Good day, ladies and gentlemen, and welcome to the Vertex Pharmaceuticals First Quarter 2018 Conference Call. At this time, all participants As a reminder, today's conference may be recorded. There will be a
Good evening. This is Michael Partridge, Senior Vice President of Investor Relations for Vertex. Tonight, we will discuss our first quarter 2018 financial results and our continued progress to build long term leadership in the treatment of cystic fibrosis. Doctor. Jeff Leiden, Chairman and CEO Doctor.
Reshma Kewalramani, Chief Medical Officer and Ian Smith, Chief Operating Officer, will provide prepared remarks this evening. Stuart Arbuckle, Chief Commercial Officer, will join us for Q And A. We recommend that you access the webcast slides as you listen to this call. The slides are available for download on our website, This conference call is being recorded and a replay will be on our website starting later tonight. We will be making forward looking statements on this call.
These statements are subject to the risks and uncertainties discussed in detail in today's press release and our filings with the Securities And Exchange Commission. These statements, including, without limitation, those regarding Vertex's marketed CF medicines, the ongoing development and potential commercialization of any triple combination regimen for cystic fibrosis, Vertex's other programs, and Vertex's future financial performance. Are based on management's current assumptions. Actual outcomes and events could differ materially. I will now turn the call over to Doctor.
Jeff Leiden.
Thanks, Michael, and good evening, everyone. 2018 is an important year for Vertex. And in the 1st few months of this year, we have continued to build on our established track record of innovation to discover, develop and deliver transformative medicines to more people with CF. The approval of SYMDEKO, our 3rd disease modifying CF medicine, offers many patients an important new treatment option. In particular, for those F508Dell homozygous patients who never started or who discontinued or can be.
The SYMDEKO launch is off to a strong start in the U. S, and we anticipate approval in the EU in the second half of this year. Today, the number of people eligible for 1 of our approved CF medicines has grown to 34,000 worldwide, and about half of these patients are currently on treatment. With the revenue and earnings growth in 2018 and beyond. Our belief that we can treat many more patients in the future, as well as to further enhance the benefit of CFTR modulators is based on our rapid progress in developing triple combination regimens that include a next generation corrector.
Earlier this year, we announced that we had initiated Phase III studies to evaluate VX-six fifty nine in triple combination with Tezacopter and ivacaftor in two groups of patients. Those with 1 F508del mutation and 1 minimal function mutation and those with 2 F508del mutations. The first sites are open for the phase 3 study in patients who have only one minimal function mutation, and we have begun to dose patients in that study. Today, we also announced the start of phase 3 development for our 2nd next generation corrector VX-four forty five as part of a triple combination regimen in the same group of patients that we are evaluating with VX-six fifty nine. This marks important progress toward our goal of advancing 2 different next generation triple combination regimens, to allow us to choose and bring forward We're also making important progress in our research and development pipeline beyond CF.
We are preparing to begin clinical development of CTX001, an investigational CRISPR Cas9 gene editing treatment in 2 devastating diseases, beta thalassemia and sickle cell disease, with our partner CRISPR Therapeutics. We also continue to make important progress with the selective NaV1.8 inhibitors, BX-one hundred and fifty and BX-one hundred and twenty eight for the treatment of pain. We look forward to generating additional data from ongoing studies of these potential pain medicines to inform future development plans. In 2018, we also expect to move 1 or more potential medicines from our internal research programs into clinical development in other diseases. I look forward to updating you on our officer.
Reshma joined Vertex in 2016 and her depth of medical knowledge paired with her experience and proven track record as a clinical leader make her an ideal successor to Doctor. Jeff Jaglitz, who will remain with us through early 2019 as a senior advisor as he transitions to his planned retirement. I'd like to personally thank Jeff for his extraordinary leadership and dedication to improving lives of people with CF and other serious diseases. I'll now turn the call over to Reshma to review the status of our CF clinical programs in more detail.
Thanks, Jeff, and good evening, everyone. Tonight, I'm very pleased to review our progress in advancing VX-six fifty nine and VX-four forty five triple combination regimens into phase 3 development and to share the initial results for once daily triple combination regimens that include VX5 61, a once daily potentiator. First, to the VX-six fifty nine triple combination regimen. During the first quarter of 2018, we announced the initiation of 2 Phase 3 study of VX 659, Tezacaftor, and ivacaftor as an investigational triple combination regimen for people with CF. The first study is evaluating the VX-six fifty nine triple combination regimen versus placebo in approximately 360 patients ages twelve and older who have a minimal function mutation.
