Vertex Pharmaceuticals Q2 2026 Earnings Report

Vertex Pharmaceuticals EPS Results

• Actual EPS: $4.73
• Consensus EPS: $4.74
• Beat/Miss: Missed by -$0.01
• One Year Ago EPS: $4.52

Vertex Pharmaceuticals Revenue Results

• Actual Revenue: $3.33 billion
• Expected Revenue: $3.23 billion
• Beat/Miss: Beat by +$103.35 million
• YoY Revenue Growth: +12.50%

Vertex Pharmaceuticals Announcement Details

• Quarter: Q2 2026
• Date: 8/3/2026
• Time: After Market Closes
• Conference Call Date: Monday, August 3, 2026
• Conference Call Time: 4:30PM ET

Vertex Pharmaceuticals (NASDAQ:VRTX) Inc. is a Boston-based biotechnology company focused on the discovery, development and commercialization of therapies for serious diseases. Founded in 1989, Vertex built its reputation on research-driven drug development and is best known for its work in cystic fibrosis (CF), where its portfolio of small-molecule CFTR modulators transformed standards of care for many people with the disease. The company operates research and development, manufacturing and commercial organizations and serves patients and healthcare systems in multiple international markets.

Vertex’s marketed products center on CFTR modulators that target the underlying cause of cystic fibrosis rather than just treating symptoms. Its approved therapies include potentiators and corrector combinations that have expanded treatment options for people with different CFTR mutations. These drugs, introduced progressively since the early 2010s, are the cornerstone of Vertex’s commercial business and have enabled broad access programs and partnerships to reach CF patients globally.

Beyond cystic fibrosis, Vertex has invested heavily in next‑generation technologies and new therapeutic areas. The company is advancing programs in gene editing and cell therapy, including a collaboration with CRISPR Therapeutics to develop gene‑editing treatments for hemoglobinopathies such as sickle cell disease and beta‑thalassemia, and it has pursued stem cell–derived approaches for type 1 diabetes following its acquisition of Semma Therapeutics. Vertex’s pipeline also includes earlier‑stage research across other serious diseases where precision genetic or cell‑based approaches may offer durable benefit.

Vertex maintains a commercial presence in North America, Europe and other international markets while sustaining a large R&D footprint to support discovery and clinical development. The company is led by Chief Executive Officer Reshma Kewalramani and a management team with deep experience in both clinical development and commercial operations. Vertex emphasizes patient access, long‑term innovation and collaboration with academic and industry partners as it seeks to expand its impact beyond cystic fibrosis into additional rare and serious diseases.

Vertex Pharmaceuticals Q2 2026 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Vertex reported second-quarter revenue of $3.3 billion, up 12% year over year, and raised 2026 revenue guidance to $13.1 billion–$13.2 billion. Management maintained its target of at least $500 million in non-CF revenue, while expecting operating expenses near the high end of its $5.65 billion–$5.75 billion range.
• Positive Sentiment: The cystic fibrosis franchise remained strong, with global revenue up 11% and ALYFTREK exceeding $1 billion in first-half revenue. Vertex highlighted rapid ALYFTREK adoption, including more than one-third of eligible patients in Germany and the U.K., and is pursuing additional approvals in younger children and rare mutations.
• Positive Sentiment: CASGEVY revenue rose to $76 million in the second quarter, up roughly 75% sequentially, while JOURNAVX revenue reached $50 million, up about 70% sequentially. CASGEVY patient initiations and infusions continued to build, and JOURNAVX prescriptions, prescriber adoption, hospital pathways, and payer coverage expanded significantly.
• Negative Sentiment: JOURNAVX’s rapid prescription growth is increasing use of Vertex’s patient support program because of remaining payer restrictions, delaying gross-to-net normalization until the first half of 2027. Management also cautioned that quarterly revenue may remain volatile as channel inventory and reimbursement patterns normalize.
• Positive Sentiment: Vertex is preparing for a potential November 30 FDA decision on povetacicept in IgA nephropathy, citing strong efficacy, monthly at-home auto-injector dosing, and a favorable safety profile. The company also advanced multiple pipeline programs, including completion of enrollment in studies of inaxaplin and VX-407, an upcoming type O islet-cell therapy trial, and the planned acquisition of Crinetics to establish a rare-endocrine franchise.

Presentation

[Operator]

Good day, and welcome to the Vertex Pharmaceuticals second quarter 2026 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. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touch tone phone. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead.

[Susie Lisa, SVP of Investor Relations at Vertex Pharmaceuticals]

Good evening all. 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 2026 financial results conference call. On tonight's call making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's Chief Executive Officer and President, Charlie Wagner, Chief Operating Officer and Chief Financial Officer, and Duncan McKechnie, Chief Commercial Officer. We recommend that you access the webcast slides as you listen to this call.

[Susie Lisa, SVP of Investor Relations at Vertex Pharmaceuticals]

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 the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission.

[Susie Lisa, SVP of Investor Relations at Vertex Pharmaceuticals]

These statements, including without limitation, those regarding Vertex's marketed medicines for Cystic Fibrosis, sickle cell disease, beta thalassemia, and moderate to severe acute pain, our pipeline, the proposed acquisition of Crinetics Pharmaceuticals, and the expected benefits of that transaction and Vertex's 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 are presented on a non-GAAP basis. I'll now turn the call over to Reshma.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Thanks, Susie. Good evening all, and thank you for joining us on the call today. Vertex's second quarter performance was excellent with strong momentum in the commercial portfolio, rapid progress across our R&D pipeline, and the announcement of the definitive agreement to acquire Crinetics Pharmaceuticals, which brings rare endocrine diseases as a fifth pillar to Vertex. Second quarter total revenue grew 12% year-over-year, driven by the strength of our Cystic Fibrosis portfolio and the growing contributions from our newer products, CASGEVY and JOURNAVX. As I've previously highlighted, this is a year of execution for Vertex across commercial, clinical, and regulatory, and on each of those fronts, we advanced significantly in the second quarter. Commercially, we delivered strong revenue growth across all diseases, made meaningful progress in reimbursed access, and continued to execute on near-term launch planning to drive the next phase of growth.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Clinically, we continue to make significant progress in advancing our pipeline, including completing enrollment in the AGLOW phase II study of VX-407 in ADPKD, tracking to complete enrollment in the AMPLITUDE phase III study in AMKD by the end of this year, and reporting results from the interim analysis cohort of AMPLITUDE in the beginning of 2027. We also remain on track to release results later this year from a proof of concept study in DM1 and an expanded population for AMKD in the AMPLIFY trial, as well as the initial patient data from VX-828 in CF. On the regulatory front, the BLA for POVI and IgAN was accepted in the U.S. with a November 30th PDUFA date. We achieved expanded labeling in record time for CASGEVY in patients ages two to 11 in the U.S.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

