Vertex Pharmaceuticals Q2 2025 Earnings Report

Vertex Pharmaceuticals EPS Results

• Actual EPS: $4.52
• Consensus EPS: $4.24
• Beat/Miss: Beat by +$0.28
• One Year Ago EPS: -$12.83

Vertex Pharmaceuticals Revenue Results

• Actual Revenue: $2.94 billion
• Expected Revenue: $2.90 billion
• Beat/Miss: Beat by +$41.09 million
• YoY Revenue Growth: +11.30%

Vertex Pharmaceuticals Announcement Details

• Quarter: Q2 2025
• Date: 8/4/2025
• Time: After Market Closes
• Conference Call Date: Monday, August 4, 2025
• Conference Call Time: 4:30PM ET

Vertex Pharmaceuticals (NASDAQ:VRTX), a biotechnology company, engages in developing and commercializing therapies for treating cystic fibrosis (CF). It markets TRIKAFTA/KAFTRIO for people with CF with at least one F508del mutation for 2 years of age or older; SYMDEKO/SYMKEVI for people with CF for 6 years of age or older; ORKAMBI for CF patients 1 year or older; and KALYDECO for the treatment of patients with 1 year or older who have CF with ivacaftor. The company's pipeline includes VX-522, a CFTR mRNA therapeutic designed to treat the underlying cause of CF, which is in Phase 1 clinical trial; VX-548, a non-opioid medicine for the treatment of acute and neuropathic pain which is in Phase 3 clinical trial; Exa-cel, for the treatment of sickle cell disease and transfusion-dependent beta thalassemia which is in Phase 2/3 clinical trial. In addition, it provides inaxaplin for the treatment of APOL1-mediated focal segmental glomerulosclerosis and co-morbidities, such as hypertension which is in single Phase 2/3; VX- 880 and VX-264, treatment for Type 1 Diabetes which is in Phase 1/2 clinical trial; VX-970, which is in Phase 2 clinical trial for the treatment of cancer; and VX-803 and VX-984 for treatment of cancer in Phase 1 clinical trial. Further, it sells the products to specialty pharmacy and specialty distributors in the United States, as well as retail pharmacies, hospitals, and clinics. Additionally, the company has collaborations with CRISPR Therapeutics AG.; Moderna, Inc.; Entrada Therapeutics, Inc.; Arbor Biotechnologies, Inc.; Mammoth Biosciences, Inc.; and Verve Therapeutics., as well as collaborations with Tevard Biosciences to develop novel tRNA-based therapies for duchenne muscular dystrophy. Vertex Pharmaceuticals Incorporated was founded in 1989 and is headquartered in Boston, Massachusetts.

Vertex Pharmaceuticals Q2 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Vertex delivered $2.96 billion in Q2 revenue, up 12% year-over-year, driven by strong cystic fibrosis demand and contributions from CASJEVY and Genavix.
• Positive Sentiment: ElefTrek was approved in the U.S., U.K., EU and Canada with reimbursement secured in England and ongoing negotiations in other markets, while the next-gen VX-828 CFTR regimen is on track to begin CF patient dosing before year end.
• Negative Sentiment: The Phase II post-bunionectomy study of Nav1.8 inhibitor VX-993 failed to meet its primary endpoint, leading to discontinuation of acute pain monotherapy and a shift in focus to combination strategies and diabetic neuropathy trials.
• Positive Sentiment: Zamylacel cell therapy for type 1 diabetes showed that all 12 patients achieved A1c <7% at one year and 10 of 12 became insulin‐free, with pivotal study enrollment completing soon and global filings expected in 2026.
• Positive Sentiment: POVITACEPT’s Phase III RAINIER trial in IgA nephropathy is on track to finish enrollment by year end, setting up a 2026 interim analysis for potential accelerated U.S. approval alongside a planned Phase II/III in membranous nephropathy.

Presentation

[Operator]

Good day, and welcome to the Vertex Pharmaceuticals Second Quarter twenty twenty five Earnings Call. All participants will be in a listen only mode. After today's presentation, there will be an opportunity to ask questions. Please note that this event is being recorded. I would now like to turn the conference over to Susie Lisa. Please go ahead, ma'am.

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

Good evening, My name is Suzie Lisa. And as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our second quarter twenty twenty five financial results conference call. On tonight's call, making prepared remarks, we have Doctor. Reshma Kewalramani, Vertex's CEO and President Duncan McKechnie, Chief Commercial Officer and Charlie Wagner, Chief Operating and Financial Officer. We recommend that you access the webcast slides as you listen to this call.