A schematic of this design is shown on slide 7. The key feature of this study is that the efficacy assessments at 4 weeks and a safety assessment through 12 weeks will form the basis of a potential NDA submission The 24 week assessment will generate data on key secondary endpoints as well as safety, but these patient enrollment in the study has begun and the first patients have been dosed. A second study will evaluate the VX-six fifty nine triple combination in approximately 100 F508 Del homozygous patients ages twelve and older. The design of this study is shown on Slide 8. The key features of and then a primary efficacy assessment after 4 weeks of additional dosing where VX-six fifty nine or placebo is added to Tezo Caster and ivacaftor.
To support a regulatory submission in the US, to treat the 508 Del homozygous population, we anticipate using the 4 week efficacy data from this study in conjunction with 24 week safety data from the study in F508DAL minimal function patients. Data from these studies of VX-six fifty nine will also be used to support planned regulatory submissions in Europe and other regions. Turning to VX-four forty five. Today, we announced the initiation of 2 phase 3 studies of the VX-four forty five triple combination regimen for patients with CF. The study designs and are shown on slides from the non clinical toxicology studies for VX-four forty five, and we expect the FDA's review of these data prior to the start of our Phase III studies.
Initiating phase 3 studies with both VX-six fifty nine and VX-four forty five gives us the opportunity to generate data for 2 different triple combination regimens and pick the best regimen to bring to patients as quickly as possible. In addition to evaluating each triple combination regimen each of these triple combination regimens in patients who have a gating or residual function mutation. Earlier this year, we announced Phase 2 results from VX-four forty five in F508delminimal Function Patients that support advancing VX-four forty five into phase 3 studies for that population. Today, we are reporting the initial phase 2 data for VX-four forty five in triple combination in F508del homozygous patients. Once again, the efficacy observed was impressive and the safety profile of Vx4 45 was similar to that observed in previously reported parts of this study.
This phase 2 study evaluated VX-four forty five or placebo in combination with Tezacastor and ivacaftor for 4 weeks after a 4 week run-in of TezaCAfter in combination with ivacaftor. In the patients who received this triple combination, we observed a significant improvement in lung function of 11 percentage points over what was obtained with Tezacaftor and ivacaftor alone. This improvement was evident by the 2nd week of the treatment period and sustained through the 4 week dosing period. These data are shown on Slide 11. The VX-four forty five triple combination was generally well tolerated, and the safety profile is consistent with what we have learned previously with this regimen.
Today, we are also reporting the initial results for the once daily potentiator VX-five sixty one when dose is part of a triple combination regimen with VX 659 or VX 445, and Tezacaster in people with 1 minimal function mutation. In these phase 2 studies mean absolute improvements in PPFEV1 of 11.7 and 12.2 percentage points from baseline through week 4 of treatment were observed for the VX-four forty five and VX-six fifty nine triple combination regimens respectively. The once daily triple combination regimens were generally well tolerated, and the safety results were consistent While we believe that the results clearly support has a role in future once daily triple combinations, the FDA has requested additional dose ranging for VX-five sixty one, including potential evaluations of monotherapy before allowing evaluation of VX 561 in late stage development. We look forward to updating you on our progress with our triple combination regimens as we advance these programs. I'll now turn over the call to Ian.
Thanks, Reshma, and good evening to everyone. 2018 is off to a strong start And tonight, I'm pleased to review our first quarter 2018 financials, the SYMDEKO launch in the U S and our 2018 full year financial guidance. Revenues first. Total CF product revenues of $638,000,000 in the first quarter of 2018 represent a 33% increase compared to the $481,000,000 we recorded in the first quarter of 2017. Our total product revenues have continued to grow each quarter as we increase the number of patients treated with our approved medicines.
Today, we estimate approximately 34,000 patients are eligible for our medicines, of which about half are being treated. We expect the eligibility and the number of patients we treat to continue to grow throughout 2018 and therefore continue to drive revenue growth. I'll make some brief comments on SYMDEKO launch in the U. S. Since the FDA approval on February 12, we have been educating healthcare providers on the medicine working with payers to secure reimbursement.
We are seeing broad coverage and access to SYindigo as the majority of commercial and government payers are reimbursing for the medicine. For the first quarter of 2018, we reported SYMDEKO revenues of $34,000,000, which reflects the initial 7 weeks of sales. We continue to prepare for the anticipated approval of this medicine Our first quarter 2018 non GAAP R and D and SG and A expenses were $360,000,000 compared to 3 13 $1,000,000 in the first quarter of 2017. This increase was primarily due to the advancement of our portfolio of triple combination regimens for CF and the investment to support the treatment of patients with our medicines globally. Non GAAP net income for the first quarter of 2018 $196,000,000 compared to non GAAP net income of $101,000,000 for the first quarter of 2017.
