Q2 2025 Vertex Pharmaceuticals Inc Earnings Call
Good day, and welcome to the Vertex Pharmaceuticals second quarter 2025 earnings call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero.
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I would now like to turn the conference over to Susie Lisa. Please go ahead, ma'am. Good evening. My name is Susie Lisa, and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our second quarter 2025 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President; Duncan McKechnie, Chief Commercial Officer; and Charles Wagner, Chief Operating and Financial Officer. We recommend that you access the webcast slides as you listen to this call. The call is being recorded, and a replay will be available on our website. We will make forward-looking statements on this call that are subject to risks and uncertainties.
Certainties discussed in detail, in today's press release and in our filings, with the Securities and Exchange Commission. These statements, including without limitation those regarding vertex marketed medicines for Cystic Fibrosis. Sickle cell disease, betaal and moderate, acute pain. Our Pipeline and vertex is future financial performance are based on Management's, current assumptions, actual outcomes and events could differ materially. I would also note that select Financial results and guidance that we will review on the call this evening, our presented on a non-gaap basis. I will now turn the call over to rashma. Thanks, Susie, good evening, all and thank you for joining us on the call today as anticipated momentum accelerated, and we executed with very strong performance, across the board, growing and diversifying Revenue with multiple new product, launches driving advancement of programs and pivotal development and progressing. The earliest stage R&D pipeline, we continue to reach more patients with more products and delivered to
$2.96 billion in revenue in the second quarter, representing 12% growth versus Q2 2024. We remain sharply focused on commercialization across multiple disease areas and the expansion of our patient reach. We are pleased with the first six months of launch performance, as well as physician and patient feedback on both A Lift Trek and CF, and our Novex in acute pain, as well as the building global momentum for Cast Chevy, our gene-edited therapy for sickle cell.
After an incredible 13-year career with the company. David initially joined vertex as a member of the board of directors in 2012 and became Chief scientific officer in 2015,
During David's tenure multiple CF medicines of advanced from research through commercialization, including, or Cami, Simcoe Tria, and a lift truck. Our disease sandbox has broadened and we successfully Advance the scientific breakthroughs that became cast Chevy and your novecks in an industry. With notoriously low R&D, success rates, David's, teams delivered, remarkable achievements year after year. David is a world-renowned physician scientist who's known for his creative and critical thinking pension for debate and commitment to building teams on a more personal level. I know him as a deeply passionate vertex, dedicated physician, and valued member of the executive team as mentioned in our earnings release. As part of this plan transition, I am delighted to announce that Mark bonage will assume the role of EVP and chief scientific officer effective February, 1st, 2026 after which David will work with Mark to ensure a smooth track.
Transition Mark joint vertex and has worked alongside David since 2016. Since that time Marcus held increasing senior leadership roles across research. Starting his SVP site, head, Boston research and most recently as SVP head of Global Research, overseeing all 5 of vertex research sites under Mark's leadership. We advance many molecules to the clinic including cast Javi and Javon for am Katie vxa 28 for CF VX 670 for dm1 and VX4. 7 for autosomal, dominant polycystic, kidney disease. Mark was also intimately involved in the diligence that led to the Alpine acquisition, which brought poetas except to vertex. I look forward to celebrating David's retirement and welcoming Marcus. CSO, when the time gets closer returning, then to R&D highlights, I'll limit my comments to the pipeline programs with the most significant new information to share specifically CF.
Pain type 1, diabetes, and the renal programs starting with CF. As of July, we've gained approval for a lift truck in the US, UK, EU, and Canada. We've also secured reimbursement for a lift truck in England, and we'll add Ireland. Shortly, patients in Germany and Denmark already have reimbursed access due to existing agreements and provisions. Across other EU member nations and Canada, we're working with reimbursement bodies to secure access for eligible patients as quickly as possible.
Possible as we continue to expand. Our existing cftr, modulator portfolio to younger age groups. We also continue to develop new cftr regimens with the aim of reaching our long-standing objective of bringing most, if not all people with CF to normal levels of cftr function, our next gen 3.0 or NG 3.0 regimen is next on Deck. The backbone of the NG 3.0 combination is VX 828. The most efficacious cftr corrector that we have ever studied in vitro and brought to the clinic. We are nearing completion of the healthy volunteer study and we remain on track to initiate a cohort of people with CF with the VX 828 regimen before the end of this year. Finally, in CF on VX 522, I am pleased to note that the data safety monitoring committee has completed its review and is endorsed restarting. The trial. We're now in the process of working to resume dosing in the Mad portion of the phase 1 2.
For the 5,000 or so patients who cannot benefit from our CFTR modulators and expect to do so in the near term, we are now shifting focus to pain, specifically peripheral neuropathic pain (PNP). We had a productive End of Phase 2 meeting with the FDA on our PNP program. While a broad PNP label remains our goal, at this time, the FDA does not see a path to a broad indication as such. Therefore, we will not be initiating an LSR trial at present.
