Merck & Co Inc

NYSE:MRK

Q2-2025 Earnings Call

[Operator]

Thank you for standing by. Welcome to the Merck & Company, Inc. Rahway, New Jersey U.S.A Q2 Sales and Earnings Conference Call. [Operator Instructions] This call is being recorded. [Operator Instructions]

I would now like to turn the conference over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

[Peter Dannenbaum, executive]

Thank you, Shirley, and good morning, everyone. Welcome to the Second Quarter 2025 Conference Call for Merck & Company Inc. Rahway, New Jersey U.S.A. Speaking on today's call will be Rob Davis, Chairman and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Lee, President of Research Labs.

Before we get started, I'd like to point out that we have items in our GAAP results such as acquisition-related charges, restructuring costs and certain other items that we have excluded from our non-GAAP results. There is a reconciliation in our press release.

I will also remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of our company's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Our SEC filings, including Item 1A in the 2024 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck & Company Inc. Rahway, New Jersey U.S.A undertakes no obligation to publicly update any forward-looking statements. During today's call, slide presentation will accompany our speakers' prepared remarks. These slides, along with the earnings release, today's prepared remarks and our SEC filings are all posted to the Investor Relations section of our company's website.

With that, I'd like to turn the call over to Rob.

[Robert Davis, executive]

Thank you, Peter. Good morning, and thank you for joining today's call. We continue to make meaningful progress in delivering our important medicines and vaccines to patients and customers while advancing our innovative pipeline. Over the past few months, we've shared a steady cadence of updates that highlight our strong clinical momentum, and our growth is increasingly benefiting from new product launches now underway with more to come.

We've also taken additional steps to augment our pipeline. Our recently announced acquisition of Verona Pharma is another example of acting decisively when science and value align. And moving with urgency to achieve our business development objectives. I have increasing confidence that our science-driven strategy will continue to generate long-term value for shareholders and for all of our stakeholders.

Turning to our second quarter results. We delivered performance in line with our expectations with revenue of $15.8 billion. Results reflect strength across oncology and animal health as well as increasing contributions from our new product launches with WINREVAIR achieving $1 billion of cumulative sales and just over a year since approval. We expect to return to growth in the second half of 2025 and remain confident in our outlook for the remainder of the year. I'm proud of the tangible progress we're making in expanding and advancing our research program across key therapeutic areas.

We're now conducting more than 80 Phase III studies across a range of therapeutic areas. And we're increasingly seeing the potential we've long spoken about validated with positive clinical trial results registrational filings and new product launches. These proof points provide me with growing confidence that we're on track to achieve our ambitions.

Moving to some notable recent news. We announced encouraging top line results from the first 2 Phase III trials evaluating elicitide, our oral PCSK9 inhibitor for the treatment of hyperlipidemia and for WINREVAIR based on the HYPERION study for patients recently diagnosed with PAH. On the regulatory front, the FDA approved and the ACIP recommended [ inflaunzia ] for the prevention of RSV in infants younger than 8 months of age who are born during or entering their first RSV season. We're well prepared to support families ahead of the upcoming season.

Additionally, the FDA has accepted our supplemental BLA for WINREVAIR in PAH and a new drug application for the fixed-dose combination of doravirine and ezlotivir for the treatment of HIV. At the IAS conference earlier this month, we highlighted new findings from our promising HIV pipeline, and we're excited about MK-8527 which has the potential to be the first once-monthly pill for HIV prevention. We also hosted an investor event to showcase our HIV programs and the important commercial opportunity they represent.

Our oncology pipeline continues to break new ground. We marked the tenth earlier stage approval for KEYTRUDA and at ASCO, presented encouraging data across multiple novel candidates further reinforcing the potential of our portfolio to help even more patients with cancer. Finally, the acquisition of Verona Pharma brings us [indiscernible] there, a novel first-in-class treatment for chronic obstructive pulmonary disease, or COPD, that complements our growing cardiopulmonary program and reflects our commitment to transformative science in areas of significant unmet need. Upon closing in the fourth quarter, we'll leverage our commercial capabilities to accelerate [ Otabera's ] successful launch and look forward to welcoming the Verona Pharma team to our company.

Overall, we are encouraged by our continued progress. Each of these impactful milestones is an important building block as we move toward a more diversified future. As I've said before, our company is entering a period of rapid transformation, which will be marked by meaningful impact on patients and the practice of medicine, and we couldn't be more excited about our future. Over the past several years, we've built the largest and most diverse pipeline in our company's recent history. We have over 20 new and potential future growth drivers, including the successful recent launches of WINREVAIR and [ cavaxo ].

We also have numerous novel late-phase compounds with potential for significant patient benefit and blockbuster commercial opportunity. candidates such as emlicitide, [ elisatbart ], [ faktmt ] and MK-3000, to name a few, represent potentially profound scientific advances, exactly the types of innovations that Merck is known for. We're committed to fully investing behind our pipeline given the tremendous opportunities we see, and we'll continue to do so with sharp focus and discipline for the benefit of the patients we serve.

Today, we announced a multiyear optimization initiative, which will redirect investment and resources for more mature areas of our business to our burgeoning array of new growth drivers, further enable the transformation of our portfolio and drive our next chapter of productive innovation-driven growth. Caroline will provide more detail on this in just a moment. In summary, we're leveraging our scientific expertise to deliver the next wave of innovation that can save and improve lives around the world.

My confidence in our ability to successfully navigate the KEYTRUDA LOE period increases with each new launch, data readout and business development transactions. I continue to see the LOE as more of a hill than a cliff, and I'm confident in our ability to grow over the long term. I want to thank our talented and dedicated global team for their hard work and commitment to delivering value for patients, shareholders and for all of our stakeholders.

With that, I'll turn the call over to Caroline.

[Caroline Litchfield, executive]

Thank you, Rob. Good morning. As Rob noted, second quarter performance was in line with our expectations I am pleased to again report that the fundamentals of our business remains strong with continued robust global demand for our diverse innovative portfolio of human and animal health products. Our commercial and operational execution enables us to generate value in the short term while we invest in the next generation of innovation and advance our pipeline for the long term. to deliver value for all stakeholders.