The increase in non GAAP net income was largely driven by the strong growth in total CF product revenues. During the first quarter of 2018, we also strengthened our balance sheet as we ended March with approximately $2,500,000,000 in cash, cash equivalents and marketable securities. Compared to $2,100,000,000 full year 2018 total CF product revenues in the range of $2,650,000,000 to $2,800,000,000 comprised primarily of combined revenues from countries where our 3 approved medicines are currently reimbursed. The midpoint of this range represents approximately 26% growth over 2017, driven by the launch of SYMDEKO and an increased number of patients treated with our approved medicines. As we have commented on previous calls, we are focused on total CF product revenues in our guidance given that some patients on KALYDECO and ORKAMBI will switch to SYMDEKO.
The timing and the amount of this switching is not yet known. We believe the overall growth of CF Product revenues is the most important because it reflects revenue growth from treat more and more CF patients. We also continue to expect combined non GAAP R and D and SG and A expenses of $1,500,000,000 to $1,550,000,000. The key investment drivers are the execution of pivotal studies for 2 triple combination regimens, supply chain investment for the potential commercial success of a triple combination regimen and the incremental investment to support the launch of SYMDEKO. Our financial profile has strengthened significantly over the past 2 years.
Our continued execution across all parts of our business has positioned us to deliver sustainable revenue and earnings growth and to continue to expand our operating margins in 2018 and beyond as we significantly increased the number of patients we
questions. Thank you. And our first question comes from the line of Geoffrey Porges with Leerink. Your line is open.
Thanks very much for taking the question and congratulations on the strong results. The only surprise really is that you're not going ahead with the pivotal trial with 561. And I wonder if you could give us a little bit more standing is to the basis for the FDA's decision. It seems a little unusual given that it's just one of the your isomers of, well, actually, it's only a deuterated version, I beg your pardon of KALYDECO, what's the basis for that caution? And, should we assume that that same standard of single drug dose finding is going to be applied through every potentiator that might potentially enter the class?
Hey, Jeff, it's Ian. Maybe we could actually separate that question into 2 parts, which, maybe have Reshma talk about the data and Jeff Liden talk about how we intend to corporate 561 into our regimen as we go forward. I would remind you back in, earlier this year, this, we We look forward to getting the results from 561. It was pending there and pending discussions with the FDA. Maybe we can give you a little more insight into that.
So, Reshma, do you want to talk about it there first and then, Jeff, on the strategy for incorporation?
Sure, sure. So as you know, in both the VX 659 and the VX 445 proof of concept studies, we had one part that included VX five sixty one in place of ivacaftor. And let me walk you through the results in terms of efficacy and safety. On the efficacy side, as as you heard in the prepared remarks, we had an improvement in PPFEV 1 of 11.7 and 12.2 percentage points, respectively, for 445 and659. Really impressive results, that we were very pleased with.
On the safety side, the results were remarkably similar to what we seen in our ivacaftor studies. And when we looked at these results both on efficacy and safety, we were very impressed with what we saw and, impressed with the consistency of the safety profile. Jeff?
Yes. So, Jeff, as you said, we got those results and obviously you need to have the phase 2 results before you go and discuss phase 2 design with the FDA, which we did over the last several weeks months. And it became clear to us that the way the FDA was looking at 561, despite the fact that, as you say, it's really a deuterated version of KALYDECO, is as a new chemical entity. And the kinds of information they're asking for, for instance, some of the dose ranging and potential monotherapy is exactly the kinds of things that they would typically ask for a new chemical entity, particularly before it goes into a combination regimen. And so our decision was our because our goal has always been to get the, best regimen to patients as quickly as possible, we decided to move forward with KALYDECO because that's the quickest route and we want to take a delay.
Having said that, I also think that a decision was probably a bit influenced by the fact that KALYDECO has been so well studied in so many thousands of patients frankly, it set a very, very high bar both in terms of efficacy and safety. And, so they have a lot of comfort with it and and that made it, I think, easier to to, enable us to move forward more quickly with that regimen. Having said all that, as Reshma said, the data for 561 is quite compelling. We do plan to take it forward into a once a day regimen. We're still in discussions with the FDA about exactly what data they're going to need in some of these, phase 1 and phase 2 studies.
But we think that's highly doable.
We just don't wanna wait.
So as soon as we know that, we'll progress those studies and we'll work out a bridging strategy that allows us to bring 561. Along with either 659 or 445, whichever one we choose to patients.
Okay. Thanks for that background. I appreciate it. I'll get in queue.
And our next question comes from the line of Geoff Meacham with Barclays. Your line is open.