Your DPN as our first PNP indication to expand the indication over time and to continue to discuss a potential Pathway to a broad PNP label turning now to a queue Pane and VX 993, another nav 1.8, inhibitor this afternoon, we share Topline results from the phase 2 trial of this molecule in the post bunionectomy setting to recap as part of our cereal Innovation strategy, we developed VX 9993 with 3 main goals first to have an IB option. Second to provide additional nav, 1.8, inhibitor candidates for potential use as co-formulation with future nav. 1.7 Inhibitors. And third to further refine dose response relationships including whether higher clinical exposure might result in Greater clinical efficacy focusing on this last point of efficacy based on the predicted clinical potency, and exposure of 9993. We powered The Phase 2 trial.
With the goal of detecting a treatment effect higher than previously, this Phase 2 trial included a placebo group, three V9993 dosage arms, and a hydrocodone reference arm. The primary endpoint was SPIT-48 compared to placebo. The results show that V9993 was safe and well tolerated, with no related adverse events and an overall profile consistent with the placebo arm. The placebo effect was well controlled and desired. V9993 exposures were achieved.
With adequate separation between doses on efficacy. VX 993 did not meet the primary endpoint and did not show statistical significance. At the 005 level, the spit 48 treatment effect was similar at both the mid and high doses and both were numerically better versus placebo. The outcome of the study combined with the totality of evidence from our preclinical models and previous nav 1.8 inhibitor clinical studies in acute pain. Suggests we are at the high end of the nav 1.8 dose response curve for acute pain in the post bunionectomy setting as such, we do not plan to Advanced VX 9993 as monotherapy in acute pain because we do not expect that it will be superior to our nav 1.8 Inhibitors. We do plan to complete the ongoing VX 9993 study of DPN to further Define the exposure response, relationship and maximal, efficacy of nav. 1.8 Inhibitors in this. Chronic pain in
Medication to close out on pain. A quick word on our NAV 1.7 inhibitor program: we're very encouraged by our strong pre-clinical progress in this program and look forward to advancing candidates for use alone or in combination with NAV 1.8 inhibitors. Transitioning now to type 1 diabetes.
The Mila cell will soon complete enrollment in dosing of its pivotal study, positioning us for global regulatory submissions in 2026. If the data are supportive, we expect about 60,000 severe type 1 diabetic patients may potentially benefit from this first Zimyo cell submission in June at the ADA meeting and concurrently in the New England Journal of Medicine. Positive data for Zamolo cell and type 1 diabetes were presented that continue to demonstrate this cell therapy's transformative potential. All 12 patients with at least 1 year of follow-up who received a full dose of Zamolo cell as a single infusion achieved ADA recommended target hemoglobin A1c levels of less than 7%, freedom from severe hypoglycemic events during the evaluation period, and greater than 70% time in range. Remarkably, 10 of the 12 patients at 12 months were insulin-free, a testament to the potential transformative benefit and durability of this therapy.
We also continue to make pre-clinical progress on our approaches to cloak the same VX-880 cells from the immune system, including improved immunosuppressive regimens, gene editing to produce hyperimmune T cells, and novel immuno protection to encapsulate these cells. We look forward to updating you as these programs advance. Finally, if you have updates on our kidney portfolio, which now has clinical-stage programs in four diseases: IgA nephropathy, AAV, and membranous nephropathy.
And adpkd or autosomal dominant kidney disease.
Diseases, first up for POV is Ian. We disclose previously that we completed enrollment of the interim analysis cohort in the Rainier phase 3 trial. Today we are pleased to share that. We are on track to complete enrollment of the full raineer study by the end of this year.
With regard to the interim analysis cohort. Once this group completes 36 weeks of treatment, we will conduct the internal analysis and if positive will file for potential accelerated approval in the US, in the first half of 2026 to close out, on Ian studies to support the launch of Pi for at-home self-administration. With a subcutaneous, auto injector are also well underway next. And consistent with this pipeline in a product potential. The second disease state where we believe policy can provide Bell control is primary membranous nephropathy. Based on strong emerging data from the Ruby 3 study. We completed our end of phase 2 meeting with the FDA and reached agreement on a phase. 2, 3, adaptive, study for traditional approval, of povey versus standard of care with the primary endpoint of complete remission at 72 weeks. This Phase, 23 study will begin later this year.
And third, we have prioritized additional diseases in which we believe POV also holds best-in-class promise based on emerging data, potential patient impact, the treatment landscape, and commercial opportunity. The next two autoimmune diseases in focus for us are generalized myasthenia gravis and warm autoimmune hemolytic anemia, or WAIHA.
So to summarize our current priority disease areas are Ian membranous nephropathy, generalized, Mya, gravis, and waha and we are deep prioritizing other indications at this time.