I'm very pleased to share that as we continue to dose the phase I/II/III study of exemlcel in Type 1 Diabetes, the IND was cleared for the blood type O islet cells in our T1D program, VX-017. We expect initiation of the VX-017 phase I/II study in the near term. Finally, with the announced acquisition of Crinetics Pharmaceuticals, we look forward to multiple benefits of the deal. Establishing a fifth pillar in rare endocrine diseases, adding to our innovative R&D pipeline, accelerating revenue growth, and enhancing long-term earnings. Tonight, I'll limit my R&D comments to new news in CF, renal, and Type 1 Diabetes, and close with some additional remarks regarding the Crinetics acquisition. Let me start with CF, where we continue to extend our market leadership. Data we presented at ECFS reinforced that ALYFTREK best restores CFTR function amongst the available CFTR modulators.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

In particular, among children with CF under 12 years of age, the majority across all eligible genotypes achieve a sweat chloride less than 30 millimoles, which is the median among CF carriers. This is remarkable because at these sweat chloride levels, CF carriers do not exhibit the manifestations of disease. In addition, we have initiated global regulatory submissions for ALYFTREK in children ages two to five. Global regulatory submissions for TRIKAFTA in patients ages one to two are also in progress. Turning to our next wave in CF and VX-828, our next generation 3.0 CFTR modulator recently completed dosing in the patient cohort and data are expected in the second half of this year. Behind VX-828, we continue to advance additional correctors in the next gen 3.0 family, and both VX-581 and VX-272 are in healthy volunteer studies. Let me close on CF with this.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Our ultimate goal has been consistent for two plus decades: to bring patients to carrier levels of sweat chloride. Frankly, ALYFTREK's remarkable results, where nearly 2/3 of younger patients achieved sweat chloride levels less than 30 millimole per liter, and for patients ages 12+, more than 75% achieved sweat chloride levels within the carrier range of CFTR function means we are very close to that goal. Given the improvements in sweat chloride, ppFEV1, pulmonary exacerbations, hospitalizations, lung transplant, and survival that we have seen in patients in clinical trials and/or the real world, we recognize that the unmet need is far lower today, and the bar for any medicine to beat ALYFTREK is very, very high. Thus, as we develop our next gen 3.0 and beyond programs, we will evaluate multiple regimens in phase I and cohorts of patients with CF.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

We will only advance assets into phase II and beyond that show promise to beat ALYFTREK. In other words, to bring even more patients to sweat chloride levels less than 30 across all genotypes with once daily dosing and excellent drug-like properties, including drug-drug interactions. Anything less would not be competitive. Moving now to our renal franchise, where we have four programs in mid- and late-stage development. Povetacicept in IgAN and primary membranous nephropathy, inaxaplin in APOL1-mediated kidney disease, and VX-407 in ADPKD or Autosomal Dominant Polycystic Kidney Disease. Let me start with the most advanced program and significant milestone. In late May, the FDA accepted our BLA for POVI and IgAN and assigned a PDUFA date of November 30th of this year.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

As a reminder, the RAINIER phase III interim analysis was a home run, delivering statistically significant and clinically meaningful results across the primary and all secondary endpoints with a favorable safety profile and consistency in the primary endpoint of change from baseline in proteinuria across all groups. We are in the final stages of launch readiness. Duncan will provide more details regarding our approach and excitement to go to market with POVI's differentiated profile of potentially best-in-class efficacy, a well-tolerated safety profile, and patient-centric administration through small volume, once monthly dosing via an auto-injector at home. We are also advancing POVI internationally. We have completed the regulatory submission for accelerated approval of POVI in IgAN in Saudi Arabia, where POVI has received breakthrough designation. Turning to POVI in membranous nephropathy, our OLYMPUS phase II/III pivotal trial is well underway.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

The phase II portion is complete, the phase III portion initiated last quarter. I'm pleased to share that the IDMC has completed its review and selected the phase III dose, 80 mg subcutaneously every four weeks. We hold fast track, orphan drug designation, and EMA Prime designations for POVI in membranous. Stepping briefly outside of renal, on POVI in myasthenia gravis, I'm also pleased to share that the 30-patient, phase II proof of concept study is on track to complete enrollment by the end of this year. Recall, this study evaluates 80 mg and 240 mg doses of POVI versus placebo for 12 weeks. Turning now to inaxaplin in AMKD. On AMPLITUDE, our pivotal phase II/III study in AMKD, we completed enrollment of the interim analysis cohort in September of last year and are on track to complete full enrollment by the end of this year.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

The interim analysis will be conducted following 48 weeks of treatment, we remain on track to share these IA results in early 2027. If positive, we would be positioned to file for potential accelerated approval in the U.S. thereafter. AMPLIFIED is our phase IIB basket study of inaxaplin in AMKD patients with either lower proteinuria or AMKD patients with diabetes. Expanded patient populations not studied in AMPLITUDE. The AMPLIFIED study has completed enrollment and dosing, and we expect to share results this fall. Lastly in the renal portfolio is VX-407 in ADPKD or Autosomal Dominant Polycystic Kidney Disease. Our AGLOW phase II study has completed enrollment. This is a proof of concept study with up to 52 weeks of treatment. We are excited about the potential for VX-407 in ADPKD and look forward to sharing more information as dosing continues and the data matures.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Let me now touch on Type 1 Diabetes. We had very constructive meetings with the FDA following our voluntary pause in order to conduct a manufacturing analysis of exemlcel. As we shared on our Q1 call, we have resumed dosing patients in the exemlcel phase I, II, III study. The new news today is that the FDA has cleared the IND for VX-017, our type O or universal donor cell product. VX-017 has a similar target product profile to exemlcel, but is designed for people of all blood types, and we expect the VX-017 phase I, II study to initiate in the near term. By designing and bringing to market VX-017, another allogeneic, off-the-shelf, glucose-responsive, insulin-producing, fully differentiated islet cell therapy, in this case, for any blood type, we anticipate doubling our market opportunity from about 60,000 to about 120,000 patients.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