Hey guys, thanks for the questions. Just have a commercial 1 and then a clinical one for SYMDEKO. When you look across the OUS approval trajectory, including Europe and Australia down the road, just what are lessons to be learned from ORKAMBI Can you help maybe abbreviate the process, reimbursement process I'm speaking about? And then, and I have a couple of follow ups on the clinical side.
Hey, Jeff. Thanks for the question. So on SYMDEKO ex US, what can we learn from our experiences with ORKAMBI? Obviously, in many countries we've been successful with getting ORKAMBI priced and reimbursement. Clearly, we'll be looking to to build on those successes in some of the markets where we haven't yet secured reimbursement for ORKAMBI, which we continue to very, very actively pursue, we have also begun discussions with some of those authorities about potential portfolio like agreements where we may be able to get accelerated access for patients to SYMDEKO.
Obviously, those discussions with ORKAMBI are very, very active. And obviously with SYMDEKO, they'll pick up more steam. When as we anticipate, we get the approval ex U S, certainly in Europe in the second half of this year. What I would stress there, Jeff, is we're not kind of waiting for SYMDEKO and then only really going to try and get reimbursement for SYMDEKO. That's not, how we're thinking about it.
As you know, patients with CF have a relentlessly progressive disease. We know that treating them as early as possible is incredibly important certainly with disease modifying agents like ORKAMBI. And so we're continuing to pursue with every degree of urgency that we can reimbursement for ORKAMBI the other thing to remember, which I think is an important point, is that the SYMDEKO approval is likely to be for, people 12 and over. And as you know, in recent years, we've expanded the indications for ORKAMBI first to 6 to 11, and hopefully subsequently down to 2 to 5. And so ORKAMBI is gonna continue to play a very, very important role for those younger children with CF.
And then just on the
That's helpful. Thanks, Stuart. And then on the pipeline side, when you think about the future triples beyond 659 or 445, I get the strategy with 561, but What would be the real objective here? Are you guys still actively pursuing more novel combinations in phase 2? I'm trying to figure out if you have an assay as predictive of FEV1, is it worth it to go into larger studies for just a few points of FEV1.
In other words, is there an upper end that's kind of worth your investment or not?
Yes, it's a great question, Jeff. And as I said before, we have now reasonably large number of additional NextGen Collectors that are flowing through research and into late, preclinical development. And and so the decision that we're gonna make and we'll have to start making it soon because some of those are moving along quickly. Is, are they significantly better do we believe than than, the 2 that are currently moving forward, 445, and659? And significantly better is really the whole profile of the medicine, right?
So it's certainly efficacy. But it's also, you know, once a day form of availability, dose, for instance, potency, all those things will go into our decision. But at the end of the day, the decision will be if we feel we have a molecule that's significantly better than the other 2, we'll take it forward into phase 1 and certainly into, you know, early phase 2. That's easy and quick to do. If we don't, we won't.
Got you. Okay. Thank you.
And our next question comes from the line of Michael Yee with Jefferies. Your line is open.
Great. Thanks. And congrats on the good SYMDEKO launch as well to start off. 2 part question, I guess, just to follow-up on the whole concept of more dose ranging studies needed for 561? I mean, I guess it would seem to be an important read through to what the regulators are saying on novel compounds.
So just to clarify, are you implying that you need to actually prove it out as a full potentiator and run it as a monotherapy program and prove that it's an active potentiator for new compounds. Just wanted to clarify that. And then the second question was on the phase 3 that are ongoing, and it sounds like started nursing patients. I mean, I presume that would be pretty fast. So while I wouldn't want you to necessarily guide on data, would you actually announce data when it's done after 4 12 weeks, or do you need to file?
Guess what would you be a disclosure policy beyond these phase 3s that we're looking forward to?
Yes, Mike. This is Jeff. I'll take the first part. Maybe, and I'll take the second one, I'm sure, the disclosure question. With respect to the first part, I never comment on what the FDA is going to launch for other people's programs.
I do think it's informative that they view 561 is a new chemical entity because as Jeff Ward just mentioned, it's quite similar to KALYDECO, but clearly different.
So I don't think it's unreasonable.
You know, obviously, as compounds get more and more different and newer and newer, you know, I I think that they're going to I have the same expectations for new commonalities pretty much across the board, but obviously that's up to that.
And Mike, it's a question of disclosure. I don't really want to design the disclosure and what we include in that at this point in time. So it will be we'll complete the study. We'll gather the data. What does the data inform us of in terms of the filing strategy?
I think that's what you could imagine as disclosing. And, the timing to that will let you know and will further into the studies. But as usual, it will be what can we do with the data? And we'll provide you that action, and we'll provide you the data that supports it. And let you know when we have that.
