Merck & Co Inc (MRK) — Q1 2024 Earnings Call Transcript

Thank you, Shirley, and good morning, everyone. Welcome to Merck's First Quarter 2024 Conference Call. Speaking on today's call will be Rob Davis, Chairman and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Li, President of Merck Research Labs. Before we get started, I'd like to point out a few items. You will see that we have items in our GAAP results, such as acquisition-related charges, restructuring costs and certain other items. You should note that we have excluded these from our non-GAAP results and provide a reconciliation in our press release. I would like to 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 Merck'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 and the 2023 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 undertakes no obligation to publicly update any forward-looking statements. During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides, along with our earnings release, today's prepared remarks and our SEC filings, are all posted to the Investor Relations section of Merck's website. With that, I'd like to turn the call over to Rob.

Thanks, Peter. Good morning, and thank you for joining today's call. We've begun 2024 with continuing momentum in our business. We're harnessing the power of innovation to advance our deep pipeline and are maximizing the impact of our broad commercial portfolio for the benefit of patients. We drove strong growth across key therapeutic areas, executed strategic business development and are now launching a significant new product in the cardiometabolic space while also preparing for the potential approval and launch of 2 additional important candidates in vaccines in oncology. We have significant opportunities ahead of us across all areas of our business, and we're highly focused on realizing them. I continue to be inspired by the dedication of our talented global team, which is working tirelessly to bring differentiated medicines and vaccines to patients through seamless scientific, commercial and operational execution. In March, we received FDA approval for WINREVAIR, a first-in-class treatment for adults with pulmonary arterial hypertension, a rare progressive and ultimately life-threatening disease. This marks the achievement of a significant milestone for our company. It exemplifies the value of our strategic priorities and demonstrates how our enduring commitment to our purpose is resulting in tangible benefits for patients. Just over 2 years since adding WINREVAIR to our pipeline, our attention now turns to the execution of a strong commercial launch where we have already seen prescriptions being written. We see a tremendous opportunity to positively impact the lives of people living with PAH. And further, the importance of this therapy to patients provides us with increased confidence in our ability to deliver sustainable long-term value for our shareholders. Strategic business development focused on the best external science remains an important priority for our company. We've demonstrated that we can leverage our deep discovery prowess to identify important acquisition targets and then add significant value through our powerful clinical research engine, our regulatory expertise and our commercial scale, which together can serve to accelerate development and enable broad global access to important medical discoveries for patients in need. Turning to our first quarter results. We achieved strong growth, reflecting robust demand for our innovative portfolio. We're pleased to reflect this momentum in our updated full year guidance, which Caroline will speak to in a moment. Turning to our broader research efforts. We're focused on advancing our expansive and diverse pipeline of leading-edge programs for the benefit of patients. In vaccines, we continue to pioneer new approaches to optimize disease prevention. In HPV, we're building on the foundation set by GARDASIL to further reduce the global burden of certain HPV-related cancers and disease by potentially providing broader protection with a new multivalent HPV vaccine and by generating data to clearly demonstrate whether or not a single dose of GARDASIL-9 provides comparable long-term protection to the approved 3-dose regimen in males and females ages 16 to 26. In pneumococcal, we presented additional compelling data for V116, a vaccine that is specifically designed to help protect against the majority of invasive pneumococcal disease in adults ages 65 and older and look forward to its potential approval in June. Each of these programs are platforms where we can provide meaningful protection to broad populations on a global scale. In HIV, in partnership with Gilead, we shared promising data from our revitalized program for a once-weekly combination of islatravir and lenacapavir in the treatment setting. We're actively progressing our comprehensive clinical program, which is focused on both treatment and prevention strategies to meet the evolving needs of the HIV community. And in oncology, we initiated several late-stage programs of novel candidates from our diverse pipeline as we work to expand our impact for patients and reinforce our leadership position over the long term. Finally, across our deep pipeline, we have significant clinical momentum in a range of therapeutic areas. Cutting-edge science is at the core of who we are, and I'm confident that Merck is well positioned to deliver the next wave of important innovations and value to patients, shareholders and to all of our stakeholders. In summary, our science-led strategy is delivering compelling proof points that we are creating a sustainable innovation engine that with continued clinical success will lead to a more diversified portfolio of growth drivers over the next decade and beyond. I again want to recognize the enormous efforts across our global organization. My confidence is strong and growing, that we are well positioned to build on this momentum and drive patient impact and value creation this year and well into the future. With that, I'll turn the call over to Caroline.

