorectal cancer continues to be an acute medical need because it doesn't respond to PD-1 inhibitors or checkpoint inhibitors.
In fact, four trials were done in the early days of checkpoint in developing these patients and the response rate was zero in three of the trials and 2% in another one of the studies. These patients present very frequently with liver metastases like it happens with metastatic colorectal cancer. The biology, and Patrick will walk you through some of this, is heavily enriched for TGFβ. In addition, some of the more recent immunotherapies that have been tried in this patient population have also been largely unsuccessful. Particularly, and I bring your attention to this and Eka will talk about it, particularly for patients that have liver metastases, which are of course more than half the patients. The second tumor of interest for today is pancreatic ductal adenocarcinoma (PDAC) for our G12D program. We recognize this remains a very competitive area of drug development, is increasingly competitive.
G12D is the most common mutation in this patient population. Importantly, these patients do have a worse prognosis than wild type patients. That's becoming very clear now that we're focusing on the development in this population. I would highlight that there is no KRAS G12D inhibitor. Not only are none of them approved, but there's no KRAS G12D inhibitor in pivotal trials in pancreatic cancer. Today there's a window of opportunity for us to move in an accelerated way for this disease with a KRAS G12D inhibitor. Very important as you think about first line therapy in patients with pancreatic cancer is the ability to combine a KRAS G12D inhibitor with chemotherapy. This is not just about the activity of the molecule or single agent, but the combinability.
With both main types of chemotherapy in this disease, gem abraxane and modified FOLFIRINOX, you need to be able to cover both in order to address the entire pancreatic population in first line therapy. We're moving in that space. I will give you an update there. Just to walk you real quick through the framework that we use to make decisions for these two programs and other programs. For the two programs we're talking about today, the first part is obvious: to establish single-agent activity. You've seen during this meeting and you'll get more data today about the single-agent activity about TGFβ bispecific in the KRAS G12D setting. That part and you've seen the safety profile we're very pleased with. That part is almost done. These are single agents, they have single-agent activity, and they're tolerable at the recommended doses for expansion. Now we need to demonstrate earlier response.
We have that data for TGFβ bispecific and Eka will show it. We are following the patients in the G12D program to establish what the durability of the responses are. The third part is to combine, and as I mentioned, standard-of-care i n both cases that would be chemotherapy. The TGFβ receptor 2 bispecific will be FOLFOX, bevacizumab. We've done that work Eka will walk you through it. For our KRAS G12D inhibitor, I mentioned two types of chemotherapy, that work is being completed as we speak. We're moving this in that direction. The fourth thing we did is ask, where is the most acute medical need? Where can we have the biggest impact for patients and over time for the business? That is in first line in combination with chemotherapy. That's our focus for us for these two programs.
We're not ruling out other investments in other areas, but those are the two areas that we're really going to have a more intense focus. With that, I'm going to stop here. Patrick Mayes can come up and walk us through the biology and how we designed our bispecific and why it is a unique approach to address TGFβ biology, which arguably is the second most important mechanism of resume tolerance from tumors other than PD-1, PD-1 axis. Eka will follow with the updates on the clinical data for both the TGFβ program and the 12 people.
I'm going to overview our f irst-in-class bispecific antibody targeting TGFβ R 2 and PD-1. We'll refer to this as INCA33890. This is what we're going to discuss. I'll take you through a bit of the importance of TGFβ in the solid tumor micro-environment, why it is such a potent immunosuppressive factor, and why we believe targeting this factor is going to be so important in these tumor types. I'll tell you a bit about the fundamentally different approach we've taken at Incyte in targeting this biology, why what we're doing is distinct from what others have tried in this space before. I'll show you a bit of preclinical data, but I'll refer you back to a presentation we made at AACR 2023, which is a much more comprehensive characterization of the molecule. Refer there too for the full profile of the molecule and then echo w alking to the clinical data.
TGFβ is a potent immunosuppressive factor in solid tumors. It acts directly on T cells, it binds to T cells and inhibits their function and their proliferation. You can see this in the graph o n the left hand p art of the slide here in blue is T cells that have been induced to proliferate. Increasing concentrations of TGFβ blunt that p roliferation, inhibit that from happening.
We could take T cells and we can treat them with a PD-1 antibody. As shown in red, PD-1 induces proliferation of T cells, induces their activation. TGFβ is a dominant factor. Even in the presence of a PD-1 antibody, TGFβ inhibits the proliferation of those cells. It speaks to the importance of TGFβ. Even in the setting of a PD-1 antibody within the solid tumor micro-environment, high levels of TGFβ are associated with an immune-excluded phenotype. This is where immune cells are present in the tumor, but they're excluded from direct contact with tumor cells. Instead, they're stuck in the tumor stroma. They're unable to form productive synapses with tumor cells and elicit that antitumor immunity. What we know is that the immune-excluded phenotype, in addition to high levels of TGFβ, are associated with PD-1 non-response in the solid tumor micro-environment.
Together with Tempis, we looked at TGFβ biology across solid tumors. This is an analysis of 16 different solid tumor types that we looked at. We looked at two different factors in this particular plot that were shown here o n the bottom right. First, TGFβ R 2 expression on the X axis, and then we looked at a TGFβ gene signature that's associated with T cells. This is on the Y axis. These two factors we looked at in various solid tumors, and you can see a high enrichment score for TGF β across solid tumors.
In particular, MSS colorectal is highly enriched f or TGFβ biology b ecause of the importance of this biology, multiple attempts have been made at targeting this pathway in solid tumors. None has yet to be successful clinically, and you can bucket these approaches into two broad categories as to how they've been engineered. First is agents which target the receptors directly. We have TGFβ R 2. It forms a heterocomplex with TGFβ R 1, and that's how the signaling occurs. Antibody approaches have been attempted targeting TGFβ R 2. Monoclonal antibodies have failed due to toxicity. Likewise, small molecule inhibitors of TGFβ R 1 inhibiting the kinase domain, which signals downstream, have been tried and have failed because of toxicity associated with the approach. TGFβ is an important factor in normal tissues around the body, and it's, I think, the narrow therapeutic index associated with broad, potent inhibition systemically.
