Greetings, and welcome to the Insight Corp Conference Call and Webcast from MSO 2019. At this time, all 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 were just shown here at ESMO as well as our development plans and the potential opportunity for the product candidate. The slides used in today's webcast are available for download on the Investors section of instac.com as are the full data slide has presented in Barcelona earlier this afternoon. I'm joined on the call today by Hervein Stevens.
Hervein will begin with a few opening remarks before Steven sides 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 leuke demagatinib to be the 1st FDA approved therapeutic for the disease. Stephen will also highlight key aspects of today's data set as well as providing a detailed summary of our ongoing development plan 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 Info's SEC filings. Included in our Form 10 Q for the quarter ended June 30, 2019. I will now pass the call over to Hervek.
Thank you, Mike, and good afternoon. Good morning, everyone. So inside, let's say clinical development portfolio for Incyte is organized against around 2 franchises. 1 is immunology oncology, the other is inflammation and auto immunity. We have 6 very important late stage projects addressing multiple indication with the potential for approval and launches in the relatively near term.
So 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 indication of the phase 3 study, rightly recently. And today, we are hosting a similar call to highlight our progress and development plans for pemigative. So pemigative has potential in a several indication and today's presentation at EXMO was on the updated conjugarcinoma data set which will be and will form the basis of the NDA which we expect to submit to the FDA very soon. So, there is a broad development plan young cholangiocarcinoma and I will pass to Stephen to speak about the disease, the cholangiocarcinoma and the other opportunities for pemigatinib.
Thank you, Herve. So, if I look at the compound itself, pemigatinib is a selective potent oral inhibitor of FGFR1, 23. In terms of Nanomotivehotencies for the 1, 23, it's 0.4 nanomotor with an IC50 for 1.5 for FGFR2 and 1 nanomolar for FGFR3. The potency is reflected in the dosing of 13.5 milligrams daily is much lower than the dose seen for the other competitors. In terms of off target activity and looking at FGFR4 and VEGFR2, You can see that We are executing a broad development plan across multiple tumor types.
Cholangiocarcinoma itself There's 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 created. Beyond cholangiocarcinoma is a broad bladder carcinoma program. We have completed recruitment in the 2nd 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 and I'll go over the schema of that in a bit and we plan an sNDA submission in 2020 in the second line setting based on this data.
And then very importantly, we 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 ducts and is looked at in terms of 3 different anatomical subtypes. Either intrahepatic cholangiocarcinoma, peri inhaler 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 cisplatinib combination therapy.
If you look at second line therapy, looking at single digit response rates of less than 10%, median progression free survival of around 3 months and an overall survival of approximately 6 months. So the prognosis of patients diagnosed in general with cholangiocostinomas for the only potential curative therapy cholangiocarcinoma is surgery, but approximately 70% of patients are diagnosed with unresectable disease. Across the spectrum, the 5 year survival rate of cholangiocarcinoma patients ranges between 5% to 15%. And 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 5202 data, which is a phase 2 study of Pemigas 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 1st cohort cohort A was in FGFR to fusions or rearrangements. Cohort B consisted of other FGFR or FGF genetic alterations, and cohort C was in patients whose cholangiocarcinoma had no FGFR 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 rate in the other cohorts, duration of response, disease control rates, progression free survival, and overall survival as well as safety. The demographics of each population are there for you and there's nothing surprising on the data other than to point out what we knew already that the vast majority of patients with FGFR2 fusions or rearrangements have intrahepatic cellangiocarcinoma. 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 grade 1 or grade 2. With very few actually only 3 patients requiring a dose reduction or interruption hyperphosphatemia can be managed with a low phosphate diet phosphate binders and diuretics and if needed dose reductions or interruptions. Probably from an overshoot of treatment, hypoglyphosphatemia, low phosphate occurred in 23% of patients. This was the most common grade 3 or greater adverse event to 12% None of these were clinically significant or serious and none led to discontinuations or dose reductions.
In terms of serious retinal detachment in this data set in this study using this dosing schedule, we saw this occur in 4% of patients. Most of 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 months 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 6.9 months. In terms of cohort B and cohort C, you can see the very poor prognosis of these patients when they have not given therapy that suffocation with a median progression free survival approximately 2 months. Just to note, the median duration of follow-up in cohort 8 15.4 months.