A silver lining to the pause we took in the exemlcel type A program is that the type O program time differential versus exemlcel has shortened. Type O is making rapid progress, and thus we are considering options to further streamline our regulatory strategy and commercialization approach. We expect to provide updated T1D plans, including timelines, later this year. We also continue to progress our serial innovation work focused on improved immunosuppression and hypoimmune programs to make our potentially one and done curative therapy available to even more patients with Type 1 Diabetes. Let me close with a few words on our announced acquisition of Crinetics Pharmaceuticals, which we detailed in a separate call last month. Crinetics is an excellent strategic fit for Vertex, with its focus on serious endocrine diseases, high unmet need, validated targets, and well-understood causal biology, as well as a strong people and culture fit.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

We believe the two lead assets, paltusotine and atumelnant, together represent a peak sales opportunity of about $5 billion. Both are small molecules that address serious diseases for patients treated by a concentrated group of specialized endocrinologists. This fits directly within Vertex's proven efficient specialty commercial model. We enter this transaction from a position of strength. We view CF as a long duration franchise with sustained growth. We continue to expect both CASGEVY and JOURNAVX to be multi-billion dollar assets, and we anticipate our emerging renal franchise could one day rival CF in revenue. In addition, we have a broad and deep pipeline in earlier stages of development. The Crinetics acquisition will add to this innovation pipeline and enhance our revenue growth and long-term earnings profile by adding a fifth commercial pillar in rare endocrine diseases.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

The transaction is expected to close in the third quarter. We really look forward to welcoming the talented Crinetics team to Vertex. With that, I'll turn the call over to Duncan for a commercial update.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

Thanks very much, Reshma. Our commercial story this quarter is one of building momentum across each of our franchises, supported by the appropriate investments to drive growth. We are very excited for the close of the Crinetics acquisition and for Vertex to establish a new pillar in specialty endocrine diseases like acromegaly, CAH, and Cushing's syndrome. Crinetics Q2 results were excellent, with strong growth in paltusotine revenue and patients treated, but I will hold any further comments until after the deal closes. Tonight, let me start with CF. CF continues to perform very well. Global CF revenue grew 11% year-over-year in the second quarter, with balanced growth across the U.S. and internationally, and continued strength from both ALYFTREK and TRIKAFTA. ALYFTREK performance has been excellent and crossed another significant milestone, exceeding $1 billion in revenue in the first half of 2026.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

In the U.S., we continue to see patients initiating ALYFTREK who are new to therapy, returning to therapy, and patients switching from TRIKAFTA. The majority of ALYFTREK revenue continues to come from these TRIKAFTA switch patients, which reflects the benefits of ALYFTREK and our success establishing ALYFTREK as the new standard of care. We are pleased with the pace at which physicians and patients are embracing ALYFTREK, given its improved sweat chloride profile and once daily dosing. We have seen accelerated uptake of ALYFTREK from the recent approvals in rare mutations, as well as patients rolling off our open label extension studies. Outside the U.S., the ALYFTREK European launches remain very strong. With no requirement for augmented liver monitoring in the E.U., we are seeing rapid uptake by patients in Europe transitioning from TRIKAFTA or one of our other CFTR modulators.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

In fact, in Germany and the U.K., more than one in three eligible CF patients are now benefiting from ALYFTREK. Globally, the CF growth drivers for the remainder of 2026 are clear. Continued ALYFTREK uptake, the label expansion into rare mutations, younger patients, and additional geographies. Shifting to heme and CASGEVY, where the momentum continues to build. During the second quarter, we delivered $76 million in CASGEVY revenue, reflecting approximately 75% sequential growth versus quarter one 2026 and over 150% year-over-year growth. This was in line with our expectations based on our visibility into patient scheduling patterns. The strength of the CASGEVY franchise continues to build.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

New data on CASGEVY at EHA with simultaneous publication in "The New England Journal of Medicine" demonstrated its transformative potential in pediatric patients as well as durable benefits, reinforcing the importance of early intervention to prevent the complications of sickle cell disease and beta thalassemia in children. Stemming from this compelling data, last month, CASGEVY became the first and only gene therapy FDA approved to treat children as young as two years old in both sickle cell disease and beta thalassemia. CASGEVY received supplemental approval in the U.S. in a record 53 days post-filing, and our first pediatric patient has already initiated therapy and conducted cell collection. Outside the U.S., CASGEVY regulatory submissions in the five to 11 age group are now complete in Saudi Arabia and the United Kingdom.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

On the reimbursement front, we're seeing strong trends in initiations in Germany after reaching a historic reimbursement agreement there, as well as continued strong uptake in the U.K., Italy, and the Middle East following the negotiations of sustainable access agreements. The CASGEVY story continues to be one of an increasingly robust pipeline of patients initiating the treatment journey. There were more CASGEVY infusions in the first half of 2026 than in all of 2025. Second quarter 2026 was also the third sequential quarter with more than 100 patient initiations, which enhances our visibility to continued growth for the rest of this year and early 2027 as patients continue to move through cell collection, editing, and infusion. Quarter-to-quarter variability in CASGEVY revenue will continue and reflects the timing of patient infusions as people choose to receive their infusions when it best suits them.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

As we look forward, we expect continued CASGEVY momentum with the pipeline of patients at every stage continuing to build. CASGEVY is well-positioned to contribute meaningfully to our $500 million non-CF revenue goal this year and to achieve its standalone multibillion-dollar potential. Turning to JOURNAVX in moderate to severe acute pain, where our launch continues to gain traction. In the second quarter, JOURNAVX generated $50 million in revenue, reflecting sequential revenue growth of approximately 70% and sequential prescription growth of approximately 45% versus quarter one 2026. Unpacking Q2 performance, revenue was positively impacted by channel build after we'd seen a drawdown in quarter one. At this stage in an acute product launch, we continue to expect some quarterly volatility in inventory build and drawdown as full line wholesalers and retail channel buying patterns normalize to reflect formulary adoption, physician awareness, and seasonality in elective surgeries.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