Next on an AIP for apol1 mediated kidney disease. We remain on track to complete enrollment. In the interim analysis, cohort of the amplitude. Pivotal trial in primary am KD this year of note, while we are able to enroll more adolescent patients, we've hit an important milestone in this study where the target number of 10 to 17. Year old am KD patients, has now been achieved after completing enrollment in the IIA. Cohort, these patients will be followed for 48 weeks of treatment at which point, we will conduct the interm analysis. And if positive will be poised to file for potential accelerated approval in the US, the Amplified study a phase 2 proof of concept study in patients with amk d and comorbidities including type 2 diabetes, is also underway. And this trial is on track to complete enrollment by the end of
2025.
To close on our kidney pipeline is VX. 407 for adpkd a first-in-class, small molecule protein folding. Corrector that is designed to treat the underlying cause of adpkd by restoring pc1 protein function, thereby, reducing total kidney volume, and preventing progression to kidney failure. As a reminder, there are approximately 300,000 patients with adpkd and there are no approved therapies that treat the underlying cause of this disease. We believe about 10% of patients with adpkd may be eligible for treatment with VX 407. This quarter will begin the VX. 407 proof of concept trial which is a 52 week single-arm study in 24 patients. That will evaluate the efficacy of the x407 as measured by height, adjusted total kidney volume, in closing vertex, has multiple phase 3 programs well underway. There are poised for Accelerated or traditional approval. These trials have either already completed enrollment or
for our on-track to do. So in 2025, they each serve a disease with high unmet need and they've secured multiple regulatory, designations including FasTrak breakthrough regenerative medicine or armik prime amongst others. All of which positions us for multiple regulatory submissions in 2026 and early 2027 with potential approvals and launches to follow accordingly as we drive to achieve our R&D milestones
Who are executing on the concurrent work of preparing, for commercialization, of these potential launches with that, I'll now turn over the call to Duncan for a commercial update.
The overall market outlook is also supported by the fact that patients are living longer.
Now, turning to the US launch of a lift Trek, our fifth therapy approved to treat the underlying cause of CF. We believe a lift Trek is the best cftr modulator available for eligible, patients. As we've discussed on prior calls versus try cafta a lift. Trek, provides further improvements in cftr function, as measured by sweat. Chloride is indicated for additional mutations, not covered by the try cafta label and offers the convenience of 1's daily dosing in the US. The early launch of a lift Trek is progressing well across all patient groups. We have seen particularly rapid uptake, in those patients, who are naive to cftr modulators, and thus newly eligible for a Lyft Trek, as well as those who previously discontinued 1 of our other cftr modulators for patients currently on trikafta many have been on therapy for multiple years have experienced incredible clinical benefits and therefore have considerable brand loyalty in this context. The pace of transitions is steady as these patients continued, their conversation.
Conversations with physicians and making decisions that balance the short-term logistics of augmented liver monitoring with the lift trick against a lifetime of potential benefits, including greater CFTR protein function and once-daily dosing. Overall, we're very pleased with the reports of a lift Trek clinical success the physicians and patients are sharing, whether they were naive to a CFTR modulator or returning to therapy.
Or have recently transitioned from Trikafta. We continue to expect that the majority of patients who are currently on CFTR modulator therapy will transition to Irexa over time, given its multiple benefits. We're also now in the process of launching a LiftTrak in England, following our recent reimbursement agreement with NHS England, as well as in Germany and Denmark, transitioning to CVY. Our transformative one-time treatment for patients with sickle cell disease and beta-thalassemia.
The cavity launches building momentum and we're pleased with the progress we're making in 2025, as well as the growth. It positions us for in 2026 in quarter 2. We've seen an acceleration across the board in patient. Initiations, sell Collections and infusions this progress is a reflection of the foundational work initiated in 2024 to build our ATC Network, expand our Geographic footprint to include the Middle East and secure, reimbursement, for cast Chevy worldwide, regarding reimbursement. 10 countries now provide access to cast, Chevy, including the US, and several European and Middle Eastern countries.
In terms of our cash, jvy launch metrics, I'm pleased to report that since launch and through the end of quarter 2 2025, firstly, we have met our authorized Treatment Center goal with more than 75 atc's. Now, activated globally. We are now dosing patients with sickle cell disease or tdt in multiple regions, including the middle east Europe and the US. And secondly, nearly 250 patients have been referred by their Physicians to an ATC to initiate the treatment process.
Approximately 115 patients have had their first cell collections, including 35 first cell collections in Q2 2025. Finally, a total of 29 patients have completed their treatment journey and received their infusions of cast, Chevy-edited cells, including 16 patients in the second quarter of 2025.
Now shifting to the launch of javax in moderate to severe acute pain, genavix received FDA approval, on January, the 30th and has been available in Channel. Since March, we continue to see a very positive reaction to this novel non-opioid option, for the treatment of moderate to severe acute pain. We're pleased with the rapid pace of payer coverage p&t committee reviews, formulary adoption, breadth of usage and Hospital uptake. We're also very encouraged by the broad range of positive.
