Conference Transcript - VRTX 2026-09-23

Dan Lundquist, Analyst — Bank of America

Welcome, everyone, to Day 2 of the Bank of America London Healthcare Conference. I'm Dan Lundquist. I'm the healthcare specialist over in New York. And very pleased to have Susie Lisa, Senior Vice President of Investor Relations with me from Vertex. All I have to talk about, Susie, not to mention, as you're saying, yesterday you had me change up all my questions, but maybe we'll start with just an intro. Can you give us an overview, anything that you want to flag today with the commercial franchise upcoming milestones for the maturing kidney and endocrinology franchises. And then we'll launch into some questions on the products.

Susie Lisa, Head of Investor Relations

Sure. Thanks for having me, Dan. Thanks for being here. And I think it is a really exciting time at Vertex with a lot of commercial progress and momentum. We call this a year of execution for us. And then an exciting lineup of upcoming catalysts in terms of data. So maybe first up I'd talk about is that we see continued expansion of our leadership in CF and it's been an exciting year there and continue to see good progress with our switch to lift track and development of our next gen 3.0 family. expansion down to ages two and up. And then for gernavics, I think on acute pain, we remain very excited and on track for tripling our prescriptions this year versus in 2026 versus 2025. And in terms of upcoming catalysts there on the chronic pain side of things, in peripheral neuropathic pain, we remain on track for our two phase three diabetic peripheral neuropathy studies to complete enrollment by the end of this year. There are 12-week studies. We haven't given definitive timelines, but I think that would put you at least roughly mid-27 for data from diabetic peripheral neuropathy, the two phase threes there. Then moving to our next commercial area now, which is chronetics and the rare endocrine space. I think very pleased with the uptake of Palsanify thus far. And we've called that a blockbuster opportunity. And then we see multi-billion in sales opportunities from Adjumelnet, where we haven't given updates on timing in terms of completing the phase three enrollment in congenital adult adrenal hyperplasia in the adult or pediatric, but look for us to do that likely on our third quarter call, November 2nd, we'll update timelines there. And then in terms of one of the biggest upcoming catalysts is in the renal area, we have the November 30th PDUFA date for POVI in immunoglobulin A nephropathy or IGAN that remains on track and pleased with the progress there for November 30th. And then with anaxipin, we just had our amplified phase two proof of concept, if you will, patient expansion population study that the results were yesterday, and then remain on track for Q1 of 27 for you to see the phase three interim analysis results. We also were excited to announce yesterday that we completed enrollment of that phase three amplitude study. And then in terms of other catalysts before year end, in the myotonic dystrophy type one space, you'll see proof of concept data from BX670 from us. And we've talked about seeing initial data from sort of the first in the NEXN 3.0 CF family 828.

Dan Lundquist, Analyst — Bank of America

Great. So maybe just digging back into the next one, what were the key takeaways from the phase two data you reported yesterday from the Amplified study?

Susie Lisa, Head of Investor Relations

Yeah, I think I'm really excited about the results and to see the consistency and magnitude and the reduction of proteinuria. So we reported UACR, which is albumin, which is the endpoint for this type of trial. But I'll do the conversion to UPCR because I think particularly with IGAM, that's how everyone is used to talking. So in cohort one, which just to remind folks was you have two APL-01 alleles and then a more modest level of proteinuria than in the amplitude phase three study. So in amplitude, you're 0.7 above and amplified, you could be in the 0.2 to 0.7 range. And so the proof of concept or the expansion here was, could you get that sort of proteinuria reduction with less dynamic range starting from a lower baseline, right? And we did see that. So the UACR reduction was 42.7, that converts to 44.7% proteinuria reduction at just 13 weeks. And so that's very consistent with the phase 2A. We saw from Amplitude, which was in just an FSGS population. So this was less severe proteinuria and minority FSGS population. And so I think very encouraging, exciting results to us there. Similarly, while not as strong a reduction in cohort two, so two APR1 alleles, as well as type 2 diabetes, the UACR reduction was 17.3%. That converts to UPCR reduction of 25.4%. So I think getting into that mid 20% level, again, at just 13 weeks is exciting, promising as well. Not as much reduction because clearly we know we're inhibiting APOL-L1, but we are not acting on their type 2 diabetes, which is also impairing kidney function. But I think a really encouraging, exciting result. And now we're looking forward to the interim analysis from Amplitude on the phase three, and then going to FDA with having a discussion in the context of Amplitude results about Amplified and seeing where things go from here.