And the median duration of
treatment
patients with bladder cancer. This is the FIGHT 201 study. This is in metastatic or surgically unresectable urothelial carcinoma. Again, cohort A in this population was FGFR3 mutations or fusions or rearrangements and 100 patients were treated dead. Cohort B had other FGFR or FG alterations and 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 and that's going to form the basis of cohort C here and 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. And 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 a few 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 and this is again looking at FGFR re mutations of fusions and rearrangements in 100 patients using 13.5 milligrams daily in continuous fashion. The first line bladder
tumors
and gene rearrangements. Target population is 372 patients and there's a 3 arm study. The first farm being tested is a combination of pemigatinib with a checkpoint inhibitor in pembrolizumab, the second arm is pemigatinib alone the third arm would be the standard of care compared to 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 the expanded secondary endpoints.
The tumor agnostic program is an important next step for pemigatinib. If you look at the evolution of therapies and how Undergone change over the targeted therapy area, we started looking at many years ago site based treatments So for example, lung cancer chemotherapy or melanoma chemotherapy and then biomarker driven approaches, but still based on histology. So for example, elk translocations in lung cancer or BRAF mutations in melanoma and now in the era of tumor agnostic biomarker approaches. Whether you look at pembrolizumab in terms of microsatellite instability high or deficient mismatch repair, with an FDA approval in 2017 or more recently, the NRTK directed therapy with an FDA approval in 2018 including a recent European approval for that. Obviously, now an important arena to address and Pemigatinib in terms of FGFR alterations will be studied.
On the next advanced metastatic or unresectable solid tumors within cohort A FGFR1, 2 or 3 fusions or rearrangements and then cohort B, again, histology agnostic to patients with activating point mutations in either 1, 2 or 3 and then cohorts see 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 twenty nineteen. This is the potential to be the 1st FGFR inhibitor for intrahepatic cholangiocarcinoma that's driven by the FGFR2 fusion or rearrangement. There are then multiple sequential opportunities in patients with FGFR gene alteration.
You can see the cholangiocarcinoma has upwards of 2 1000 to 3000 new patients in terms of incidents globally. The bladder cancer opportunity takes that to approximately 15,000 to 20,000 new patients globally and then if you add in the solid tumor population that I was talking about, you could be able to upwards of another 15,000 new patients and will be obviously later in the development paradigm. Donna, that ends my prepared remarks and I'll now ask you to open the line for questions and answers. Thank you.
Thank you. 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 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 Calangio 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?
Yes, I would take that. I mean, as you can imagine, the number of patients with cholangiocarcinoma carrying the rearrangement and fusion that we are looking at is relatively small. So the commercial deployment that we would be using is obviously going to be proportional to the amount of work that needs to be done. And we have to realize that in many cases a single doctor would not see many of these patients in a given year. So there are some large centers where you could imagine having a team of some individuals meeting with physicians, etcetera, but a lot of the work will be done on the diagnostic 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 patient has been diagnosed.
So it will be an un traditional commercial deployment, if you want to think about it, in the U. S. Where we would start right to be the first we are anticipating we are still looking at it, but we are anticipating that there will be a field based individuals who are going to be prepared on this project and will probably share some of of the activity with other products for us. So 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 who are dedicated to this project.
And that will change and I would say the same applies to Europe when when it would be time to do that in Europe for cholangiocarcinoma. And then as we go to the next indication, which could happen relatively quickly after then there would be probably a very different approach where for bladder cancer or diagnostic tumor that with there is enough potential to justify having dedicated feed people. So I see that the 2 step effort the first one, I mean, the first step in Corangio alone is going to be meaningful because it is a new drug for inside. So, it's important. It's going contribute to the growth of the organization, etcetera.
But at the same time, we have to be conscious that it's relatively limited total commercial opportunity.
Thank you. Our next question is coming from Ren 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 reduction and outside of reducing the dose, are there ways to clinically prophylax or treat these patients so that you can you can keep them at the appropriate dose? And and just as a as a second follow-up question.
The author in discussing, you know, talked about other FGFR inhibitors largely saying that that they're equivalent. I guess without giving away your potential marketing strategy, how do you envision the competitive landscape and 3 to 5 years and how do you differentiate, with others that are coming to the market? Thank you.