[Susie Lisa, SVP - 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. These statements, including without limitation, regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, beta thalassemia, and moderate to severe acute pain, our pipeline, 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 will now turn the call over to Reshma.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

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 in pivotal development and progressing the earlier stage R and D pipeline. We continue to reach more patients with more products and delivered $2,960,000,000 in revenue in the second quarter, representing 12% growth versus Q2 twenty twenty four. We remain sharply focused on commercialization across multiple disease areas and expansion of our patient reach.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

We are pleased with the first six months of launch performance as well as physician and patient feedback on both Elephtrak in CF and GERNAVEX in acute pain. As well as the building global momentum for KASJEBI, our gene edited therapy for sickle cell disease and beta thalassemia. In addition to this commercialization focus, research and clinical progress remain paramount. And to that end, we continue to rapidly advance the four programs in pivotal development and are working with urgency to begin our fifth in primary membranous nephropathy. Before I cover R and D highlights for the quarter, I would like to acknowledge our CSO, David Alschuler's retirement a year from now and the planned CSO transition to Mark Bunnich, our current SVP and Global Head of Research.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

David will be retiring from Vertex effective 08/01/2026 after an incredible thirteen 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 have advanced from research through commercialization including ORKAMBI, SYMDEKO, TRIKAFTA and Alluvtrac. Our disease sandbox has broadened and we successfully advanced the scientific breakthroughs that became KASJEVY and JERNAVICS. In an industry with notoriously low R and D success rates, David's teams delivered remarkable achievements year after year.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

David is a world renowned physician scientist who's known for his creative and critical thinking, penchant for debate, and commitment to building teams. On a more personal level, I know him as a deeply passionate Vertexian, dedicated physician and valued member of the executive team. As mentioned in our earnings release, as part of this planned transition, I am delighted to announce that Mark Bonage will assume the role of EVP and Chief Scientific Officer effective 02/01/2026, after which David will work with Mark to ensure a smooth transition. Mark joined Vertex and has worked alongside David since 2016. Since that time, Mark has held increasing senior leadership roles across research starting as SVP Site Head Boston Research and most recently as SVP Head of Global Research overseeing all five of Vertex's research sites.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Under Mark's leadership, we advanced many molecules to the clinic including Kaschevy and Gynavix, inaxiplin for AMKD, VX828 for CF, VX670 for DM1 and VX47 for autosomal dominant polycystic kidney disease. Mark was also intimately involved in the diligence that led to the Alpine acquisition, which brought povitacicept to Vertex. I look forward to celebrating David's retirement and welcoming Mark as CSO when the time gets closer. Returning then to R and D highlights. I'll limit my comments to the pipeline programs with the most significant new information to share, specifically CF, pain, type one diabetes and the renal programs.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Starting with CF. As of July, we've gained approval for AlifTrek in The U. S, U. K, EU and Canada. We've also secured reimbursement for AlifTrek in England and will add Ireland shortly.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Patients in Germany and Denmark already have reimbursed access due to existing agreements and provisions. And across other EU member nations in Canada, we are working with reimbursement bodies to secure access for eligible patients as quickly as 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 three point zero or NG three point zero regimen is next on deck. The backbone of the NG three point zero combination is VX-eight twenty eight, the most efficacious CFTR corrector that we have ever studied in vitro and brought to the clinic.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

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-eight twenty eight regimen before the end of this year. Finally in CF, on VX-five twenty two I am pleased to note that the Data Safety Monitoring Committee has completed its review and is endorsed restarting trial. We're now in the process of working to resume dosing in the MAD portion of the Phase onetwo for the 5,000 or so patients who cannot benefit from our CFTR modulators and expect to do so in the near term. Now shifting to pain. First in peripheral neuropathic pain or PNP.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

We had a productive end of phase two 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, we will not be initiating an LSR trial at present. Instead, in light of the discussions and clear agreement with the FDA regarding approval requirements for diabetic peripheral neuropathy or DPN, we will begin a second DPN Phase three study shortly in order to secure DPN as our first PNP indication for sousetrigene. Recall we have breakthrough therapy designation for the DPN indication.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Also note that our first phase three study of sousetrogene in DPN is already well underway And with the near term initiation of the second DPN study, our goal is to complete enrollment of both of these trials by the 2026. We look forward to working with the agency to secure 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 acute pain and VX-nine ninety three, another Nav1.8 inhibitor. This afternoon we shared top line results from the Phase two trial of this molecule in the post bunionectomy setting. To recap, as part of our serial innovation strategy, we developed VX-nine ninety three with three main goals: First, to have an IV option.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Second, to provide additional Nav1.8 inhibitor candidates for potential use as co formulation with future Nav1.7 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 nine ninety three, we powered the phase two trial with the goal of detecting a treatment effect higher than previously achieved. This phase two trial included a placebo group, three VX993 dosage arms and a hydrocodone reference arm. The primary endpoint was SPID-forty eight compared to placebo.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

The results showed that VX-nine ninety three was safe and well tolerated with no related SAEs and an overall profile consistent with the placebo arm. The placebo effect was well controlled and desired nine ninety three exposures were achieved with adequate separation between doses. On efficacy, VX-nine ninety three did not meet the primary endpoint and did not show statistical significance at the point zero five level. The SPIT-forty eight 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 Nav1.8 inhibitor clinical studies in acute pain suggest we are at the high end of the Nav1.8 dose response curve for acute pain in the post bunionectomy setting.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