Thank you, Rob. Good morning. As Rob noted, we have had a strong start to the year with robust growth across our business, which reinforces the confidence we have in our outlook. We are also making strategic investments to leverage leading-edge science to save and improve lives around the world, positioning us to continue to deliver long-term value for patients, customers and shareholders. Now turning to our first quarter results. Total company revenues were $15.8 billion, an increase of 9% or 12% excluding the impact of foreign exchange. The impact from exchange is primarily driven by the devaluation of the Argentine peso, which was largely offset by inflation-related price increases consistent with market practice. The following revenue comments will be on an ex-exchange basis. Our human health business continued its momentum with double-digit growth of 13%, driven by oncology and vaccines. Sales in our Animal Health business increased 4% across both companion animal and livestock products. Turning to the performance of our key brands. In oncology, sales of KEYTRUDA grew 24% to $6.9 billion, driven by increased uptake from earlier-stage cancers and continued strong demand from metastatic indications. In the U.S., KEYTRUDA grew across a broad range of tumors. In earlier-stage cancers, the increase was largely attributable to non-small cell lung cancer following the launches of KEYNOTE-671 and KEYNOTE-091. In the metastatic setting, we saw strong uptake from the recent launch of KEYNOTE A39 in first-line advanced urothelial cancer. Outside the U.S., KEYTRUDA growth was driven by continued uptake in earlier stage cancers, including high-risk early-stage triple-negative breast cancer and renal cell carcinoma as well as continued strong demand from patients with metastatic disease. Inflation-related price increases consistent with market practice in Argentina also contributed to growth. Alliance revenue from Lynparza and Lenvima grew 7% and 10%, respectively. WELIREG sales more than doubled to $85 million, driven by the additional indication following FDA approval of LITESPARK-005 for certain patients with previously treated advanced renal cell carcinoma as well as increased uptake in certain VHL disease-associated tumors. Our vaccines portfolio delivered strong growth, led by GARDASIL, which increased 17% to $2.2 billion, driven by global demand. Sales also benefited from the timing of shipments in China and CDC purchasing patterns in the U.S. VAXNEUVANCE sales grew to $219 million, driven by continued uptake of the pediatric indication in the U.S. and ongoing launches in international markets, particularly in Europe. In the U.S., VAXNEUVANCE sales also benefited from CDC purchasing patterns. Sales in our Animal Health business grew 4%. Livestock sales growth was driven by price actions as well as demand for swine and poultry products. Companion animal growth reflects price actions. 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 81.2%, an increase of 4.3 percentage points driven by reduced royalty rates for KEYTRUDA and GARDASIL, which went into effect at the beginning of this year as well as favorable product mix. Operating expenses decreased 4% to $6.4 billion, a charge of $656 million related to the acquisition of Harpoon Therapeutics this quarter was lower than the $1.4 billion of charges a year ago for certain business development transactions. Excluding these charges, operating expenses grew 8%. We remain committed to investing appropriately to realize the promise of our extensive early and late-phase pipeline and support the promotion of our key growth drivers. Other expense was $87 million. Our tax rate was 16.1%, including the impact from the Harpoon transaction for which no tax benefit was recorded. Taken together, earnings per share were $2.07, which includes a $0.26 negative impact from the charge related to Harpoon. Now turning to our 2024 non-GAAP guidance. The operational strength of our business has enabled us to raise and narrow our full-year revenue guidance. We now expect revenue to be between $63.1 million and $64.3 billion, reflecting strong year-over-year revenue growth of 5% to 7%, including the negative impact from foreign exchange. At the midpoint of this range, operational strength in our business of approximately $600 million is partially offset by an incremental headwind from foreign exchange of approximately $400 million using mid-April rates resulting in a full year negative impact from foreign exchange of approximately 3%. Our gross margin assumption is now expected to be approximately 81%. Our estimated range of operating expenses is between $25.2 million and $26.1 billion, which does not assume additional significant potential business development transactions. Other expense is expected to be approximately $250 million. Our full-year tax rate is unchanged between 14.5% and 15.5%. We assume approximately 2.55 billion shares outstanding. Taken together, we are increasing and narrowing our expected EPS range to $8.53 to $8.65. This is a $0.07 increase at the midpoint despite an incremental headwind from foreign exchange of approximately $0.05 using mid-April rates, resulting in a full-year negative impact from foreign exchange of more than $0.30. As you consider your models, there are a few items to keep in mind. The increase in our sales guidance is driven by the strong performance across our current product portfolio, led by KEYTRUDA, which continues to experience growth from additional indications and patient demand. For GARDASIL, second quarter ex-U.S. growth will be adversely impacted by shipment timing to China. This year, we expect more evenly distributed quarterly shipments to China. Recall, in 2023, we accelerated shipments from the second half to the first half of the year, which primarily impacted the second quarter. Over the near and long term, we remain confident in our ability to protect many more people from HPV-related cancers and drive growth of GARDASIL. Sales of LAGEVRIO in the first quarter were driven by an extended wave of COVID-19 in Asia Pacific markets. LAGEVRIO continues to be an important treatment option for certain patients with COVID-19. So we continue to anticipate full-year sales to be lower than last year. We are excited to provide a novel treatment option for adult patients with pulmonary arterial hypertension, following the recent FDA approval of WINREVAIR. We are seeing high interest from patient groups and a range of relevant prescribers. We are also making good progress in enabling access. Several payers have already established coverage policies consistent with the label and STELLAR study criteria, while others are in the process of developing their policies. As we go forward, we intend to provide an appropriate level of transparency to enable insight into the impact we are having on patients, including prescription data and revenues. In summary, we are confident in a successful launch of WINREVAIR, consistent with our prior expectations and look forward to providing updates on our progress. 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 and plan to increase it over time. Adding compelling science to our pipeline through business development remains a high priority. We maintain ample capacity given our strong investment-grade credit rating and cash flow to pursue additional science-driven value-enhancing transactions. We will continue to execute a modest level of share repurchases. To conclude, we remain confident in the near- and long-term outlook of our business, driven by the global demand for our innovative medicines and vaccines as well as our exceptional pipeline. Our unwavering commitment to using the power of cutting-edge science to improve the lives of the patients we serve has put us in a position of financial and operational strength. Our excellent execution and continued investments in innovation will enable us to deliver value to patients, customers and shareholders now and well into the future. With that, I'd now like to turn the call over to Dean.