Rena, Steven, I'll start off and I'll also comment on your second question, but Irvin may add to that. So 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 diary management, so that cytokine phosphate are well understood and controlled and both by the physicians in patients. And then if needed, if needed diuretics to eliminate phosphate, I think, it's almost universal across 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, there is beyond, you know, people run into trouble with a particular side effect and 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 But in terms of what we saw with serious central retinopathy, we have a 4% rate in this particular data set And it may be to do with 1, the population to the intermittent dosing and we'll see how this evolves across the program the tumor types. And when we see the use of continuous dosing, so I don't want to comment those competitors, but you did bring it up. But 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 they're different off target effects, different things evolve. You saw on one of our early sides of the profile of our compound versus competitors and it's clearly different in terms of hitting potency wise nanomolar ranges for 1, 23, we can dose at much lower levels compared to them. We used 13.5 there often in the hundreds. So, we'll see. From an efficacy point of view, I haven't seen it as mature a data set as ours were the competitors.
And they don't, in terms of reported data, we haven't seen the degree of independently firm response that we have seen today. So, we'll see. I'll hand it over to Erve if you want to say anything else?
No, no, I think I mean, at the beginning of every differentiation is a question of of the specificity of the profile. And what we see is that among the other products that are targeting FGF. We have the most specific products. So we hope that that will translate into the clinic. It is true that it's an emerging therapeutic profile and we should be very careful not to compare bladder data with conjugate 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 at takes of the commercial success will come also from the sequence of approval. So we will be 1st in Toronto carcinoma. That's now is something we can I would say as the submission dossier is being finalized and prepared? I think in bladder cancer in the second line, we will obviously be hinds.
I still have a question on who will be first in the first line setting where we are initiating our pivotal studies and we have the tumor agnostic setting where also it will be a question of sequence of launches. So I see based on what we know today that we will be the 1st or second in each of these. And I think if you give us a very good position to, to be successful on the market on top of the profile that will be clarified over the next few few months when we get new data on the on the other tumor side. So, overall, I think it's a it's a position that is going to be competitive and it's a market that with the new indication coming beyond conangio will become meaningful to insight in terms of growth of our revenue over the next 5, 6 years.
Thank you. Our next question is coming from Michael Schmidt of Guggenheim. Please go ahead.
Hey, this Kelsey Goodwin on for Michael. Congrats on the data. Previously, you said I think about 33% overall response rate would be the bar for planning clinical meaningfulness, I guess. Obviously, you've cleared that today, but is there any other hurdle, in your view for approval for pull anything duration related? Thank you.
Kelsey, it's Steven. No, I think you focus on the strict resist definition and that was the primary endpoint and that's fair 35.5%. But if you look at that plot, you can see 80% plus of the patients have some degree of response including long term stable disease. So that 82% disease control rate is another very important endpoint. That translates into the median PFS of 7 months in the setting and actually the median overall survival or not, although not controlled of 21 months.
But remember the context, single digit response rates for second line chemotherapy, PFS of 3 months OS of 6 months, So, we think all of that obviously is going to be up to regulators in the end. Adds up to something that is real clinical benefit for patients. We obviously very confident in the submission in terms of that.
Thank you. Our next question is coming from Mark Fram of Cowen and Company. Please go ahead.
Hey. Thanks for answering my questions. Would it be possible to break out the PSS data by line if there be maybe as a as a read through to what might happen in the frontline trial?
Even. So I'm not I can't comment on data that we haven't shown today because not in the public setting. Obviously, down the park future presentation, including manuscript may help you with that answer. So I'm not going to give you a satisfactory answer today, but it looks like that this 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.
So it looks like although not controlled in this using the therapy in a targeted setting in this population with a 21 month over survival that beyond any prognostic implication is a real treatment effect. Whether it's going to be different in whether the patients are second, third, fourth or line. I just can't comment on it at the moment.
And given the I mean, the impact on OS seems to be much more significant than even PFS. Is there are many of these patients staying on drug post progression?
No, that does not say Steven again. I don't know. I think it's got to be careful of commenting on that. It's not a randomized against the control and there may be issues around this disease having a different prognosis to the non FGFR mutated. But again, having said all of that, it's extremely encouraging both the speaker today and the discussions 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. And then thinking about the the tumor agnostic trial, it's structured to just go straight to full enrollment, or are there kind of a key gating interim analysis to open up full enrollment to that 300 something patients?
Yes. I mean, we have the ability to look at response at intervals during the study in appropriate ways given the statistical design. And obviously, if there's if you're not seeing a 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. But 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.