As such, we do not plan to advance VX993 as monotherapy in acute pain because we do not expect that it will be superior to our Nav1.8 inhibitors. We do plan to complete the ongoing VX993 study of DPN to further define the exposure response relationship and maximal efficacy of Nav1.8 inhibitors in this chronic pain indication. To close out on pain, a quick word on our Nav1.7 inhibitor program. We're very encouraged by our strong preclinical progress in this program and look forward to advancing candidates for use alone or in combination with Nav1.8 inhibitors. Transitioning now to type one diabetes.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Zemila Cell will soon complete enrollment and dosing of its pivotal study, positioning us for global regulatory submissions in 2026, if the data are supportive. Recall we expect about sixty thousand severe type one diabetic patients may potentially benefit from this first Zemila Cell submission. In June at the ADA meeting and concurrently in the New England Journal of Medicine, positive data for Zamyla cell in type one diabetes were presented that continue to demonstrate this cell therapy's transformative potential. All twelve patients with at least one year of follow-up who received a full dose of Zamylacil as a single infusion achieved ADA recommended target hemoglobin A1c levels less than 7%. Freedom from severe hypoglycemic events during the evaluation period, and greater than 70% time in range.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Remarkably, 10 of the 12 patients at twelve months were insulin free, a testament to the potential transformative benefit and durability of this therapy. We also continue to make preclinical progress on our approaches to cloak the same VX-eight 80 cells from the immune system, including improved immunosuppressive regimens, gene editing to produce hypo immune islet cells and novel immunoprotection to encapsulate these cells. We look forward to updating you as these programs advance. Finally, few updates on our kidney portfolio, which now has clinical stage programs in four diseases: IgA nephropathy, AMKD, membranous nephropathy, ADPKD or autosomal dominant kidney disease. Starting with povitacept, a number of autoimmune diseases are driven by uncontrolled B cells.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

By controlling B cells, POV is designed to restore immune balance for patients and holds the potential to have transformative benefit across multiple disease states. POV was specifically engineered for better tissue penetration and to deliver optimized targeted dual inhibition of the BAF and APRIL cytokines, which both play a key role in the pathogenesis of B cell mediated autoimmune diseases. First up for POVY is IGAN. We disclosed previously that we completed enrollment of the interim analysis cohort in the RAINIER Phase III trial. Today we are pleased to share that we are on track to complete enrollment of the full RAINIER study by the end of this year.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

With regard to the interim analysis cohort, once this group completes thirty six weeks of treatment, we will conduct the interim analysis and if positive will file for potential accelerated approval in The U. S. In the 2026. To close out on IgAN, studies to support the launch of POV for at home self administration with a subcutaneous auto injector are also well underway. Next and consistent with its pipeline and a product potential, the second disease state where we believe POV can provide B cell control is primary membranous nephropathy.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Based on strong emerging data from the RUBI-three study, we completed our end of phase two meeting with the FDA and reached agreement on a phase twothree adaptive study for traditional approval of povi versus standard of care with the primary endpoint of complete remission at seventy two weeks. This Phase twothree study will begin later this year. And third, we have prioritized additional diseases in which we believe povi 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 WAHA. So to summarize, our current priority disease areas are IgAN, membranous nephropathy, generalized myasthenia gravis and WAHA.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And we are deprioritizing other indications at this time. Next on enaxaplin for APOL1 mediated kidney disease. We remain on track to complete enrollment in the interim analysis cohort of the AMPLITUDE pivotal trial in primary AMKD this year. Of note, while we are able to enroll more adolescent patients, we have hit an important milestone in this study, where the target number of ten-seventeen year old AMKD patients has now been achieved. After completing enrollment in the IA cohort, these patients will be followed for forty eight weeks of treatment, at which point we will conduct the interim analysis and if positive, will be poised to file for potential accelerated approval in The U.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

S. The AMPLIFIED study, a phase two proof of concept study in patients with AMKD and comorbidities including type two diabetes is also underway. And this trial is on track to complete enrollment by the 2025. To close on our kidney pipeline is VX407 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 three hundred thousand patients with ADPKD and there are no approved therapies that treat the underlying cause of this disease.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

We believe about ten percent of patients with ADPKD may be eligible for treatment with VX407. This quarter we'll begin the VX407 proof of concept trial which is a fifty two week single arm study in twenty four patients that will evaluate the efficacy of VX407 as measured by height adjusted total kidney volume. In closing, Vertex has multiple Phase III programs well underway that are poised for accelerated or traditional approval. These trials have either already completed enrollment or are on track to do so in 2025. They each serve a disease with high unmet need.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And they've secured multiple regulatory designations including Fast Track, Breakthrough, Regenerative Medicine or RMAT, PRIME amongst others. All of which positions us for multiple regulatory submissions in 2026 and early twenty twenty seven with potential approvals and launches to follow. Accordingly, as we drive to achieve our R and D milestones, we're 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.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Thanks very much Reshma. I will focus my comments tonight on the CF franchise including the launch of ElifTrex in The US, the continuing global launch of Kasjevi and The US launch of Genavix in moderate to severe acute pain. Starting with CF. Our CF franchise continues to deliver strong results as we grow the number of eligible patients taking our CFTR modulators.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