Now turning to our second quarter results. Total company revenues were $15.8 billion, a decrease of 2%, both nominally and excluding the impact of foreign exchange. As expected, results were impacted by a decline in sales of GARDASIL in China of approximately $1.3 billion, reducing growth by 9 percentage points. Excluding these sales, global growth was 7%, primarily driven by strength in oncology and Animal Health as well as new products, WINREVAIR and [indiscernible] which are each up to an outstanding start. The following revenue comments will be on an ex exchange basis.

In oncology, sales of KEYTRUDA increased 9% to $8 billion with growth in both U.S. and international markets, driven by robust demand from metastatic indications and increased uptake in earlier-stage cancers. Usage in tumors predominantly affecting women, including those with starting breast, cervical and endometrial cancers was a key contributor to growth. In addition, we saw increased use of KEYTRUDA in combination with [indiscernible] in first-line locally advanced urothelial cancer. We also received positive feedback from health care providers following the recent launch of a treatment regimen with KEYTRUDA for certain patients with resectable locally advanced head and neck cancer based on KEYNOTE 689.

This is the first perioperative anti-PD1 regimen approved for treatment of patients with this disease. Our broader oncology portfolio achieved another quarter of strong growth. Of note, weired sales increased 29% to $162 million predominantly driven by increased use in certain patients with previously treated advanced renal cell carcinoma in the U.S. In vaccines, GARDASIL sales were $1.1 billion, a decrease of 55%, driven primarily by China. Excluding China, sales declined 4% due to lower sales in Japan, reflecting the expiration of reimbursement for the catch-up cohort and timing of public sector purchases in certain international markets. Sales growth of 2% in the U.S. was attributable to price and higher demand, partially offset by CDC purchasing patterns.

In [ New Macoco ], capvaxive sales were $129 million, driven by demand from both retail pharmacies and nonretail customers, including integrated delivery networks and clinics. We remain well positioned to help protect more adults from invasive pneumococcal disease and drive continued growth moving forward. [indiscernible] sales increased 20%. In the U.S., growth benefited by approximately $60 million from CDC stockpile activity, partially offset by competitive pressures. The benefit to [ Vexavance ] was offset by a drawdown of CDC stockpile inventory for [ RotaTeq ] and Farafex, resulting in a net neutral transaction.

Outside the U.S. growth in certain international markets was offset by a competitor preferential recommendation in Japan. Following the recent FDA approval and ACIP recommendation, we are excited to have started taking orders for ENFLONSIA, our monoclonal antibody for the prevention of RSV lower respiratory tract disease in infants entering their first RSV season. ENFLONSIA's compelling clinical data and operational simplicity make it an important option for parents and providers. We have made great progress in achieving the milestones necessary to help ensure a successful launch and are well positioned to help protect infants from RSV lower respiratory tract disease.

In cardiovascular, WINREVAIR continued its strong momentum with global sales of $336 million. As Rob noted, in just 15 months since launch, cumulative net sales of WINREVAIR have already exceeded $1 billion. This achievement is a testament to both the impact WINREVAIR had for patients with pulmonary arterial hypertension and our ability to pay a leading-edge science with execution excellence even in disease areas that are new to us. In the U.S., more than 1,600 new patients received a prescription during the quarter. We are continuing to see a steady increase in the percentage of new prescriptions for patients with background therapies do not include a prostacyclin.

Outside the U.S., we continue to progress with approvals and reimbursement, including in Japan, where we expect a launch later in the third quarter. Overall, the ongoing launch of WINREVAIR continues to meet our high expectations, and we look forward to positively impacting the lives of more patients with PAH. Our Animal Health business delivered very strong growth, with sales increasing 11%. Livestock growth reflects higher demand across all species as well as sales from the [ ACAS ] portfolio acquired from Elanco. Companion animal sales growth reflects price. Growth in both segments also benefited from improved supply.

I will now walk you through the remainder of our P&L and my comments will be on a non-GAAP basis. Gross margin was 82.2%, an increase of 1.3 percentage points driven by favorable product mix. Operating expenses increased to $6.6 billion including a $200 million charge related to the license agreement with [ Hanre ]. Excluding this charge, operating expenses grew 4%, reflecting disciplined investments in support of our robust early and late phase pipeline as well as key growth drivers. Other expense was $54 million. Our tax rate was 15%. Taken together, earnings per share were $2.13.

Turning to our outlook. As Rob noted, our company is rapidly moving to a future with a diversified set of growth drivers, each with the potential to address important unmet patient needs. We have a compelling array of novel pipeline candidates as a result of our steadfast commitment to innovation and our long-standing efforts to invest with discipline. To ensure we are well positioned to maximize the many opportunities in front of us, we have announced a multiyear optimization program. This portfolio management program will enable us to fully reinvest $3 billion of cost savings from lower growth areas of our business to higher potential areas in order to have maximum impact.

It will also allow us to leverage technological advancements to enable productivity and streamline our operations. Taken together, our overall investment will continue to increase, a reflection of the many compelling opportunities we have. We are confident these actions will position us to deliver value for patients customers and shareholders as well as drive long-term growth.

Now turning to our 2025 non-GAAP guidance. We expect full year revenue to be between $64.3 billion and $65.3 billion. This range represents growth of 1% to 2%, and excluding a negative impact from foreign exchange of approximately 0.5% using mid-July rates. Our gross margin assumption remains approximately 82%. Our guidance of $200 million of costs related to the impact of tariffs is unchanged, pending the outcome of additional potential government actions. Operating expenses are now assumed to be between $25.6 billion and $26.4 billion. This range continues to include the $300 million milestone to [ Lenava ] for the tech transfer that was completed earlier this month. This guidance does not assume the proposed acquisition of Verona or additional significant potential business development transactions.