We are building a pain franchise for the long term and are focused on the following four critical markers of success: prescription growth, breadth and depth of prescribers, the addition of JOURNAVX to hospital and IDN pathways, and broad payer coverage. These are the building blocks of a sustainable, long-term, multi-billion-dollar business. We are extremely pleased with the prescription growth we continue to build, which is ahead of our forecast for 2026. The breadth and depth of prescriptions across a wide range of settings of care, as well as the clinical impact of JOURNAVX, continue to be very strong and all augur well for the long-term growth of JOURNAVX in acute pain. The consequence of this rapid prescription growth is that we are seeing greater use of the PSP program than we forecast as securing unrestricted payer access and physician education catches up with prescription growth.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

Let me break down what I mean by that. At this point, we have a total of 260 million lives covered out of a total possible of approximately 320 million. Of the 260 million covered lives, 180 million of them have unrestricted coverage. This means that there are 60 million lives yet to be covered and about 80 million lives who have coverage, but with some form of restriction, making some of them eligible for the PSP program. These restrictions are usually very minor in nature, such as a 14-day quantity limit or a prior authorization to indication. As we continue to educate physicians and their office staff about the quantity limits and prior authorizations, we expect the PSP to be triggered less frequently and therefore more revenue to be recognized.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

Let me now provide you with some more details on prescriptions, prescribers, and access before concluding our thinking on the PSP program and gross to net. In terms of prescriptions, quarter two 2026 JOURNAVX prescriptions totaled approximately 535,000 and just over 900,000 for the first half of 2026. The prescriptions continue to be split roughly 50/50 between the hospital and retail channels. In both channels, monthly prescriptions were approximately 50,000 in January and doubled to approximately 100,000 in each channel in June. In terms of prescribers, we added approximately 18,000 new HCP prescribers to JOURNAVX in Q2 2026 and are pleased that JOURNAVX is now on 1,400 hospital and 130 IDN pathways in terms of formulary, protocol, or order sets. These are important metrics as we seek to convert practices and continue to embed the use of JOURNAVX among our target physicians.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

We've also made further progress with respect to access. We recently signed agreements to expand reimbursed access to JOURNAVX with two additional Medicare Part D plans effective from July 1st. With these additions, three of the big four Medicare Part D plans now provide covered access alongside the three large commercial PBMs. As mentioned, this brings the total covered lives for JOURNAVX to approximately 260 million out of a total possible of 320 million, and within that, approximately 180 million lives with unrestricted access. Our goal continues to be to ensure the prescribing experience for physicians and patients is as seamless as possible in a market where the delivery of the medicine is highly time sensitive. We will continue to work to educate physicians to navigate the minimal quantity limits and prior authorizations that exist and secure ever broader coverage.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

In the meantime, we will maintain the PSP program so that patients who are prescribed JOURNAVX can get it. We continue to see this as a strategic choice as we seek to convert physician practices away from decades of reliance on opioids to ongoing and sustained use of JOURNAVX for many years to come. As a result, we continue to expect gross to net to normalize in line with other branded oral medicines, but now in the first half of 2027. To conclude on pain, we also continue to be on track to exceed our goal of more than tripling the 550,000 prescriptions and more than tripling revenue from 2025 into 2026, as well as delivering more than $500 million in revenue from CASGEVY and JOURNAVX combined in 2026. Let me conclude with an update on our commercial readiness in renal and specifically POVI in IgAN.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

With the FDA's acceptance of our BLA and the November 30th PDUFA date, we are in the final stages of commercial launch preparation. We're investing in our renal franchise and the nephrology community for the long term, given our innovative pipeline of multiple potentially transformative kidney disease medications that address the underlying causes of serious renal conditions. Our goal is for POVI to be physicians' first choice among disease-modifying therapies for IgAN. And we know from our market research and from nephrologist feedback that physicians are looking for treatments that meaningfully and rapidly reduce proteinuria, have a favorable tolerability profile, and offer a seamless treatment experience from access through patient support to convenient dosing. We believe POVI has the winning trifecta of efficacy, tolerability, and ease of use for patients and physicians alike.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

With dual BAFF/APRIL inhibition, POVI has clear best-in-class potential and delivers effectively on all the needs we've heard from the community in research and advisory boards, making it the ideal first choice after baseline therapy with ACE/ARBs and SGLT2s. We have completed the hiring of our renal field force, of whom about 90% have nephrology experience and was built with the breadth of our renal pipeline in mind. We anticipate that we will have the largest field force among the novel APRIL or APRIL-BAFF therapies for IgAN. Our payer conversations are also proceeding well. In the U.S., approximately 70% of patients with IgAN have commercial coverage. From our engagements with payers, their awareness of IgAN and the new BAFF/APRIL inhibitors is high. Payers understand the unmet need, have a good understanding of the KDIGO guidelines, and how the new therapies fit into treatment pathways.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

Payers are also very aware of the strength of the POVI phase III interim analysis data and POVI's November 30th PDUFA date. Our market access teams continue to actively engage with payers to prepare for the upcoming launch of POVI. Additionally, we will provide robust patient support programs drawing on our decades of experience in CF. POVI in IgAN is the first component of our emerging renal franchise, and we're excited to bring it to nephrologists and to their patients. We believe POVI's trifecta of efficacy, tolerability, and ease of use delivers exactly what nephrologists are seeking. Just as we've done for over a decade in CF, POVI's success will be driven by a field force delivering a high science cell fueled by a potentially best-in-class product, broad reimbursement, and robust high-quality patient programs.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

We are very excited to commercialize POVI and IgAN and begin building our multibillion-dollar renal franchise at Vertex. I'll now turn the call over to Charlie to review the financials.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

Thanks, Duncan. As Reshma noted, Vertex's second quarter results demonstrate our consistent strong performance and attractive growth profile. Second quarter 2026 total revenue of $3.3 billion increased 12% year-over-year, with growth balanced between the U.S. and international markets. As expected, Q2 2026 revenue growth reflects an approximate 170 basis point benefit from foreign exchange rates. Q2 2026 global CF revenue grew 11% year-over-year, and new disease areas also contributed, with CASGEVY delivering $76 million compared to $30 million in Q2 of 2025, and JOURNAVX's revenue of $50 million compared to $12 million in Q2 of 2025. As a reminder, Q2 2025 results also included $21 million of collaboration revenue. Q2 2026 U.S. CF revenue grew 9% year-over-year, led by strong volume growth from ALYFTREK uptake, continued performance from TRIKAFTA, and higher realized net price.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