Reported by both Physicians and patients. I'll detail several key elements of our ongoing launch
22 million commercial lives as a result. We now have formal coverage from 2 of the 3. Large National pbms and anticipate adding the third before year. End in addition, we now have national agreements in place with the 2, largest hospital group purchasing organizations to make genavix available to acute pain, patients, in their Network member hospitals. In Medicare, we continue to engage with plans to secure coverage. And for Medicaid patients through mid July, we added 6 State plans. Since our quarter 1 earnings, call for a total of 16 states with legislation that ensures access is available without prior authorization or step. Edit requirements. We continue to expect the coverage across commercial Medicare and Medicaid pairs will continue to expand through 2025.
We are prioritizing the PNT Committees at approximately 150 healthcare systems and roughly 2,000 hospitals. The majority of these 2,000 hospitals ladder up to one of the 150 healthcare systems. Last quarter, we disclosed that more than a third of these target healthcare systems had taken steps to initiate the PNT review of Janav. I'm very happy to report that over a third of these priority target healthcare systems have now added Janav to their formularies, protocols, or order sets, and many more have Genavix under active consideration. In addition, at the hospital level, about 500 of the 2,000 hospitals with...
Targeting have also added janav to their formula is protocols or order sets.
3 presents are encouraging for the near and long-term outlook, for genavix. With excellent breadth of usage to date across a wide range, of inpatient and outpatient settings pain, conditions and physician Specialties in line with the broad label.
Lastly, more than 110,000 prescriptions were successfully filled for Genavix across retail and hospital settings. As of mid-July, we remain tremendously excited about our opportunity to transform the treatment of pain and will continue to invest as we see warranted, given the rapid contracting and formulary progress we have made, as well as the prescriber and patient feedback. We believe now is the time to make additional investments in our commercial activities behind Genavix. This includes additional marketing activities in Q3, as well as field support, as we continue to secure more access and hospital formulary wins over the coming months. We have high confidence that we are in the early days of creating another multi-billion dollar franchise for Vertex. To conclude, we are well on our way to establishing a new era of commercial diversification at Vertex as we execute on multiple launches in CF, sickle cell disease, TDT, and acute.
Pain and begin the build-out for the next wave of launches in a number of disease areas with high unmet need. We look forward to bringing our transformative therapies to Millions more patients and to keeping you updated on our progress. I'll now turn the call over to Charlie to review the financials.
Thanks Duncan vertex is Q2 2025 Revenue. Growth accelerated as expected and our results demonstrate our consistent strong performance and attractive growth profile. Second quarter 2025 total revenue, increased 12% year-over-year to 2.96 billion US Revenue growth of 14% year-over-year was driven in CF by ongoing patient demand and favorable Grosse tete versus prior year and also included contributions from Cass. Chevy javax and collaboration Revenue as expected Revenue outside the US rebounded, this quarter, and was up 8% year-on-year, including healthy, CF growth, and a contribution from cast, Debbie included in total revenue and the regional growth rates was 30 million of cast Chevy Revenue. 12 million, from janav and 21 million of collaboration Revenue. Second quarter of 2025 combined non-gaap R&D acquired, IPR, and d and sgna. Expenses, were 1.24 billion compared to 5. 4, 3,
IPR andd non-gaap operating expenses increased 24%. Year-on-year driven primarily by the continued advancement of our broad pipeline including clinical trials for Ian pain, and type 1 diabetes, as well as the buildout of commercial capabilities. In pain, second quarter, 2025 acquired IPR, andd expenses, were 2 million compared to 4.4 billion in the second quarter of 2024 which included the acquisition of Alpine. Immune Sciences. Second quarter, 2025 non-gaap operating income was 1.33 billion. Compared to a non-gaap operating loss of 3.15 billion. In the second quarter of 2024. Second quarter, 2025 non-gaap effective tax rate was 19.4%
1.2 billion compared to a net loss of 3.3 billion in Q2 of 24.
Second quarter 2025 non-GAAP earnings per share were $4.52 compared to a loss per share of $12.83 in the second quarter of 2024, primarily due to higher revenue and disciplined operating spend, as well as the impact of the Alpine AIP R&D expense in the second quarter of 2024. We ended the quarter with $12 billion in cash and investments after deploying approximately $395 million to repurchase more than 800,665 shares in the second quarter. In May, we announced a new $4 billion share repurchase program, building upon our existing $3 billion share repurchase program, which was authorized in 2023 and had $570 million remaining as of June 30th. Our priorities for cash deployment remain unchanged: innovation and growth fueled by investment—both internal and external—followed by share repurchases. Now switching to guidance, we are reiterating all elements of our financial guidance, including our 2025 total revenue guidance range of $11.85 billion to $12 billion.