Dan Lundquist, Analyst — Bank of America

And maybe can you provide any color on the safety profile? I know that there were five people who had, you know, some AEs of transamines elevations. Just any thoughts on that, whether it's a source of concern?

Susie Lisa, Head of Investor Relations

Yeah. So I think important to recognize that overall, there were no SAEs SAEs related to Anaxapalene and no liver SAEs. We did see the five patients with transaminase elevations, as you said, they were all isolated, asymptomatic, and they all resolved. But you did see two discontinuations of these patients, two in each cohort. And so I think that, again, the important thing is that they all resolved, but you did see two in each cohort discontinue. I think not uncommon or surprising necessarily in small molecule drug development. We certainly have experience and have seen this in CF. And I think obviously Amplitude, the much larger study, will be sort of the definitive safety outlook. But I think we're pleased with that. Look, a small study and some small numbers. But again, back to the resolution and no SAEs encouraging to us. otherwise, you know, well-tolerated.

Dan Lundquist, Analyst — Bank of America

And how are you thinking about potential next steps in these specific subgroups? You alluded to, you know, the amplitude study will be out next year. It's a much broader population, much bigger study. Just how do you think about these two populations?

Susie Lisa, Head of Investor Relations

Yeah. So if I might parse words a bit, right, it is a narrower population. In some ways, it's a bigger study, narrower population. So for amplitude, it is 2A polo-1 alleles. And again, that severe proteinuria 0.7 or above. I think with the results from Amplified getting from 0.2 to 0.7 and seeing very consistent results, at least on a phase two basis, that's encouraging to us. And if you think about the patient population, it doesn't line up exactly with Amplitude or Amplified, but broadly speaking, 2F1 alleles and no comorbidities, we view that as 150,000 patients. Vast majority of those are in the U S probably 80% or so. And a majority of them we would say are in the severe that 0.7 or, or above. And then if you take people with two equal one alleles, kidney disease, and some sort of comorbidity, whether it's diabetes or HIV, et cetera, that adds another hundred thousand patients. So getting to two 50 total.

Dan Lundquist, Analyst — Bank of America

Got it. Okay. And how are you thinking about the competitive positioning in AMKD, BCD, some of, you know, what else is out there from a volunteer standpoint?

Susie Lisa, Head of Investor Relations

Yeah, I think that we're clearly, you know, sort of years ahead with phase three interim analysis data early next year. And if the data are supportive, we'll move to filing as quickly as possible. And I think you have seen some other data in the field, but very heterogeneous populations unlike very narrowly defined populations that we think can you can draw your conclusions from um and uh we'll we'll wait and see how um how the landscape develops but i think particularly you can add to um the excitement we have in in renal broadly right povy and igam will be our first commercial launch but then to follow up quickly potentially with with an accident, I think will be exciting and is helping us kind of carve out, um, a leadership space in disease modifying therapies in renal, which is an area that's had sort of repurposed cardiovascular meds for a long time. So, um, a lot of excitement and buzz around what we're doing because recall after that, you also have POVY being studied in primary members nephropathy. And then we have another compound in, uh, also in a phase two study that's completed enrollment, um called the aglow study and that's for autosomal dominant polycystic kidney disease which is another 330 000 patients so large rare diseases rare disease populations and um i think uh really trying to carve out a leadership position with um novel disease modifying therapies maybe one last one um for me on an exploit um can you just help us think about what would be good data for amplitudes interim next year to something from some of the expectations? We haven't given a bogey and recalled the endpoint here, although the parasol meeting is happening today, I believe, right? The endpoint here for accelerated approval is the slope of EGFR. So it's a controlled study where you have anaxoplin on top of standard of care and then placebo on top of best standard of care. And I should have mentioned that on Amplified, very high levels of background therapy, sort of well-treated patients with ACEs, ARBs, SGLT2s, and GLP-1s for the diabetics. And so it is a 48-week endpoint of EGFR slope and essentially separation of the curve. So we haven't given a bogey there, but I think with the 47.6% reduction you saw in the phase 2a at 13 weeks. Now with what you've seen in the more modest proteinuria arm, I think we feel confident that that type of proteinuria reduction at 13 weeks will translate to a change in the slope or starting to approach stabilization, particularly compared to placebo, because these patients progress at twice the rate in terms of the deterioration of their EGFR versus sort of traditional kidney diseases. We'll also report out UPCR for amplitude, but the FDA endpoint for accelerated approval is the EGFR slope.