We continue to make progress with younger patients, patients with rare mutations and patients in new geographies. The overall market outlook is also supported by the fact that patients are living longer. Now turning to The US launch of AlifTrek, our fifth therapy approved to treat the underlying cause of CF. We believe AlifTrek is the best CF modulator available for eligible patients. As we've discussed on prior calls, versus Trikafta, ElefTrex provides further improvements in CFTR function as measured by sweat chloride, is indicated for additional mutations not covered by the Trikafta label, and offers the convenience of once daily dosing.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

In The US, the early launch of ElefTrek 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 ElefTrek, as well as those who previously discontinued one of our other CFTR modulators. For patients currently on Trikafta many have been on therapy for multiple years, have experienced incredible clinical benefit and therefore have considerable brand loyalty. In this context the pace of transitions is steady as these patients continue their conversations with physicians and make decisions that balance the short term logistics of augmented liver monitoring with the Liftrec 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 LiftRec clinical success that physicians and patients are sharing, whether they were naive to a CFTR modulator, are returning to therapy, or have recently transitioned from TRIKAFTA.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

We continue to expect the majority of patients who are currently on CFTR modulator therapy will transition to ElefTrek over time given its multiple benefits. We're also now in the process of launching Elefrec in England, following our recent reimbursement agreement with NHS England, as well as in Germany and Denmark. Transitioning to Casjevi, our transformative, one time treatment for patients with sickle cell disease and beta thalassemia. The CASJEVY launch is 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 two, we've seen an acceleration across the board in patient initiations, cell collections and infusions.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

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 Kashyvi worldwide. Regarding reimbursement, 10 countries now provide access to Kashyvi, including The US and several European and Middle Eastern countries. In terms of our CASJEVY launch metrics, I'm pleased to report that since launch and through the 2025, firstly, we have met our authorised treatment centre goal with more than 75 ATCs 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 two fifty patients have been referred by their physicians to an ATC to initiate the treatment process.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Approximately one hundred and fifteen patients have had their first cell collections, including thirty five first cell collections in quarter two twenty twenty five. And finally, a total of twenty nine patients have completed their treatment journey and received their infusions of CasJevi edited cells, including 16 patients in the 2025. Now shifting to the launch of Genavix in moderate to severe acute pain. Genavix received FDA approval on January 30 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.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

We're pleased with the rapid pace of payer coverage, P and T committee reviews, formulary adoption, breadth of usage and hospital uptake. We're also very encouraged by the broad range of positive Genavix experiences reported by both physicians and patients. I'll detail several key elements of our ongoing launch. One, we continue to make great progress with payers, which is a testament to their appreciation for the Genavix clinical profile and the importance of offering a novel non opioid option in the treatment of acute pain. As of mid July, across commercial and government payers, approximately one hundred and fifty million lives, or roughly half of all lives covered in The US, have reimbursed access to Genovix.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

With commercial payers, our negotiations continue to progress very favourably. We recently reached a formal coverage agreement with a second large national pharmacy benefit manager to make Genavix available to their customers, representing an incremental 22,000,000 commercial lives. As a result, we now have formal coverage from two of the three large national PBMs and anticipate adding the third before year end. In addition, we now have national agreements in place with the two largest hospital group purchasing organisations to make Genavix available to acute pain patients in their network member hospitals. In Medicare, we continue to engage with plans to secure coverage.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

And for Medicaid patients, through mid July, we added six state plans since our quarter one earnings call for a total of 16 states with legislation that ensures access is available without prior authorization or step edit requirements. We continue expect the coverage across commercial, Medicare and Medicaid payers will continue to expand through 2025. Two, we are prioritizing the P and T committees at approximately 150 health care systems and roughly 2,000 hospitals. The majority of these 2,000 hospitals ladder up to one of the 150 health care systems. Last quarter we disclosed that more than a third of these target health care systems had taken steps to initiate the P and T review of Genavix.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

I'm very happy to report that over a third of these priority target healthcare systems have now added Genavix 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 we're targeting have also added Genavix to their formularies, protocols or order sets. Three, prescribing patterns 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 the 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.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

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 multibillion 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.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

Thanks, Duncan. Vertex's Q2 twenty twenty five revenue growth accelerated as expected and our results demonstrate our consistent strong performance and attractive growth profile. Second quarter twenty twenty five total revenue increased 12% year over year to $2,960,000,000 U. Revenue growth of 14% year over year was driven in CF by ongoing patient demand and favorable gross to net versus prior year, and also included contributions from CASJEVY, GERNAVIX, and collaboration revenue.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

As expected, revenue outside The US rebounded this quarter and was up eight percent year on year, including healthy CF growth and a contribution from CASJEVY. Included in total revenue and the regional growth rates was $30,000,000 of CASJEVY revenue, 12,000,000 from Gernavix, and $21,000,000 of collaboration revenue. Second quarter twenty twenty five combined non GAAP R and D, acquired IPR and D, and SG and A expenses were $1,240,000,000 compared to $5,430,000,000 in the 2024. Excluding ALPN related acquired IPR and D, non GAAP operating expenses increased 24% year on year, driven primarily by the continued advancement of our broad pipeline, including clinical trials for IgAN, pain, and type one diabetes, as well as the build out of commercial capabilities in pain. Second quarter twenty twenty five acquired IP R and D expenses were $2,000,000 compared to $4,400,000,000 in the 2024, which included the acquisition of Alpine Immune Sciences.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