More recent approaches have worked upstream of the receptor to try to minimize the toxicity associated with broad inhibition. These approaches can be characterized as agents which target the processing of ligand or the engagement of ligand with receptor, either using a trap or a monoclonal antibody. These approaches can be characterized as being partial inhibitors of TGFβ. This is what gives them the therapeutic index necessary to be able to dose in humans. This partial inhibition profile has yet to be successful in terms of eliciting efficacy in cancer. The approach we've taken is different. It's distinct from what others have tried. Here, we're taking a cell-targeted approach where we are targeting TGFβ R 2 on tumor-infiltrating lymphocytes and potently and completely inhibiting that signal on those cells, thus having full activity on the cell type of interest and avoiding the systemic toxicity associated with pathway inhibition.
How have we achieved this cell-targeted approach? We have generated a one-by-one bispecific antibody, and we're utilizing a dock and block mechanism of action here. The first thing we did was engineer a very high-affinity PD-1 binding arm for this antibody. This binds to and inhibits PD-1 on all PD-1 positive cells in a body. We then engineered and tuned a TGFβ R 2 arm in a way that it allows for potent and complete inhibition of TGFβ R 2 only in the context when the PD-1 arm of the antibody is prevalent. No inhibition of TGFβ signaling occurs on cells that do not have PD-1 expression, thus avoiding the toxicity associated with raw TGFβ inhibition in the body. An example of this selectivity is shown here on the graph on the left.
This is an example of a cell line that has TGFβ R 2 expression but no PD-1 expression. The control for this experiment is in blue. This is a monoclonal antibody targeting TGFβ R 2. It inhibits completely the signaling through the TGFβ pathway via Phospho-Smad, whereas the bispecific shown in red has almost no signaling inhibition in this context. If you look, this is an isogenic system. The only change being made in this cell is the introduction of PD-1 expression on the right, and the control looks the same. You see potent and complete inhibition of TGFβ signaling, whereas in this context the bispecific antibody has complete inhibition of the pathway, even to a greater extent than the monoclonal antibody. In summary, we have a potential first-in-class bispecific here. This is a context-dependent inhibitor of TGFβ signaling in tumor-infiltrating lymphocytes.
We believe there's strong rationale for this agent in tumor types where TGFβ is highly enriched. This includes a number of tumor types where immune checkpoint inhibitors have not been a pproved and are not used, such as o varian cancer and MSS colorectal cancer, which w e'll talk about today.
We believe this also has a PD-1 better approach and potential. In tumor types where ICI is approved, PD-1 is used, and this provides the opportunity to expand the responsiveness in those t umor types as well. I will stop here and pass i t over to Eka.
Thank you, Patrick. I'll now switch to clinical data that was presented on Friday as Pablo mentioned. This is a schematic of a phase I trial that we presented d ose escalation was done in selected tumor types from 100 mg- 1500 mg given every two weeks IV. We also tested 900 mg every four weeks. We arrived at three recommended doses for extension and randomized patients with selected tumor types. Those were selected based on the TGFβ data signature that Patrick mentioned. The biggest enrichment was for colorectal cancer. The biggest group was patients with MSS colorectal cancer in this extension. In parallel, we also tested selected tumor types in combination regimens with focus with standard-of-care relevant for colorectal cancer such as FOLFOX- bevacizumab, Pertuzumab, bevacizumab, and cetuximab.
Dose escalation with 900 mg has been completed and now we are enriching and enrolling more patients in extension cohorts, particularly with FOLFOX and bevacizumab to support the safety database for the phase III trial. This is baseline demographics and characteristics of 260 patients that were treated in the monotherapy cohort as of July 25, 2023. This is a pretty mature data set, 52 patients are still ongoing, majority have discontinued. It should be noted that discontinuations due to treatment-related adverse events were extremely rare. Only 4.6% of patients discontinued due to adverse events. The other thing I want to note here is that it's a very advanced patient population. As you can see on the bottom of the slide, there is 35 months from initial diagnosis. Multiple lines of therapies were given to these patients, median of 3 and range of 1- 9.
Again, biggest set is in MSS colorectal with 114 patients treated with this trial. Safety summary: we escalated doses up until 1,500 mg without dose-limiting toxicities (DLTs), 1,500 mg exceeded maximum tolerated dose. There was one DLT of myocarditis but there were also other severe immune-related adverse events, those endocrine and CNS events in later cycles at this dose level, and we stopped enrolling patients at that dose level and extended those levels below. 300, 600, and 900 were extended and that's the data set I want to focus and present.
Now i t should be noted that treatment-related adverse events and grade 3 events are very rare. This compares very favorably to approved checkpoint inhibitors. There were, especially in the 900 mg group, large group, 110 patients. We had very few grade 3 events in single-digit percentages, very few serious treatment-related adverse events. There were few treatment delays and only two patients discontinued due to adverse events. When we look at the immune-related adverse events as reported by investigators, again 5% grade 3 events. We also looked at infusion reactions. There were some infusion reactions of grade 4, two events, one leading to discontinuation, other one with rechallenge. Those happened at lower doses. Once we evolved training of the sites on infusion rates and premedications, secondary prophylaxis for premedication, those events reduced and there were no grade 3 or higher events at 900 mg.
A bit more granular view of safety profile with treatment-related adverse events is decreasing frequency and 5% gut help. Again, few events r ates with treatment-related adverse events are mostly skin toxicities in rash and pruritus. Also, one transaminase increase in 900 mg. Here we have slide describing pharmacokinetics and anti-drug antibodies. Very favorable and typical, I would say, for bispecific antibody. There is some treatment-mediated drug distribution at the lower doses. We did have anti-drug antibodies in 78% of patients, but that did not affect PK, so it did not affect concentration at 900 mg in large cohorts of patients that we had. We also did analysis of ADA versus adverse events and ADA versus efficacy, and there was no correlation there. It did not also correlate with infusion reactions.
We did paired biopsies and evaluated, among other things, CD8 cells, and there was increase in cycle 2 day 15 on treatment, and this extent of this increase correlated with the efficacy, enriched for the efficacy in responders versus non-responders, and finally efficacy data. Here we focus on MSS colorectal cancer. We had 105 patients treated and available at RDS at those three dose levels that I listed before. This was heavily pre-treated patient population, so 93% of those patients received this treatment as third line and beyond. They had two prior lines of therapy. 70% had active liver metastases, and those were large active metastases. I will show a couple of representative cases. 16 of those patients responded, and most surprisingly, I must say for myself personally, as that has never been reported before, those patients with liver metastases also had responses.