Other expense is expected to be between $300 million and $400 million. We now assume a full year tax rate between 15% and 16%. We assume approximately 2.51 billion shares outstanding. Taken together, our EPS guidance is $8.87 to $8.97. This range includes a negative impact from foreign exchange of approximately $0.15 using mid-July rates. As you consider your models, there are a few items to keep in mind. We remain confident in the outlook for our launch products and continued growth across oncology and Animal Health as well as our return to growth in the second half of the year.

In China, GARDASIL channel inventories remain elevated and demand continues to be soft. As a result, we will not resume shipments to China through at least the end of this year. As we look to the balance of the year for GARDASIL, Japan will be a more significant headwind to growth in the second half of the year as we lap the increase in vaccinations from the catch-up cohort in 2024. Overall, we expect full year growth for GARDASIL, excluding China. Next, we expect other revenue to be significantly lower in the second half of the year. While we actively manage the impact from foreign exchange through our revenue hedging program, based on mid-July rate, we expect to see a negative impact from our hedges, which is reflected in other revenue. Finally, we expect operating expenses to be roughly evenly split between the third and fourth quarters, excluding business development expenses.

Now turning to capital allocation. where our strategy remains unchanged. We will prioritize investments in our business to drive near and long-term growth. We will continue to invest in our innovative pipeline including the initiation of many new late-stage clinical trials across multiple novel candidates, each of which has the potential to meaningfully address important unmet medical needs. We remain committed to our dividend with the goal of increasing it over time. Business development remains a high priority as evidenced by our acquisition of Verona Pharma which we expect to finance through a combination of cash on hand, commercial paper and new debt issuance. We maintain the ability within our strong investment-grade credit rating to pursue additional science-driven value-enhancing transactions going forward. We continued our pace of share repurchases with approximately $1.3 billion in the quarter. We expect to maintain a similar level of repurchases in each of the third and fourth quarters of 2025, given our strong balance sheet.

To conclude, we are confident in the outlook of our business driven by global demand for our innovative in-line portfolio and launches. We maintain our steadfast commitment to bringing forward medically significant innovations that will enable us to deliver value to patients, customers and shareholders well into the future.

With that, I'd now like to turn the call over to Dean.

[Dean Li, executive]

Thank you, Caroline. Good morning, everyone. In the second quarter, we continued to see strong momentum across the pipeline. Today, I will cover updates from our cardiopulmonary, infectious diseases, HIV and oncology programs. First, on the proposed acquisition of Verona Pharma. Building on what Rob noted earlier, we have been following the strong progress of the Verona team for a number of years. [ Octavier ] is the first novel mechanism for the inhaled maintenance treatment of COPD in more than 2 decades. It is a dual inhibitor of phosphodiesterase and for with bronchodilatory and nonsteroidal anti-inflammatory properties. As such, it is an important maintenance therapy option for patients who are persistently symptomatic.

[ Octavier ] is used to improve symptoms of COPD for better breathing and to reduce the number of Flarx. Phase III trials that evaluated [ Octavier ] as monotherapy or with background therapies in patients with moderate to severe symptomatic COPD demonstrated clinically meaningful improvement in lung function. These results provided strong validation that culminated in an FDA approval in June of 2024. We are eager to complete the acquisition and work with the Verona team advancing ongoing work in bronchiectasis and evaluate utility in additional indications, combination therapies and alternative formulations.

Now to focus on WINREVAIR. Evidence continues to accumulate for WINREVAIR's strong clinical benefit across a broad spectrum of patients with pulmonary arterial hypertension. The Phase III HYPERION trial evaluating WINREVAIR in adults recently diagnosed with PAH, was stopped early based on review of available data from the program. Despite the early stoppage Positive top line results announced last month shows that adding Wierevir on top of background therapy significantly reduced the risk of clinical worsening events compared to background therapy alone. Detailed findings will be presented at a scientific congress later this year. Additionally, the FDA granted priority review for a supplemental biologics license application to update the label for WINREVAIR based on data from the Phase III ZENITH trial instead of PDUFA date of October 25.

As a reminder, ZENITH was the first positive trial in PAH with a primary endpoint comprised entirely of major outcome measures and the first Phase III study in PAH to be stopped early for overwhelming efficacy. Caroline mentioned, the Ministry of Health, Labor and Welfare in Japan has recently granted approval for WINREVAIR.

Moving to enlicitide. Positive top line results were announced from the Phase III core REIT heterozygous familial hypercholesterolemia and core reef add-on clinical trials for enlicitide, our investigational once-daily oral PCSK9 inhibitor for the treatment of adults with hyperlipidemia on lipid-lowering therapies, including at least the statin. Of note, the CDC estimates that in the United States, more than 1 million people have heterosis familial hypercholesterolemia and approximately 86 million adults older than 20 have high cholesterol. Both trials met their primary and all key secondary endpoints, demonstrating statistically significant and clinically meaningful reductions in LDL cholesterol for patients receiving elicited versus placebo. Detailed findings will be presented at future medical meetings.

Finally, we are eagerly awaiting results from the core reef lipids Phase III trial in the broader hyperlipidemia population, and I am pleased to report that we recently completed enrollment for the Phase III core outcomes trial. Next, the infectious disease. Last month, the FDA approved ENFLOSIA, our long-acting monoclonal antibody for the prevention of respiratory sensitiavirus lower respiratory tract disease in infants born during or entering to first RSV season. ENFLONSIA is the first and only option designed to protect infants with the same dose regardless of weight.

The CDC's Advisory Committee on immunization practices, subsequently voted to recommend ENFLONSIA for use in infants younger than 8 months of age for their first RSV season and include this new option in the vaccines for children's program, an important step in ensuring access. This vote is provisional and we await confirmation. In vaccines, we initiated the first Phase III clinical trial for our investigational quadrivalent dengue vaccine D181. The Mobilize 1 study will evaluate the safety, immunogenicity and efficacy of a single dose of V181 for the prevention of dengue disease caused by any of the 4 dengue virus serotypes, regardless of prior exposure. According to the World Health Organization, about half of the world's population is now at risk of dengue with an estimated 100 million to 400 million infections occurring each year.