So that Pembro is example in MSR high endometrium, So, if you established the driver, you've 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. So, we put that total in to allow ourselves to expand in different entities, but it may not be needed.
Thank you. Our next question is coming from Vikram Proet of Morgan Stanley. Please go ahead.
Hi. Thanks for taking the question. So I had one on response rates and how those trended from your last update to today's update. So, some patients achieved complete responses as of, the update this morning. So I just wanted to see if you could kind of help us characterize what the baseline characteristics were of the patients who achieved CRs and how those responses can we have trended throughout their time on drug?
Yes, Victor, it's Stephen. 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 it'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 entertained yet. That would be interesting if that was the case but there's nothing special about it. Obviously, while the study is still open, we'll continue to follow patients and see if things change, but when you got an 82% disease control rate, I think it's encouraging enough, but nothing special to point out there's a difference in the CR patients versus the PRs, 1st and non responders currently.
Understood. That's helpful. Thank you. And then, as a quick follow-up, if I could ask a question on PFS. So I know that you're not able to at this time kind of break out the results beyond what's reported in the in the release from today.
But anything you can help us think through and characterize or 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 9 months. Today it's roughly 7 months. So how should we think about how that's trended?
Yes. Firstly, thank you for your question. I think this is, 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 it can be small accidents around the median. And by that, I mean, the curve can suddenly drop down when it matured. So that one event didn't happen, it would have been 8, 9 months versus 6.9 now.
And that's really all it is. You have to remember it's a medium, it's a single point on a curve over time. It's not the totality of the curve. And we don't think they're substantially different in any way. Just maturity of the data set.
Thank you. Our next question is coming from Evan Sigerman of Credit Suisse. Please go ahead.
Hi there. Congrats on the data. Definitely strong OS and the cohort a. So just looking kind of more broadly at your Pemigatinib program, how are you going to differentiate this from competitive products, not just in cholangial carcinoma? That's kind of your key indication.
But also in bladder and the more broad tumor agnostic indication? Thank you.
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 would 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 FGF in the clinic today. Specifically, we are we have a profile that is avoiding SGFR 4, which is always important because we know it has an impact on on the clinical profile. As you can see from the data we have in Conjio here, on the fairly large numbers, there is 100 patients, 100 and 40 total and 100 patients in AA.
So, we are starting to see emerging a profile of very good efficacy, very few patients or very few small number of patients having to drop out of treatment because of side effects. A few dose interaction, but most, I think, 80% of patients receive the planned dose for for their treatment. So that's very encouraging on the first translation of this good preclinical profile into clinical efficacy and safety that as it is we look at it today is very favorable. So that at the end of the day would be the key to the competitive situation between these products. And we are very confident that our profile is very good from that standpoint.
The other thing I spoke about earlier is a sequence of launches. So obviously in Colombia will differ a small relatively smallish type of market as the patient population is relatively limited. We are working on the 1st line bladder where I think we are in a relatively competitive situation in terms of timing And as we said, we are initiating the agnostic where we could end up being in the bid position in that setting. So I think that will have an impact on adoption curve for each of these products. And being 1st in Colombia, maybe also in agnostic and first line bladder.
We are somewhere in the race. It's putting us in a very good position. And when you look at the potential overall for the molecule. And that's why we have this call today in fact is introducing the new molecule now that has a good, you know, chance to go through the regulatory process. 1st in terms of carcinoma is that when you add the rest of the ratable population and the clinical profile and the adoption curve, then we believe it could become over time a very, meaningful contributor to inside the revenue.
And that's why we speak about it as a sort of today, there is a bit like the kickoff of the new product now moving through the finish line, which I think is always a very important event for our company. Great.
And then just as a follow-up. So in the FIGHT 205 trial, can you help me better understand the additive impact of combining pembro with some in urothelial cancer?
It's Steven. So that's a it'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 immunoresponsor by FGFR inhibition. So it's testing that hypothesis together.
So that's that arm. There's a pemigatinib alone on 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 PD L1 low and if they PD L1 positive pembro alone. So, I think it's a superb study. You'll get the contributions of care of each individual thing.
You'll test the hypothesis of making potentially cold or lukewarm tumors hot with their combo. And as everybody said, we go in at 1st line looks like ahead of everybody else.
Thank you. Our next question is coming from Gilbert Kinsey of RBC Capital Markets. Please go ahead.