9 out of 16 had active liver metastases, and seven had no liver metastases. There was no correlation of those versus efficacy that we could tease out from here, which is again not surprising for immunotherapy. Duration of treatment was 7.3 months, and I'll show you on the next slide swimmer plots for patients, for responders basically, and you can see that these are confirmed responses in the majority of the patients. The bottom swimmer plot is not confirmed but ongoing, so confirmable. There is another one that discontinued before confirmation, but the rest of them are confirmed responses. I should note here also that there is this one patient that discontinued early due to actually low grade troponin increase and continued to have response for one year, so eight months beyond discontinuation, but quite striking response in this patient.
This is a 73-year-old gentleman with stage 4 MSS colorectal cancer with multiple visceral metastases: liver, lung, also bone metastases. This patient had prior FOLFOX, bevacizumab, and FOLFIRI treatment, was treated at low dose at 300 mg, and achieved PR at 28 weeks and confirmed at 32 weeks and remained on treatment for another year. You can see how big these liver mets are t hese are not small liver lesions. These are clinically relevant but clinically active big lesions that show shrinkage. We have this target lesion measured, and also there are non-target bigger lesions, which also show another case.
Again, patient with prior two lines, actually four lines of therapy here: FOLFOX, bev, and FOLFIRI, and some additional including investigational agents, treated at 900 mg, achieved PR at 8 weeks and confirmed at 16 weeks, and currently still on treatment 10 months +, again big liver lesion shrinking. I think it's very illustrative of what it concerns those patients. We also saw responses and efficacy in other tumor types where we would not expect immunotherapies to work, among them in patients that have been previously treated with immunotherapies. As you can see here in blue, we have patients that have received prior checkpoint inhibitors. We have responders among head and neck patient and as well as non-small cell lung cancer patients, pretty impressive responses in ovarian cancer patients. We have also marked the patients here that have very low PD-L1 staining of less than one CPS score.
Amongst those patients as well we have some responders. This data increases our confidence that these biologies that Patrick described has proof of concept, strong proof of concept with clinical efficacy in tumor types that would otherwise not respond to immunotherapy, and also coupled with very favorable safety profile. Based on this we started combinations relevant for earlier lines of therapy in colorectal cancer. We have now cleared in those escalation cohort of patients for bevacizumab and FOLFOX, FOLFIRI- bevacizumab, bevacizumab and cetuximab. We are currently enrolling larger cohort focusing on FOLFOX and bevacizumab in preparation of supporting phase III trial with additional safety data. The combination looks good. There is no overlapping toxicity that we could tease out from patients treated so far. To conclude, 900 mg is selected as a recommended dose. It has favorable PK profile.
There is very little effect of ADA or actually no effect of ADA on PK at this dose level. There are responses observed in MSS colorectal cancer patients including ones with active liver metastases. Currently we are preparing phase III trials that Steven is going to describe in a minute. I will switch now to KRAS G12D inhibitor. The key takeaways here. We all know that KRAS is one of the most common driver oncogenes relevant in solid tumors and G12D is the most relevant one and most common one from an isoform. Amongst them we have inhibitor which is potent and selective. It's on and off inhibitor and hopefully today I'll be able to convince you that we have a potential to be the first selective G12D selective therapy for G12D mutated pancreatic cancer.
KRAS G12D cancer again it's a molecular, it belongs to KRAS proteins, molecular switches that control multiple signaling cascades that promote cellular proliferation and survival. This isoform G12D is most common mutation more relevant in cancer with close to 40% of patients having G12D mutation, also enhanced multiple lung cancer and 15% of colorectal cancer. Now G12D confers poor prognosis in terms of response to chemotherapy, also overall survival and when compared to wild type KRAS wild type, but also other G12 isoforms. Compared to other KRAS mutations it confers prognosis. This is a data that was presented by Patrick's group in 2024. We have G12D inhibitor INCA0734 which binds KRAS protein inactive and active forms as they switch to pocket and it's a picomolar concentration so it is potent.
It is also selective with more than 80-fold selectivity in different assays and you can see some of them on the right side of the slide. We have presented number of preclinical data in xenografts and syngeneic tumor models and this was all in the poster at AACR in 2024. I will today present clinical data that was actually presented from scientific podium this afternoon. This is from this phase 1 trial where we conducted dose escalation in G12D-mutated tumors from 200 mg- 1600 mg QD. We also tested twice a day regimen with 600 mg twice a day in parallel. We did additional exploration in PD cohort at two dose levels, 600 and 1000, with paired biopsies. We did some food effect work which enabled us to administer drug.
Now with food we selected two dose levels, 600 mg and 1200 mg, and randomized patients across those two dose levels in this patient. The largest cohort we have is in pancreatic cancer and also colorectal cancer and additional work is ongoing in other tumor types. We further enriched 1200 mg which we selected out of those two RD extensions and focusing on second one I think, pancreatic cancer. We also tested combinations with chemotherapy regimens for pancreatic cancer. Both commonly used chemotherapy regimens are gem abraxane and FOLFIRINOX. We also actually combined with TGFβ receptor 2 PD-1 bispecific and currently the first dose level is ongoing. This is a patient disposition and baseline characteristic. As of August 1st cutoff we have enrolled 138 patients on monotherapy. The largest group here again is pancreatic cancer with 83 patients followed by colorectal cancer.
This is less mature data set so more than half of the patients are still ongoing. 75 patients are still on treatment. I should note here that there are no toxicity-induced dose discontinuation. No patient has discontinued treatment due to adverse events. Very heavily pretreated population with multiple prior lines of therapy. Focus here again is on pancreatic cancer and as you can see in this data set in these 83 patients treated at various dose levels only 13 were second line patients. Majority were third line and plus. Safety profile, no DLTs were observed. We arrived at all the way up to 1500 mg-1600 mg without any DLT. MTD was never reached. However, we stopped dose escalation and decided to expand 600 mg and 1200 mg based on emerging PK and PD data that I will go through in a minute.
Once again, I would like to mention that no patients discontinued treatment due to adverse events. The most common treatment-related adverse events leading to dose reductions were nausea, decreased appetite, and fatigue. The majority of adverse events were grade one and grade two, and I will show it on the next slide in a bit more granular way. These are treatment-related adverse events with frequency of 5% and above in decreasing incidence. As you can see, GI toxicity is on top of the list. The majority of those cases are grade one, so half of them are grade one. Very few grade two and grade three events, including nausea, diarrhea, vomiting, and fatigue, which are the common ones. We also looked at our database for myelosuppression, skin toxicity, et cetera. They're isolated cases, but there is no signal. We do not observe it in lung cell.