Okay.
Thanks. Thank you. Our next question comes from the line of Ying Huang with Bank of America Merrill Lynch. Your line is open.
Hi. Thanks for taking my questions. Maybe I have one on a Pinnacle trial design for the phase 3s. You're testing the Phase 3 for homozygous patients in about 100 patients where while you're testing on the guess, triple combo in the, pedrozax patients in, I mean, sorry, the, 180 patients for the HEARTME trial. So so I'm wondering, if the trial for homozygous patient sufficiently powered to show superiority in efficacy, or it's most likely a supplemental trial, to, compare the efficacy.
And then secondly, maybe commercial side, on the SYMDEKO launch. Can you tell based on the early experience of who are the patients taking SYMDEKO today? Are those mostly patients who were not tolerant of ORKAMBI before, or you're seeing also some other patients, switching to SYMDEKO? Thank you.
Hey, Ying, just before Reshma gives you the answer, I just want to correct one of your, points. And we are obviously doing 2 different Phase III trials, 1 in hetmin's, 1 in 508, 508 patients. The hetmin Phase III study does have 360 patients in, and the 508-five zero eight, Phase III study has 100 patients in. And now may be, Rashna can help you understand how the HETMIN study will lead and how 508-508 would follow.
Sure. Sure.
So for each of our programs, VX 659 and VX 445, the programs are actually very similar. So I'll use 659 as an example, but it's very similar to 445. In each program, there's gonna be a study of 300 and 50 patients total for hetmin patients and 100 patients total for homozygous and 508 gel patients. Now the 360 patients for hetmin, that comes from a desire that we have to look at things like pulmonary exacerbation, which is going to take more patients. With regard to the 508 homozygous, study, that is well powered.
Indeed, if you just look back at our proof of concept studies, you can see fairly substantial improvements in things like sweat chloride, ppFEV1, and even CFQR.
And Ying, on the SYMDEKO launch, obviously, we're just 7 weeks into the launch at the end of Q1, but we are able to tell in this early stage of the launch where those patients are coming from. And we're seeing a mix, we are certainly seeing patients transition from ORKAMBI and KALYDECO based on the strength of the clinical data But perhaps more importantly, we're also seeing, use in patients who were not being treated with a CFTR modulator prior to the approval of SYMDEKO And that's really in two areas. 1, one you mentioned, which is those, homozygous who had been initiated on ORKAMBI, but unfortunately had to discontinue the medicine. And then we're also seeing use in patients who were naive, who had never been, initiated on a CFDL modulator, and we're also seeing SYMDEKO being used in those. And obviously, those last two patient groups are incredibly important because, you know, those are patients who are not being treated with a disease modifying agent prior to the launch Cindigo.
Got it. Thank you.
Thank you. Our next question comes from the line of Karen Flynn with Goldman Sachs. Your line is open.
Hi, thanks for taking the question. Maybe I was just wondering if you could give us a little bit more detail on the couple cases of rash that you saw with, in the triple combo phase 2 that you just closed and just any idea of you know, which of the agents that might be tied to and, anything you can say on that front. And then, a question for Ian just on SYMDEKO. Can you quantify any inventory for the quarter? Thanks.
Sure. So let me start with the question that you had on the clinical side. Where we are right now is that we've completed our proof of concept studies for both VX-six fifty nine and VX 445. And what that means is we've treated about 200 patients. In that 200 patient, experience, We have a low incidence of rash overall and a low severity.
We have no serious events. These rashes have resolved with discontinuation of treatment or interruption. And and interestingly, on that latter point, We've had a couple of cases where patients have interrupted their therapy for a period and then restarted and completed their course without trouble. To give you some context for this KALYDECO and ORKAMBI, the rashes that we're seeing our next gen program are very similar in incidents and quality is what's been seen there. And you can look in the USPI and you'll see or Tandy is about a 7% and and KALYDECO is about 13% or so.
Terrence, to your question on SYMDEKO, I first draw you to the, kind of the top line revenues, CF Total revenues and comment on that. Which is, the inventory in the channel at December 31, 2017 was similar to the inventory in the channel at at March 31, 2018. So what that tells you is that, the, the, the channels remained even, between those two periods and therefore, the revenue number is real demand in Q1. After your question to SYMDEKO, there was some slight channel build, but that was offset to some channel decline on the colliderconor can be from December 31 period. In summary, total CF revenues in Q1 were the real demand and it was not channel built.
Great. Thanks a lot.
And our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is open.
