Greetings, and welcome to the Incyte Corporation conference call and webcast from ESMO 2019. At this time, all participants are on a listen only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. It is now my pleasure to introduce your host, Mike Booth, Head of Investor Relations. Thank you. You may begin.
Thank you, Donna. Good afternoon from Barcelona, and good morning to those of you joining us from the U.S. Welcome to our conference call and webcast to discuss the pemigatinib data that was just shown here at ESMO, as well as our development plans and the potential opportunities for the product candidate. The slides used in today's webcast are available for download on the investor section of incyte.com, as are the full data slides as presented in Barcelona earlier this afternoon. I'm joined on the call today by Hervé and Steven. Hervé will begin with a few opening remarks before Steven provides us with some important context on the disease of cholangiocarcinoma, the evident unmet medical need, and the rationale and potential for FGFR inhibition, and specifically, the potential of pemigatinib to be the first FDA-approved therapeutic for the disease.
Steven will also highlight key aspects of today's data set, as well as providing a detailed summary of our ongoing development plans for pemigatinib beyond cholangiocarcinoma. We will then open for your questions. During the question and answer session, I ask that you limit yourself to one question, and if needed, one follow-up, as this will enable as many of you to ask questions as time allows. Before we begin, however, I need to remind you that safe harbor rules govern our remarks today and any forward-looking statements that we may make. I therefore encourage you to review the risk factors detailed in Incyte's SEC filings, included in our Form 10-Q for the quarter ended June 30th, 2019. I will now pass the call over to Hervé.
Thank you, Mike. Good afternoon, good morning, everyone. Incyte's late-stage clinical development portfolio for Incyte is organized around two franchises. One is hematology oncology and the other is inflammation and autoimmunity. We have six very important late-stage projects addressing multiple indications with the potential for approval and launches in the relatively near term. A couple of months ago, we hosted a thematic call on vitiligo after our data were presented at the World Congress of Dermatology. Since then, we announced the initiation of the phase III study relatively recently. Today, we are hosting a similar call to highlight our progress and development plans for pemigatinib. Pemigatinib has potential in several indications, and today's presentation at ESMO was on the updated cholangiocarcinoma data set, and will form the basis of the NDA, which we expect to submit to the FDA very soon.
There is a broad development plan beyond cholangiocarcinoma, and I will pass to Steven to speak about the disease, the cholangio data, and the other opportunities for pemigatinib.
Thank you, Hervé. If I look at the compound itself, pemigatinib is a selective potent oral inhibitor of FGFR 1, 2, and 3. In terms of nanomolar potencies for the 1, 2, and 3, it's 0.4 nanomolar with an IC50 for 1, 0.5 for FGFR2, and 1 nanomolar for FGFR3. The potency is reflected in the dosing of 13.5 milligrams daily, which is much lower than the dosing seen for the other competitors. In terms of off-target activity and looking at FGFR4 and VEGFR2, you can see that the nanomolar potency is much higher and there's much less of a chance for off-target activity for pemigatinib. We are executing a broad development plan across multiple tumor types. Cholangiocarcinoma itself is a planned new drug application submission in the second half of this year in the second line under the breakthrough therapy designation.
The basis of that submission is the data presented today, which I'll go over in a bit. The pivotal trial in the first line setting versus chemotherapy has also been initiated. Beyond cholangiocarcinoma, there's a broad bladder carcinoma program. We have completed recruitment in the second line in terms of intermittent dosing and will complete recruitment soon in terms of continuous dosing. We'll also initiate a trial in the first line versus standard of care, I'll go over the schema of that in a bit. We plan an sNDA submission in 2020 in the second line setting based on this data. Very importantly, we're also initiating a solid tumor agnostic program, which I'll go over the schema of also. Cholangiocarcinoma itself is a heterogeneous tumor that arises in the bile ducts.
It is the most common primary malignancy of the bile duct, and is looked at in terms of three different anatomical subtypes, either intrahepatic cholangiocarcinoma, perihilar, or distal cholangiocarcinoma. The focus of our work and of our presentation today is on intrahepatic cholangiocarcinoma. There is no well-established treatment following the failure of chemotherapy in the first-line setting, the basis of which is gemcitabine and cisplatin combination therapy. If you look at second-line therapy, you're looking at single-digit response rates of less than 10%, median progression-free survival of around three months, and an overall survival of approximately six months. The prognosis of patients diagnosed in general with cholangiocarcinoma is poor. The only potential curative therapy for cholangiocarcinoma is surgery, but approximately 70% of patients are diagnosed with unresectable disease. Across the spectrum, the five-year survival rate of cholangiocarcinoma patients ranges between 5%-15%.