Here, there is a PK profile focusing on two dose levels, 600 mg and 1200 mg. Those dose levels at steady state cover IC95 more consistently at 1200 mg higher dose. Also, when we looked at ctDNA change from baseline in pancreatic cancer patients, there was deeper and quicker reduction at higher dose. That's why we selected 1200 mg as the dose to move forward. These deep reductions in ctDNA also correlated with clinical responses. We actually did this, which we were complimented today. We did it real time during the dose escalation, and it really helped us with the dose escalation, selection of the dose. Here is efficacy slides of waterfall plots, and I'm going to take time to walk through this slide slowly, so indulge me for a minute. It's a busy slide, and we show a lot of things here to be as transparent as possible.
We have waterfall plot with scans in 50 patients. We include in our denominator all patients that were treated and discontinued treatment or had at least one scan, so 54 patients included in the denominator. The majority of those patients received treatment as third line +. There are only nine patients that were treated as a second line in this data set, in this 54 patients. The third point I want to make is that the majority of those patients only had one scan, and many of them are still ongoing. 27 out of those 54 only had one scan. We know from other G12X, so default C and D inhibitors, that actually responses can take place on a second and subsequent scans. With all of this said, we have 34% response rate and high disease control rate of 86% person illustrated case here.
This 69-year-old gentleman with stage 4 pancreatic cancer was diagnosed in last year 2024, extensive mets, liver, lung, peritoneal, which usually do worse, previously progressed on FOLFOX and received this treatment at 1200 mg, received treatment without interruptions, have deep reduction of disease including the primary tumor, which is actually harder to treat. Usually the primary pancreatic lesions do not respond as well. This patient has a large reduction of pancreatic mass and was assessed then on two subsequent scans and had a confirmation of PR on 20- 24 weeks. AZO treatment still continues on as of today. Continues on treatment. In conclusion, we have a molecule that has manageable toxicity profile, bipolar bowl. We have selected a dose now based on ctDNA, PK coverage of the target. We have very promising early clinical efficacy, still confirming durability of responses.
We have combined with two different chemotherapy regimens, gem abaraxane and modified FOLFIRINOX. Gem abraxane has finished dose escalation, we're extending. For FOLFIRINOX, we are still waiting for completion of the DLT evaluation period for the last couple of patients and we plan to expand this as well. With this, I will pass on to Steven to discuss next ones.
Yeah, thank you. Eka, Patrick, Pablo. The reason I'm standing here is important in that you can see we are about to go into the next phase of development. I'll outline the why behind that and then we'll invite everybody up here for a Q and A. Just to go back to the framework that Pablo gave you up front and reset it based on the data you just saw. If you look at the framework in terms of establishing single agent activity and the safety profile, both for TGFβ and for KRAS G12D, you saw the efficacy signals given to you in the monotherapy data. Safety profile for the TGFβ, you saw mostly IR-related AEs and a DLT at 1500, which is not the dose we'll be taking forward. For the G12D profile, you saw the GI safety profile.
In terms of monotherapy single agent activity for both, you saw what is striking single agent activity for TGFβ in microsatellite stable colorectal cancer, particularly for the liver metastases, which is unprecedented in terms of immunotherapies. For G12D, I'll just paraphrase the discussion today at the session. They said remarkable activity and potentially the best single agent activity seen in PDAC with a G12D-directed agent to date. Durability of response demonstrated with TGFβ receptor 2. What's becoming common with immunotherapies is once patients respond, those responses are very long. You saw duration of therapy for the majority of patients greater than 24 weeks. One could argue that for the KRAS G12D, we still have to wait a bit longer to see durability of response, which is obviously what we'll be doing before triggering the registration program.
The profile when combined with standard-of-care is ongoing now as Eka alluded to, but we cleared the initial safety hurdles in terms of DLTs and very importantly for the G12D compound, we've demonstrated that both for gem abraxane and for modified FOLFIRINOX. Why is that important? If you look at real world use of those regimens in first-line pancreatic ductal adenocarcinoma, it's about 50%, 50%. We feel it's very important to be able to combine potentially with both chemotherapy regimens. Lastly, this is a clear medical need in very large tumor types. Quantitatively, these are enormous problems across the world and massive unmet need in terms of microsatellite stable colorectal cancer and pancreatic ductal adenocarcinoma. Let's go back to microsatellite stable colorectal cancer. It is one of the most common cancers seen worldwide. It's a leading cause of cancer death.
In fact, if you look at the United States, Western Europe, Japan, there's nearly 2 million people diagnosed with colorectal cancer and about a little north of 400,000 of those are stage 4 metastatic patients. Unfortunately, the long-term survival for patients with stage 4 metastatic microsatellite stable colorectal cancer is dismal, 16% 5-year survival rate. As both Pablo and Eka pointed out, immunotherapies in microsatellite stable colorectal cancer have little to no activity. Particularly in patients with liver metastases, that's become almost a clinical marker of the lack of immune responsiveness. Hence, that very important signal seen in patients with liver metastases. The standard of care in the first-line setting in terms of chemotherapy is FOLFOX bev or FOLFOX EGFR. The FOLFOX bev regimen is used regardless of RAS status, whether you're mutant or wild type, regardless of the sidedness of the tumor, whether you're left or right sided.
The EGFR combo is used mostly for left-sided tumors and is more commonly used in Europe. Ballpark response rates for these chemotherapy regimens are in the 50%- 60% range. PFS 8 months, top end 11 months, and overall survival 30 months. Speaking to the massive unmet medical need in this population, as Patrick showed you, TGFβ expression is extremely high in the tumor micro-environment in microsatellite stable colorectal cancer and is probably, outside of PD-L1 expression, the dominant marker of T cell unresponsiveness. There's an opportunity here to establish a novel regimen in first-line microsatellite stable colorectal cancer that builds on the current most common standard of care, which is VEGF combined with the chemotherapy FOLFOX bev. It's a broad population, independent of RAS status, independent of sidedness, and reminder that about 70% of patients have liver metastases.