Turning to HIV. Earlier this month, we hosted an investor event coinciding with the International Ag Society Conference on HIV sign. At the conference, we presented findings from a Phase II study of MK-8527, a novel NRTTI candidate being evaluated as an oral option for HIV pre-exposure prophylaxis. The data support the targeted monthly dosing schedule of MK-8527 and which has the potential to enable rapid onset of protection within 1 hour of intake without the need for a loading dose. These findings support the initiation of 2 Phase III studies one, to evaluate the safety and efficacy of MK-8527 among people at greater likelihood of HIV 1 exposure, expressive 11 and a separate study in women and adolescent girls expressive can in collaboration with the Gates Foundation.

We believe MK-8527 has the potential to be an important new option for people at high risk for HIV. At IAS, we also presented data for the combination of Vezlotivir, an investigation of NRTTI anchor therapy and ulaniverine, an investigational RTI being evaluated as a potential once-weekly regimen for the treatment of adults living with HIV. The Phase II study in adults with suppress HIV is ongoing. Finally, the FDA accepted for review the new drug application for the fixed dose combination of doravirine and evloterver, an investigation of once-daily oral 2-drug regimen for the treatment of adults living with HIV I that is very logically suppressed on antiretroviral therapy. The target action date is April 28, 2026.

Moving to oncology. During last month's investor event at ASCO, we showcased how we have leveraged our foundational position with KEYTRUDA to create a diverse pipeline by successfully executing on our oncology strategy and advancing key pipeline candidates. We are uniquely positioned to advance cancer care with a broad, differentiated portfolio and pipeline spanning immuno-oncology, precision medicine and tissue targeting. The strategic ambition is to develop leading assets in all 3 segments so that in a world of combination therapies, our pipeline will be optimally positioned to continue to change the practice of clinical oncology.

With regards to tissue targeting, through our collaboration with Daiichi Sankyo, we now have 3 Phase III trials evaluating infinitumab, deruxtecan, IDI esophagE-01 and in unresectable advanced or metastatic esophageal squamous cell carcinoma, ID prostate 01 in metastatic castrate-resistant prostate cancer and ID8 Lung-02 in relapsed small cell lung cancer. KEYTRUDA continues to generate compelling data and regulatory approvals. We recently received FDA approval for its use as part of a perioperative treatment regimen for certain patients with resectable locally advanced head and neck squamous cell carcinoma based on the KEYNOTE 689 study.

This marks the 42nd indication and the tenth earlier-stage approval for a KEYTRUDA-based regimen. Earlier intervention has the potential to improve outcomes and reduce the burden of disease in this patient population. In ovarian cancer, positive progression-free survival and overall survival results for KEYTRUDA plus chemotherapy with or without bevacizumab were announced in certain patients based on the Phase III KEYNOTE V96 study. This is the first immune checkpoint inhibitor-based regimen to demonstrate a statistically significant overall survival benefit in ovarian cancer. We plan to present the results at an upcoming medical meeting.

And finally, the Ministry of Health, Labor and Welfare in Japan, granted approval for [indiscernible] for certain patients with advanced renal cell carcinoma. As we look to the second half of this year, we anticipate multiple important milestones. In oncology, the upcoming PDUFA date for subcutaneous pembrolizumab on September 23. In the cardiopulmonary space for Wind River, the October 25 PDUFA date for the FDA label update based on the Phase III ZENITH trial, presentation of detailed findings from the HYPERION study and the primary completion date in September of the Phase II CADENCE study in pulmonary hypertension due to left heart disease. For elicitide, begin presenting the detailed results of Phase III trials from the core reef development program at major cardiovascular conferences. And finally, the closing of the Verona Pharma acquisition in the fourth quarter. I look forward to providing further updates on our progress.

And now I turn the call back to Peter.

[Peter Dannenbaum, executive]

Thank you, Dean. Shirley, we're ready to begin Q&A now. We request that analysts limit themselves to 1 question today in order to get to as many questioners as possible. Thank you.

[Operator]

[Operator Instructions] I think our first question comes from Daina Graybosch with Leerink Partners.

[Daina Graybosch, analyst]

I wonder if you could help us understand cadence that you said has a September primary completion date. Specifically, can you help us put the outcomes in context? I think you have a couple primary outcomes or primary and first secondary PVR and a reduction or an improvement in 6-minute loss distance. What's your bar for success on both of those. And if you replicate those outcomes in Phase III, can they support registration in this FEP indication? Or will you have to show benefit on a hard cardiovascular or a mortality outcome as well?

[Dean Li, executive]

Daina, thank you very much. This is Dean. As you're talking about WINREVAIR, we have a lot of data in pulmonary artery hypertension. The data that we're exploring outside of pulmonary artery hypertension is in cadence, and it is in a select population with heart failure it's generally 1 that has hemodynamics that's a little bit more reminiscent of PAH than other diseases -- and so we're really interested to study whether we can move out of PAH but focus on those who have heart failure and have a PH physiology. In terms of the outcomes, you're right, it's PVR at 6 minutes. I would say probably the most important thing just because this is a patient population that's very different than a PAH population. The most important signal for me is really the PVR. I think the 6-minute walk will be also important. But to me, it's whether or not we can make a substantial impact on in this patient population that is not PAH. In terms of this question of whether or not 1 would need to do a Phase III. I would say that we'll have to see the data. But my expectation in front of the data is, I would imagine that the FDA would be interested in a Phase III trial to really demonstrate the effectiveness of this treatment in this broader patient population.

[Operator]

Our next question comes from Vamil Divan with Guggenheim Securities.

[Vamil Divan, analyst]

Maybe I'll just stick with WINREVAIR. One is actually a follow-up to the earlier question and then 1 question of myself. So just following up on the cadence discussion, I don't know if Dean or if someone could just maybe quantify the patient population as you mentioned patients maybe hemodynamically a little more. skewed all we've seen on the pay side, but just a sense of the market size, it would be helpful because we've been getting a lot of questions on how to think about the opportunity. But my other question, my main question is actually the ex U.S. uptake of unnerve there's just sort of a little bit of growth in the second quarter. I know you're just kind of getting going with the launch ex U.S. I'm curious just as a relatively expensive product, recent as launch because your ex U.S. sort of strategy at all evolved given sort of the threat of most aeration pricing? Are you thinking differently about what sort of pricing you might accept for whenever ex U.S. or which markets you may be targeting relative to what you were thinking a year or 2 ago? And just any sense of the sort of broader ex U.S. market opportunity in PAH specifically for wind would be helpful.