Second quarter twenty twenty five non GAAP operating income was 1,330,000,000.00 compared to a non GAAP operating loss of $3,150,000,000 in the 2024. Second quarter twenty twenty five non GAAP effective tax rate was 19.4%. Second quarter twenty twenty five net income was $1,200,000,000 compared to a net loss of $3,300,000,000 in '24. Second quarter twenty twenty five non GAAP earnings per share were $4.52 compared to a loss per share of $12.83 in the 2024, primarily due to higher revenue and disciplined operating spend as well as the impact of the Alpine AIP R and D expense in the 2024. We ended the quarter with $12,000,000,000 in cash and investments after deploying approximately $395,000,000 to repurchase more than 8 and 65,000 shares in the second quarter.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

In May, we announced a new $4,000,000,000 share repurchase program, building upon our existing $3,000,000,000 share repurchase program, which was authorized in 2023 and had $570,000,000 remaining as of June 30. 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 to $12,000,000,000 representing growth of approximately eight percent 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 AlifTrex in The U.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

S, followed by other regions later this year. Recall that Aliftrec carries a meaningfully lower royalty burden than Trikafta and extends our composition of matter patent protection to 2,039. Revenue guidance also includes Kasgevi 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 Kasgevi revenue. As patient initiations and cell 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.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

In addition, guidance reflects additional revenue contribution from Gernavix in the second half due to gains in sustainable payer 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 and D, acquired IPR and D and SG and A expenses in a range of 4,900,000,000.0 to $5,000,000,000 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 100,000,000 in projected IP R and D charges.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

We will continue to invest a majority of our operating expenses into R and D, given the momentum in our multiple mid- and late stage clinical development programs with four and soon to be five Phase III studies ongoing and multiple Phase IIs. In addition, given progress with respect to reimbursement and access and the size of the opportunity for Gernavix, as Duncan mentioned, we increasing our investment in marketing and commercial initiatives to support the launch 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.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

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 twenty five, growing and diversifying our revenue with the launch of two new products in The U. S, ElifTrac and Gernavix, continuing the global launch of Kasjevi and making significant pipeline progress across the portfolio. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

I'll now ask Susie to begin the Q and A.

[Operator]

We will now begin the question and answer session. And your first question today will come from Jessica Fye with JPMorgan. Please go ahead.

[Jessica Fye, MD & Equity Research Analyst - Biotechnology at JP Morgan]

Hey, guys. Good afternoon. Thanks for taking my questions. I had a couple on pain. So for the additional commercial efforts behind Geronavix, was that increase always planned as coverage came into place?

[Jessica Fye, MD & Equity Research Analyst - Biotechnology at JP Morgan]

Or is that a reaction to what you're seeing as you kind of continue to launch so far? And then for Suzetra gene in DPN, I think you said you'd complete enrollment in both Phase 3s by the 2026. I'm just curious, can we expect enrollment completion for the first Phase three trial much sooner than that? Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Jess, this is Reshma. Let me split that into two parts. I'll take the second part first and then I'll ask Duncan to comment. Yes, I think that the first DPN might well enroll ahead of the second DPN because it started ahead of time and the enrollment is going very well. I will ask Duncan to comment on GERNAVIX.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

As you know, it's really important to secure payer coverage as we ramp commercial efforts behind that. Duncan, any more comments on how you're thinking about commercialization?

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Sure. And thank you for the question, Jess. So obviously, we're now about five months or so into the launch and I'd say there's sort of three factors that are really driving our thinking. Firstly, as Reshma just alluded to, we're very pleased with the progress we're making with payer coverage on hospital formularies, particularly considering how lengthy P and T processes can be. Secondly, we're receiving incredibly positive feedback from physicians and patients on how well Genavix is working for them clinically.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

And thirdly, we've seen both in the face to face arena with our sales organization as well as in the digital arena, we've seen Genavix to be incredibly promotionally responsive. So based on those three factors, yes, we are thinking that now is the right time to augment our spend in marketing and field support. I would add the last comment that we do anticipate that field support would still sit within the specialty model.

[Jessica Fye, MD & Equity Research Analyst - Biotechnology at JP Morgan]

Thank you.

[Operator]

And your next question today will come from Salveen Richter with Goldman Sachs. Please go ahead.

[Salveen Richter, Biotechnology Equity Research at Goldman Sachs]

Good afternoon. Thanks for taking my questions. So with regard to the strategy in pain here, can you help us understand now that you won't be moving forward with a broad PNP label today, maybe what your plan is around running these DPN trials and then whether it's taking next generation drugs or so forth to move into LSR or any of the other smaller indications like small fiber neuropathy or some of the others? And then secondly, in light of the Joronevax launch that's progressing here, maybe help us understand how to think about gross to net over the balance of the year and beyond. Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Sure thing. Sami, let me take those questions. With regard to our plans in PNP, it remains our goal to get a broad PNP indication. Our conversations with the FDA at this recent meeting were very productive. They were open minded.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

They were very open to ongoing discussions, but it was equally clear that at this time, they do not see a path to PNP. That's just not where they are. However, we have a clear agreement on DPN. So the first order of business for us is to secure the DPN indication, hence the, start of the second DPN study. We can broaden that indication and we had really good conversations of how that could occur.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

As you point out, small fiber neuropathy that could be one broadening of the label. It 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 real big prize for us remains broad PNP.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And we think that the way to get there might well be with ongoing conversations with the agency and with our NAV 1.7 plus NAV 1.8 portfolio. So what I would say is here now secure VPN, work to broaden the indication and might be one step at a time, SFN is one example of a next indication and then broaden all the way to PNP as we are able to have more conversations with the agency. Any comments that you want to add to gross to net, Charlie?