In terms of biomarker diagnosis, this covers 85% of the population, with the other 15% made up of the microsatellite high, some BRAF mutant tumors, and then obviously other biomarkers like HER2. But 85% would be covered by this regimen potentially. Where are we? We have durable single-agent activity, a manageable tolerability profile demonstrated by Eka's data set in late-line microsatellite stable patients. The responses are observed both in patients with and without liver metastases, and the profile thus far provides an opportunity for combination in first-line microsatellite stable colorectal cancer with the standard of care chemotherapy. With some ongoing safety work, going to be clear, we're planning the initiation and we speak now of a phase 3 registrational program in early 2026 for first line microsatellite stable metastatic colorectal patients in combination with standard-of-care. We've aligned with regulators on the schema and the primary endpoint of progression free survival.
Turning to pancreatic ductal adenocarcinoma, this is probably the most RAS-addictive cancer with no targeted therapies for the specific mutation KRAS G12D patients. It's a rapidly progressive disease with extremely high mortality, less than a 10% five-year survival rate. In Western Europe, North America, and Japan, 210,000 patients, of which greater than 90% carry a RAS mutation, of which 40% of those have a G12D mutation. First and second line metastatic treatment is limited to combination with single-agent chemotherapy, and because of the severity of the disease and the lack of tolerability of the regimens up front in these patients, most patients do not make it to second line regimens. Chemotherapy is associated with many grade 3 and 4 toxicities, particularly myelosuppression as well as neuropathies. The care standard, as I said up front, is argued between gemc abraxane versus modified FOLFIRINOX, probably split 50/50 with some regional differentiation.
Response rates in the 20 40% range, median PFS 5.5 monthsto -8 months, and overall survival of 8.5 to 11.7 months with those chemotherapy regimens. Where are we with our KRAS G12D in pancreatic ductal adenocarcinoma? Again, a solid proof of concept. As the speaker said today, remarkable activity and maybe probably the best data seen in the G12D mutated patients to date. G12D mutations are known to carry a worse prognosis than other patients with a manageable safety profile in the heavily pretreated population. Ongoing enabling work with the chemotherapy combination is important. Both gem abraxane plus modified FOLFIRINOX. We feel we have the first potential targeted therapy for KRAS mutated PDAC patients. We'll continue to do the enabling safety work and continue to evaluate the durability of response, which is immature based on the data set Eka showed you today.
We'll be aligning with regulators on the registration program. Pending those, we'll be going into registration in first line PDAC in combination with both chemotherapy regimens also in 2026. I'll summarize again, large patient population by size, significant unmet needs, certainly in the cancer setting, probably the most significant unmet needs in terms of microsatellite stable colorectal cancer and pancreatic ductal adenocarcinoma. To reiterate the importance for us of going to first line to make the most difference for patients in this condition, we feel that's an important strategic choice that we've made. The TGFβ bispecific, the efficacy and safety data support that advancement. A novel regimen in the broadest population in combination with FOLFOX and bevacizumab. To reiterate, we'll be initiating a phase III program in early 2026. The G12D probably a little behind, but single-agent activity demonstrated manageable safety profile.
The ongoing enabling work with safety and then the durability that needs to be finally assessed before we trigger the program. The intent is to start that program as soon as those milestones are achieved and to be the first potential targeted therapy for KRAS-mutated G12D patients.
Pancreatic cost? No. With that, I'll ask Pablo to come up and the other two speakers to join us all on the program up here. There are about 100 people online. We'll first take questions in the room and we'll move into online.
Thank you. Patrick, Eka, Steven, starting the room, please.
Hi there. Evan Seigerman from BMO Capital Markets. At ESMO last year the focus of your event was really on your CDK2 inhibitor, the gynecological cancers. This year, talking about G12D and TGFβ. These data are fantastic. I don't want to deny that, but it seems that the effort's a bit inconsistent. How should I swear?
How? You're thinking more broadly about solid tumor development. In that one year we're talking about one topic. The next year we're focused on G12D and pancreatic cancer.
You're correct. Last year I focused with CDK2, C DK2 inhibitor program was obviously ahead and generated efficacy data in ovarian cancer. That program, I would say, is today the most advanced CDK2 inhibitor in development. We're developing, as you pointed out, in the brain cancer. I think that the approach that we're taking with these three programs is quality science, quite honestly. In CDK2, we generated data, some data in breast cancer. That work hasn't stopped, but it hasn't been the main focus. Early on it was obvious that we had responses and a lot of stable disease with CDK2 in bladder and resistant ovarian cancer. We agreed to chase that signal, which is what we're doing.
We found out the combination with bevacizumab and our goal in the long run is platinum sensor ventures. We're basically maintenance up to first line. We think in patients post chemo bed that need maintenance, which is long duration of therapy for 12, 15, 18 months. Oral molecularly targeted therapy with an excellent safety profile could have a big advantage over intense competition that continues to emerge in ovarian cancer. Now for these two programs, we once again follow science for TGFβ. As Patrick explained, we had the hints that the biology gave us about the importance of the TGFβ pathway in particular MSS colorectal and others. Early on we saw responses in MSS colorectal. We accelerated development there. We enrolled more than 100 patients. We have a very strong efficacy signal and we've done the combination work. I think for the KRAS G12D inhibitor was most straightforward.
We knew where to go from the beginning, you know, in fact, even though it was clear which patients to go after, the pancreatic signal emerged faster than the others. We are doing some work in colorectal. I think we have a unique advantage in EGFR treated colorectal cancer because the ability to combine with cetuximab, which I think some recruitment pedals may have difficulty. I gave you a very long answer. I think what we're doing with these programs is we establish some scientific principles at the beginning and then in a disciplined and thorough way, we chase science driven signals and we make decisions based on the emerging data and we'll continue to do that. We're not going to go everywhere all at once.
We are being deliberate in how we pick these opportunities in order to use to have disciplined use of capital at the same time trying to address medical needs. Michael?
Thanks. Michael Schmidt with Guggenheim on the G12D program. I know that discussion today talked about t he GI portability on your molecule and one of the others, and just wondering if you could share any insights or i nsights from your combination work that you've b een doing with chemotherapy. Let's focus on GI, and there was a comment today by discussing about diarrhea specifically. I'm not sure why they focus on that, but maybe you can talk about a little bit more, gram, or what we're seeing?