Representing growth of approximately 8% at the midpoint at current exchange rates. This Outlook reflects our expectation for continued growth from our portfolio of CF medicines, including the ongoing launch of a lift Trek in the US followed by other regions later. This year, recall that a lift truck carries a meaningfully lower royalty, burden than try cafta and extends, our composition of matter patent protection to 2039 Revenue
Guidance also includes cast Chevy Revenue. As we treat more patients in geographies, where we have secured, regulatory approval and reimbursement. Given the duration of the patient Journey, we have high visibility into custody Revenue as patient initiations and sell collections continue to ramp. We expect, commensurate increases in infusions, but note that because the timing of infusions is predicated on patient scheduling choices, there may be Revenue variability from quarter to quarter in addition, guidance, reflects additional Revenue contribution from javax in the second half due to gains in sustainable pay or coverage. Recently announced positive coverage decisions are included in our Revenue. Guidance overall, we are confident in our ability to deliver another strong year of Revenue growth for vertex in 2025.
We are also reiterating guidance for Combined non-gaap R&D acquired IPR, andd and sgna expenses in a range of 4.9 to 5 billion for the full year 2025, though, we expect to be at the high end of this guidance range consistent with prior commentary. This range includes approximately 100 million in projected, IPR and D charges. We will continue to invest a majority of our operating expenses into R&D given the momentum in our multiple mid and late stage clinical development programs with 4 and soon to be 5 phase 3, studies, ongoing and multiple Phase 2 in addition, given progress, with respect to reimbursement and access. And the size of the opportunity for journalists is Duncan mentioned, we are increasing our investment in marketing and Commercial initiatives to support the lawn.
In the second half of this year, we expect an immaterial cost impact from tariffs in 2025, based on what we know today, due to our significant us presence and our geographically diverse supply chain. Of course, given the dynamic nature of the Tariff situation, including the potential for sector specific tariffs. This Outlook is subject to change and finally, on guidance there is no change to our expected full year 2025 non-gaap effective tax rate in the range of 20.5 to 21.5% which implies a higher effective tax rate in the second half of the year. We do not anticipate recent tax legislation to have a material impact on our expected effective tax rate in 2025 in closing vertex. Yet again, delivered strong results in Q2 25 growing and diversifying, our Revenue with the launch of 2, new products in the US, a lift Trek in javax continuing. The global launch of cast Chevy and making significant pipeline progress, across the portfolio. These and other anticipated, Milestones of continued progress in multiple disease areas,
Details are on slide 17. We look forward to updating you on our progress in future calls. I'll now ask Susie to begin the Q&A.
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And your first question today will come from Jessica fee with JP Morgan. Please go ahead.
Was that increase always planned as coverage came into place, or is that a reaction to what you're seeing, as you kind of continue to launch so far. And then for Susan, in DPN, I think you said you'd complete enrollment both phase 3s by the end of 2026. I'm just curious. Can we expect enrollment completion for the first phase 3 trial, much sooner than that, thank you.
Hey, Jess, this is Ryman. Let me split that into 2 parts. I'll take the second part first, and then I'll ask, um, Duncan to comment. Yes. Um, I think that, uh, the first DPN might well enroll ahead of the second DPN, because it started ahead of time, and the enrollment is going very well. Um, I will ask Duncan to comment on your novecks, um, as you know, um, it's really important to secure. Pay your coverage as we ramp, um, commercial efforts behind that Duncan. Uh, any more comments on on how you're thinking about commercialization. Sure. And
To say this sort of 3 factors that are really uh driving our thinking, firstly as reeshma just alluded to, we're very pleased with the progress. We're making with payer coverage and Hospital foreign roads. Uh, particularly considering how lengthy pnt processes can be, uh, secondly, we're receiving incredibly positive feedback from Physicians and patients on how well genomics is working for the
Clinically, uh, and thirdly, we've seen both in the uh, face-to-face arena with our sales organization, as well as in the digital arena, uh, we've seen Janatics to be incredibly responsive. So, based on those three factors, yes, we are thinking that now is the right time, uh, to augment our spend in marketing, uh, and field support. Although I would, uh, add the last comment that we do anticipate that field support would still sit within uh, the specialty model.
Thank you.
And your next question today will come from Saline Richter with Goldman Sachs. Please go ahead.
Good afternoon. Thanks for taking my questions. So with regard to the strategy and pain here, can you help us understand? Now that you won't be, you know, moving forward with a broad um, PNP label today, maybe what your plan is around, you know, running these DPN trials and then whether it's taking Next Generation, drugs or so forth to move into LSR any of the other um, smaller indications like um, small fiber neuropathy or or some of the others and then secondly, um, in light of of the Journey of X launch that's progressing here. Um, maybe help us understand how to think about growth to net over the balance of the year and Beyond thank you.