Thank you, Caroline. In the first quarter, we continued to make progress with a steady cadence of clinical regulatory milestones across our pipeline. Today, I will provide updates from our cardiometabolic disease portfolio, HIV and vaccine programs and close with advances in our oncology pipeline. As Rob and Caroline noted, late last month, we received approval from the FDA for WINREVAIR, our first-in-class active and signaling inhibitor for the treatment of those living with pulmonary arterial hypertension to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events. WINREVAIR is a novel therapeutic option that targets a new PAH treatment pathway and is indicated to treat a broad PAH population. This approval marks a significant step towards our goal of transforming the treatment journey for many patients with PAH. WINREVAIR is currently being reviewed by the European Medicines Agency with a decision anticipated in the second half of this year. The Phase III ZENITH and Hyperion studies evaluating patients with more advanced disease and those earlier on in their disease journey, respectively, are ongoing as well as the Phase II cadence trial evaluating WHO Group II pulmonary hypertension, a type of left heart disease. Our commitment extends to a broad range of pulmonary hypertension, informed by results from the Phase II cohort of the Phase II/III insignia PAH study evaluating MK-5475, our inhaled soluble guanylate cyclase stimulator and the STELLAR trial results for WINREVAIR, we have made the decision to focus the development of MK-5475 on WHO Group 3.1 pulmonary hypertension associated with COPD, and not further proceed in PAH. PH-COPD is an area of significant need with no specific therapies currently approved. Our HIV pipeline continues to advance. Last month, presentations at the conference on retroviruses and opportunistic infections, reinforce progress in our strategy to develop less frequent dosing regimens for managing and treating HIV. We believe these programs have the potential to help address adherence, stigma and other challenges faced by some individuals taking daily antiretroviral pills. In collaboration with Gilead, safety and efficacy findings were presented from a Phase II study evaluating a once-weekly oral combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor and lenacapavir, a first-in-class capsid inhibitor for the treatment of adults living with HIV. At 24 weeks, the trial met its primary endpoint and in a secondary endpoint maintained a high rate of viral suppression. Additional longer-term data will be presented at a later date. In addition, safety and tolerability data were presented for MK-8527 a novel oral NRTTI candidate from 2 Phase I trials that evaluated ascending single dose and multiple doses in adults 18 to 55 years old, not infected with HIV. MK-8527 is being investigated as a potential monthly option for HIV pre-exposure prophylaxis. Vaccines remain an important element of our pipeline, and we are making progress across several programs. Findings from multiple Phase III trials of V116, our investigational 21 valent pneumococcal conjugate vaccine were presented at the meeting of the International Society of pneumonia and Pneumococcal Diseases last month. V116 was shown to be immunogenic for all 21 serotypes covered by the vaccine, including a pneumococcal vaccine naive and vaccine experience adults as well as those at increased risk for pneumococcal disease. If approved, V116 would be the first vaccine specifically designed to address the majority of serotypes that cause invasive pneumococcal disease in adults, ages 65 and older. The target action date is June 17. The meeting of the CDC's Advisory Committee on immunization practices is scheduled shortly thereafter. Since the initial approval of GARDASIL, a steady flow of clinical and real-world evidence has been generated to support the favorable efficacy, effectiveness, safety and long-term durability of protection against certain human papillomavirus-related cancers and diseases in both males and females. Despite the proven public health benefit of HPV vaccination, the latest global cancer statistics from the International Agency for Research on Cancer indicate there is more to do to help increase vaccination rates. The latest statistics from 2022 ranked cervical cancer as the fourth most common cancer globally in terms of incidence and mortality in women and the leading cause of cancer death in 37 countries, predominantly in sub-Saharan Africa, South America and Southeast Asia regions. At the Urogen Congress last month, we disclosed plans to build on the development of GARDASIL with a new clinical program to identify a novel multivalent HPV vaccine candidate with the potential to extend protection against a broader array of HPV types. This includes several types known to disproportionately impact African and Asian populations