12 mg is 1,200 mg is what we're moving forward and enriching with additional patients. We have seen GI toxicities, majority grade 1 cases, manageable with anti-diarrhea and antiemetics. There are very few grade 3 cases, no discontinuations due to this.
Combination with chemo.
Combination with chemo is ongoing with FOLFIRINOX. Gem abraxane was tolerated without any dose-limiting toxicities, so we don't have to dose reduce, we don't have to dose reduce chemo, and we do not have to dose reduce those that we chose for the next exposure.
You have to remember right when you look at a certain % with a certain grade toxicity, that's diarrhea. That person has one day of that grade diarrhea that gets counted automatically there. I think Eka gave you more granularity, and what I always look for is dose discontinuations, dose reductions, dose interruptions, and from that perspective we're comfortable that this has proven to be a well-tolerated drug at these doses and the combination with chemo. As we pointed out in the presentation, we're about to clear the dose escalation period for the FOLFIRINOX and nab-paclitaxel is done.
Could you speak to competitive positioning around your KRAS G12D program? As you noted there's not much of a second line opportunity versus first line. You have Revolution Medicines with two assets here. Maybe put that in context for us especially as you think about combining with standard-of-care?
KRAS in general with pan-KRAS, and for specific inhibitors, obviously, it has become extraordinarily competitive in the past couple years. When we look at all the data available, including two or three of the presentations today, in the last couple of days, we are convinced that when you look for G12D-specific patients, G12D-mutated patients, the balance of efficacy and safety that we have is best in class. If there's somebody that is comfortable, perhaps, but we are very comfortable with the tumor reductions that we're seeing. The tolerability, and now as Eka pointed out, the tolerability in combination with chemotherapy, we can combine with both main types of chemotherapy for pancreatic cancer. Let's remember the gem abraxane and FOLFIRINOX are used in about 50% of the patients. If you can cover the entire chemotherapy spectrum with a precisely targeted G12D inhibitor, we think that's going to be an advantage.
Now, second line, we think that train has left the station. That second line study is ongoing. They're probably going to file next year. We expect that to be positive. As Steven pointed out, patients with pancreatic cancer, the opportunity really is reduced dramatically in second line. We think that the big opportunity here for patients and for the business is in first line in combination with chemotherapy. Our goal now, as we continue to monitor the emerging data to make sure we're making the right decisions, is to move to implement those studies, the first line study, as quickly as possible. If the data changes over the next six months, we'll act accordingly. Right now, the plan based on what we have today is to move as quickly as possible to first line PDAC combination with chemotherapy, and we think we can be very, very competitive there.
Rem Benjamin from Citizens. Here's two questions. One, in your framework, one thing that was missing is the comparison of other drugs in development, whether it's drugs currently in development or ones that are already established. I'm kind of curious as to when does that get factored in to that. The other is, I think Eka, you were mentioning that the MSS, the gene signature that was used to not just identify MSS CRC, I think you said it was utilized in clinical trial as well. I'm kind of curious, how heterogeneous is that gene signature, does it represent a correlation with response, and could you use it for patient selection? Retuning patient selection.
Let me address the first one and then Eka and/or Patrick can address the gene signature. We are constantly monitoring our competitors and when we look at, let's take this two more times.
I think I explained our precision is a big competitor. As for G12D pancreatic cancer, obviously we're fully aware of who's leading the race in second line. We have a chance to compete in first line and figure out a very competitive profile. Nothing that I saw in the last couple of days changes in my mind our competitive positioning for G12D inhibitor and PDAC. I think for a first line MSS colorectal, there's less activity. The way we look at it is we have unprecedented single agent response in fifth or fourth line ancestral rectal for immunotherapy. There are four trials historic of Neva, Pembra, et cetera. Three of them had a 0% response rate. One had a 2% response rate. We showed 15% response rate today. Newer immunotherapies in the same context have shown no responses in patients with liver metastases.
Like I walked you through the data in patients with liver metastases. We think relative to other immunotherapies in developing sense colorectal, we think right now we have unprecedented single region activity and the combined ability of the chemotherapy has now been established. When I look at the broader landscape outside of that, there are other entrants in this space. Again, looking at the single agent activity that we've shown in third, fourth line, I would argue we have a best in disease right now or comparable to some of the best interventions in the disease. The goal is to execute as fast as possible to go into first line colorectal in combination chemotherapy. We want to address the gene signal.
Definition of MSS colorectal. Is that what the question was, Andy?
No, it's about the TGFβ.
Patrick shows this data. I have to elaborate on that. That MSS colorectal, which is basically MSI negative, right, so microsatellite stable colorectal cancer, holds high in TGFβ signature based on the assays that we used and the published literature as well. We selected patients with MSS colorectal extension cohorts based on this data. We have not screened patients for TGFβ signature in clinical trial. We just centrally confirmed their MSS status.
Yes. The question is, can we enrich for any markers that would be associated with response? I think we're looking at a number of exploratory measures. Included in that is the TGFβ gene signature. We've got gene signatures associated with T cells, specifically other gene signatures, other factors within the TGFβ pathway, the ligands, the receptor itself. We're looking at those measures. Data that was shown on Friday in the presentation was also PD-L1 level. We saw correlation with response in PD-L1 greater than 1%. I think that is another marker, obviously that's an assay that's used. It's there. That was an association that we saw in September.
Let me just complete the thought. We may decide to incorporate some of this in subset analysis in this study. To be clear, the study will be no commerce other than obviously patients with certain mutations, wild type, right and left side, MSS colorectal.
All right, Matt, thanks for having us a ll the data following up on this CRC program with a 90. You did see some kind of activity across maybe KRAS mutant patients. Other things that you wouldn't want t o exclude those in the phase III. Are you continuing to explore some of those other tumor types that you showed here or maybe you haven't shown yet?
Let me take the second part and then we can talk about whether we have a cross range of mutations. We showed the data that we generated so far. I think, as expertly said, it's very intriguing, particularly ovarian cancer data. I think the response rate is ranging about 28% in the ovarian cancer population. Interesting results in head and neck, not unexpected. Interesting results in non-small cell lung cancer. At this point, we're being very deliberate in how we continue to expand this program. MSS colorectal is an intense focus. We will generate additional data on the tumor types and we'll make decisions based on that emerging data map. Those programs are not being accelerated right now. The second part.