Dan Lundquist, Analyst — Bank of America

Great. So maybe sticking with renal, we'll shift to POVI. So you mentioned that on November 30th, very exciting opportunity, it would be your first renal launch. Can you just frame the competitive dynamics? You have two therapies that are already approved, both of which have been off to a good start, just trying to help kind of think about the initial launch opportunity at IGAN?

Susie Lisa, Head of Investor Relations

Yeah, I think they have been off to a good start. We're excited to see that. I think it speaks to the unmet need, right? IGAN patients are biopsy diagnosed. They're typically pretty young in their forties and otherwise healthy and sort of in these ticking time bombs, waiting to see how fast they progress. So I think that speaks to the early launch. But even with that, it still leaves, you know, I don't know, 159,000 patients in the U.S. to go after. Again, it's a rare disease, but a pretty relatively large rare disease population. And we're excited to come to Mark with what we think is sort of the perfect trifecta of differentiation. So more to come in terms of data, but believe we have potential for best in class in terms of efficacy. Recall we had just 36 weeks in our interim analysis compared to peers that We're at 40 weeks and really, I think, looked best or near best in terms of protein reduction, hematuria resolution, as well as GDIGA1 reduction and the percentage of patients getting to Cadego guidelines. I think a good safety profile. And then the third pillar of our trifecta is, we believe, clear differentiation in terms of patient administration characteristics. So we are monthly or every four week dosing with very small volume, 0.46 ml, and it's an auto injector. And that compares to one peer who is a weekly injection and one peer who is monthly, but it is closer to two mls, which gets more painful and it's pre-filled syringe, which requires more dexterity. So I think in this type of chronic disease, as we've seen in other areas, right, patient convenience, adherence, compliance, all of that does matter. So obviously, a big focus on the patients who are yet on drug, a large opportunity, but we'll go after switchers as well and certainly aim to, you know, have a really commanding market share over time.

Dan Lundquist, Analyst — Bank of America

And in terms of what's driving physician choice, what do you think that the key aspects they're going to take into account when deciding to prescribe COVID?

Susie Lisa, Head of Investor Relations

Yeah, I think certainly patient adherence to compliance, that will be part of it. But I do think that if this is a chronic therapy, you hear some people say stable is stable in terms of EGFR. Our view is that if you can get more protein reduction, no one wants protein in their urine or physicians don't want their patients to have it. No one wants blood in their urine. And if you're taking this every year and you're getting a percentage point or two more in protein reduction, that's compounding over time. And so our belief is that you will see efficacy as a key driver, as well as the patient convenience aspect in terms of driving physician and patient choice.

Dan Lundquist, Analyst — Bank of America

And maybe shifting a little bit to the pre-commercial activities and commercial activities, how's your Salesforce planning to detail the product that I gained? Do you expect that this Salesforce build out will allow you to support multiple launches in Nefrology?

Susie Lisa, Head of Investor Relations

Yes. Yeah. So the investment in the renal sales force is, is we have made the vast majority of that this year. We sort of had headquarter corporate types a year ago and then have fully built out our sales force. Very pleased to see vast majority of them have prior nephrology experience. I think, because they're excited about the profile of POVI as well as the pipeline behind that. And again, this space in renal, the halo effect that we'll be able to carve out. They are launch ready. We've been having pair discussions for over a year now as well. And I think ready to go and also excited about POVI's pipeline and the product potential. thinking about physicians who are saying, oh, if I get to know the ins and outs of COVID, then potentially I can treat both my IGAN and my PMN patients, as well as many of them do know us from our ongoing AMKD work too.