and individuals of African and Asian descent. First-in-human studies are scheduled to start in the fourth quarter of this year. In addition, we announced plans to conduct 2 randomized, double-blind multiyear clinical trials in females and males ages 16 to 26 years to examine the short- and long-term efficacy and immunogenicity of a single dose of GARDASIL-9 versus the currently approved 3-dose regimen. The goal of these studies is to generate data that clearly demonstrates whether or not a single dose of GARDASIL-9 provides comparable long-term protection to the approved regimen, while also satisfying the high standards required by regulatory authorities. The clinical trials are anticipated to start enrolling in the fourth quarter. In oncology, we continue to focus on our 3-pillared strategy comprised of immuno-oncology, precision molecular targeting and tissue-targeting agents. In immuno-oncology, September 2024 will mark a decade since the first approval of KEYTRUDA in metastatic melanoma. KEYTRUDA has since amassed approvals for 39 indication and continues to reinforce its reputation as a foundational therapy for certain types of cancer. Building on the recent FDA approval for KEYTRUDA in combination with chemotherapy for the treatment of FIGO 2014, Stage II through IVA cervical cancer, we recently announced that the pivotal KEYNOTE-A18 trial met its primary endpoint of overall survival, potentially providing a new standard of care for these patients. Our commitment to providing better options to prevent and treat cervical cancer remains strong. Also, in women's cancer, the Phase III KEYNOTE-868 trial, known as NRG-GY018 was granted priority review by the FDA for the first-line treatment of patients with primary advanced or recurrent endometrial carcinoma. This agency has set a target action date of June 21. Outside of the U.S., the European Commission approved KEYTRUDA in combination with platinum doublet chemotherapy as neoadjuvant therapy followed by adjuvant KEYTRUDA in adult patients with non-small cell lung cancer at high risk of recurrence based on the Phase III KEYNOTE-671 study. This marks the first approval in Europe for an anti-PD-1 PD-L1 therapy as part of a treatment regimen for the neoadjuvant followed by adjuvant treatment of resectable non-small cell lung cancer based on positive overall survival results. Next to precision targeting. Building on the success of KEYTRUDA for certain patients with non-small cell lung cancer, earlier this month, we announced the initiation of the Phase III clinical trial for MK-1084, an investigational oral selective KRAS G12C inhibitor in combination with KEYTRUDA for the first-line treatment of certain patients with metastatic non-small cell lung cancer. The decision to proceed to Phase III was based upon early promising evidence from a Phase I study showing antitumor activity and a manageable safety profile. KRAS is one of the most prevalent oncogenes in human cancers, and G12C is the most common KRAS mutation in patients with non-small cell lung cancer. In the tissue targeting space, we are moving with speed and rigor to advance a broad pipeline of antibody-drug conjugates with multiple planned and ongoing Phase III trials. In just over 6 months, we have made remarkable progress in our collaboration with Daiichi Sankyo. Recently, we announced that the first patient has been dosed in the Phase II/III REJOICE OVARIAN01 trial evaluating the efficacy and safety of raludotatug deruxtecan, an investigational CDH6 directed DXDADC in patients with platinum-resistant ovarian cancer. We are poised to begin a Phase III study evaluating ifinatamab/deruxtecan, a B7-H3-directed ADC in small cell lung cancer, a notably difficult-to-treat tumor type. New treatment options are desperately needed for these patients where the prognosis remains poor. We are pleased to have recently completed the acquisition of Harpoon Therapeutics, which provides novel T cell engagers, including MK-6070, an investigational delta-like ligand 3 targeting T cell engager, also being evaluated in certain types of small cell lung cancer as well as neuroendocrine tumors. Finally, please mark your calendars for the evening of Monday, June 3, where we will host an investor event at ASCO in Chicago and provide an update on our diverse portfolio of immuno-oncology, precision molecular and tissue-targeting agents. Looking forward, June promises to be a busy month with 3 regulatory action dates, including V116 for prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults. KEYTRUDA for primary advanced or recurrent endometrial carcinoma; and patritumab/deruxtecan for advanced EGFR-mutated non-small cell lung cancer. We continue to execute on our strategy with a focus on operational excellence and look forward to providing further updates on our progress throughout the year. And now I will turn the call back to Peter.