We have looked at various mutations, left-sided, right-sided, clinical and molecular characteristics of those responders versus non-responders. What we presented was TBR1 stain and the system polarization, as you saw. Otherwise, we have significant clinical o therwise correlation. We are not excluding any patients with KRAS mutation and that's not planned. We will exclude patients that have alternative first line therapies such as MSI High BRAF at the right time. This is a very small section.
Thank you, Pablo. Eric Schmidt from Cantor. Two questions quickly on the G12D, maybe to dive a little bit deeper into Salveen's question. What actually are you trying to solve for with regard to a front line pancreatic cancer trial in a world where we do have a KRAS multi inhibitor that seemingly is looking terrific? Look for better safety, better efficacy, better convenience, what have you. Then, maybe I missed it. Was there PFS data from the G12D in pancreatic? Is that not yet sure?
The second, real quick, no, the data are not mature. We'll have the PFS data over time and we'll update you all with those results as they emerge. As Eka mentioned, half the patients only have one scan.
We can tell you confidently there's periods of tumor shrinkage, there's PRs, but we need time to establish durability and that could conceivably, I think it's unlikely based on what we've seen so far, conceivably change our decision making. Why would you install on first line? I think what our colleagues, as you mentioned, Revolution Medicines, have done is impressive. However, when you look at the second and third line data and as Eka mentioned, we had a very advanced patient population, it was a very small number of second line patients in that waterfall plot. Their data in third plus line was 22% response rate. We'll see where our response rate lands, but we think we're going to be very competitive and perhaps numerically significantly better than that. That's point number one. The second is, I think in part because of the profile of the pan-KRAS inhibitor.
When you look at the most recent update, the dose intensive chemotherapy in that combination was 63%, which tells you they're compromised in the dose of the chemo and they haven't combined with FOLFIRINOX, which as I mentioned is used by about half the population of pancreatic cancer. That's what we're trying to solve. We're trying to develop a G12D inhibitor that can be used for all patients with G12D mutated PDAC with any chemotherapy. By maintaining the intensive chemotherapy, we expect to overcome resistance, which obviously they try to overcome by the pan-KRAS coverage. We try to overcome resistance and maybe get better results. It could turn out that both ideas were working equally well. In my experience, and I think the room probably shares this, the molecular precisely targeted therapies tend to win out. We'll see, I think that's something we'll be following.
Yeah, Stephen Willey from Stifel . Can you just talk about the levels of TGFβ inhibition that you're achieving at the doses that you move forward for the purposes of expansion, and then maybe just quickly on the KRAS asset, when should we be thinking about next update from a timing perspective? And presumably that includes the single-agent duration of response data, but should we also expect some chemo combo data at that point as well? Thanks.
Yeah, let me take the second one real quick, and then Eka or Patrick can address the TGFβ target engagement question. Honestly, we haven't decided. It will be over the next few months, and as we accelerate these decisions and implement these studies, we'll give you clarity where we are with the data. Looking at the next few months, I can't come up with the right venue.
It may have to be a standalone update to tell you where we landed with the response rate, what's the duration of response, and obviously over time we'll have efficacy with the chemotherapy. I think the safety of the chemotherapy, that's pretty much clear. I think we need a week or two to make sure the FOLFIRINOX combination clears the official DLT period, but then obviously we'll generate longer-term follow-up and we'll provide updates in a timely fashion over the next few months. You want to address occupancy?
I mean, I guess a couple things. We were achieving full occupancy of both arms even at the 300 mg dose. I think that the dose response you saw there, we're saturating early. The 900, I think, is the PK. It's the lack of ADA effects at the 900 dose. I think there's part of the rationale there because of the precise mechanism here. It's challenging to get a real definitive measure of inhibition in tumor infiltrated lymphocytes in a tumor microenvironment where there's.
High levels of TGFβ, high levels. Of Schron cells which have the same factor. We're measuring it. I would say it's a qualitative assessment. It's tough to get numbers on that. I'll refer you back to the PK plot where we had a line there. It was EC90 from MLR assay, well above that MLR, EC90 coverage at the dose selecting going forward. Based upon our preclinical measures and the modeling that we did, we think we're more than enough in giving both PD-1 and TGFβ episodes.
Mark Frahm from TD Cowen, maybe as you're clearing safety shortly for the G12D combo, is that really all you need to finalize the design and start the process of finalizing the regulators and initiating the phase IIIs? Or do you think you need a pretty good sense of what the efficacy looks like of that combination and the patient number that might be needed to get to there?
Apologies. Let me see if I can clarify this because I think it's a very important point, right. Because of the competitive intensity in this space, we're not standing still waiting for this data. The team is preparing protocols, preparing interaction with FDA. We are moving forward. What we're doing is tracking the data and seeing where the air falls out and seeing if we need to change that decision. It's possible. The planning for first-line pancreatic cancer study is ongoing. The interaction with FDA will happen in the near term. We'll show the data, show the design. The thesis that combining a G12D inhibitor with chemotherapy in pancreatic cancer holds, and I don't need a lot of data to follow that signal. It's a relatively obvious thing to do when you think about it. Obviously, we want safety, we want a good number of patients.
We're going to show the FDA that we've done our diligence and we want to see the durability of the cohort that echoes show to confirm that we have indeed a good durability of those responses. All that is going in parallel. Once we have the green light, we'll accelerate the process.
Maybe on the TGFβ program, as the slides mentioned, both FOLFOX and FOLFIRI are used depending on center preferences. I think the slide said you're moving forward with FOLFOX combination in first line. Is that am I overinterpreting that you're not going to do first line full period? Is there some sort of synergistic or safety reason that's driving that decision?
We tested both combinations just in planning. Both were combinable, both were tolerable. We chose FOLFOX as it's the most commonly used regimen in first line.
It was just to keep the study simple, to be honest with you. We could do both if necessary, and you know, if we decide to go in second line or just as you know, you switch. That wasn't used in first line, using second line. We could have, we will have that data necessary anymore in the room online.
Okay, great. We will switch to some of the online questions. The first was regarding the G12D program specifically. Can you remind me, can you remind us of how many of the responses for the G12D program at 600 mg, 1,200 mg doses were confirmed versus unconfirmed? We've gotten this question a couple times online.