Dan Lundquist, Analyst — Bank of America

And maybe just kind of thinking about the long-term relevance of EGFR agents for IGAN. So we've been seeing a stabilization across the board. Any thoughts about how important that metric is as it relates to the field?

Susie Lisa, Head of Investor Relations

Certainly, it is critical, but I also think that there is well-understood now continued base of evidence, right, that UPCR reduction highly correlates to EGFR stabilization. And in addition, I think it's important to think that EGFR stabilization is in itself a proxy for time to end-stage renal disease and delaying the onset of need for death dialysis or not need, but delaying the onset to dialysis or need for transplant or potentially death. So I think, you know, well understood of the correlation there. I think having the ultimate one- or two-year EGFR data is important, but I think that it won't hinder us in our launch that we won't have that EGFR data because of the magnitude of our protein reduction, as well as the other parameters I mentioned, like hematuria, GDI, GA1, and getting people to guidelines.

Dan Lundquist, Analyst — Bank of America

And do you think, are you planning to report the full two-year EGFR data, or do you think you could take an earlier look perhaps to secure the traditional approval?

Susie Lisa, Head of Investor Relations

I'd say that's still a TBD. We're looking at the POVA opportunity as in the entire global opportunity. And although it is significant in the U.S. with 150,000, 160,000 patients and similar size in Europe, there are even more patients in Asia. And we think the total global population is north of 1.5, maybe 1.6 million patients. And we are not focused just domestically, but looking at the global opportunity and regulators outside the US, whereas the FDA has made it clear they'll take a one-year EGFR endpoint. Regulators in other regions will not at this point. So we are looking at the entire a global opportunity, and I'd say more to come in terms of where our strategy ultimately lands.

Dan Lundquist, Analyst — Bank of America

And, you know, you mentioned PMN in the broader conversation about the POV opportunity. How does IGAN de-risk PMN in your view, and how do you think about the size of that opportunity?

Susie Lisa, Head of Investor Relations

Yeah, I think that with the dual BAF-APRIL inhibition, our mechanism of action, right, the autoantibody that you look at there is GDIGA1 in IGAN. It's PLA2R in PMN. And I think that's where you could see potentially even more compelling data from our Ruby 3 phase 2, the basket study that we did. So I think, again, this gets back to sort of how Vertex likes to operate in terms of understanding the causal biology and having validated biomarkers and sort of what you measure in phase two is what you measure in phase three, and you can de-risk your going from proof of concept to a phase three study. So we're excited about PMN. There's no pathway to accelerated approval there. It's a 104-week study. We moved from, it's a combo phase two, three, and we moved into phase three, chose the dose from phase two and moved into phase three earlier this year, continued to enroll and dose patients. And it's a significant opportunity as well. But I think the ultimate patient size is, I'd have to go back and check, but I think it's probably something closer to maybe 150,000 patients between U.S. and Europe. So maybe half the size of IGAN and a little smaller, but also a significant global opportunity as well.

Dan Lundquist, Analyst — Bank of America

And what gives you confidence in potential for POBE and GMG? You know, what type of profile do you think COVID would need to show to be competitive in that space?