Thank you, Dean. We're ready to begin the Q&A session. Thank you.

This is probably one for Dean. Obviously, you guys have been focused on building out your cardiometabolic franchise now. You have the sotatercept launch underway. You've got an oral PCSK9 in late-stage development. You have a GLP glucagon also moving forward for NASH, I believe. But I guess I'd just be curious how you think about the opportunity in obesity broadly as, on one hand, it seems like it could align with your current footprint. But on the other hand, it seems like Merck has gone more towards specialty markets and away from kind of primary care. So maybe just would love your thoughts there, Dean, as you think about building out.

Thank you very much. We are excited about our developments in the cardiovascular metabolic area. While you mentioned the programs that have the most visibility at the moment, I want to assure you that more programs will become visible in the coming years. Regarding your question about GLP and obesity, there are two perspectives to consider: one focused on GLP and the other on obesity. From the GLP perspective, significant research has shown its effects in diabetes, weight loss, and more recently, cardiovascular outcomes and sleep apnea. We are particularly interested in MASH as an important outcome. We believe there will be distinct populations, whether classified as obese or NASH, within the GLP space. Each of these populations will require a molecule that effectively addresses their primary concerns. For instance, in the case of NASH, we consider our drug to be very tolerable, achieving a notable reduction in liver fat along with a weight loss of 10% to 12%. Different outcomes may necessitate different molecules. In terms of obesity, there is significant work being done. However, I foresee a potential new wave where considerations about oral medications, their tolerability, accessibility, combinations, muscle preservation, and other outcomes become crucial. It’s possible that the best molecule will vary across these subpopulations. Therefore, I wonder if we will see a division within the patient population when we discuss obesity, and we believe there might be an opportunity there.