Outside the U.S., CF revenue grew 12% year-over-year, driven by strong ALYFTREK launches, timing of orders in certain geographies, as well as the benefit from FX. Note that global CF revenue growth for the first half of 2026 was 8%, including the benefit of prior year U.S. price increases and foreign exchange. We expect both of these factors to contribute less to growth in the second half of the year. Our second quarter 2026 gross margin was 85.6%, an expected sequential step down from Q1 of 2026. This step down reflects the impact of product mix as well as manufacturing network investments in various products.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

As our new products, particularly CASGEVY, increase in revenue contribution with higher cost of goods sold than our small molecule CF products, we continue to expect full year gross margin of just under 86%, roughly in line with this quarter's result. The impact from product mix and manufacturing network investment costs will be more pronounced in the second half than they were in the first half of 2026. Turning to operating expenses. We continue to invest appropriately given the attractive opportunity presented by our ongoing and near-term launches, as well as our attractive mid and late-stage pipeline. Second quarter non-GAAP R&D expense of $889 million increased 1% year-over-year, with steady progress across multiple phase III studies and the earlier stage pipeline.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

Non-GAAP SG&A expense of $520 million increased 45% year-over-year, driven primarily by commercial investments split roughly evenly between pain and renal. We also recorded $21 million in acquired IPR&D expense in the quarter. Note that while R&D continues to account for nearly 2/3 of our operating expenses, the modest growth rate reflects that we are in a period where we can redeploy dollars from programs that wind down to fund programs that are new or scaling up. In contrast, much of our commercial spending is to build new businesses and thus is incremental, as reflected in the higher year-over-year growth rates when compared to R&D spending. Our second quarter 2026 non-GAAP effective tax rate was 21.1%, including some one-time expenses.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

Year-to-date, our non-GAAP effective tax rate was 20.4% within our guidance range of 19.5%-20.5%. Our second quarter 2026 non-GAAP earnings per share of $4.73 represents 5% growth versus prior year, reflecting strong revenue growth as well as investments in our pipeline and commercial capabilities. Turning to the balance sheet. We ended the quarter with approximately $13.6 billion in cash and investments. During the second quarter, we deployed approximately $455 million to repurchase roughly 1 million shares. This activity reflects our ongoing commitment to returning value to shareholders while maintaining the flexibility to act on strategic growth opportunities. Of course, our top priority for capital deployment remains investing in innovation, as evidenced by our recent announcement to acquire Crinetics for approximately $8.8 billion net of cash acquired.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

Turning to guidance. Given our strong first half performance and the momentum across the business, we are raising our full year 2026 total revenue guidance to a range of $13.1 billion-$13.2 billion. 2026 revenue guidance reflects continued strong performance from the CF franchise, including ALYFTREK and TRIKAFTA, as well as growing year-over-year contributions from CASGEVY and JOURNAVX. We continue to expect revenue of $500 million or greater from our non-CF products. Our outlook also continues to include an expected 150 basis point benefit from foreign exchange net of our hedging program.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

As I previously mentioned, we continue to expect full year gross margin of just under 86%. On operating expenses, we are reiterating our combined non-GAAP operating expense guidance of $5.65 billion-$5.75 billion, though we now expect to be at the high end of that range. This reflects continued investment in our late-stage clinical pipeline and the commercial infrastructure and activities that support our new launches and revenue diversification. We continue to expect our non-GAAP effective tax rate to be in the range of 19.5%-20.5% for the full year 2026. I would note that today's guidance does not yet reflect the pending Crinetics acquisition, which is expected to close in the third quarter. Given the anticipated timing, we expect the impact to 2026 revenue and non-GAAP operating expenses to be relatively modest. We will provide updated guidance for 2026 around the time of closing.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

As a reminder, we expect to fund the transaction through a combination of cash on hand and proceeds from a $4.5 billion term loan. We expect the transaction to become accretive to non-GAAP operating income in 2029. In summary, Vertex delivered strong second quarter results. Our commercial launches and diversification are gaining momentum. We continue to invest with discipline in both innovation and commercialization. Overall, our financial performance and outlook remain compelling. With expanding CF leadership, hemon pain scaling, renal on the doorstep of launch, and the addition of a fifth pillar in specialty endocrine through the pending Crinetics acquisition, Vertex is exceptionally well-positioned for continued growth. Our high success rate in R&D and our disciplined specialty commercial model allow us to maintain industry-leading margins even as we step up investments to support our launches and pipeline.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

With this unique profile, we are well-positioned to continue expanding our impact for patients, investors, and all stakeholders. We look forward to updating you on our continued progress across multiple disease areas with key upcoming milestones detailed on slide 19. I'll ask Susie to begin the Q&A period.

[Susie Lisa, SVP of Investor Relations at Vertex Pharmaceuticals]

Seth, can you kick us off?

[Operator]

Will do. We will now begin the question-and-answer session. To ask a question, you may press star then one on your touch tone phone. If you are on a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. Our first question for today will come from Salveen Richter with Goldman Sachs. Please go ahead.

[Salveen Richter, Analyst at Goldman Sachs]

Good afternoon. Thanks for taking my questions. Two for me. One is, you announced that the phase II/III OLYMPUS study for POVI in pMN is going to move to phase III with an 80 mg dose every four weeks. Can you frame what signal this was based on and whether you or the DSMB, or what you or the DSMB saw in the phase IIB portion to move forward? On the pain front, it was really nice to see the progress here. Maybe help us understand where the bottlenecks lie now or what needs to be worked on with regard to formulary as well as the payer dynamics as you look at copay, et cetera. Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Sure thing, Salveen. Let me kick us off with the first question, which is about POVI in membranous. The phase II's complete. The phase III was already initiated, you might recall, a couple of months ago as we designed it as a seamless phase II/III. The DSMB was asked to base their decision, and it was their decision because we do not have access to the unblinded data to look at on efficacy PLA2R, which is the biomarker equivalent in membranous as Gd-IgA1 is to IgAN. Of course, they had full access to the safety results as they made their decision. I suppose in many ways it's not surprising that they picked the 80 mg dose given the RUBY-3 results, where you could see that the 80 mg had a very nice reduction in PLA2R. That's how the decision was made.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Study's well on its phase III portion. We look forward to getting that study enrolled and completed. Duncan, I'm going to turn it over to you for a little commentary on JOURNAVX scripts and what more we're working on.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