[Dean Li, executive]

Yes. I'll take the science question. This is Dean. In relationship to patients who have left car failure, Oftentimes, they have pulmonary hypertension and not pulmonary arterial hypertension, and it's due to increased pressures in the left heart, often measured by a wedge pressure that then backs up to the pulmonary artery. That's not the patient population that we're most interested in. We're most interested in the patient population who has heart failure and their pulmonary hypertension is elevated at a rate or a degree that is out of proportion to what their left heart pressures are. So in some sense, when I say a pulmonary arterial hypertension-like physiology, that's what this patient population is, and that's why we chose that.

In terms of the dimension -- how to dimension that, I would just say that to a large degree, that dimension is underdiagnosed in cardiology because there's no treatment for it. In those patients, there's very limited numbers. I would say that if you look at estimates in the absence of any treatment for these patients, I think they're going to be in the range of what in the range of pulmonary arterial hypertension in some factor maybe above that. But I do believe that unlike pulmonary arterial hypertension, where there's very good epidemiology, here in this physiology, I don't know that the epidemiology is so certain because there hasn't been a treatment. And when oftentimes, there's not a treatment, the epidemiology, one has to be a little bit thoughtful about.

[Robert Davis, executive]

And Vamil, this is Rob. As it relates to the ex U.S. business, overall, to your point, it is still very early in the launch. And really, we're going to really see most of the reimbursements coming in the second half of this year, and that's when you're really going to see growth. But if you look at what happened in the quarter, we're actually seeing contracting in the markets where we are currently marketing the drug like Germany. It's off to a good start. What you saw from the revenues, actually, there was a pricing adjustment in the quarter that, that's why it appeared flat. But as we look forward, we do continue to see a strong opportunity for growth. And just to contextualize, you might recall, this is about 90,000 patients worldwide roughly half of that is the United States. The other half is Europe in Japan. And we expect -- we, I think, recently got approval in Japan. So that's coming in the back half of the year. and then we expect broader reimbursement to Europe. So as we sit here today, it's early, but I would say it's on track.

[Operator]

Our next question comes from Chris Shaw with JPMorgan.

[Christopher Schott, analyst]

I just wanted to dig into the $3 billion restructuring announcement. I know you mentioned in the press release you're planning to fully reinvest that. But just when we balance what seems like a large ramp in the pipeline and the Phase III programs over the next few years against this cost initiative. Can you just help us a little bit of how we should think about either operating margins or absolute OpEx growth trending in the next few years? I'm just trying to get my hands around like what that looks like in any -- just qualitative sense you can provide?

[Robert Davis, executive]

Yes, I appreciate that, Chris. Maybe I'll give a high-level answer, and then Caroline can fill in some of the details. If you look at what this is about, this is as we sit here today and look at really the impressive opportunity we have with these 20-plus launches, we will and we need to fully fund behind those launches. We need to continue and we will fully fund behind our Phase III pipeline on an R&D basis, to be able to do that and to continue to -- so we will be growing our spend over time, but we want to do it productively and efficiently. And that's why we're looking to reallocate money from and resources from the slower growth areas of the business to fully fund into the fast-growing areas of our business. So really, this $3 billion that we've referred to is a reallocation within our portfolio from the slow-growing areas to the faster-growing areas with continued expectation that you're going to see overall growth in spend, hopefully, though, at a more productive level than you would have otherwise seen. And with those investments, as I said, targeted to our pipeline, making sure we fully fund the Phase IIIs and to preparing for the commercial launch. But maybe Caroline can build out some details.

[Caroline Litchfield, executive]

Yes. So I think you've covered the headline as well, Rob. In terms of this $3 billion saving opportunity, that will come through productivity across our enterprise. It will impact the R&D line, SG&A as well as cost of goods. That said, we will reinvest all of that $3 billion plus further investments, especially in R&D, given the strength of our pipeline as well as in SG&A over time as we launch the new products and look to excel in the marketplace with those launches in order to drive long-term growth for our company.

[Operator]

The question comes from Asad Haider with Goldman Sachs.

[Asad Haider, analyst]

3-parter on GARDASIL. First, on GARDASIL U.S., you noted positive price and demand offset by CDC purchasing recognizing that CDC purchasing dynamics are always lumpy. They've also been a significant driver over the year. So maybe just speak to your level of confidence on the demand dynamics from that channel in the current environment, and then maybe also just as it relates to the potential for ACIP recommendation towards lower gas of doses in the U.S. Can you just update us on how you're thinking about the range of outcomes into the ACIP meeting this fall -- and then finally, on China, GARDASIL Carolina, I think you said node shipments through at least the end of this year. So any early thoughts on how you're thinking about 2026 would be helpful.

[Dean Li, executive]

So this is Dean. I guess I'll take the ACIP question first, and then I'll leave the other questions to Caroline and Rob. I can't speculate what the ACIP may do I just want to emphasize how confident we are in the safety and efficacy of G9 GARDASIL 9. But I would emphasize that I think 1 of the things that has become clear to the ACIP is that there is a clear disparity between the stringent clinical requirements outlined by the FDA versus the ACIP proposals that's there. And the FDA has been very clear on the high evidentiary standard required for a single dose. I mean, they keep emphasizing to us efficacy against disease endpoints, not just infections, data in males and females. And this is something that's emphasized to us because we get reminded that HPV-related cancers in males is actually I think now trending higher than cervical cancer in females. They have a very high statistical bar in a long-term they want very long-term viability of protection. In terms of the ACIP, there's no agenda posted for the August, September and October. However, this was sort of a topic that got postponed. So we imagine that there will be discussion about it. but we are very clear on the safety and efficacy and the clear disparity between the FDA's high evidentiary standard and any data to date in relationship to a single dose.