For patients with unresectable or metastatic cholangiocarcinoma, median survival is less than 1 year. That is the backdrop of the disease. The presentation today of the FIGHT-202 data, which is a phase II study of pemigatinib in patients with previously treated locally advanced or metastatic cholangiocarcinoma, was presented today at the ESMO conference. This is the FIGHT-202 study. There were 3 cohorts to the study. The first cohort A, was in FGFR2 fusions or rearrangements. Cohort B consisted of other FGFR or FGF genetic alterations, and cohort C was in patients whose cholangiocarcinoma had no FGF or FGFR genetic alterations. The dosing schema was pemigatinib 13.5 milligrams daily, 2 week on, 1 week off. The primary endpoint is an independently confirmed overall response rate in cohort A. That's in patients with FGFR2 fusions or rearrangements.
Other endpoints was overall response rates in the other cohorts, duration of response, disease control rate, progression-free survival, and overall survival, as well as safety. The demographics of each population are there for you, and there is nothing surprising on this data other than to point out what we knew already, that the vast majority of patients with FGFR2 fusions or rearrangements have intrahepatic cholangiocarcinoma. In terms of safety, the most common adverse event of all grades was hyperphosphatemia, which is an on-target effect of FGFR inhibition. Most of this was all low grade 1 or grade 2, with very few, actually only three patients, requiring a dose reduction or interruption. Hyperphosphatemia can be managed with a low phosphate diet, phosphate binders, and diuretics. If needed, dose reductions or interruptions. Probably from an overshoot of treatment, hypophosphatemia, low phosphate, occurred in 23% of patients.
This was the most common grade 3 or greater adverse event at 12%. None of these were clinically significant or serious, and none led to discontinuations or dose reductions. In terms of serous retinal detachment in this data set, in this study, using this dosing schedule, we saw this occur in 4% of patients. Mostly, these were grade 1 or grade 2, with a grade 3 or greater rate of 1%, and none resulted in bad clinical sequelae. In terms of efficacy, in cohort A, the overall response rate was 35.5%. You can see there were no responses in terms of size reduction in cohort B or cohort C. The median duration of response in cohort A was 7.5 months, and if you can look at that curve, the vast majority of patients have some degree of tumor size reduction with an 82% disease control rate.
This is all by independent central review. In terms of the median progression-free survival, you can see the curves here on slide 14 for cohort A, cohort B, and cohort C. For cohort A, the median progression-free survival is 6.5 months. In terms of cohort B and cohort C, you can see the very poor prognosis of these patients when they're not given therapy that's efficacious, with a median progression-free survival of approximately two months. Just to note, the median duration of follow-up in cohort A is 15.4 months, and the median duration of treatment for these patients was 7.2 months. Pemigatinib is also under evaluation in patients with bladder cancer. This is the FIGHT-201 study. This is in metastatic or surgically unresectable urothelial carcinoma. Cohort A in this population was FGFR3 mutations or fusions or rearrangements, and 100 patients were treated there.
Cohort B had other FGFR or FGF alterations. There were 40 patients treated there. The primary endpoint is overall response rate. There was a strategic switch in this program to dose patients then with continuous dosing. That's going to form the basis of cohort C here. That's another 100 patients. In terms of the safety and efficacy to date, for this population of patients, we presented it at ESMO last year in 2018. You can see in terms of safety there is what is expected for this population in terms of GI side effects, hyperphosphatemia, and other side effects. Again, the efficacy seen in the FGFR3 mutated or fused population in cohort A is shown in the plot over there, with again, the majority of patients having some degree of response to the therapy.
The continuous dosing cohort on slide 17 will complete enrollment by the end of 2019. This is again looking at FGFR3 mutations of fusions and rearrangements in 100 patients using 13.5 milligrams daily in continuous fashion. The first-line bladder trial is being initiated versus standard of care, and this is slide 18. This is metastatic or unresectable urothelial carcinoma in cisplatin-eligible participants whose tumors express FGFR3 mutations of fusions and gene rearrangements. Target population is 372 patients, and there's a three-arm study. The first arm being tested is a combination of pemigatinib with a checkpoint inhibitor in pembrolizumab. The second arm is pemigatinib alone, and the third arm would be the standard of care comparator arm, either chemotherapy or pembrolizumab. The chemotherapy would be for patients who are not PD-L1 positive. The primary endpoint of the study is progression-free survival and there are standard secondary endpoints.