Hi, thanks very much for taking my questions. I guess first off on the triple combo phase 3 obviously a lot of enthusiasm amongst sites, and we're hearing about sites needing to really filter patients as to who is eligible for the study. So I guess my first question is really how are you managing that operationally, the potential for healthier or more highly motivated patients to come into these phase threes and maybe perhaps skew the results or reflect a different population studied in phase 2. And then I had a quick follow-up on 561.
Sure. So, we have the benefit of having worked with CF patients in this community for some time now and executing not only phase 2 studies, but phase 3 studies as well in the patient populations that we're studying now in DX 659 in VX 445. And the inclusion and exclusion criteria, the discussions with sites the way that the sites are screening patients and such are, are fairly well, described and what we're doing in phase 3 is similar to what we ourselves just completed in phase 2. So I feel very good about how the operations are running and the timelines on which we are enrolling these studies.
Great. And then actually maybe a question on 445. You mentioned you're awaiting the FDA review of non clinical talks. Just wondering if you could say whether there was any were any notable observations there, or if that's just a box check.
Sure. You know that the, preclinical talks, the chronic tox results are standard fair. We've looked at it. We don't see any thing in there. But of course, the agency has to review that.
And our next question comes from the line of Phil Nadeau with Cowen and Company. Your line is open.
Good afternoon. Congratulations on the progress and thanks for taking my question. First one question on 4 45 in the homozygous data. It did look like there were some liver enzyme elevations in that study is there anything to be concerned about there? Are those rates similar to what you've seen for other agents in the past?
Sure. So, we've looked at the safety as you can imagine in great detail and no, we don't see anything interesting or different there, very much what we've seen, with our other trials.
Again, and second on the QD regimen and when it can move forward, do you have a rough sense of how long the dose exploration that you need to do will take. Is that something that you think you could finish in 2018, or is this, possibly a multi year process?
Yes, thanks. Well, we're still in discussions with the agency and so it's a little too early to give you a precise answer.
I think we'll know very soon.
And when we do, we'll let you know what the plan is, but most of what we're hearing about is and fairly straightforward so far. But until we finalize those discussions, I don't want to give you precise timelines.
Great. Thanks for taking my questions.
Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open.
Hey, guys. Good afternoon. I thought I'd I'd change it up and ask about the CRISPR program for a second. So you've mentioned, I think CRISPR has mentioned that you've filed the CTA. You've gotten 1 approved.
It sounds like farmer still pending. Can you just talk a little bit about what the next steps are in terms of starting dosing and what items are less pending to get the other CTAs approved and open some more sites?
Yeah, Matt. This is this is Jeff. Thanks for the the question. Maybe just to give folks a little background, I know you're aware of this. We're actually planning to study CTX001 and 2 related to different diseases, beta thalassemia and sickle cell disease.
Beta thal. We've submitted multiple CPA's, as you mentioned, for beta thal. One of those has been approved. And we expect to begin dosing later this year for beta thal in Europe. In the U.
S, we are on track to file an IND for Ciplocals disease and will also file outside the U. S. Again, depending on exactly when we do that, we anticipate starting dosing soon thereafter. So my hope is we'll be dosing in both diseases this year, and that should allow start to generate some data in patients. Thanks.
As you know, these will likely be the 1st gene editing trials in people. Pretty excited about that.
And I would just actually add to it. We are very excited as 1st gene edited trials in patients, but also say that this was came from a collaboration with Closter Therapeutics. Part of our, let's say, expansion and growth opportunity is we form these collaborations and give us product opportunities. And I just want to say that we're very happy with that collaboration with Christopher Therapeutics. The progress we've made there and the partnership to progress this opportunity towards the clinic.
It's pretty exciting for us at this stage in a very different disease CF. Thank
you. Our next question comes from the line of Cory Kasimov with JP Morgan. Your line is open.
Hey guys, this is Sean on for Cory. Congrats on the quarter and thanks for taking my question. Just another one maybe on the once daily. So understanding that the absolute difference for 45 and 659 was similar, but when looking at the placebo adjusted data for 659, it looks to be quite a bit better, at least on PPF ED1 since the placebo did quite poorly. Maybe if you could just comment on that.
And then did this contribute at all to the decision not to move directly forward with 4 45 in the once daily? Just kind of thinking that given 240 milligram dose for the 659 is being used for the other trials. Was there maybe a desire to look at this specific dose rather than the 400 before making the final decision in addition to all the things that the FDA is asking for?
Yes, thanks for the question. Actually, as we look at the data, the thing that's impressed us most, Sean, is the consistency of the data. I mean, it's pretty remarkable to me to see, you know, 4 to 6 different phase 2 trials with different agents in different combinations that are all generating almost identical results, not only in terms of PPF EV1, by the way, but in terms of sweat chloride, in terms of CFQR, etcetera. And it's obviously very important that these are placebo controlled studies and that we're seeing statistical significance and very small numbers of patients. So I guess our interpretation is what's remarkable is the consistency across the board between different regimens.