Interesting. So I mean let me um take those questions um with regard to our plans in PNP
Uh, it remains our goal to get a broad PNP indication from our conversations with the FDA. At this recent meeting, we were very productive. They were open-minded, and they were very, um, open to ongoing discussions. However, it was equally clear that, at this time, they do not see a path to PNP; that's just not where they are. However, um, we have a clear agreement on DPN. So, the first order of business for us is to secure the DPN indication, hence the um, start of the second DPN study.
We can broaden that indication, and we had really good conversations about how that could occur. As you point out, small fiber neuropathy could be one. Um, broadening of the label could be by way of mono- or polyneuropathies. It could be by way of distal or proximal, and there are certainly ways in which we can augment that label.
The, the real big prize for us remains broad PNP. And we think that the way to get there, uh, might well be with ongoing conversations with the agency and um, with our nav 17, plus nav 1.8 portfolio. So what I would say is here and now secure, DPN work to broaden the indication and might be 1 step at a time sfn, is, is 1 example of a next indication, and then broaden all the way to PNP, um, as we are able to have more conversations with the agency.
Um uh any comments uh that you want to add to gross to net Charlie?
Contribution in the second half of the Year again. The the elevated gross to Net in the early days is a result of our patient support programs. As we continue to expand our coverage. Those programs will start to Fall Away. Gross to net will normalize over the course of the year. Um, but beyond that, I'm not going to provide further detail.
Your next question today will come from Jeff mumm with City Bank. Please go ahead.
Okay. Good afternoon, guys. Thanks for the question. I just have a couple on pay original. I want to ask you about the implications, you know, of the FDA feedback and the 993 data.
I guess the first question is, could the strategy in chronic pain involves to to now include you know, broader indications such as joint, pain, Etc. In other words like outside of PMP.
And then on 993. You think it makes sense to look at a more of a pan 1.7 1.8, uh, 1.7 mechanism. At least involving maybe multiple isoforms. Just to try to maximize the, uh, the treatment effect that wasn't sure. Uh, kind of what the, what the strategy is there from a pipeline perspective. Thank you.
Sure thing, uh, let me do chronic pain first and then we'll come back to 993, um, just on chronic pain. I I think the, um, the approach is, um, as we just described, um, for the previous question, DPN first,
Then add on, um, single indications, but work with the agency to get to Broad PNP. Um, they have, uh, we've had these discussions. They've left us with some questions. We need to talk with each other some more on musculoskeletal, which is, I think, the point you were raising. I do think, um, that this, um, class of compounds, um, can work based on the data that we saw, for example, with VX1-150 and osteoarthritic pain. But we're still very focused, first and foremost, on acute and then neuropathic. We will get to the musculoskeletal, but I don't see that in the highest priorities.
On 9993 and uh what the plan is with regard to acute pain. Um,
The big next step for us on acute pain, obviously, is launching your Novecks.
We have our IV formulation with the 993 version, and we now have 2 potential molecules that could be used with the NAV1.7 molecule. That's making very good progress on the bench, but I would say the big next thing to look for us to do in acute pain is combination NAV.1718. Remember, pre-clinical, what we see is a synergistic, not additive effect, and so that's going to be really important.
I hope that helps. Okay.
Yep, thank you.
Sure thing.
And your next question today will come from Ellie Marrow with UBS. Please go ahead.
Hey guys, thanks so much for taking the question. Just to follow up on Javx for me, um, so just first, can you comment a little bit more on how the progress and the real-world evidence generation is going at some of these key health systems and how you expect that to impact the cadence of PNT formulary placement? Um, and then just second on gross to net. I know you mentioned that there's been, um, you know, use of patient support programs initially in the launch. Just what should we expect going forward in terms of the use of the patient support programs as we think about growth in net from here? Thanks.
You bet, Ellie let me take the first half of your question and I'll ask um Duncan to to talk to you a little bit about the PSP patient support, uh, programs.
the Cs presenting those papers, um, in upcoming conferences, uh,
The PSP program in place, uh, in order to provide a seamless experience for patients uh in advance of payer coverage. Um, and as we noted in our prepared remarks and as Charlie commented on a couple of minutes ago, um, as we see our coverage with payers, increasing over the course of this year, uh, that program becomes unnecessary. Uh, and essentially we will, uh, retire that program, uh, as we see National coverage, obviously, we're not quite at that point yet. Uh, but that is, uh, the plan by the end of the year uh, is to conclude uh, that program and as Charlie alluded to earlier. I don't think we're providing specific growth to that Guidance with regard to that program.
And your next question today, will come from tazeen Ahmed with Bank of America. Please go ahead.
Hi guys. Um maybe to switch the subject up a little bit. Can I ask a couple on Pi? Um is it your plan to launch with the auto injector when you go live on on Ian and then in terms of the indications that you're prioritizing on a go forward basis? You've included, um, GMG I'm just curious about where you think you could particularly differentiate given that it seems like that's a pretty credit
Market already. Thanks.