A tumor-agnostic program is an important next step for pemigatinib. If you look at the evolution of therapies and how they've undergone change over the targeted therapy area, we started looking at, many years ago, site-based treatments. For example, lung cancer chemotherapy or melanoma chemotherapy, then biomarker-driven approaches, still based on histology. For example, ALK translocations in lung cancer or BRAF mutations in melanoma. Now in the era of tumor-agnostic biomarker approaches, whether you look at pembrolizumab in terms of MSI-high or deficient mismatch repair with an FDA approval in 2017, or more recently, the NTRK-directed therapy with an FDA approval in 2018, including a recent European approval for that. Obviously now an important arena to address, pemigatinib in terms of FGFR alterations will be studied. On the next slide, you can see the study which is now open, FIGHT-207.
These are histology independent, advanced metastatic or unresectable solid tumors within cohort A, FGFR 1, 2, or 3 fusions or rearrangements. Cohort B, again, histology agnostic, the patients with activating point mutations in either 1, 2, or 3. Cohort C, anybody else in terms of other point mutations. The primary endpoint would be objective response rates in these cohorts and standard secondary endpoints. The initial approval for pemigatinib is expected in the second half of 2019. This has the potential to be the first FGFR inhibitor for intrahepatic cholangiocarcinoma that's driven by the FGFR2 fusion or rearrangement. There are multiple sequential opportunities in patients with FGFR gene alterations. You can see the cholangiocarcinoma has upwards of 2,000-3,000 new patients in terms of incidence globally. The bladder cancer opportunity takes that to approximately 15,000-20,000 new patients globally.
If you add in the solid tumor-agnostic populations that I was talking about, you could be having upwards of another 15,000 new patients that will be obviously later in the development paradigm. Donna, that ends my prepared remarks. I'll now ask you to open the line for questions and answers. Thank you.
Thank you. The floor is now open for questions. If you would like to ask a question, please press star one on your telephone keypad at this time. 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 handset before pressing the star keys. Once again, that is star one to register questions at this time. Our first question is coming from Tyler Van Buren of Piper Jaffray. Please go ahead.
Hi, guys. Thanks so much for taking the questions. With respect to commercial build, could you just speak towards how big the sales force dedicated to pemigatinib will be that you will build next year, and whether it will be specifically dedicated to cholangio or whether it will be part of the Jakafi sales force, and how you expect to compete with some of the other FGFRs out there that will be launching as well?
Yeah, I will take that. As you can imagine, the number of patients with cholangiocarcinoma carrying the rearrangement and fusion that we are looking at is relatively small. The commercial deployment that we will be using is obviously going to be proportional to the amount of work that needs to be done. We have to realize that in many cases, a single doctor would not see many of these patients in a given year. There are some large centers where you could imagine having a team of some individuals meeting with physicians, et cetera, but a lot of the work will be done on the diagnostics and then on understanding how we can work with the diagnostic units or companies in order to be able to direct our commercial effort to the place where a patient has been diagnosed.
It will be an untraditional commercial deployment, if you want to think about it. In the U.S., where we will start, where it will be the first, we are still looking at it, but we are anticipating that there will be fields-based individuals who are going to be prepared on this project and will probably share some of their activity with other products from [Phlow]. It's not going to be dedicated from the field-based standpoint, but obviously in the headquarter, we'll have a team of people who are dedicated to this project. That will change. I would say the same applies to Europe when it will be time to do that in Europe for cholangiocarcinoma.
As we go to the next indication, which could happen relatively quickly after, there will be probably a very different approach where for bladder cancer or diagnostic tumors, there is enough potential to justify having dedicated field people. I see it as a two-step effort. The first step in cholangio alone is going to be meaningful because it is a new drug for Incyte, so it's important. It's going to contribute to the growth of the organization, et cetera. At the same time, we have to be conscious that it's a relatively limited total commercial opportunity.
Great. Thanks again.
Thank you. Our next question is coming from Reni Benjamin of JMP Securities. Please go ahead.
Hi. Good morning. Thanks for taking the questions, and congrats on the results. Steven, can you talk a little bit about the key AEs which led to dose reductions? Outside of reducing the dose, are there ways to clinically prophylax or treat these patients so that you can keep them at the appropriate dose? Just as a second follow-up question, the author in discussion talked about other FGFR inhibitors, largely saying that they're equivalent. I guess without giving away your potential marketing strategy, how do you envision the competitive landscape in three to five years, and how do you differentiate with others that are coming to the market? Thank you.