[Caroline Litchfield, executive]

And then in terms of the commercial, in the United States, we saw strong growth driven by price and demand, but that was mostly offset by the CDC channel, where there was a buy down in the second quarter this year greater than what we had seen in the second quarter of 2024. As we look at our opportunities for GARDASIL, we do expect growth in 2025 and beyond. But that does not contemplate any change in the dosing schedule for the United States. And we'll need to see what happens as the ACIP continue those discussions. As it pertains to China, as noted in the prepared remarks, demand remains soft and inventory remains elevated. We are on the ground doing all we can to activate demand, both with females as well as now with males. That said, we will not ship further product this year, and we will assess at the year-end on what the appropriate schedule should be for 2026. I should note, GARDASIL China represents a fraction of our company now, much less than 1%. We're not counting on it for growth. we are counting on our new products, the excellent execution we have in our existing products to drive growth for our company in the second half of this year and into the future.

[Operator]

Next question comes from Evan Seigerman with BMO Capital Markets.

[Evan Seigerman, analyst]

As we think about business development going forward, I'd love if you could expand on your approach to diligence in assets between Chinese and Western companies. I'm specifically asking in context of the recent Barona acquisition versus a recent collaboration announcement by a competitor for Chinese PDE3/4 inhibitor.

[Dean Li, executive]

Well, this is Dean. We have a very high standard, whether it's from China or from the United States. But in specific relationship to your question about Verona I mean, Verona is a company we have followed at least for 5 years. It's -- we were always intrigued by it because they had a dual inhibitor of PDE3 and 4 with the possibility of bronchodilatory and nonsteroid or anti-inflammatory properties. And as we watched it, we had recognized that it could be the first novel mechanism, and it is now the first novel mechanism to get approved for inhalation for COPD. And so for us, the fact that it's approved within the United States and the fact that we've talked to patients and physicians who use it we believe that it lays a beachhead or groundwork for this field and our ability to move that quickly with Verona is an advantage to us, especially when we're a company who is revisiting our roots in cardiopulmonary cardiometabolic. And we believe that there are other innovations around this pathway that will be important. But having that first-mover advantage within the United States and more broadly is really important -- when we looked at other assets within this space, specifically related to China, they were not in that position of a first-mover advantage, which we thought was critical for Merck to enter the field.

[Operator]

Our next question comes from Umer Raffat with Evercore.

[Umer Raffat, analyst]

I feel like there's been a ton of interest in the valuation paid for your Chinese partner, Lenova on the PD-1 VEGF. And my question is, Considering the ongoing Phase I is an open-label study, can we reasonably assume everything is in fact on track and you are still in a position to start a potentially registration Phase II like a KEYNOTE-21G in the next few months?

[Dean Li, executive]

Yes. So this is Dean. In relationship to PD-1, VEGF, you're exactly right. We've been interested in the dual signaling in this space for some time. I would actually mark 2018 as our interest in relationship to our broad collaboration with our collaborators, [ Aisa ]. In relationship to the Lenava program itself, everything is going exactly as planned. Now clearly, we're keeping an eye on the external environment and external data. But as related to Lenava program moving forward, that is going exactly as planned as we -- according to the plan, when we initiated the partnership with Lenava.

[Operator]

Next question comes from Akash Tewari with Jefferies.

[Akash Tewari, analyst]

So we're seeing an increase in patient adds for WINREVAIR after some modest decreases over the last few quarters. what's the right cadence when you think about this going forward, not only for the rest of 2025, but really 2026 and onwards. Now that you have the Hyperion and ZENITH results. And really, what's your progress in terms of progressing venrivir into earlier lines of setting, are you starting to see doctors adopt this medication more aggressively? And then maybe if I could just sneak in 1 more question. On the Hanz GLP1 asset, can you confirm that, that drug has actually moved into the clinic?

[Robert Davis, executive]

Yes. Maybe I'll start, and Caroline can add as well. So I appreciate the question on WINREVAIR. As we look, we've been pretty consistently adding 400 to 500 patients per month. So I wouldn't read that the 1,600 in the quarter relative to some shift. It has been actually pretty steady, and we do continue to expect to see that kind of steady growth going forward as we move through the rest of the year. So that would -- I think that was the first part of the question and then maybe Caroline can take the next part.

[Caroline Litchfield, executive]

And then the second was how we're doing in penetrating the different patient segments. What we have as of now is 75% of the use is for patients with triple therapy or a background prostacyclin. That is increasing as we move forward. And indeed, of the 1,200-plus physicians that have now prescribed WINREVAIR, more than 50% of those have prescribed the product in patients that are less severe or on dual therapy. So that gives us a lot of confidence in our future as we continue to not only help those severe patients, but increasingly move into those patients who are less severe.

[Robert Davis, executive]

I think it's safe to say that HYPERION and ZENITH both are contributing to that growing confidence. So everything is moving as we would hope it would as we entered the space.

[Dean Li, executive]

I think just to mention something in WINREVAIR, I mean I've actually talked at many of the KOLs at the major center. I think there's just a stream of information that will be helpful. It's not 1 event per se. I think a label update would be really important. I do think that many of the KOLs have been waiting to see the data from Hyperion because it gives them a sense of prescribing it earlier in their journey. So they'll be very interested in that. There is a patient population in PAH, for example, who are overlapped with connective tissue diseases. And they're going to want to see the culmination of all that data across trials. And that data individually, and that data pooled will be very important. And clearly, clearly, the continued Soteria and the fact that the adverse effects and all of this sort of thing are well within the label are things that are going to create an interest of the KOLs to begin to adopt this earlier in the journey and to other patient populations such as connective tissue disease. In relationship to the handset GLP-1, we said that moving to clinic this year, and everything is on schedule.

[Operator]

Our next question comes from Terence Flynn with Morgan Stanley.