I wanted to touch on some of your work in lung cancer, specifically with KRAS G12C, echoing Dean's comment. So this space is becoming increasingly crowded. Maybe walk me through what you believe differentiates your assets today from the currently approved one or from the pan-KRAS assets in development.

Yes, this is one of my favorite projects, so I appreciate the question. KRAS is one of the most significant driver mutations in various cancers. More broadly, pan-RAS is also important. Specifically, KRAS G12C represents a small percentage of all KRAS and RAS mutations, but it is notably prevalent in non-small cell lung cancer, affecting about 12% to 15% of that patient group. We have extensive data related to this population, particularly from the KEYNOTE-189 study, which involves chemotherapy combined with immunotherapy. To compete effectively in the first line, we need a powerful compound targeting KRAS. The market is competitive, but the focus should be on a compound that demonstrates strong efficacy as a monotherapy and maintains its effectiveness when combined with other treatments, such as pembro, without requiring dose adjustments. This potential is exciting for us, especially since we reported a 71% objective response rate in combination therapies, which is why we are moving forward with this.

Maybe focusing on the pipeline on areas that you do not highlight as often, specifically immunology. And then a lot of the discovery work that you talk about in CNS. With immunology with a TL1A, can you just help us understand where we are on the Crohn's study there and also the Pandion acquisition, like in just Phase II. And then CNS, you highlight how many folks you have doing discovery research. How do you feel about the distribution of your efforts in CNS there? So just 2 areas not highlighted in the press release, but I think are important to your overall portfolio.

Thank you very much. I will begin with immunology, particularly in the TL1A area. We believe TL1A will be highly effective, showing strong efficacy as well as good tolerability. The Phase III clinical trial for ulcerative colitis has already commenced and is currently recruiting participants. We are optimistic about announcing the start of the Phase III trial for Crohn's disease and welcoming patients in the coming months. We are very excited about advancing TL1A into Phase III to clearly demonstrate the distinct advantages we have observed with our compound. Additionally, we are exploring TL1A’s potential beyond inflammatory bowel disease, as we see promising implications for other conditions. Notably, TL1A offers anti-inflammatory effects, and there is reason to believe it could significantly impact fibrosis, particularly in Crohn's disease. We are also interested in examining other diseases, such as those affecting the lungs, where fibrosis plays a critical role. Furthermore, we have additional projects progressing from the Prometheus acquisition that are not related to TL1A, alongside other internal initiatives moving forward with Alacrity.

I want to ask some on pneumococcal vaccine. You mentioned several times V116 is customized for adults 65 and older. In the ACIP meeting, they discussed a recommendation in adults 50 or older. And I wonder if you could comment on where you think that ACIP recommendation will end up for V116. And on V117, I wonder if you could talk about how the stack scene, which I believe is now in Phase I is customized for pediatric patients.

Yes, let me start by saying that we were very pleased with the overall tone and discussion coming out of the ACIP meeting. Regarding V116, we are confident in the strength of the data behind it. Dean has mentioned some of the clinical readouts that we have seen. It's important to note that V116 covers 83% of the serotypes causing disease in adults, which is 30% more than PCV20. This significant design targets the most prevalent serotypes in adult disease. Therefore, we believe the value proposition of V116 is very compelling. When considering cost-effectiveness, it will be a highly cost-effective vaccine. This is why we've noticed the ACIP raising questions about the 50 to 65 age group in addition to the 65 and older group. While I don't want to preempt the ACIP's recommendation, I want to emphasize our strong belief in the value of the data and the benefits this vaccine will bring to patients in the pneumococcal area. Overall, I expect that we'll see broad coverage from the ACIP.

Yes. I would just add, again, we want to be respectful of ACIP and the FDA. But you did point out something that I think is something that clearly we took notice. When Rob talks about that 83% versus 50% and 30% more, and the specific question that you're asking about 50 to 64, I would remind everyone that dropping that age for universal vaccination has been considered previously for other vaccines. And they could not come to a situation where they thought that it would be a good idea based on cost-effectiveness and as such. And by increasing it from 50% to 83%, we believe that we changed the calculus, and that made why there is renewed interest in lowering that age based on the broader coverage given for V116.