Okay. Reni, it's Steven. I'll start off, and I'll also comment on your second question, but Hervé may add to that. In terms of adverse events, obviously the key thing, and it's on target, is phosphate management both in terms of appropriate use of phosphate binders, dietary management, so that diet-high in phosphate are well understood and controlled, and both by the physicians and the patients, and then if needed, diuretics to eliminate phosphate. I think it's almost universal across the board. As you saw in the study population when well-managed, that it was not an issue in terms of either dose reductions or interruptions. Obviously, when you're out in the real world, that's going to take an education and an effort on our part to make sure people do the appropriate same thing, because keeping dose intensity is going to be critical in terms of getting the efficacy.
In terms of the other side effects, beyond people run into trouble with a particular side effect, the need to either interrupt or reduce, there's nothing special that needs to be done. What's interesting, and there shouldn't be any cross-trial comparison made, standalone data. In terms of what we saw with serious central retinopathy, we have a 4% rate in this particular data set. It may be to do with, one, the population, two, the intermittent dosing. We'll see how this evolves across the program in other tumor types and when we see the use of continuous dosing. I don't want to comment versus competitors, but you did bring it up.
However, if that ends up panning out, that would be a really good thing for us in terms of the profile of the drug and obviously very good for patients to have a very low rate of that particular adverse event. I think it's always dangerous to say when you look at different chemicals that they're equivalent, because with more widespread use and as different patients are treated, and there are different off-target effects, different things evolve. You saw on one of our early slides the profile of our compound versus the competitors, and it's clearly different in terms of it hitting potency-wise, nanomolar ranges for one, two, and three. We can dose at much lower levels compared to them. We use 13.5. They're often in the hundreds. We'll see.
From an efficacy point of view, I haven't seen as mature a data set as ours with the competitors. In terms of reported data, we haven't seen the degree of independently confirmed response that we have seen today. We'll see. I'll hand it over to Hervé if he wants to say anything else.
I think at the beginning of every differentiation is the question of the specificity of the profile. What we see is that among the other products that are targeting FGF, we have the most specific product. We hope that that will translate in the clinic. It is true that it's an emerging therapeutic profile, and we should be very careful not to compare bladder data with cholangio data or different type of products in different settings with different exposure, because I think all of that could evolve over a period of time. That being said, we have a product that is very specific and has a good profile as we have demonstrated here, and the key aspect of the commercial success will come also from the sequence of approval. We will be first in cholangiocarcinoma.
That now is something we can say as the submission dossier is being finalized and prepared. I think in bladder cancer in the second line, we will obviously be behind. There is still a question on who will be first in the first-line setting where we are initiating our pivotal study. We have the tumor agnostic setting where also it will be a question of sequence of launches. I see based on what we know today, that we will be either first or second in each of these, and I think it will give us a very good position to be successful on the market on top of the profile that will be clarified over the next few months when we get new data on the other tumor types.
Overall, I think it's a position that is going to be competitive, and it's a market that with the new indication coming beyond cholangio, will become meaningful to Incyte in terms of growth of our revenue over the next five, six years.
Great. Thank you.
Thank you. Our next question is coming from Michael Schmidt of Guggenheim. Please go ahead.
Hey, this is Kelsey Goodwin on for Michael. Congrats on the data. Previously you said, I think about 33% overall response rate would be the bar for clinical meaningfulness. I guess obviously you've cleared that today, is there any other hurdle in your view for approval? For example, anything duration related? Thank you.
Yeah, Kelsey, it's Steven. I think you focus on the strict RECIST definition, and that was the primary endpoint, and that's fair at 35.5%. If you look at that plot, you can see 80%-plus of the patients have some degree of response, including long-term stable disease. That 82% disease control rate is another very important endpoint. That translates into the median PFS of seven months in the setting, and actually the median overall survival, although not controlled, of 21 months. Remember the context, single-digit response rates for second-line chemotherapy, PFS of three months, OS of six months. We think all of that, obviously, it's going to be up to regulators in the end, adds up to something that is real clinical benefit for patients, and we're obviously very confident in the submission in terms of that.
Great. Thank you so much.
Thank you. Our next question is coming from Marc Frahm of Cowen and Company. Please go ahead.
Hey. Thanks for taking my questions. Would it be possible to break out the PFS data by line of therapy, maybe as a read-through to what might happen in the front-line trial?
It's Steven. I can't comment on data that we haven't shown today, because it's not in the public setting. Obviously, down the park, future presentation, including manuscripts, may help you with that answer. I'm not going to give you a satisfactory answer today. It looks like that this entity is not chemotherapy responsive. I just, in the prior question, told you single-digit chemotherapy response rates, low PFS, very low overall survival. It looks like, although not controlled, in using the therapy in a targeted setting in this population with a 21-month overall survival, that beyond any prognostic implication, there's a real treatment effect. Whether it's going to be different in whether the patients are second, third, fourth, or fifth line, I just can't comment on at the moment.