Thank you. Good afternoon, Salveen. As you know, our goal with JOURNAVX is to fundamentally transform how pain is treated and to move physician practices away from decades of reliance on opioids. In terms of our progress, we're very pleased with the prescription numbers that we're seeing. We're also very pleased with the increased number of hospitals that have adopted JOURNAVX, now 1,400 or so, with 130 IDNs having it on formularies. We have also now secured two additional Medicare Part D plans to cover JOURNAVX starting from July the 1st. Overall, our progress is going very well. I would add that those prescriptions are coming from a broad range of physician types and being used in a broad range of pain types consistent with our label.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

In terms of the payer side and access, we're very pleased with the coverage that we've secured to date. 260 million lives, and that's ahead of those two Medicare Part D plans coming in. I would say we have obviously more work to do to secure the final elements of access for JOURNAVX. We also have to make sure that those patients whose physicians might have, say, a quantity limit are able to navigate that in order to ensure the patient can secure access. In the meantime, we have the PSP program in place and anticipate that we'll continue to see prescriptions transition to increasing growth in revenue in the second half of 2026. Indeed, as we've communicated before, that our gross to net will ultimately normalize at the same level as other oral branded medicines in the pharmaceutical arena.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

We're very happy with the progress. We have a little bit more work to do. We are very happy with where we're at right now in terms of physician adoption, payer coverage, and hospital usage.

[Operator]

The next question will come from Geoff Meacham with Citibank. Please go ahead.

[Geoff Meacham, Analyst at Citibank]

Hey, guys. Afternoon. Thanks for the question. Have two quick ones. The first one in CF on VX-828 or the other assets in phase I. What are some of the clinical attributes you're looking for? I wasn't sure if you're looking for perhaps a nominally better treatment effect or if there is a potential to not need liver monitoring, for example, in future combos. Second question on JOURNAVX. You guys have had substantial discussions with payers, hospital systems, physicians on acute pain. In these conversations, have you gotten any perspectives or context on DPN? Like what the clinical profile needs to show as we look to the data end of the year or beginning of next year, or what the access and reimbursement could look like in this setting. Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Sure thing, Geoff. Let me take the second question first. On JOURNAVX, we have been hyper-focused on JOURNAVX and acute pain to make sure that we get all of those reimbursement contracts done and get access. I think it would be just very fair to say we've spent all of our time hyper-focused on acute pain. We'll have more to say on where we are with DPN, the data, what payers are looking for, what doctors are looking for, et cetera, in the coming months. For here now, it's acute pain. On VX-828 and the next-gen molecules, just to give you all of the numbers, VX-828 is the first of the next gen. The second and third are VX-581 and VX-272. We are looking for potential improvement in efficacy, i.e.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

More people who can get down to less than 30 millimoles. Of course, we're looking for safety as well. The monitoring will depend on what the results in the clinical trial are. Sure, there's opportunity for monitoring to be different with this VX-828 program. It just depends on what the actual results are through the clinical trial program. Last thing to say, once daily dosing, really good-looking DDIs as well as other drug-like properties remain really important as I mentioned in my prepared remarks.

[Operator]

The next question will come from Jessica Fye with JPMorgan. Please go ahead.

[Jessica Fye, Analyst at JPMorgan]

Hey, guys. Good afternoon. Thanks for taking my question. Maybe for Reshma, I'm curious if you expect to see material differentiation on eGFR across the new IgAN products like POVI and its competitors. If so, over what time horizon do you think any differentiation on that endpoint would become apparent? Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Sure thing, Jess. As we've discussed before, in IgAN in particular, you could say this for homogeneous proteinuria kidney diseases in general, good reductions in proteinuria should, based on everything we know, result in stabilization of GFR. I expect that to be the case with APRIL/BAFF inhibitors as well. I think, so that your question is asking a very important second point, and to me, the most important point. What is the differentiation we can expect between various molecules if you have more reduction in proteinuria or hematuria or in the case of IgA nephropathy, Gd-IgA1, these inciting antibodies? I think for that, the answer is, it's really about time to ESRD. That's to say time to dialysis, transplantation, or death.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

I do expect that the medicine that has the stronger reductions in proteinuria, the medicine that gets more patients to less than 0.5 or 0.3, better improvements in hematuria and Gd-IgA1 are more likely to have an improved profile when it comes to that ultimate endpoint. Proteinuria, one-year GFR, two-year GFR, these are all endpoints on the way to that ultimate endpoint, I think that's where you'll see the real differentiation.

[Jessica Fye, Analyst at JPMorgan]

Great. Thank you.

[Operator]

The next question will come from Cory Kasimov with Evercore ISI. Please go ahead.

[Cory Kasimov, Analyst at Evercore ISI]

Hey, good afternoon, guys. Thanks for taking the question. Wanted to ask about inaxaplin in the AMPLITUDE study, what kind of data would be necessary in that interim analysis to file for accelerated approval? Basically, what constitutes a win with this first data look? Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Sure thing. Cory, I think you're asking about AMPLITUDE, the core study that's now in phase III, in patients with two APOL1 alleles, moderate to heavy proteinuria, and depressed GFR. We were really pleased and remain very pleased that the agency has provided, and we have an agreement with the agency for a potential accelerated approval based on the primary endpoint at the time of the IA, which is one-year GFR. That's what our agreement is based on. Obviously, we're also going to look at the proteinuria, the agreement with the agency for the potential to file for accelerated approval based on the interim analysis is one-year GFR.

[Cory Kasimov, Analyst at Evercore ISI]

Great. Thank you, Reshma.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

You bet.

[Operator]

The next question will come from Brian Abrahams with RBC Capital Markets. Please go ahead.