Firstly, I understand that Merck does not provide product-level guidance, but considering the significance of WINREVAIR and the interest from investors, could you share any information regarding WINREVAIR's contribution to guidance? The second question is for Dean regarding REJOICE-Ovarian and precision oncology in general. Is there any understanding in the field about the overlap concerning FRalpha? Additionally, regarding patritumab, although the data for HER3 indicate high expression in advanced patients, there is substantial development occurring in this advanced area. How does Merck plan to position or sequence patritumab?

Yes. Maybe, James, I'll start. And thank you for the question. The short answer is, unfortunately, we don't provide product-level guidance. So I don't think we want to get into trying to tell you what we see WINREVAIR as being a contributor in 2024. But with that said, I think it's important to make a few points just so you understand how we're seeing it. First of all, we're very excited to provide this novel treatment for patients with PAH. As you know, we think this will be a game changer in that space. We were well prepared for the launch. And I can tell you the launch, although very early, is going well so far. We've seen an increasing number of prescriptions being written. We've seen repeat prescriptions, and that's coming both from the COE space, from the Centers of Excellence, which is about 150 in the United States, as well as from non-COEs, which is a good development. We've already begun making shipments to patients' homes. And hopefully, we'll have patients being dosed very soon, if not already. And then I think the other thing I'd note is the prescribers as well as the locations are both from the Centers of Excellence and also non-COE. So that's something to note. And then finally, from a payer perspective, we're seeing good access. No real limits. In fact, we already have several payers who have established coverage policies. And I think as Caroline pointed out in the prepared comments, very consistent with the label and what we saw in STELLAR. But the fact that we've seen policies enacted giving coverage to patients already this quickly after launch, we see as a good sign. It's obviously early. But everything so far looks quite good. So our confidence in a successful launch has not changed. We continue to see this consistent with our expectations. And as we move forward, we'll give you appropriate level of transparency. But I just want to give flavor, even though we can't give the specific guidance you were asking for.

Yes. I'll add a bit regarding WINREVAIR. It's important to highlight that our indication is broad and based on STELLAR. We expect ongoing data flows to enhance our understanding in this area. We have ongoing studies, including STELLAR, SOTERIA in open label, ZENITH focusing on mortality and morbidity, and HYPERION, which is earlier in the disease process. We anticipate European activities taking place in the second half of 2024. I want to stress that self-administration is feasible for healthcare professionals, and we foresee a demand for innovation as self-administration becomes more common. You raised several questions, some of which were about ovarian cancer and, more broadly, tissue targeting and ADCs. To summarize, we are exploring cancers that involve IO and chemo combinations. We consider whether an IO agent can be paired with a chemo agent, looking at KEYTRUDA and newer tissue targeting IOs, such as recent immune engagers from Harpoon. We also consider precision targeting in chemotherapy, like RAS, and the role of ADCs. Regarding HER3 patritumab, it's progressing in EGFR non-small cell lung cancer. We see strong data with B7-H3 in small cell lung cancer and potentially prostate cancer. Regarding CDH6, the ovarian data from raludotatug is particularly compelling, especially initial findings from our partners at Daiichi Sankyo. The overall results for that patient population are impressive, and the effect across various biomarker subsets has caught our attention. I hope this provides a clear overview, and thanks for the question.

I'm just trying to think through your next-gen HPV vaccine. And I guess, how should we think about potential penetration rates with a revaccination opportunity with the new broader-spectrum HPV, especially in patients who have already taken GARDASIL 9.

Revaccination in relationship to HPV, is that what the question is?

I'm having a hard time answering your question because I need to first develop a G9+ that functions exceptionally well. Once that happens, it will be beneficial because there are patient groups that would greatly benefit. However, I want to highlight our discussion about cancer, particularly early-stage cancer, which is the critical period when treatment and potential cures are most effective. Additionally, we focus on cancer prevention. A question we often receive is about certain patient populations that require a vaccine. For instance, in Scandinavia, there's over a 90% reduction in cancer incidents reported. Moreover, with the recent findings from the American Cancer Society, we are curious if a successful G9+ vaccine could fundamentally alter recommendations for cervical cancer screening for women and also contribute to reducing various other cancers in both men and women beyond cervical cancer.