Given that the impact on OS seems to be much more significant than even the PFS, are many of these patients staying on drug post-progression?
No, that does not. It's Steven again. I don't know. I think you've got to be careful of commenting on that. It's not a randomized against a control, and there may be issues around the disease having a different prognosis to the non-FGFR2 mutated. Again, having said all of that, it's extremely encouraging. Both the speaker today and the discussants alluded to the fact that this is very interesting overall survival at 21 months, and there may well be a treatment effect here. If that's the case for patients, it's really great. I'll leave my comments at that.
Okay. Thinking about the tumor-agnostic trial, is that structured to just go straight to full enrollment, or are there key gating interim analyses to open up full enrollment to that 300-something patients?
Yeah. We have the ability to look at response at intervals during the study in appropriate ways, given the statistical design. Obviously, if you're not seeing response in a particular entity, you would curtail enrollment versus expand enrollment. I think what's part of your question is how many patients you would need to get a tumor-agnostic indication for a particular genetic driver. That remains to be seen with regulators. I will tell you, and there's an opinion piece published by the FDA on this. Once you have a drug that's already approved with maybe more than one indication, like pembro's example in MSI-high endometrium. If you establish the driver, you already have a track record for safety, you may not need huge numbers of patients with a particular mutation to get it across the finish line.
We put that total N in to allow ourselves to expand in different entities, but it may not be needed.
Okay, great. Thank you.
Thank you. Our next question is coming from Vikram Purohit of Morgan Stanley. Please go ahead.
Hi. Thanks for taking the question. I had one on response rates and how those trended from your last update to today's update. Some patients achieved complete responses as of the update this morning. I just wanted to see if you could help us characterize what the baseline characteristics were of the patients who achieved CRs and how those responses may have trended throughout their time on drug.
Vikram, it's Steven. If I, again, understand your question, it's going to be hard to answer. This is a much more mature, larger data set with longer follow-up, and that's what happens in clinical trials. You get very small differences in response. I don't think that there's anything different compared to when we reported this prior. Is there something special about the complete responses versus the partial responses, either in terms of a biomarker or demographic? Not that we've ascertained yet. That would be interesting if that was the case. There's nothing special about it. Obviously, while the study is still open, we'll continue to follow patients and see if things change. When you've got an 82% disease control rate, I think it's encouraging enough. Nothing special to point out if there's a difference in the CR patients versus the PRs versus the non-responders currently.
Understood. That's helpful. Thank you. As a quick follow-up, if I could ask a question on PFS. I know that you're not able to, at this time, break out the results beyond what's reported in the release from today, but anything you can help us think through and characterize for how or why the PFS may have ticked down a little bit from the prior update? I think at the last time you reported it was roughly nine months. Today, it's roughly seven months. How should we think about how that's trended?
Yeah. Firstly, thank you for your question. I think you have to look at a PFS curve, and I encourage you to look at it and maturity of data sets and how many people are at risk, because there can be small accidents around the median. By that I mean the curve can suddenly drop down when it matures. If that one event didn't happen, it would've been eight, nine months versus 6.9 now. That's really all it is. You have to remember the median's a single point on a curve over time. It's not the totality of the curve. We don't think they're substantially different in any way. It's just maturity of the data set.
All right, great. Thank you.
Thank you. Our next question is coming from Evan Seigerman of Credit Suisse. Please go ahead.
Hi there. Congrats on the data. Definitely strong OS in the cohort A. Just looking more broadly at your pemigatinib program, how are you going to differentiate this from competitive products, not just in cholangiocarcinoma, that's kind of your key indication, but also in bladder and the more broad tumor-agnostic indication? Thank you.
Yeah. I can try again. There is still a lot of unknown on the clinical profile of these different competitors, so everything is obviously dependent on the emerging data that will be coming out in the next few months. What we see from the profile of the product is that we have the most selective of the available FGFs in the clinic today. Specifically, we have a profile that is avoiding FGFR4, which is always important because we know it has an impact on the clinical profile. As you can see from the data we have in cholangio here on a fairly large number, there is 100 patients, 140 total, and 100 patients in arm A. We are starting to see emerging a profile of very good efficacy. Very few patients, a small number of patients having to drop out of treatment because of side effects.