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

Yes. I mean on gross to net, obviously it's elevated in the early months of the launch. We had said all along that volume would ramp up ahead of revenue with the most significant revenue contribution in the second half of the year. Again, 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.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

Gross to net will normalize over the course of the year. But beyond that, I'm not going to provide further detail.

[Operator]

Your next question today will come from Jeff Maycomb with Citibank. Please go ahead.

[Geoff Meacham, Managing Director at Citi]

Good afternoon guys. Thanks for the question. Just have a couple also on pain. Rich, I want to ask you about the implications of the FDA feedback and the September data. I guess the first question is, could the strategy in chronic pain involve to now include broader indications such as joint pain, etcetera, in other words, like outside of PMP?

[Geoff Meacham, Managing Director at Citi]

And then on September, do you think it makes sense to look at a more of a pan 1.7 mechanism, at least involving maybe multiple isoforms just to try to maximize the treatment effect? I wasn't sure kind of what the strategy is there from a pipeline perspective. Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Sure thing. Let me do chronic pain first and then we'll come back to nine ninety three. Jeff, on chronic pain, I think the approach is, as we just described for the previous question, DPN first, then add on single indications, but work with the agency to get to broad PNP. We've had these discussions, they've left us with some questions. We need to talk with each other some more.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

On musculoskeletal, which is I think the point you were raising, I do think that this class of compounds can work based on the data that we saw, for example, with VX-one 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 September and what the plan is with regard to acute pain, the big next step for us on acute pain, obviously launch GERNAVIX. We have our IV formulation with the September version and we now have two potential molecules that could be used with the NAV17 molecule that's making very good progress on the bench.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

But I would say the big next thing to look for us to do in acute pain is combination NAV1718. Remember, preclinically what we see is a synergistic not additive effect. And so that's going to be really important. I hope that helps.

[Geoff Meacham, Managing Director at Citi]

Okay. Yes. Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Sure thing.

[Operator]

And your next question today will come from Ellie Merrill with UBS. Please go ahead.

[Ellie Merle, ED - Biotech Equity Research at UBS Group]

Hey guys. Thanks so much for taking the question. Just two on GERNAVEX for me. So just first, can you comment a little bit more on how the progress in 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? And then just second on gross to net, I know you mentioned that there's been use of patient support programs initially in the launch.

[Ellie Merle, ED - Biotech Equity Research at UBS Group]

Just what we should expect going forward in terms of the use of the patient support programs as we think about gross to net from here? Thanks.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

You bet. Ellie, let me take the first half of your question and I'll ask Duncan to talk to you a little bit about the PSP patient support programs. So formulary coverage Ellie is going really well hospitals and with the integrated delivery networks and some extremely some very large prominent programs with lots of procedures have added Genavix, frankly faster than I would have expected given how long PNP committees normally take. With regard to evidence generation, I'll speak to a couple of studies that we're running in terms of life cycle management. We have a Phase four trial in a variety of, let's call it plastic surgery indications and another one in a variety of orthopedic conditions.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And the emerging data look really good, not only in terms of pain control, but also in terms of reducing opioid use and having patients go through an opioid free journey. And I expect that you're going to see us presenting those papers in upcoming conferences. Duncan, can I ask you to make a couple of comments on the PSP program?

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Yes, sure. So just to step back, we put in the PSP program in place in order to provide a seamless experience for patients in advance of payer coverage. And as we noted in our prepared remarks and as Charlie commented on a couple of minutes ago, as we see our coverage with payers increasing over the course of this year, that program becomes unnecessary and essentially we will retire that program as we see national coverage. Obviously, we're not quite at that point yet, but that is the plan by the end of the year is to conclude that program. And as Charlie alluded to earlier, I don't think we're providing specific gross to that guidance with regard to that program.

[Ellie Merle, ED - Biotech Equity Research at UBS Group]

Got it. Thanks.

[Operator]

And your next question today will come from Tazeen Ahmad with Bank of America. Please go ahead.

[Tazeen Ahmad, MD - US Equity Research at Bank of America]

Hi, guys. Maybe to switch the subject up a little bit. Can I ask a couple on POVY? Is it your plan to launch with the auto injector when go you live on iGAN? And then in terms of the indications that you're prioritizing on a go forward basis, you've included, gMG.

[Tazeen Ahmad, MD - US Equity Research at Bank of America]

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.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Yes. Tazim, on povi, you have it exactly right. We plan to launch in the IGAN indication, which of course is the first indication with the auto injector. And just to confirm, gMG, you mean myasthenia not membranous?