Susie Lisa, Head of Investor Relations

Yeah, we're really excited about the opportunity in Myasthenia gravis. It stems largely from a trial in China looking at a wild-type tacky that had excellent results in a Myasthenia gravis population. It was a China-only study, but I think I'm very encouraged by the results. And then we view myasthenia gravis is kind of this poster child of B cell mediated diseases, if you will. And also know that we have an engineer tacky, right? That's engineered specifically for higher potency and better tissue distribution. So we're excited about the potential in myasthenia gravis. We have a small phase two proof of concept study that we, I think it's about 30 patients. We're looking to enroll as quickly as possible, and then it's 12-week follow-up, and we'll see the results and move from there. Clearly, a lot of agents in this space, but I think still unmet need in terms of many of them need to be cycled on and off, whereas the autoantibodies don't. And so if you could have a chronic therapy that didn't require that cycling, I think that could be, again, with monthly dosing, small autoinjector, et cetera, I think that's the opportunity there that works. great um so moving away from um uh renal and talk touching on crinetics so um can you remind us some of the rationale and why now is the right time for the crinetics acquisition how do you think endocrinology fits within the broader protects portfolio yeah thanks for the question so um we have a very strict uh r&d strategy criteria that need to be met in order for us to pursue a disease area internally or externally. A few of the criteria include understanding the human causal biology. Are there validated biomarkers? Are there relatively, can we see a pathway to a transformative effect that could help engender pretty efficient clinical development and regulatory pathways? Is it a specialty commercial infrastructure that can deliver it? And the specialty endocrine, the rare endocrine space that Chronetics has carved out fits all of those criteria really, really well. And I think that we have confidence in our due diligence process that when we identify an asset that does meet all those criteria, and there aren't many, right, and it can take some time to find them. When we identify an asset, we have confidence that we don't need to wait for phase three for it to be de-risked, that we can do due diligence and have confidence, right? If you recall, COBE was phase two ready, right? And we surveyed the landscape and identified that and do feel confident that we have potential best in class data there. So we identified Pranavix as fitting all of these criteria and didn't want to wait for it to be further de-risked from Adjamel Nant Phase 3 data or potentially see another bidder in the space get interested in it. So we decided to act and are really excited to have them on board. And I think over time, you know, in addition to the ongoing potential for Pelsonify to only be a blockbuster in acromegaly, I think we see lots of potential in atumelna across a couple of different disease areas and then some upside from the pipeline as well. existing commercial sales force, some really great medicinal chemists at targeting tough targets, if you will, and fits in over time with our type 1 diabetes work in the endocrine space.

Dan Lundquist, Analyst — Bank of America

And how would you say you're thinking about the opportunity in CAH, how that could be differentiated vis-a-vis chronicity for ad2 melanin?

Susie Lisa, Head of Investor Relations

I think the important thing to where we would seek to differentiate is not only can you see your androgen levels come down, but that you can do that simultaneously with being at physiologic doses of glucocorticoids. And I think the opportunity lies in the fact that you can see if the androgen levels are coming down with some other therapies, glucocorticoids are still staying quite high above at supra physiologic doses. So our belief is the adjuvant profile can be differentiated in going to physiologic doses of glucocorticoides and still being able to maintain your androgen levels at lower levels where you want them to be.

Dan Lundquist, Analyst — Bank of America

Got it. So maybe shifting to the pipeline more broadly, how will the initial data for VX670 and DM1 expected later this year inform the development plan and positive positioning?

Susie Lisa, Head of Investor Relations

Yeah. So VX670 and in myotonic dystrophy type one, obviously huge unmet need, obviously a tricky space. Right. But I think that we feel that there's definitely differentiation in our approach. When we signed a deal with Entrada a few years ago, right, We had surveyed the landscape and felt that our approach to have an oligo was desirable over, say, messenger RNA because we felt it's important to be acting in the nucleus of the cell as opposed to the cytoplasm where messenger RNA is working. We also felt that delivery of that cargo is important and wanted to go with a cyclic peptide, circular peptide approach as opposed to a transferrin receptor. That said, I think clearly this disease state is challenging. Is splicing the right indicator? Are the endpoints of QMT or VHOT the right ones? There's a lot to learn, I think, from both competitors and our data. But we are, it's primarily safety as an endpoint, but we are measuring splicing QMT and VHOT. And we'll see later this year.

Dan Lundquist, Analyst — Bank of America

And would you say that you've had any learnings from the recent failure of Dysorin and DM1?

Susie Lisa, Head of Investor Relations

I think that initially we had seen that the splicing index was relatively low. I think it was just at 11%. Is that the right indicator or not? But really it came down to mechanism of both the cargo and the delivery, as I mentioned. So wanting to be with an oligo versus siRNA and then wanting to use a cyclic peptide as opposed to a transferrin receptor, we think that's the differentiation, but clearly a lot to learn in this disease space. So that's why we run the trials and we'll see how it looks.

Dan Lundquist, Analyst — Bank of America

I know at times it feels like with Vertex, people narrow in on certain products or businesses such as CF. Is there anything that you believe within the pipeline, which is fairly broad, that's not getting enough attention?