A few dose interruption, most, I think 80% of patients receive the planned dose for their treatment. That's very encouraging on the first translation of this good preclinical profile into a clinical efficacy and safety that, as it is we look at it today, is very favorable. That, at the end of the day, will be the key to the competitive situation between these products. We are very confident that our profile is very good from that standpoint. The other thing I spoke about earlier is the sequence of launches. Obviously cholangio will be first. It's a relatively smallish type of market as the patient population is relatively limited. We are working on the first-line bladder, where I think we are in a relatively competitive situation in terms of timing.
As we said, we are initiating the agnostic, where we could end up being in the lead position in that setting. I think that will have an impact on adoption curves for each of these products. Being first in cholangiocarcinoma, maybe also in agnostic and for first-line bladder, we are somewhere in the race, is putting us in a very good position. When you look at the potential overall for the molecule, and that's why we have this call today, in fact, is introducing this new molecule now that has a good chance to go through the regulatory process first in cholangiocarcinoma, is that when you add the rest of the addressable population and the clinical profile and the adoption curve, we believe it could become, over time, a very meaningful contributor to Incyte's revenue.
That's why we speak about it as a sort of today, it's a little bit like the kickoff of the new product now moving through the finish line, which I think is always a very important event for a company.
Great. Just as a follow-up, in the FIGHT-205 trial, can you help me better understand the additive impact of combining pembro with pemigatinib in urothelial cancer?
Yeah, Steven. That's a hypothesis being tested around whether checkpoint blockade with an FGFR inhibitor, in this case our drug, will actually help enhance the immunotherapy, potentially make tumors that are either cold or lukewarm, in inverted commas, hotter and more responsive. There's an emerging science around it. There's been a couple of recent publications around the ability of FGFR tumors, which are traditionally cold tumors from an immunology point of view, being made more immunoresponsive by FGFR inhibition. It's testing that hypothesis together. That's that arm. There's a pemigatinib alone arm to see what FGFR inhibition alone does first line, and then the standard of care, which are now from a regulatory point of view, the standard of care, either chemotherapy if they're PD-L1 low, and if they're PD-L1 positive, pembro low. I think it's a superb study.
You'll get the contributions of care of each individual thing, and you'll test the hypothesis of making potentially cold or lukewarm tumors hot with that combo. As Hervé said, we go in at first line, looks like ahead of everybody else.
Thank you very much for that. I appreciate it.
Thank you. Our next question is coming from Gilmore Kasioni of RBC Capital Markets. Please go ahead.
Good morning. I'm on from Brian Abrahams' team today. Thanks for taking our question. Again, on differentiation, there's another FGFR inhibitor, derazantinib, in development for cholangiocarcinoma, and they seem to highlight their ability to inhibit the CSF1 receptor in addition to the FGF receptor as an added mechanism of potential anti-tumor activity through effects on tumor-associated macrophages. I just wondered if you had any thoughts on whether pemigatinib also inhibits this CSF1 receptor and any potential role for this mechanism in the activity you're observing.
Yeah, it's Steven. Thank you for your question. To my knowledge, we don't. Obviously, they have a different profile in terms of their compound selectivity, and we'll see how that pans out. In terms of published data from the [auremolimab] compound to date, I think they published a phase II in about 29 patients. They have a low 20% response rate that they've reported. We'll see. You don't make cross-trial comparisons, certainly, because we haven't done that, don't want to talk about another competitive agent. To date, the data I've seen hasn't pointed to increased efficacy.
Thank you.
Thank you. Our next question is coming from Alethia Young of Cantor Fitzgerald. Please go ahead.
Hey, guys. Sorry. Thanks for taking my question. Congrats on the data. Two, maybe can you just talk a little bit about the first-line trial and does this potentially increase your confidence and the potential opportunity there? I guess I just wanted to talk about cohort B and C. Did you hypothesize that you probably would see no effect there? I just kind of wanted to see how you think about that since there is activity across different isoforms. Thanks.
Thanks, Alethia. It's Steven Stein. The first-line study is going against the care standard, against gemcitabine plus the platinum agent. It's just underway now. Obviously, you're going to have the same operational challenge around finding the patients with a particular driver mutation to test. It'll be a very, very important question to answer. Does targeted therapy, can it advance from a second-line setting to a first-line setting and potentially surpass chemotherapy in that setting? We'll see, and that's why we're conducting that study. The cohort BC thing is really interesting. We didn't know up front. We didn't expect activity in C at all. In B, we didn't know, and that's why we did the test, right? There is some stable disease, but no classic RECIST responses there.