We don't see a difference between 561 any of those small differences are limited just due to the patient numbers. And so, no, that didn't drive any of our decision making nor do I believe it drove the FDA's decision making about how to proceed in 561. It's really just a matter of their view that this is a new chemical entity and their desire to have the appropriate early data set before we move Phase 3 and we'll look at that.
Okay, great. And then sort of just a modeling question. Can you maybe refresh our memories on the breakdown for the number of residual function mutations provided, it looks like the number of residual function mutations listed on the Kalydeco on the SYMDEKO labels are about the same, 16 for Kalydeco, 17 for SYMDEKO. So kind of just based on your announcements in conjunction with the approvals for on residual patients. It looks like there should be about 1500 patients that are currently covered ages 2 plus for a clatico in the U.
S. I'm just wondering roughly how many patients is this for SYMDEKO giving that this is in 12 plus and then how many additional residual function patients are there OUS?
So Sean, we'll get back to you after the call. You did ask for the bloke. Just want to make sure what your ask was let us know the total RF patient population. We'll get back to you at the call with that.
And our next question comes from the line of Dane Leone with BTIG. Your line is open.
You. Congrats on starting those studies. I wanted to ask, kind of a follow-up to an earlier question. Regarding the rash, appearance generally in your commentary about seeing it in around 13% of patients with KALYDECO, I was just curious, can you could you elaborate any more in terms of the safety profile that you're seeing with 561 And is there any reason to think that the extended half life of the molecule could exacerbate some of the safety profile that we've seen with KALYDECO? Thank you.
Sure. So when we looked at the data from VX5 1 in either the 659 program or the 445 program, what we see is real consistency with regard to efficacy. As well as the safety profile.
And just to be clear, as Reshma said before, both the incidence and severity of rash are very low here. They're similar to what we've seen with with the other medicines. And as you know, that that hasn't in any way affected the uptake or utility of those medicines. So we're very pleased with the overall benefit risk profile.
Our next question comes from Carter Gould with UBS. Your line is open.
Results and impressive data. I guess, 2, I guess for Jeff, now that you've got clarity on the phase 3 designs and you're entering a little bit more of a execution phase right now, any shifts in focus or attention on the BD front?
And then just on
the 4 45, once a day combo, just the, this, the quality of life data, the seaborne looked a bit anomalous speech, add some context around that. On the active arm seemed relatively consistent with the prior studies? Thank you.
Thanks for the questions. Both good questions. First one on BD. Really there isn't a shift. As Ian said in his prepared remarks, we have been accelerating revving up our BD efforts for the last several years with the same consistent strategy around CF platforms and early stage transformative products.
We continue to look and be very active in that space. You can expect to see us do more deals similar to the ones that we've done already, say, with that Christopher and Moderna. A Perion, etcetera. And because we have more firepower, we have more flexibility in terms of the size of those fields. So some of them may be even larger than the ones we've done already.
So I don't think there's really a change, but there's certainly a very active effort. It's just part of our a focus on diversifying our pipeline beyond CF, both through internal research and external collaborations or acquisitions. Maybe Reshma, do you want to comment a little on the placebo arm and see if you are? Sure.
Sure. So, as we looked at the CFQR results across 659445, actually across all the doses that we studied and in all the populations that we studied, what you see is big double digit improvements in CFQR. In this study that the 1445 study, you you rightly point out that there's anomaly in the placebo group. And in essence, there are 2 patients that are just plain different, and that difference is what drove that, CFQR value there. But you're right.
It's an anomaly, and it comes from 2 patients out of 8 small numbers.
Our next question comes from Alethia Young with Credit Suisse. Your line is open.
Hey, guys. Thanks for taking my questions and congrats on all the progress. 1, on the NAV 1.8, the VX-one hundred and fifty, to talk a little bit more about your strategy there. I know you have the data, where do you plan on presenting it and how do we think about moving forward in the Phase III and commercializing? And then just you know, kind of also, can you just talk about there's a preference at this point between, you know, true M and A or kind of doing more partnerships like you've done in the past?
Yes, this is Geoff with you. Thanks for the questions. With respect to pain, as we've said before, we don't really think about pain as one disease. It's multiple diseases that are a little bit different inflammatory acute neuropathic, etcetera nor does our pain program have one compound in it? We have VX-one hundred and fifty, as you know, for which we have positive data in both OA and, and in acute pain.