Yeah, uh, to see, um, on POV, um, you have it exactly right. Uh, we plan to launch in the Ian indication which of course, is the first indication with the auto injector.
And uh, just to confirm GMG you mean my senior not membranous.
Yeah, that's correct.
Yeah. Um, you know, the, the the my senior indication is um, very, uh, exciting for us. And it is 1 of the ones that we've prioritized, maybe 4 lines of reasoning to to share with you. The first, is there remains very high unmet need in this area. We don't have any medicines that Target the underlying cause of disease. And as you know, um, some of the medicines being used need to be cycled on and cycled off and in the off period that gives the opportunity for the auto antibodies to redevelop and call continue to cause, um, uh, damage at the, at the junction.
The the Toby mechanism is a dual April bath inhibition.
Uh, appealing and, uh, points to, uh, strong, uh, treatment effects. The third is that I expect the regulatory pathway to be an efficient development pathway. And the last is, as you put all of this together and think about the underlying cause of the disease, high unmet need, the emerging data from others in this class, and then you think about the fact that POV was specifically engineered to have best-in-class properties in terms of potency, binding affinity, as well as tissue distribution. This is why we're so excited about my senior.
and your next question today will come from Evans sagerman with BMO Capital markets. Please go ahead. Hi guys. Thank you. Hi guys, thank you so much for taking my question. Another follow-up kind of on the pipeline in a product for POV, can you kind of walk me through the rationale for prioritizing the indications? Such as GMG, warm, autoimmune, humidity anemia? Of course, I again, was it clinical data early data kind of pre-clinical or commercial considerations that drove these decisions.
Senior, its emerging data from the class.
Taking into account that POV has this, uh, benefit of being engineered to be best-in-class. So, um, there's the emerging data. There's also consideration, um, given.
what exists in the marketplace and whether it treats the underlying cause of disease and whether we have a transformative medicine and certainly takes into account, our ability to be successful commercially, all of those have gotten into US prioritizing, IAM membranous, myasia and waha and just to close out on that prioritizing from me. For um, my senior means we are ready to go to the agency to have our discussion on what the pivotal program looks like and prioritizing for waha means we are awaiting a final data set that we expect towards the end of this year.
I hope that helps.
Great. Thank you.
You bet.
And your next question today will come from Divya with Cowen and Company. Please go ahead.
Hi, this is Divya on for a Phil. Um, I just had 2 questions um, on June aics, 1 is just got a little bit technical but um I was curious for patients that are getting free samples. If they are to show up at a retail pharmacy, I was curious if you could walk me through the protocol for how they actually are able to secure.
Um, the free drug, and the second is, I was curious if you could comment on the split of Janavicius.
You bet Duncan, can I ask you to comment? Um, first, uh, maybe quickly on how free samples work and then um a little bit more detail on um, page physician types and split between hospital and Retail. Absolutely. Thank you for the question. So in terms of the free samples, these are provided uh through the patients physician uh their supplied to the patient by The Physician uh and they do not show up in the retail data. Um in terms of the split of retail versus Hospital prescriptions um about 65% uh of the prescriptions are in the weekly IQ via data that you see for retail prescriptions uh the remainder are in the hospital space. Uh and in terms of the types of Physicians uh using genetics it it is a broad uh range. It's about 15,000 for
Physicians, uh, are now prescribing genetic genetics? Uh, we're seeing um, many more patient. Uh, sorry, Physicians hundreds of Physicians, come on, um, each week. Uh, and the types of Physicians are general surgeons plastic surgeons orthopedic surgeons, uh, dentists and, um, anesthesiologists and they are prescribing for a broad range of treatments consistent with the label. Um everything from sprains and strains through reconstructive surgery uh to to total knee replacements.
And your next question today, will come from David Risinger with Lee ring Partners. Please go ahead.
Yes, thanks very much. Uh, so I have, uh, 2 questions. Please first on your novecks. Um, I was wondering if you could comment on the number of commercial lives with unrestricted access.
And then second, with respect to VX-828, could you please provide a little bit more color on your expectations for the profile of this candidate? Thanks very much.
Nursing Dave, let me, um, take the A2A question and then I'll ask Duncan to comment on. Um, your Novex. So 828, I said in my prepared remarks, it is the most, um, efficacious um CFTR corrector that we've ever studied in vitro that we've advanced in the clinic. I expect that, um, it is going to have, um, most if not all patients get to carrier levels of sweat chloride. I expect a good safety profile. I expect a good DDI profile based on the pre-clinical data. To wrap up on 828, um, we do uh continue to track towards uh initiating the CF cohort before the end of this year.
Duncan Journal Acts.