[Tazeen Ahmad, MD - US Equity Research at Bank of America]

Yes, that's correct.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Yes. The myasthenia indication is very exciting for us and it is one of the ones that we've prioritized. Maybe four lines of reasoning 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.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And as you know, 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 autoantibodies to redevelop and continue to cause damage at the junction. The Tovy mechanism is a dual April bath inhibition, I. E. It dampens down the B cells, both the earlier B cells and the plasma cells, which is of course the underlying cause of myasthenia.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

The second is emerging data in this class is a very appealing and points to a strong treatment effect. The third is that I expect that the regulatory pathway is going to be an efficient development pathway. And the last is, as you put all of this together and you think about the underlying cause of 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 myasthenia.

[Operator]

And your next question today will come from Evan Sagerman with BMO Capital Markets. Please go ahead.

[Evan Seigerman, MD & Senior Research Analyst at BMO Capital Markets]

Hi guys. Thank you so much for taking my question. Another follow-up kind of on the pipeline and the product for PoVY. Can you kind of walk me through the rationale for prioritizing the indications such as gMG, autoimmune hemolytic anemia, of course, IGAN? Was it clinical data, early data kind of pre clinically or commercial considerations that drove these decisions?

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Evan, this is Reshma. Let me take that one for you. All of the above. So as you know, RUBI-three and RUBI-four give us good insight into a basket of renal indications and a basket of heme indications. And we have emerging data, for example, in membranous, which points us to best in class potential in that disease, which has no other treatment.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And it gives us an indication of best in class potential for WAHA or warm autoimmune hemolytic anemia. So it is indeed emerging data from our own datasets. Sometimes as in the case with myasthenia, it's emerging data from the class, taking into account that POVY has this benefit of being engineered to be best in class. So, there's the emerging data. There is also consideration, 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.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

All of those have gotten into us prioritizing IgAN, membranous, myasthenia and WAHA. And just to close out on that prioritizing for myasthenia 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 dataset that we expect towards the end of this year. I hope that helps.

[Evan Seigerman, MD & Senior Research Analyst at BMO Capital Markets]

Great. Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

You bet.

[Operator]

And your next question today will come from Divya Rao with Cowen and Company. Please go ahead.

[Divya Rao, Vice President at Cowen]

Hi, this is Divya on for Phil. I just had two questions on Jirnavix. One is just a little bit technical, but 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, the free drug. And the second is I was curious if you could comment on the split of Drinabix scripts and how much are coming from maybe retail pharmacies versus hospitals And any insights into the type of physicians prescribing Drunavix? Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

You bet. Duncan, can I ask you to comment first maybe quickly on how free samples work? And then a little bit more detail on physician types and split between hospital and retail.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Absolutely.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Thank you for the question. So in terms of the free samples, these are provided through the patient's physician. They're supplied to the patient by the physician and they do not show up in the retail data. In terms of the split of retail versus hospital prescriptions, about 65% of the prescriptions are in the weekly IQVIA data that you see for retail prescriptions. The remainder are in the hospital space.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

And in terms of the types of physicians using Genavix, it is a broad range. It's about 15,000 physicians are now prescribing Genavix. We're seeing many more patients sorry, physicians, hundreds of physicians come on each week. And the types of physicians are general surgeons, plastic surgeons, orthopedic surgeons, dentists and anesthesiologists. And they are prescribing for a broad range of treatments consistent with the label, everything from sprains and strains through reconstructive surgery to total knee replacements.

[Operator]

And your next question today will come from David Risinger with Leerink Partners. Please go ahead.

[David Risinger, Senior Managing Director, Biopharma at Leerink Partners]

Yes. Thanks very much. So I have two questions please. First on Geronavix, I was wondering if you could comment on the number of commercial lives with unrestricted access. And then second, with respect to VX-eight twenty eight, could you please provide a little bit more color on your expectations for the profile of this candidate? Thanks very much.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Sure, thanks, Gabe. Let me take the eight twenty eight question and then I'll ask Duncan to comment on Geronavix. So eight twenty eight, as I said in my prepared remarks, it is the most, efficacious CFTR corrector that we've ever studied in vitro that we've advanced into the clinic. I expect that, it is going to have most, if not all patients get to carrier levels of sweat chloride. I expect a good safety profile.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

I expect a good DDI profile based on the preclinical data. To wrap up on 08/28, we do continue to track towards initiating the CF cohort before the end of this year. Duncan, Jurnavix?

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

Yes. Thank you for the question, David. So obviously, we are extremely pleased with 150,000,000 lives covered in just a few months. To get to the answer to your question, 84,000,000 of those lives are unrestricted. I can tell you that every single contract we have negotiated to date, every single one of those is for unrestricted access, which we define as you know as no prior authorization or step edit.

[Duncan McKechnie, EVP & Chief Commercial Officer at Vertex Pharmaceuticals]

So what that means, of course, is that based on high demand for Genavix, there are of course some plans that have put in place coverage of Genavix in advance of any agreement with us. And in those situations, there can be a prior authorization or step edit. Obviously, we'll be working to reduce that ratio over the balance of the year. But at this point, 150,000,000 lives covered, two out of the three PBMs are covering and we're working with the third as you'd expect. And every single agreement we have done is for unrestricted access.