I think as the discussant said on the podium today, it's probably likely one potential explanation is that those particular genetic defects there aren't drivers, aren't driving the disease. Abrogating the pathway there seems to have no effect. I don't have a better explanation. As I've told you now, I think it was a very important test to do. I think it potentially serves as an internal control because you can see the lack of response there, you can see the lack of PFS. It's quite glaring to see in terms of the curve, although that wasn't a formal comparison.
Great. Thanks.
Thank you. Our next question is coming from Stephen Willey of Stifel. Please go ahead.
Yeah. Hi, thanks for taking the question, and congrats on the data. Just a quick question on patient screening and then a quick follow-up if I may. It looks like there are about 85 patients that came into the trial with a confirmatory diagnosis, and then it looks like you screened another 1,200 or so to find the remaining 86. I guess that implies a hit rate of something around 7%, which I think is about maybe 2x lower than what we've seen in the literature. Just kind of wondering how you're thinking about this 7% number. Is this something that's just kind of site specific, or do you think this may somehow, I guess, change your perspective on enrollment timelines into phase III?
That's a good pickup, and thanks for commenting on it. I think it's dangerous to fully extrapolate to that would be the real number seen around the world. There are obviously biases. You're right, 85 patients had a preexisting Foundation test, and then beyond that, hit about a 7%-8% hit rate. The literature repeatedly points to a much higher rate of 10%-15% seen for intrahepatic cholangio when it's in a non-biased testing setting. You create your own bias by conducting a study, by telling sites you want to do it, by sites having either local testing or the pre-screen. I don't think that's the case. I think the rate is based on all the available literature around the 10%-15% rate. There are other issues around also histology, by the way. Not everybody-- There were classic gallbladder cancers in there.
There were Ampulla of Vater cancers. There were other bile duct cancers that made that population a little distorted without getting into too much granular detail. It is a data set, but I believe the rest of the literature to be correct. I'll just leave it at that.
Okay, that's helpful. Then just a quick follow-up. I know the patient subgroup breakout here is based on relatively small numbers. I guess when you just look at the response decrement that's associated with a prior treatment exposure, whether it be second-line, third-line, or third-line plus patients, it doesn't really appear to be all that significant. I guess, just wondering if you expect that trend to kind of hold as you move upstream into the FIGHT-302. Thanks.
No, I think that's a good thought. I try to allude to that indirectly in that with a targeted therapy, it may not matter what line, number one, and I think that's what you're indirectly saying. You may see the same degree of activity. Two, these patients may be a little chemo unresponsive if they have the FGFR2 fusion or rearrangement. Obviously, that's going to be key to our test in the first-line setting. Against chemotherapy in this population, will targeted therapy be better than chemotherapy? I think it's interesting, as you say, that there may not be a line difference in terms of the activity of the drug, and we'll see.
All right. Thanks for taking the questions.
Thank you. Our next question is coming from Christopher Marai of Nomura Instinet. Please go ahead.
Hello, this is Jackson Harvey on for Christopher Marai. I just have a follow-up on the hyperphosphatemia and the dose interruptions and reductions. At what level of hyperphosphatemia would a doctor decide to reduce dose or interrupt dosing? Also, if the dose is interrupted, how long does it take for levels to return to normal? Thank you.
Yeah, thanks for your question. I think at a very high level, there was a slide in the presentation on patient disposition by cohort. If you look at cohort A, which is the one of interest, just to mention again, there were literally, of the 107 patients in that cohort, four that discontinued for adverse events in total, across the board for all adverse events. It was a very uncommon occurrence to have a discontinuation. I can't give you specifics because it's more of the art rather than the science of medicine on when a doctor will be more concerned or not. It's something we're going to have to do when hopefully we get approved and commercialize the product, is help to educate you. We don't even want them to get to a state where they are concerned.
With the proper use of binders, diet, and potentially diuretics, they won't even get there and have the need to be concerned. Remember, what they're worried about here is actually quite interesting, is from the high phosphate that you'll get calcium binding, and you'll get the strange ossification that can occur in soft tissues. It's a very rare event, so we don't even want to get anywhere near there. I can't give you an exact number now.
Great. Thank you.
In terms of the phosphate level. Yeah. Thanks.
Thank you. Once again, that is star one if you do have any questions at this time. Our next question is coming from Salveen Richter of Goldman Sachs. Please go ahead.
Yes, hi. Thank you for taking the questions. This is Maryana Breitman on for Salveen. I have one on dosing. Would you consider continuous dosing for second line? It looks like that's the direction in which PEM is moving. Would checkpoint inhibition make sense in combination with pemigatinib in cholangiocarcinoma? Thank you.