[Brian Abrahams, Analyst at RBC Capital Markets]

Hey, guys. Thanks so much for taking my question and congrats on the quarter. On pain, we've seen some data published recently from another NaV1.8, I'm just curious how you see the acute pain dynamics playing out with additional entrants into the market potentially. Then secondarily, just on exemlcel, just wondering if you could talk about the potential impact to launch timing if you do end up syncing the filing with 017. Thanks.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Thanks for the kind words, Brian. Maybe I'll do the pain one first and then come on to Type 1 Diabetes. I did see the publication. Maybe, Brian, what I'll say is that ever since Vertex published VX-150, which you'll remember was the molecule circa 2017 or so, we saw a spike in others following in our footsteps and pursuing NaV1.8 as a target. What I'll say is that we decided not to advance VX-150 because we didn't think it had, as I described at the time, the perfect drug-like molecule properties that we were looking for, and we bypassed 150 in favor of what is now suzetrigine or VX-548. We know the space very well, we know the molecule well, and we know that every time we publish a patent, there's a slew of followers.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Maybe if you say, "Well, what's the takeaway from that?" I think that there is a high appetite in the biopharma industry to make non-opioids. There is high unmet need for non-opioid effective pain medicines that have not only the right efficacy, but the right safety tolerability drug-like properties profile. I really like where we are, well on the market with JOURNAVX, and I'm very much looking forward to the possibility of NaV1.7/1.8 combination, and I've never felt better in Vertex history for the fact that that may come to pass for us to be able to bring that to the clinic. Switching then to the Type 1 Diabetes program. Let me just say what I said in my prepared remarks. I may have gone a little quick there.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

The exemlcel program is in phase I, II, III, backup, and dosing, and because it's a type A program, it serves about 60,000 people in the U.S. and Europe. The 017 program, because it's type O, has the potential to serve 120,000 people because it's the universal donor type O. Now what we're trying to do is see if we can't get the type O program to go even faster and bring that program out either first or very close behind. That's what we're working on in terms of both the regulatory approach and the commercial approach. I don't have a timeline for you today, but we should be able to tell you our exact plans with timelines in the back half of this year. I am very excited about the opportunity to perhaps bring type O out first or very close behind.

[Brian Abrahams, Analyst at RBC Capital Markets]

Super helpful. Thanks, Reshma.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Yeah.

[Operator]

The next question will come from Evan Seigerman with BMO. Please go ahead.

[Evan Seigerman, Analyst at BMO]

Hi, all. Thank you so much for taking my question, and congrats on the progress. You've maintained the expectation for at least $500 million of non-CF revenue this year, while CASGEVY and JOURNAVX delivered roughly $125 million this quarter. As you think about the path to this target, should we expect that the majority of the upside comes from accelerating patient starts with CASGEVY, continued growth with JOURNAVX, or kind of a relatively balanced contribution from both franchises?

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Evan, I'll ask Charlie if he wants to make any additional comments on our guidance on the $500 million.

[Charlie Wagner, COO and CFO at Vertex Pharmaceuticals]

Evan, thanks. As you pointed out, so far in the first half of the year, CASGEVY and JOURNAVX combined delivered about $200 million in revenue, so we're well on our way to achieving our target of $500 million+. In that first half, CASGEVY's been a bigger contributor than JOURNAVX. I'm not willing to give further color on the balance of the year other than to say we're very confident in getting to that $500 million+.

[Operator]

The next question will come from Michael Yee with UBS. Please go ahead.

[Michael Yee, Analyst at UBS]

Hey, thank you for the question. I guess the IgAN competitor data to your eGFR data is hot off the press, and it's out there on the tape, and you can see that the approved product has essentially a stabilization of eGFR, if not slightly above baseline. To what extent, Reshma, given that you have an approval coming up soon, should we think about comparing the two, either from a launch perspective or perhaps given the strong numbers that they're putting up, it speaks to the significant market opportunity and you both can get equivalent share. Maybe just talk a little bit about the data that the competitor is putting up and how you think about your launch. Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Sure thing. Mike, I did just see the eGFR data, but I've just seen the top-line number, and as you say, it shows a stabilization right around zero. That is what we should expect given the proteinuria reduction. That seems very much in line. With regard to what it means for the povetacicept IgAN program, I would say all the more reason. If anybody needed a little bit more conviction, you can certainly look at these data that were presented today, look at the proteinuria reduction, look at the GFR, and reconfirm for yourselves that significant reductions in proteinuria should and have resulted in GFR stabilization. It makes a lot of sense to me. For what I see for POVI, I see us putting up very strong numbers on proteinuria.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Numerically, the best out there, 52% change from baseline in terms of proteinuria reduction, 70+ % reductions in hematuria, and 70+ % reductions in Gd-IgA1. That bodes very well for POVI. I'll emphasize, Mike, the patient-centric attributes of delivery. Once monthly, small volume, 0.46 mils via an auto-injector. I think when you put all of that together, real excitement for me for what POVI may bring to patients once the PDUFA date comes and goes and we have the opportunity to launch.

[Michael Yee, Analyst at UBS]

Good. Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

You bet.

[Operator]

The next question will come from Tazeen Ahmad with Bank of America. Please go ahead.

[Tazeen Ahmad, Analyst at Bank of America]

Hi, good afternoon. Are you still planning on presenting additional data from the RAINIER study this year? If so, what level of data and where could that be? Secondly, for POVI and gMG, it's becoming an increasingly competitive space, so how are you thinking about what additional benefit your drug could provide into this space, either with efficacy, safety, or dosing frequency? Thanks.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Yeah. Yes, on RAINIER, we are planning to present data. The conferences don't like it when we suggest the name when submissions have been made, but acceptances haven't come through yet. Maybe I'll just leave it at, yes, we plan to present the full RAINIER IA data set. We're looking forward to do so, I'll say at a fall conference, and I'll leave it to your imagination for which one. On gMG and POVI, this one is really exciting. You gave me three options for why we're excited about POVI and gMG efficacy, safety, or patient benefits administration, all three. This is another one of those trifectas that Duncan has talked about. On efficacy, there is another molecule, a wild type TACI, so not engineered for optimal potency, binding affinity, or tissue distribution, that has already shown substantial efficacy benefit.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Remember, that's a wild-type TACI compared to POVI, which is an engineered TACI. That's on efficacy. On safety, POVI does not need to have a cycle on and a cycle off. That gives real benefit on safety, but that also has the secondary benefit on efficacy because you don't have that off period where the autoantibodies are allowed to return. The third is same thing, auto-injector. We have to figure out whether it's the 80 or 240, but in either case, it'll be auto-injector once monthly at home, low volume dosing. Of your options, I expect POVI to be better across the board on all three dimensions.

[Operator]

The next question will come from Phil Nadeau with TD Cowen. Please go ahead.