[Operator]

And your next question comes from William Pickering with Bernstein. Please go ahead.

[William Pickering, Senior Analyst - US SMID-Cap Biotech at Bernstein]

Hi, thank you very much for taking my question. Just a couple from me. One was on No Pain Act. I was a little bit surprised to see that Gernavix was not included in the draft rule that was published, I guess, it's about a month ago. And any kind of concerns or kind of process to get that on the list for 2026?

[William Pickering, Senior Analyst - US SMID-Cap Biotech at Bernstein]

And then second was with Kashyvi. Just 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.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Thing. Well, let's do Kashyvi first. As you heard Duncan talk to on his prepared remarks, we are seeing an acceleration in the momentum. And part of that is simply having patients at various points in their journey. So there are a lot more patients who've now had cells collected and ready to be infused and that's what we're looking forward to in the back half of this year.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

With regard to cycle time, yes, I do think that there is opportunity for improvement. I'd say, I think we said it was going to be somewhere around four to five months for the full process. 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 the cycle time comes down as we make progress overall.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

On the No Pain Act, so you know that the draft proposal included some language that says that because GERNAVIX is not specifically indicated for postsurgical pain, it was not included on the draft list. Clearly, Geronavix is indicated for postsurgical pain. Indeed, both Phase three RCTs were in postsurgical pain, one in abdominoplasty, one in bunionectomy. I think we're going to be able to get this confusion resolved. And I do expect that that GERNAVIX will be on the final list, which is due this fall.

[Operator]

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

[Terence Flynn, Equity Research Analyst at Morgan Stanley]

Great. Thanks so much for taking the questions. Just wondering, had two questions. The first is on Jirnavix, if you can just confirm if there's any inventory in the second quarter that we need to think about as we do the math on a dollar per script basis. And then on the September Phase II data, just wondering if you think you need to make tweaks to the preclinical models at all here, given that data and particularly as you think about the NAV 1.7 assets that you're developing? Thank you.

[Charles Wagner, EVP, COO & CFO at Vertex Pharmaceuticals]

Terence, could you just maybe rephrase the first part of your question? We didn't quite get it here.

[Terence Flynn, Equity Research Analyst at Morgan Stanley]

Yes. Sorry. Was there any inventory in 2Q for Gernavix?

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Terrence, on Gernavix, you know the buying patterns for hospitals are variable. So we see the normal variability for buying patterns in hospital, but no inventory to speak of. On September, this is a really important question you ask about, how did our preclinical models perform. So the reason it was really important for us to do the September 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 were referencing to make sure that our models are properly trained. And what we saw with nine ninety three coming into the Phase two study is a molecule that was predicted to be more potent, a molecule that we could dose higher and the exposures are very, very high.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

So our models would predict this is at the 99.999% to the EC50. So 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 exposures of the mid and high dose. Nonetheless, the efficacy for the medium and high dose, as 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.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

And we know that our this medicine is not likely to be superior to our existing molecules. So this is a very important Phase II result and that's why we're pleased to have completed the study and to have gained this information. We are now able to be at the leading edge with our models.

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

Nick, we'll take one more question please.

[Operator]

And your last question today will come from Mohit Bansal with Wells Fargo. Please go ahead. Great.

[Mohit Bansal, Managing Director at Wells Fargo Securities]

Thank you very much for taking my question. Just wanted to check-in on the most saver nation and the letters government has sent out here. Given that your exposure to Medicaid, do you see any risk there? I mean, you could be protected because of the orphan disease, but just wanted to make sure it is not on the cards. Thank you.

[Reshma Kewalramani, President, CEO & Director at Vertex Pharmaceuticals]

Mohit, we have not received a letter. The lines of communication are open. We are able to have good dialogue with DC and we're paying close attention and digesting the latest news. But I can confirm that we did not receive a letter.

[Mohit Bansal, Managing Director at Wells Fargo Securities]

Got it. Thank you.

[Operator]

This will conclude our question and answer session as well as conference call. Thank you all for attending today's presentation. A replay of today's event will be available shortly after the call concludes by dialing 774-0529 or

Participants

Executives

• Susie Lisa, SVP - Investor Relations
• Reshma Kewalramani, President, CEO & Director
• Duncan McKechnie, EVP & Chief Commercial Officer
• Charles Wagner, EVP, COO & CFO

Analysts

• Jessica Fye, MD & Equity Research Analyst - Biotechnology at JP Morgan
• Salveen Richter, Biotechnology Equity Research at Goldman Sachs
• Geoff Meacham, Managing Director at Citi
• Ellie Merle, ED - Biotech Equity Research at UBS Group
• Tazeen Ahmad, MD - US Equity Research at Bank of America
• Evan Seigerman, MD & Senior Research Analyst at BMO Capital Markets
• Divya Rao, Vice President at Cowen
• David Risinger, Senior Managing Director, Biopharma at Leerink Partners
• William Pickering, Senior Analyst - US SMID-Cap Biotech at Bernstein
• Terence Flynn, Equity Research Analyst at Morgan Stanley
• Mohit Bansal, Managing Director at Wells Fargo Securities