Hi. Yeah, thanks for your question. It's Steven. Obviously this program was quite far advanced in terms of intermittent dosing. We are seeing this degree of efficacy, which we believe is very important to patients and should hopefully get us an approval. We haven't tested yet continuous dosing in cholangiocarcinoma. Obviously, we're doing that in bladder cancer, it's something we could clearly consider down the pipe to see if it will have additional efficacy and still have the right therapeutic ratio. To date, immunotherapy hasn't had great success in cholangiocarcinoma, checkpoint inhibitors on their own haven't shown effects in terms of getting them across the finish line for approval.
Given my comments, which you obviously picked up on, around FGFR potentially enhancing that in terms of the tumor microenvironment, it's again something that may be worth testing again down the pipe to looking at concomitant FGFR inhibition plus checkpoint inhibition in cholangio. It just hasn't been done yet.
Got it. As a follow-up, could you address the safety of continuous versus intermittent dosing, at least what you see in bladder?
We haven't published our data yet. You'll have to wait to see that. Obviously, we're going to be really interested in that too. Be very careful of cross-trial comparisons, particularly to other drugs and other disease settings. However, saying that, should this same rate in terms of the central serous retinopathy pan out in other settings with continuous dosing, they'll be very good for patients and for our drug as a differentiator. We'll see what the data shows, and I can't answer your question yet till we have our continuous dosing data.
Got it. Thank you very much for taking the question.
Thank you. Our next question is coming from Jay Olson of Oppenheimer. Please go ahead.
Oh, hi. Thanks for the presentation, and thanks for taking my questions. Can you comment on the timing of a potential registration filing for FIGHT-207? Longer term, would you consider doing a first-line tumor agnostic study and/or a combination tumor agnostic study with pembro or some other IO? Thank you.
Yeah. Jay, hi. It's Steven. Thank you. We'll see. If you look at our penultimate slide of the presentation, slide 21, we put it around 2023, but it's going to be a little hard to estimate right now. If we see knock-it-out-of-the-park efficacy with a particular oncogenic driver in a population, could we do it earlier? Potentially, but we'll just have to wait and see what evolves. I think it's safest to think of it as an opportunity around that timeframe currently. Again, given comments on targeted therapy in general in terms of personalized medicine, yes, that could then move into earlier lines and particularly first-line settings, and then beyond that, even in certain diseases when appropriate, either in adjuvant type population.
You have to sort of move up that when you first show efficacy in metastatic populations. I think your last question there, if this whole story continues to evolve of FGFR inhibition making cold tumors hotter, making the immune environment more responsive to checkpoint blockade, and that story continues to evolve beyond bladder cancer and elsewhere, then yes, you could test it elsewhere in a systematic fashion, particularly maybe in a tumor-agnostic fashion. That's a little bit down the pipe. Thank you.
Thank you. Ladies and gentlemen, our last question today is coming from Cory Kasimov of JP Morgan. Please go ahead.
Hi, this is Nina on for Cory. I'll just ask a question about the serious retinal detachment. I know you've talked a lot about how we can't necessarily read through between the various indications, just curious, from the ESMO data presented last year on FIGHT-201, it looks like there was one discontinuation due to serious retinal detachment. Did you see any discontinuations in this study for the same reason? Also, is there any reason that you can think of why we should expect a different rate of serious retinal detachment between the two indications? Thanks.
Yeah. It's Steven. The one patient who had a serious event of the four total is that same patient. There's no additional patient who had a discontinuation there. In terms of your second question, we'll see. We need our continuous dosing information. It'll be in bladder cancer. Is there a difference between bladder and cholangiocarcinoma patients? I don't know yet. It's a very encouraging signal, as I keep saying, to only have a 4% rate, to only have the one serious event. If that ends up being the case in continuous dosing in bladder, that would again be great for patients and for us, but we'll see. I just don't know yet. I don't think the expectation should be with continuous dosing that the rate would go down. It'll either be the same or maybe go up because you're hitting the target more.
Again, we'll see what it pans out in the actual data. Thanks.
Thank you. At this time, I'd like to turn the floor back over to Hervé for closing comments.
Okay. Thank you. Thank you all for the time today and for your questions. We look forward to speaking with you at our third quarter call, as well as seeing you at upcoming investor and medical conferences. For now, we thank you again for your participation in the call. Thank you and goodbye.
Ladies and gentlemen, thank you for your participation. This concludes today's event. You may disconnect your lines and log off the webcast at this time. Have a wonderful day.