Susie Lisa, Head of Investor Relations

I think that we've, in type 1 diabetes, we've had some stops and starts most recently, a manufacturing pause that's been resolved. But I think that that could be a really exciting, essentially a functional cure type of therapy. I think the street feels type 1 diabetics are really well controlled. There's not much need there when, in fact, only 25% of them are at recommended HVA1C levels. And this is, you know, you go from 35, 40 units of exogenous insulin a day to not needing any, right? So I think that's exciting, but more to come. And we need to update on timelines later this year or early next year. So stay tuned. I think that...

Dan Lundquist, Analyst — Bank of America

Sorry, what was that in development?

Susie Lisa, Head of Investor Relations

Type 1 diabetes. It's our first gen, Zamyla cell, is currently in a phase 1, 2, 3 study. And then we've recently announced, and that's for type A and AB blood types. And then VX017 is a universal donor of type O stem cell bank. And that's approaching the clinic, but more to come in terms of timelines there. So I think T1D and then I think sort of sleeper upside, we mentioned DM1 potentially. and we continue to be really pleased with the commercial progress of Kestiavi. And then I think the outlook for continued growth in CF has, I guess, less controversy there to talk about as a development space now, but we continue to be excited by the progress Ali's making in terms of conversions and then the next-gen work that we're doing too.

Dan Lundquist, Analyst — Bank of America

So we made 30 minutes without actually touching on CF. And I brought it up. Yeah, you did, although I was shipped to it eventually. So can you talk us through the evolution of Alitrec from here? What are going to be the key driving factors? I think there's been more enthusiasm of late in terms of that launch starting to really continue its momentum. So just trying to think about that.

Susie Lisa, Head of Investor Relations

Sure. So Trikafta is a terrific drug. And many patients are getting down to carrier or normal type levels of sweat chloride. But what a LiveTrack offers is even more patients getting to those levels, as well as once daily. And you have to take CFTR modulators with a fatty meal. So once daily is more than just a simple convenience, right? It can help impact a healthy diet, et cetera. So, and I think the strength of the launch has been accelerated a bit by the launches in UK and the EU, where you do not see the need for six months of incremental liver monitoring like you do in the U.S. I think even in the US, whereas for some patients, it might not be the right time for to add on that incremental liver monitoring, they may perhaps they can wait until the summer months when it is more appropriate. So I think that's why you're seeing the strength of the launch. It's the focus on sweat chloride, as well as the once daily, and then not having the incremental liver monitoring outside the U.S. and continued progress in the U.S. And you will see, we've talked about in younger patients, we're getting two-thirds of them to the carrier levels of sweat chloride, and you'll see data, NACFC, even in older patients and adult patients, that's where we still have a little bit more room to go in terms of unmet need, that if you overlay sort of the distribution of normal or carrier patients of sweat chloride, that the overlay of a LivTrek is looking very strong and you're getting, you know, more than 50% of adult patients there too.

Dan Lundquist, Analyst — Bank of America

And, you know, are there any learnings from the recent updates in the space about some competitive data that was a little bit lackluster that you're taking as you think about development of your own program?

Susie Lisa, Head of Investor Relations

I think that it does point to what we have said, that we feel, particularly with our recent label expansion into virtually all rare mutations, that specific binding site is not what matters. and we don't name our binding sites, but I think as evidenced by the multitude of commercial products we have, that we have chosen very good binding sites, a range of them. I think that drug-drug interactions and safety, et cetera, are all perhaps harder than they appear from outside in CF and also the importance of, and this is another one of our R&D criteria, right, is having ideally human-based assays, not solving things in rodents, but solving things in human cells from a preclinical basis. And so our human bronchial epithelial cell assays, I think, continue to be a real key advantage for us in terms of predicting future success of any future product. But the unmet need is shrinking given how good Tri and Allie are. And so potentially over time, you could see us look to report more on things like reduction in pancreatic enzyme replacement therapy, or potentially even more improved dosing, et cetera, as well as continuing to make progress if we can on sweat chloride.

Dan Lundquist, Analyst — Bank of America

So that's actually a good transition question to sort of why we we should start to expect from the next generation CFTR modulators and in your term, what will it take to move those forward in the clinic? And to your point that you're bringing up, you know, given what we've seen with TRECAPTA with CalPTREC, you know, what it, where is the ball going in terms of what you're trying to accomplish?