Good morning. I'm Owen from Brian Abraham's team today, and thanks for taking our question. Again, on differentiation, there's another FGFR inhibitor, derazantinib in development for cholangio carcinoma, and they seem to highlight their ability to inhibit the CSF 1 receptor in addition to the FGF receptor. As an added mechanism of potential anti tumor activity through effects on tumor associated macrophages. And I just wondered if you had any thoughts on whether pemigatinib also inhibits the CSF 1 receptor and any potential role for this mechanism in the activity you're observing.
Yeah, it's Steven. So thank you for your question. So to my knowledge, we don't, and obviously, they have a different profile in terms of the economy selectivity. And we'll see how that pans out. In terms of published data data from the ARQule compound to date.
I think they published the phase 2 in about 29 patients. They have a low 20 percent response rate that they've reported. So, we'll see. I mean, you don't make cross trial comparisons and I certainly we haven't done that, don't want to talk about another competitive agent. But to date, the data I've seen hasn't pointed to increased efficacy.
Our
next question is coming from Althia Young of Cantor Fitzgerald. Please go ahead.
Hey guys. Sorry, thanks for taking my question. Congrats on the data. To 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? And then I guess I just wanted to talk about cohort B and C.
Did you hypothesize that you probably would see no effect there? And I just kind of want to see how you think about that since there is activity across different isoforms? Thanks.
Thanks, Lydia. It's Steven Stein. The first line study is going against the case standard against gem, uh,citabine plus platinum agents. 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.
And it'll be a very, very important question to answer, does targeted therapy, can it advance from a second line set into a first mindset in and potentially supply. So, surplus chemotherapy in that setting. So, we'll see and that's why we're conducting that study the cohort B. C. Thing is really interesting.
So, we didn't know upfront. We didn't expect activity in C at all. But in B, we didn't know and that's why we did the test, right. There is some stable disease, but no classic resistive responses there. And I think as the discussion said on the podium today, there's probably likely one potential explanation is that those particular genetic defects there aren't drivers, aren't driving the disease, so aggregating 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 you can see the lack of response there. You can see the lack of PFS. So, it's quite a glaring to see in terms of the curve, although that wasn't a formal comparison.
Great. Thanks. 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. Okay. So it looks like there are about 85 patients that came into the trial with a confirmatory diagnosis, and that would like, you screened another 1200 or so to find the remaining 86.
I think that implies a hit rate of something around 7%, which I think is about maybe 2x lower than what we've seen in the, in the literatures. So just kind of wondering how you're thinking about this, 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 enrollment timelines into, the phase 3?
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 the, you're right, 85 patients had a pre existing foundation test. And then beyond that, at about a 7, 8% hit rate, The literature repeatedly points to a much higher rate of 10% to 15% seen for intrahepatic cholangio when it's in a non biased testing set in. This is a, you create your own bias by conducting a study by telling such you want to do it by sites having either local testing or the prescreen.
I don't think that's the case. I think the rate is based on all the available literature. Around the 10% to 15% rate. There are other issues around also histology by the way. So not everybody there were classic gallbladder cancers in there.
They were in puller barter cancers. There were other bile duct cancers that made that population a little distorted without getting too much granular detail, but 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. And then, just a quick follow-up. Again, I know the patient subgroup, breakout here is is is based on real small numbers. But I guess when you just look at the response decrement that's associated with prior treatment exposure, whether it be second line, third line airline plus patients.
It doesn't really appear to be all that significant. And I guess just wondering if you expect that trend kind of hold as you move upstream in the fight 3 of those? Thanks.
No, I think that's a good thought. I mean, I try to allude to that indirectly in that with a targeted therapy, it may not matter what line number 1. And I think that's what you indirectly say. And you may see the same degree of activity 2, these patients may be a little chemo unresponsive if they have the FGFR2 fusion or rearrangement. And obviously that's going to be key to our test in the first line setting, right?
Against chemotherapy in this population, we'll target a 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.
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 hyper fatemia and the dose interruptions and reductions. At what level of hyperphosphatemia would a doctor decide to reduce dose or interrupt dosing? And also if the dose is interrupted, how long does it take for levels to return to normal?
Thank you.