[Terence Flynn, analyst]

I was just -- I wonder if you could offer any preliminary perspective on how a 15% tariff on pharmaceuticals would impact your 2026 outlook. Recognize you're not going to give guidance at this point, but I was just wondering if you could help frame for us the potential impact there? And then any insight if this would be phased in over time or if this would be implemented more near term?

[Robert Davis, executive]

Yes. Terence, this is Rob. I appreciate the question. Maybe I'll take the second part of it first. So we need to see more clarity both from the administration and just overall as to exactly how this is going to play out. So it's still not clear exactly how this relates relative to the 232 investigation and the timing, so to speak, whether these apply now or will be phased in until they're further guidance, I can't really speak to it. But what I would tell you is as we look at -- and I don't want to get '26 guidance because we're not giving forward guidance. But as you look at '25, I would tell you, if this was implemented immediately, it would be minimal impact based on all the work we've done around inventory management and moving our manufacturing to the U.S. We're very well positioned overall as we look forward to be able to do that. And we have made very good progress as we look at even '26. We'll give the specific guidance as we move forward. But for '25, this would be minimal.

[Operator]

This next question comes from Courtney Breen with Bernstein.

[Courtney Breen, analyst]

Coming back to the comments you've made around the cost savings program and the reallocation of this. Can you give us a little bit of context on your intentions to with KEYTRUDA, specifically recognizing that, that asset is coming nearer to the end of its life cycle, yet there are still many launches as well as a subcutaneous product launch ahead. And so how you're planning on a allocating in the context of KEYTRUDA, SG&A relative to the newer opportunities that you need to fund in both R&D and those new launches.

[Robert Davis, executive]

Yes. Courtney, thank you for the question. As you think about where we sit in oncology and maybe contextualize, and I'll answer the question. Obviously, we've been the leader in IO therapy with KEYTRUDA. And as we've consistently said, we have every intention of not only being and continuing to be the leader but to broaden our leadership across the broader suite of oncology assets we have, which, as you know, now across the tissue targeting agents antibidrug conjugates across all of the small molecules we have, we have one of the broader, if not the broadest pipeline now moving forward in the oncology space. So as you look at the spend, to your point, we're not necessarily looking to pull back spending on oncology. We're going to grow and it's about reallocating the resources and adding to those resources as we start to move away from just being focused on KEYTRUDA to the broader suite of opportunities. So you're going to see other oncology gross spend as KEYTRUDA is pulled back.

[Peter Dannenbaum, executive]

And next question comes from [ Chung Win ] with UBS.

[Unknown Analyst]

It's just 1 on the 1 big beautiful bill expanding the orphan drug exclusion under the IRA and how that affects the timing of KEYTRUDA's potential selection for IRA price cuts? So when KEYTRUDA was initially approved, it carried an orphan designation, its first nonorphan indication was proves about a year later. So does this 1 big beautiful bill update effectively shift KEYTRUDA's IRA selection from 2028 to 2029. And then would the presence of biosimilars, by that time, actually mean KEYTRUDA won't be selected for IRA.

[Robert Davis, executive]

Yes. I appreciate the question. So maybe just from a policy perspective, we are very supportive of the language that was put in, in support of orphan drugs. We've long believed that investing behind orphan and rare disease is important and that the more we can do to support that, it is something which will benefit patients going forward. So in that sense, we're very much supportive of of what the 1 big beautiful bill included in that regard. As it relates specifically to your question, you are correct that -- so KEYTRUDA did launch with an orphan indication in melanoma in 2014. The first nonorphan indication was in lung cancer in 2015. And based on the reading of the bill, as you've done, if you look at what is in there now, that would imply that you would expect now to see the drug selected for negotiation in '27 for implementation of the negotiated price in '29. I'm not going to speculate to whether or not it continues to be included or not as it relates to the LOE then pending LOE. We'll have to see how that plays out. But I also think it's important to also understand with all this said, what we're focused on is how do we grow the business post the impending LOE of KEYTRUDA and drive for sustainability in our business long term. So that is our focus. This is nice, but does not change that fundamental view of our business.

[Operator]

Our next question comes from Tim Anderson with Bank of America.

[Timothy Anderson, analyst]

A couple of long-term questions for Rob. So Rob, you continue to describe the loss of KEYTRUDA as being more of a hill than a cliff. Our model shows the same, but I don't think investors and consensus really believe that -- and you say you're confident in return to growth downstream of that period. So 2 questions. On the Hill comment, can you just remind investors the biggest offsets that you see today for how losing a product that's 50% of your revenues, the time of expiry will, in fact, not be a cliff. And then second, when you talk about confidence in growth over the longer term. Can you put parameters around that when that would be likely we showed trough revenues 2031. That would be [ 3 ] years past patent expiry. All part is that a realistic time frame for when consistent growth would return?

[Robert Davis, executive]

Yes. Jim, thank you for the question. Actually, I very much appreciate it because this is the core of the valuation thesis for our company. And my own view of this is that I do think the Street underappreciates the power of what we have in our pipeline. And as we see that play out, as I've consistently said, as we see those proof points continue to play out, and I would point to when River is the first. We're now seeing it with cabbaxib. I think clazrovumab will be another one. We have enlicitide coming stack TMT, all of these opportunities as they roll out, I think that confidence will grow over time. But to your specific question, what are we focused on. Recall that we've given guidance in a broad sense to the fact that we see over $50 billion of potential opportunity from our different therapeutic areas, starting with oncology, broad-based oncology. We now have over 60 Phase III clinical studies, I think, across was it 13 different tumor types, which will be coming over the next 5 years, incredibly broad across our antibody drug conjugates across all of the small molecules.

We have the individualized neoantigen therapy, the list would go on. But we think those alone are over $25 billion, and we had an opportunity at ASCO to begin to talk about some of that, and we will continue to show more of that as we go forward. Our confidence there is better today than it was even at ASCO with every card return, we feel better about that going forward. And then you look beyond that in the cardiometabolic, we've directed to approximately $15 billion in the cardiometabolic space. really what's foundational elements coming from Wind River, which we talked about, and we continue to be very enthused by what we're seeing there. Enlicitide or oral PCSK9 and we continue to think is a huge opportunity, and we'll continue to focus on what we have in MK-6024, which is our MASH product. We're going to see, I think, data later this year. We continue to feel very good about that. So our overall suite of the cardiometabolic space, we feel very good about. That's the $15 billion ophthalmology, I think, is underappreciated with a multibillion-dollar opportunity.