Have VX-one hundred and twenty eight, which is a fast follower that we're also very excited about. And I'd also remind you that in pain, both oral formulations IV formulations are important, particularly for acute pain. So this is sort of a complicated chess game where we have to decide what's the best medicine for the best indication and the best formulation out of our pipeline, which is growing. In a way we're doing that is to do some exploratory studies in phase 2 in these multiple indications. And I think we should have the data from those later this year, early next year, and that would allow us to make a decision about how to move forward.
I know, you know, some folks have asked me, well, isn't that gonna slow you down? Actually, my, my assertion would be it's gonna actually speed us up because if we do phase 2 correctly and we really end up and the right dose, right medicine, right disease, and right formulation, it's gonna allow us to move much more quickly in phase 3. And we're particularly excited about that because, obviously, areas like acute pain, we're sitting in the middle of this horrible opioid epidemic. And if we can demonstrate new oral agents, for example, that have the potency of opioids without these potential, we think there's going to be a very favorable regulatory environment, but we want to make sure we have all the data we need to take advantage of that.
Alethia, I'll take your second question, which is, I'll first say that M and A versus licensing, we just view those as as a tactic in terms of execution. And, and so as Jeff said earlier, we have 3 broader strategies in how we think about the outside world to Gotex. And that is look at everything in CF, to see whether it complements our own approach. Secondly, Do we have the possibility of expanding our scientific footprint beyond small molecules and maybe beyond gene editing now and And then secondly, thirdly, sorry, what product opportunities are there? And if those product opportunities come the way of licensing more M and A, Again, that's just the tactic of how you incorporate those into the company.
To Jeff's comment earlier, also we, we do have more capital available today. As you saw in the first quarter, we added close to $500,000,000 of capital. We went from $2,100,000,000 to $2,500,000,000 of cash and We have no debt. So, we, we, we do have more capability today to, to add to our pipeline. You know, the question is also, do you think you're going to get involved in large M and A and utilization of our own share count?
No, we don't believe that. We're focused on more earlier stage, high science ideas. As a company. We have lots of growth in front of us with CF, and that's where our focus is in transit in terms of driving revenue growth and capital accumulation. And we'll look at early stage opportunities in other disease areas.
Operator, this is Michael Parker. We have
time for one more question.
Certainly. And our last question will come from Robin Karnauskas with Citi. Your line is open.
Hi, guys. Thanks for taking my question, and don't worry. My kids are not in the closet at this time. So I appreciate
it. We we look forward
to that on every call, Rob.
I know. I know. Even though it
is bring bring your kid to work day, so I saw that ironic. So I guess the first question is to follow-up you asked about what exactly, you know, when will we see the data, you're saying when you complete the study, you'll you'll assess when you say complete, is that 4 weeks, or could that be 12, or could that even be 24? Just a sense of like, you know, it's what do you find as complete? And how do you keep those placebo patients on, the triple placebo for hetmin. And the other other question I had was you had a great quarter of SYNOCO you know, what are you thinking about the back end?
You know, like, reasonable assumptions can get you above your guidance. So I was just kind of thinking when you see a great strong, robust, 7 weeks of sales, how can you temper our expectations going into the back of the year? As a reason why you didn't raise guidance this quarter?
Thanks Robin. I'll let go that I'm glad you didn't lock your kids in the positive game.
So firstly, to your first question, just
to remind you that the HEATMID study, which is the lead study with 659, our anticipation is that, we'll provide you the data, based on what we expect to file upon. And, so when you look at the design of that study a 4 week efficacy endpoint and a 12 week safety endpoint. So, so we would want to run through the 12 weeks, because that's the basis of of the filing. So you'd anticipate that we would run through that period of 2, at least 12 weeks. We would collect the data.
We'd have to obviously analyze it and we'd provide a disclosure on that 6 59 study in the admin patients, which would complete, you know, using the 4 12 week, 12 week data. After your question regarding revenue expectations, we reiterate our guidance on the call tonight, 2,650,000,000 to 2.8 We did have a strong first quarter. We've got to see how the year progresses. We have built in growth, into that into that guidance. The main growth we do anticipate will come from those markets that we see that is already reimbursed from all three products.
And the main growth in terms of adding patients we see will be through SYMDEKO. And so we're holding on our guidance at this point in time, and we'll see how the year goes. And potential drivers of growth outside our guidance could be getting some of the markets where we're not currently reimbursed actually reimbursed and launching in those markets. And we'll update you at that time.
Great. Thank you.
Thank you. And this concludes today's question and answer session. I would now like to turn the call back to Mr. Michael Partridge for closing remarks.
Thank you, Chelsea. Thank you everybody for tuning in to the call this evening. The Investor Relations team will be available tonight for any follow-up questions that you have. Good night.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone, have a great day.