Thanks for your question. I think at a very high level, and there was a slide in the prison patient on patient disposition by cohort. And if you look at cohort A, which is the one of interest, just to mention again, there were literally of the 107 patient in a cohort 4 that discontinued for adverse events in total across the board for all adverse events. So, it was a very uncommon occurrence to have a discontinuation. To terms, I can't give you specific because it's more of the art rather than the science of medicine on when a doctor will be more concerned or not.
But it's something we're going to have to do and when hopefully we approved and commercialize the product is help to educate you because we don't even want them to get to a state where there are concerns. So, 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 like the 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 that, but I can't give you an exact number now.
Great. Thank you.
Thank you. Our next question is coming from Silveen Richter of Goldman Sachs. Please go ahead.
Yes. Hi. Thank you for taking the questions. This is Mariana Breitman on for Salveen. I have One, on dosing, would you consider continuous dosing for 2nd line?
Because it looks like that's where, you know, the direction in which PEM is moving. And also, would checkpoint inhibition make sense, in combination with Pemigatinib in Calanjo carcinoma? Thank you.
Hi. Thanks for your question, Steven. So obviously this program was quite far advanced in terms of intermittent dosing. We're seeing this degree of which we believe is very important to patients and should hopefully get us an approval. We haven't tested yet continuous dosing in aglandiocarcinoma.
Obviously, we do that in bladder cancer. And it's something we could clearly consider down the path 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 and checkpoint inhibitors on their own haven't shown an effect in terms of getting them across the finish line for approval. But given my comments, which you obviously picked up on around FGFR potentially enhancing that in terms of the tumor microenvironment again, something that may be worth testing again down the park. So, looking at concomitant FGFR inhibition plus checkpoint inhibition in Calandra just hasn't been done yet.
Got it. And as a follow-up, could you address the safety of continuous versus intermittent dosing? At least what what you see in Platter?
Yes. So we haven't published our data yet. You'll have to wait to see that. And obviously, he's going to be really interested in that too. And then be very careful of crosstalk comparisons, particularly to other drugs and other disease settings.
Again, but however saying that should this same rate in terms of the central serious retinopathy, the pan out in other settings with continued dosing. They'll be very good for patients and for our drug as a differentiator, but we'll see what the data shows, and I can't answer your question yet until we have our continuous dosing data.
Got it.
Thank you very much for taking the questions.
Thank you. Our next question is coming from Jay Olson of Oppenheimer. Please go ahead.
Hi, thanks for the presentation and thanks for taking my questions. Can you comment on the timing of potential registration filing for FIGHT 207. And then longer term, would you consider doing a 1st line tumor agnostic study, and or a combination tumor agnostic study with Pembro or some other IO. Thank you.
Yes. Jay, hi, it's Steven. Thank you. We'll see. I mean, if you look at our penultimate slide of the prison patient slot 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 it involves. I think it's safest to think of it as an opportunity around that timeframe currently. And then 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 an adjuvant type population. But you have to sort of move up that when you first show efficacy in metastatic populations. And then 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 Check Boyd's blockade and the 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, but that's a little bit down the pipe. Thank you.
Thank you. Ladies and gentlemen, our last question today is coming from Corey Aspenaz of JPMorgan. Please go ahead.
Kory. So I just asked a question about the, Ferris retinal detachment. I know you've talked a lot about how we can't necessarily read through the various indications, but just curious from the ESMO data presented last year on sites 201. It looks like there was one discontinuation, due to serious retinal attachment. Did you see any discontinuations in this study for the same reason.
And then also, is there any any reason that you can think of why we should expect a different rate a serious retinal attachment between the two indications? Thanks.
Yes, Steven. So the one patient to have a serious event of the 4 total is that same patient. So there's no additional patient who had a discontinuation there. In terms of your answer, your second question, we'll see. I mean, we need our continuous dosing information.
It'll be in latter 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. Attorney of the one serious event.
If that ends up being the case in continuous dose and name data, that would again be great for patients and for us, but we'll see just don't know yet. I don't think the expectation should be with with continuous dosing that the rate would go down, it'll either be the same or maybe go up because you hit in the target more. But 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 Harvey for closing comments.
Okay. Thank you. Thank you all for the time today and for your questions. So we look forward to speaking with you at our third quarter call as well as seeing you at upcoming investor and medical conferences, which for now, we thank you again for your patient in the call. Thank you, and goodbye.
Ladies and gentlemen, thank you for your participation. This concludes today's event. May disconnect your lines and log off the webcast at this time. Have a wonderful day.