We just recently went through our HIV portfolio with approximately $5 billion of opportunity. And we feel very good about that and the data we have and where our portfolio is going to go. It's very important. Immunology is another $5 billion which is important to focus on animal health, you look at the quarter of the growth we showed in Animal Health this quarter. This business is going to be a fast-growing business for this company throughout our long-range plan period and is really based on a new product story very much like the human health business, we're actually just got approval in Europe for NUMELVI, our JAK inhibitor for dermatitis. We just got approval for our injectable and once annual in the United States. Those are the first of multiple new product offerings coming in that business. That is going to allow us to more than double it by the time we get out to the mid-2030s.

And then all of this excludes what else we're going to do in business development, the fact that we just did Otter, which added another multibillion-dollar opportunity that wasn't in that $50 billion when we said it is further block -- building block being added as well. And then we still have a lot to do on business development. We've been very clear. We're not stopping. And we have an early stage pipeline, which as we move into '26 and especially into 27, you're going to see increasingly things coming out of our Phase I pipeline into our Phase II, which will be visible that are all very exciting. So all of that is why if I sit and look at where we're at, I feel very good.

And then obviously, we continue to have subcutaneous KEYTRUDA and the base of what we believe will be the KEYTRUDA business, which we will continue to be able to benefit for patients through those offerings. So I think your characterization is fair. I actually agree with it. And as far as though, as it looks to how quickly we get back to growth, it would be one where I would say I don't want to get specifics on years, but we've been very clear. We want to minimize the cliff, which I think we have done. That's why I talk about the Hill, and we want to get back to growth quickly. And I do see a path to do that, and I'm confident we will. And I think if you go back to the JPM presentation we gave, we had a slide in there which was a representation, if you will, the [ con ] of opportunity within our long-range plan, that kind of gives a profile very similar to what you just described.

[Peter Dannenbaum, executive]

I know we're over time. We have time for a few more questions.

[Operator]

Our next question comes from Alex Hammond with Wolfe Research.

[Alexandria Hammond, analyst]

For enlicitide, the team has highlighted it as a platform to add other cardiometabolic assets on to. With that context, what combinations and indications could we expect? And when could we receive updates.

[Dean Li, executive]

Yes. So thank you very much for the question. So just to reset, our ambition is that this is going to be the first oral PCSK9 and it will not just be first. It will be the best in relationship to everything that we've seen from competitor data. And we expect to have it the most effective oral LDL-lowering option, and it should have confidence in cardiovascular outcomes that are comparable, but actually, we believe could be better than the biologics. And we think that with the data that we have, we recognize that 70% of patients with ASCVD even treated with statins do not treat the LDL cholesterol.

So when you think about that, LDL is 1 axis in relationship to cardiovascular outcomes. And LDL, clearly, there would be combinations that you would make with enlicitide to even deepen that response and more. So that's a combination that would be advanced that can advance quickly. But I think there's also evolving data in relationship, and we will see that probably from others in relationship to, for example, LPL. I think in that patient population, if reducing LP-led is indeed shown to be important for lowering cardiovascular outcomes than the potential of having an Lp(a) molecule that can do that, but also recognizing that PCSK9 at further reduction of Lp(a) and in the patient populations who have high liter the way that I've treated them is I give them PCSK9, that a combination there may be something that's really important. And then the future other combinations essentially related to other access I talked about LDL, LP(a). We would clearly be interested in inflammatory accesses and other accesses in combination. So elicitide is a really important molecule. It is a molecule that we believe can serve as a platform to be driving cardiovascular outcomes in increments of 20%, 25%, 30%, and we're very excited for that future.

[Peter Dannenbaum, executive]

We have time for 2 more questions, please.

[Operator]

Our next question comes from James Shin with Deutsche Bank.

[James Shin, analyst]

One for Dean. Dean, I appreciate everything is on schedule for MK 2010, but was Merck notified of no biopharms interest in Lenova. And does that have any bearing on Merck's commitment to 2010 or the development of a PD-1 VEGF bispecific more broadly?

[Dean Li, executive]

I would just emphasize our commitment is based on our interest in the space since 2018. So our commitment has not changed. And as I've said, the Lenova program that we have is moving forward as planned. In terms of notification or not notification, that's something that we don't comment in terms of business development.

[Peter Dannenbaum, executive]

The next question comes from Mohit Bansal with Wells Fargo.

[Mohit Bansal, analyst]

So I have a question regarding the guidance. So if I compare the guidance on FX basis versus the prior quarter, it does seem like you lowered the upper end of the growth from -- just wanted to understand if there is a change in the operational business that we need to be aware about.

[Peter Dannenbaum, executive]

Your line cut out. I think the question was about the -- you see a reduction in the guidance. But can you talk about guidance, Caroline?

[Caroline Litchfield, executive]

So the guidance that we've given this quarter is to maintain the midpoint for revenues and to increase EPS by $0.03. There was a very modest tailwind from foreign exchange. And that has really offset a few headwinds. The first would be a low level of coped cases during the summer season, which has impacted our outlook for [indiscernible] The second is we have seen an early entrant of a biosimilar for pembrolizumab in Argentina, which has impacted revenues there. All of that said, we are confident in our ability to drive growth in our business this year of between 1% and 2%. And when you exclude the impact of the headwind of trying as GARDASIL, we have underlying growth of between 6% and 8%. So we're confident in our future despite the uncertain macro environment that do exist for our industry.

[Peter Dannenbaum, executive]

Great. Thank you all very much for your questions. As always, Investor Relations is available for any follow-ups. Thank you very much.

[Robert Davis, executive]

Thank you.

[Operator]

Thank you. This concludes today's conference. We thank you for your participation. At this time, you may disconnect your lines.