Uh, to get to the answer to your question. Uh, 84 million of those lives are unrestricted. Uh, I can tell you that for every single contract we have negotiated to date. Every single 1 of those is for unrestricted access which we Define as, you know, as no prior authorization or step edit. So what that means, uh, of course, is that based on high, uh, demand for genomics. There are of course, some plans, uh, that that have put in place coverage of genavix in advance of any agreement with us and in those situations, um, there can be a prior authorization or step edit, uh, obviously we'd be working uh, to reduce that ratio uh, over the balance of the year. But at this point, 150 million lives covered 2 out of the 3. Pbms, uh, are covering and we're working, uh, with the third as you'd expect. Uh, and every single agreement we have,
Done is for unrestricted access.
And your next question comes from William Pickering with Bernstein. Please, go ahead.
Hi, thank you very much for taking my question. Um, just a couple from me. Uh, 1 was on the, the no pain act, that was a little bit surprised to see that. Janav was not included in the um, uh, the the draft rule that was published. Um, I guess is about a month ago and any any kind of concerns or kind of process to get that on the list for 2026 and then second was with cast Chevy. Just um, what are you seeing in terms of the cycle time, from cell collection to infusion and do you see potential for that to accelerate going forward? Thank you.
Sure thing.
First, um, uh, as you heard, uh, Duncan talked to, um, his prepared remarks. Um, we are seeing an acceleration in the momentum, and part of that is simply having patience at various, uh, points in their journey. So, there are a lot more patients who've now self-collected and are ready to be infused. And, um, that's what we're looking forward to in the back half of this year with regard to cycle time. Um, yes, I, I, I do think that there is, um, an opportunity for improvement. I'd say we said it was going to be somewhere around 4 to 5 months for the full process. Um, and that's kind of where we see it. Of course, it makes a difference if the patient is a TDT patient or if the patient is a sickle cell disease patient.
Easier for cell collection with our tdt patients. We have plans in place to ensure that um the cycle time um, comes down as uh, we make progress overall.
On the no pain, um, act. So, you know that the, um, uh, the draft proposal, um, included some language, uh, that says that because, uh, your novecks is not specifically indicated for post-surgical pain, it was not included on the draft list.
Clearly, your Novecks is indicated for post-surgical pain. Indeed, both Phase 3 RCTs were in post-surgical pain, one in abdominal plasty and one in bunionectomy. I think we're going to be able to get this confusion resolved, and I do expect that your Novecks will be on the final list, which is due this fall.
And your next question today will come from Terence Flynn with Morgan Stanley. Please go ahead.
Great. Uh, thanks so much for taking the question, uh, just wondering, um, at 2 questions. The first is on journ novecks. If you can just confirm, um, if there's any inventory in in the second quarter that we need to think about as we, um, as we do the math, on on a dollar, prescript basis. And then on the, um, 993, Phase 2 Data, just wondering if
If you think you need to make any tweaks to the pre-clinical models at all here. Um given that data and particularly as you think about the nav 1.7 assets that you're developing, thank you.
Thanks. Could you, uh, could you just maybe rephrase the first part of your question? We didn't quite get it here.
Sorry. Was there any inventory in uh, 2q for Jan novecks.
You asked about um how did our pre-clinical models perform?
So the reason it was really important for us to do the 993 study and go up to the dose levels we did and to ensure that in this study, we saw good dose separation between the low medium and high dose is exactly to do what you, uh, were referencing to make sure that our models are properly trained. And what we saw with 993 coming into the phase. 2, study is a molecule that was predicted to be more potent in molecule that we could dose higher. And the exposures are very, very high. So, our models would predict this is at the 99.999%, uh, to the ec50. So, multi multi, multi multi-fold the ec50 levels. And what we learned from this is, we do, indeed, get very high exposures, and we do indeed. Get separation of exposure.
Exposures of the mid and high dose.
Nonetheless, the efficacy for the medium and high doses. You can see in the press release is about the same different than low dose, but the same to each other. And this is what lets us know that now, we are at the very high end of the dose response curve. And we know that our, um,
This medicine is not likely to be superior to our existing molecules. So this is a very important um phase to result and and that's why we're pleased to have completed the study. And to have gained this information, we are now um able to be at the Leading Edge with our models.
Nick, we'll take one more question, please.
And your last question today will come from mohead bonsal with Wells Fargo, please go ahead. Please go ahead.
Great. Thank you very much for taking my question. Um,
Just wanted to check in on the most favored nation and the letters. Uh government has sent out here given that your exposure to Medicaid. Do you see any risk there? Uh I mean you could be protected because the orphan disease but just wanted to make sure uh it is not on the cards. Thank you.
Oh it, we have not uh, received uh, a letter, the lines of communication are open. Um, we are able to have good dialogue, um, with, um, DC. Um, and we're paying, uh, close attention and digesting the latest news, but I can, uh, confirm that we did not receive a letter.
Got it. Thank you.
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