Susie Lisa, Head of Investor Relations

Yeah. So I think as Raishman said in our Q2 call in August, right? If the, this next gen 3.0 family isn't a clear step above Allie, given how good Allie is, right? Then it's not something that will, that will move forward. So you need to see clear differentiation if it's, you know, there's still limited meat, but even more in terms of sweat chloride reduction or potentially ancillary therapy reduction or dosing improvement, et cetera. So in this next gen 3.0, and then there's a next gen 4.0 behind that, if, you know, if there is room to improve upon Allie, we aim to be the firm that will do that. And so that's the work that's ongoing, but it needs to be clearly differentiated from Allie in order to move it on to a phase three.

Dan Lundquist, Analyst — Bank of America

And maybe thinking sort of more broadly and strategically, are there, you know, you've moved into endocrinology, are there other therapeutic areas that you thought that, you know, could be of interest to protect?

Susie Lisa, Head of Investor Relations

Yeah, so I think it's a really exciting time because now we are commercial in four disease areas, CF, heme, acute pain, and endocrinology with a fifth soon to come with potential POVI-IGAN launch before the end of this year. And we see all of them as having significant unmet need and large patient populations and making really exciting progress there. But, you know, you could see a neurology call point, right, with Mycenae Gravis, potentially other areas there. You know, I would say that BD continues to be an area of focus for us, remain ever vigilant. A lot of time and attention on integrating chronetics as well as possible. But we'll still look to do potentially earlier stage tuck-ins for a little while here. where we focus on the Cronetics acquisition. It was about two years between Alpine and Cronetics. Cronetics is a little bit bigger, but we'll continue to look in other areas. But then some earlier stage pipeline work in, yeah, I think you could see us continue to add new verticals over time, but lots of room to run in existing ones that we have.

Dan Lundquist, Analyst — Bank of America

So maybe in the closing minutes, we can just touch on pain. So you mentioned, you know, there's a number of trials that are upcoming. Can you just remind us sort of what the glide path there is on the pipeline side? And then also, you know, any recent, you know, momentum and sort of metrics that you can share on success for Jornavix?

Susie Lisa, Head of Investor Relations

Yeah, so maybe I'll start on the acute pain side with Jornavix. And we remain well on track in 2026 to triple the number of prescriptions from 2025. So something north of a million six. really pleased with the breadth of prescribers, with the breadth in terms of settings of care, right? It's a very broad, moderate to severe acute pain label. And we're seeing uptake from emergency rooms, anesthesiologists, plastic surgeons, OBGYNs, dentists, et cetera. So really building a strong base for the long-term sustained growth of gernavics. Continuing to make progress on revenue conversion and bringing down growths to net, remain on track to get to something more normalized by middle of 2027 and working through remaining reimbursement contracts, et cetera. So, and lots more marketing initiatives. We just did another round. Jason Tatum came into the office, Lindsay Vaughn, we've signed now and lots of other marketing issues. And I think exciting to see now investigator studies, single center series of total knees that are done with 80, 90% opioid free. And those are getting published by physicians, not sponsored by Vertex and getting presented at medical conferences. And as we get on more formularies and discharge order sets, continue to see the momentum build. And then in terms of chronic pain, peripheral neuropathic pain, I mentioned the two DPN phase threes are on track to complete enrollment by the end of this year. They're 12 week studies. So you could see data, you know, mid 2027 potentially. And then we also remain in late preclinical development on a 1.7 inhibitor. Recall, Genavix inhibits the sodium ion channel 1.8, which propagates the pain signal. 1.7 initiates it. So we think that having a combo 1.7, 1.8 inhibitor could have synergistic effect in terms of the efficacy. And we're getting closer and excited about the potential there. I think that's all the time we have. sorry the combo is in in clinical the um so we have uh gernavix is a one eight inhibitor which is commercialized and then a one seven is still pre is in we have clinical we have chemical matter but we are not yet in the in the clinic and then we need to do our intent would be combination work over time so first mono and then combo for one i don't think we develop it as mono we go right to combination therapy.

Operator

Inject bolus oil rather than oil.

Susie Lisa, Head of Investor Relations

No, oil.

Operator

Thank you, Susie. Appreciate it.

Susie Lisa, Head of Investor Relations

Thanks, everyone.