It's an excellent question. Let me point out a couple of things before I give you the exact numbers. One of the challenges with the data set, and where Eka was very transparent, she presented the data, is it's a relatively mature data set. After patients had only one scan, one scan, there's no way you can be confirmed by definition, no matter how good the response is. We looked at the subset of patients that had two scans or discontinued due to progression or any other factor. That's the truly evaluate patient population, either two scans or discontinued before the second scan. Three of those are confirmed responses, two are confirmable, meaning there are PRs that are still on therapy to be confirmed, and there are three stable diseases. Two are 29%, one at 22% tumor shrinkage. Others obviously could become PRs.
What that tells you is the response rate that we presented, and all the information is in your waterfall chart. You have the number of scans at the bottom, you have the arrows telling you which one is ongoing. All the information is presented clearly. Obviously, an immature data set needs time for the confirmations to come in. That's part of the data we'll continue to follow to continue the decision-making process that I described earlier.
Great. I know Eka, you spoke about this b riefly during the presentation, but given the high ADA rate with INCA0890, what gets you confident that this will not impact long-term efficacy?
Confidence comes from the number of patients we treated at 900 mg, and we have assessed PK after several cycles of treatment, and there was no at 900 mg. That's how we chose.
We also characterize babies non-neutralizing i t doesn't have any effect on the b inding of the antibody, and no effect. O n activity, as we mentioned.
Our next question is would you consider combining INCA0890 with INCA0734 in MSS CRC patients who also have a G12D mutation? Seems like a unique opportunity specifically for Incyte?
The work has already started. That combination has already started. We're doing dose escalation. We will have that data in just a few months, I think, near the first dose. We agree it's an excellent idea, and we're the only company that has both programs in the same place. That work is taking place.
Great. Now related to 0890, can you talk about what guided your plan to advance the 900 mg dose of the bispecific given it's on the higher end of the recommended dose levels. Can you comment on the efficacy and safety profile you observed at 1,200 mg? Was that the MTD? How does that shape the level of confidence in the therapeutic window?
At 1,500 we exceeded MTD. We treated few patients at 1,200, but then we chose 900 based on the emerging data. There were no GI toxicities at 1,200. Because of the ongoing events at 1,200 mg, there were some severe adverse events that are described in the presentation. We de-escalated and we went forward with 900 mg. Also, at that time the ADA and PK data came in at 900. There was no efficacy associated with higher dose. There was no exposure response curve indicating that we had to go higher. We basically decided to move forward.
I mean more likely than not. I think it's pretty clear this is a PD. It's a PD-1, better the PD-1 inhibitor with the TGFβ receptor 2 antibody. The dose response for efficacy is likely to be flat. As Patrick mentioned, we have full target engagement at lower doses. The reason to push the dose was to make sure that ADAs did not impact the PK, as a result the efficacy of the drug. That's why the 900 dose was selected. This again, and I think the discussion said it very well today at the KRAS session, it was a multi-part decision making for the dose selection including efficacy, safety, PK and PD, and the understanding of the target engagement that we needed.
For the G12D inhibitor, will you prioritize chemo combination versus monotherapy? In what setting would you pursue? Would you consider bringing this forward as a monotherapy in PDAC?
Not at this time. The reason is we want to focus, laser focus, on the first line program, appending some of the data points that we just discussed. We're going to go fast in first line PDAC combination with two types of chemotherapy. Within second line, our competitors are far ahead of us and the market opportunity is much smaller because a lot of the patients with pancreatic nerve reporters unfortunately never progress to second line therapy. At this point, we'll continue to generate the data that you heard Eka, and we'll update you on those results. We have no plans to initiate the second line, which is traditional triad with the G12D and everything.
Great. I just want to also check if t here's additional questions in the room. Okay. We have two more online. For the f or our CGF data, bispecific, want to understand from your perspective, how does FC compare to nurses showing 7% partial response and 43% stable disease with no cardiac or liver babies?
Yeah, the first point I would make on the back end of that question, which is the safety. We have not seen cardiac events at the recommended dose for expansion. That was seen at the 1,500 mg dose. I don't think that is a difference really. I think we have twice the single lesion activity that they showed in terms of responses, which I think positions us very well to be competitive. At this point, while the data continues to emerge, we think that the fact that we have a harsh simulation activity, the combinability with chemotherapy, and the safety profile that Eka detailed, I think we have a very good opportunity for scientists. Some of our competitors have been point.
I know this question was asked earlier, which has come up a couple times specifically, so maybe we could talk again about our confidence in the 1,200 mg dose moving forward and how we think this compares to Revolution Medicines that has shown 22% or?
Let's start with the safety side. There are two data sets from Revolution Medicines and we should just focus on Revolution Medicines. I mean, there are a lot of competitors in this space. Revolution Medicines is obviously the one that's ahead and everybody's mind seems to be that the pan-KRAS has shown 22% and 29% in third and second line PDAC . That is in all KRAS mutations. I have not seen recently a breakdown by G12D versus G12V, the two most common in KRAS mutations. Let's keep that in mind. The data for the G12D selective inhibitor is better. I have not seen what plans they have for that molecule. The pan-KRAS is moving; obviously, the second line trial is almost done in terms of enrollment. The first line, they've said openly, they're not going to combine FOLFIRINOX. They're combining with gem ab.
I pointed out the dose and gem ab seems to be compromising the regimen, and I don't think it's the case with ours and the fact that we can provide full FOLFIRINOX in a tolerable manner. We'll have that confirmation in a couple of weeks, but it looks to be that way. We think it opens that entire door for us, which basically makes this a broadly applicable intervention in patients with first line cold cancer.
Also related to some news today, can you compare and contrast your G12D data with the DFH375 monotherapy data for the KRAS G12D inhibitor and PDAC ? What key differences do you see between the respective patient populations?
Gen fleet, yeah, I can comment on the patient population. I think my first reaction with that is the mild suppression. Clearly, the activity was really interesting. I mean, the response rate was high. I mean, it was 40%, 41% was reported today, but there was quite a bit of neutropenia, and it may not be high grade neutropenia, but when you combine with a regimen that's perfectly mild suppressive, like gem abraxane or poly, I think that could be complicated. I see, I have no idea what the plans are, but I see that as a strong plan. Second line, whether you can combine with full dose chemotherapy for first line. You know, we look forward to seeing that data.
Great. Any final questions in the room? All right, back to Pablo for closing remarks.
Thank you very much everyone for coming. Thank you to the 100+ people that were online. We look forward to continue to update you in these exciting programs and have a great rest of the meeting and safe travel home. Thank you.