[Phil Nadeau, Analyst at TD Cowen]

Good afternoon. Thanks for taking our question. There's a lot of focus on the upcoming data from one of your competitors where we're going to get incremental sweat chloride reductions above TRIKAFTA. We're curious to hear Vertex's opinion on how you're going to interpret that data. Is there a level of sweat chloride reduction that would get your attention? Or Reshma, as you've suggested in the prepared remarks, is it more about simply the proportion of patients who get to less than 30 millimoles per liter and the exact reduction maybe isn't as meaningful because it can be influenced by things like baseline characteristics? Thanks.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Yeah. Phil, I think you have it right on our perspective. Where we sit today with ALYFTREK, we already know we can get 2/3 of patients to less than 30. That's that normal or carrier threshold. Furthermore, if you think about as all physiologic parameters do, there is a Gaussian distribution around that median sweat chloride of 30. If you superimpose across all age groups the ALYFTREK data on the carrier data, more than 75% of people across age groups overlap that distribution. With those kind of data, I think that the bar is exceptionally high and rests on getting more patients to less than 30. That is the mark, and that's the mark that we or anyone else has to hit in order to have a competitive medicine.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Of course, it goes without saying, it has to be safe, it has to be well-tolerated, it has to have good DDIs, it has to be once daily. On pure efficacy, it has to be a molecule that gets more patients to less than 30 in terms of sweat chloride.

[Phil Nadeau, Analyst at TD Cowen]

Thank you.

[Operator]

The next question will come from Terence Flynn with Morgan Stanley. Please go ahead.

[Terence Flynn, Analyst at Morgan Stanley]

Hi. Thanks for taking the question. I had another one on inaxaplin. I was just wondering if you can help set expectations for the upcoming AMPLIFY phase II trial, how to think about any read-through to AMPLITUDE. Thank you.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Yep. AMPLIFY is the study that's phase II. It's the expanded AMKD population. By that I mean it's the population with two APOL1 alleles. In one arm of the basket study, it's two APOL1 alleles diabetes, and in the other arm it's two APOL1 alleles and let's call it modest proteinuria. Low-grade proteinuria. The way I would frame it up is the study is completed. We are on track for us to be able to share results this fall. What I'd be looking for and looking to understand is, can we derive benefit on proteinuria when you have very modest proteinuria to start with? This is 0.2-0.7 g of protein as opposed to 0.7 g and above. Of course, it all comes down to what the mean entry baseline level of protein is.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Or in the case of diabetes, can we alter the proteinuria when you have a second kidney disease involved? These are questions worth studying, but they're clearly different populations than AMPLITUDE, which is why we specifically did not include them in the phase II original study of inaxaplin, and equally why we didn't include them in the phase III study called AMPLITUDE. We're super excited to look at these results. We're going to learn a lot. I'm very happy, and I think you'll see the wisdom of our approach, given what has happened in the field for others to keep these populations, which are expanded populations, separate and look at each one individually in this basket AMPLIFIED study.

[Operator]

The next question will come from Mohit Bansal with Wells Fargo. Please go ahead.

[Mohit Bansal, Analyst at Wells Fargo]

Okay, thank you very much for taking my question. Just maybe a question for Duncan, if you want to help with the prescription trends here for JOURNAVX. Obviously prescription growth is very strong, but how should we think about the prescribing behavior in terms of how many days of therapy physicians are writing? Has it changed at all in last few quarters or so? It does seem like you have good access, you have good prescription. This is probably a missing piece which could improve here. Thank you.

[Duncan McKechnie, Chief Commercial Officer at Vertex Pharmaceuticals]

Hi, Mohit. To answer your question specifically, as I think we've communicated before, in hospitals, the prescription duration is around about five days or so. In retail, it's around about 12, 14 days. On average, you net out at around about 10 or 11 days or so for each JOURNAVX prescription. Candidly, that dynamic has not changed since the launch because it's really driven by the dynamics of the institution that the patient's in rather than anything else. To answer your question simply, those are the numbers, and it has not changed over the last few months.

[Susie Lisa, SVP of Investor Relations at Vertex Pharmaceuticals]

Last question please, seth.

[Operator]

The last question will come from Ellie Merle with Barclays. Please go ahead.

[Ellie Merle, Analyst at Barclays]

Hey, guys. Thanks for taking the question. In terms of the DM1 program, what would be good data at the data update in the second half, and how are you thinking about it in the context of the broader competitive landscape in DM1? Thanks.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

Sure, Ellie. Maybe I can take that one. In DM1, as you know, there hasn't been a clear correlation between the various endpoints that others in the field have looked at, albeit with different approaches. What people have tended to do in their phase II studies to get an early read is look at splicing, a functional endpoint called vHOT, and another functional endpoint called QMT. vHOT is sort of how long does it take to open, close your hand, and QMT is a measure of muscle function. What I would say is that of all of those, splicing is an important one, and we certainly are looking at splicing. These measures of muscle function are also something that we're looking at.

[Reshma Kewalramani, CEO and President at Vertex Pharmaceuticals]

The reason I like this approach, compared to anything else has more to do with mechanism of action, and that has to do with the fact that it's an oligo, which others are also trying, but it's an oligo linked to a circular peptide to a nuclear localizing domain peptide, which we believe will allow it to get into the cell and get into the nucleus where it has to do its work. That is a plus, I would also say some of the other programs, in order to get into the cell, have used mechanisms that have some safety tolerability concerns, and that has not been a concern through the circular peptide program that we use. For the efficacy endpoints in phase II splicing, and we will also look at these QMT and vHOT endpoints, albeit in small numbers of patients.

[Operator]

That will conclude our question and answer session as well as our conference call for today. Thank you for your participation. A replay will be available shortly after the call concludes by dialing 1-855-669-9658 or 1-412-317-0088 using replay access code 10208186. Thank you for attending today's presentation. You may now disconnect.

Participants

Executives

• Susie Lisa, SVP of Investor Relations
• Reshma Kewalramani, CEO and President
• Duncan McKechnie, Chief Commercial Officer
• Charlie Wagner, COO and CFO

Analysts

• Salveen Richter, Analyst at Goldman Sachs
• Geoff Meacham, Analyst at Citibank
• Jessica Fye, Analyst at JPMorgan
• Cory Kasimov, Analyst at Evercore ISI
• Brian Abrahams, Analyst at RBC Capital Markets
• Evan Seigerman, Analyst at BMO
• Michael Yee, Analyst at UBS
• Tazeen Ahmad, Analyst at Bank of America
• Phil Nadeau, Analyst at TD Cowen
• Terence Flynn, Analyst at Morgan Stanley
• Mohit Bansal, Analyst at Wells Fargo
• Ellie Merle, Analyst at Barclays