This is Caroline. I'll just add that as we sit here today, we all know there are many, many people around the world that have not received a vaccine to prevent them against, to help protect them from HPV-related cancers. With the possibility of improving upon G9 with a multivalent vaccine, we're hopeful that we can provide further protection, especially for different population groups. And we will price the vaccine appropriately based on the benefit that it will provide. So we're looking forward to continuing to see growth in GARDASIL and see how the science evolves with our clinical programs.

I have a few questions on KEYTRUDA subcu. It may not be scientifically sexy, but of course, it could be quite commercially meaningful. So we'll see that data, I believe, later this year. Any risk whatsoever to that readout? Or can we consider it to be a slam dunk? Second question is when the subcu launches in the U.S., presumably next year, will uptake be fast or slow or somewhere in between? And then eventually, how much can a subcu account for the franchise on a volume or patient basis?

So I'll take the first part of that. I remind myself, nothing is slam dunk once you place innovative drugs in patients. So I'll answer that question. But I think you highlighted really the pembro plus hyaluronidase that we're advancing. I would disagree a little bit. I do kind of think it's sexy in some ways. And that D770, we will be sharing that data by early 2025. The reason I think it's really an important innovation is to really increase the access. You've seen the number of early-stage cancer readouts that are coming through with pembrolizumab and KEYTRUDA and especially in the earlier stages when we talk about KEYNOTE-671, when we talk about in renal cell carcinoma, where we have OS benefit. I think this is going to be really, really important for patients. It will also be important in patients for treatment, especially in those who have monotherapy and those especially combos with oral agents because it just makes it so much more accessible. So we think this is an important program and that it could have substantial impact on patients and their access to PD-1, where we know the foundational elements of PD-1. And in terms of financial...

Yes. Tim, I'll provide some insights on the uptake and the proportion of the patient population this can serve. Firstly, we believe that the strength of the clinical data for the IO agent is crucial. This builds confidence in KEYTRUDA. Secondly, the delivery mechanism plays a significant role as we leverage the data we have and the broad application of KEYTRUDA. As we prepare for the launch, our aim will be to set an appropriate price to encourage rapid adoption. We anticipate seeing substantial adoption. By 2028, if we consider patients on monotherapy with KEYTRUDA, those using combinations with oral agents, and individuals moving into earlier disease stages through our adjuvant and neoadjuvant efforts with KEYTRUDA, this represents about 50% of the patient population at that time. This is the addressable market for our subcutaneous offering. We are also exploring opportunities in the metastatic setting, both in institutional care and for those receiving care outside institutions. The patient benefits include ease of use, as it allows administration outside of hospital settings. The time and share of treatment are reduced when using a subcutaneous option compared to intravenous delivery. Additionally, this change reduces the time patients spend in chairs, enabling more patients to receive care, which we believe enhances access and improves the overall provision of care. This is beneficial for both patients and providers, which leads us to anticipate strong uptake of this significant treatment when we launch it.

I just wanted to ask you for ASCO on June 3. Are there any specific readouts updates that you're very excited about presenting?

I believe there will be a continuous flow of data, along with follow-ups and several key discussions related to various cancer types such as gastric, hepatocellular, biliary, bladder, and non-small cell lung cancer. We will address numerous programs that you may have noticed appearing on the clinical trial website, especially those tied to a range of Phase III developments involving familiar molecules as well as newer candidates like bomedemstat, the KRAS program, and various antibody-drug conjugates. We will provide updates not only on the Daiichi Sankyo ADCs but also on others like TROP2 Claudin. Expect comprehensive discussions about these compounds, some at the ASCO conference and others during the ASCO investor event.

Great. Thanks, Louise. I know we have several more people in the queue. We're going to go an extra 5 or 10 minutes to try to get to as many questions as possible.

Trung Huynh from UBS. On the WINREVAIR launch, thanks for the comments today on access and coverage. On approval, you noted that 2/3 of your PAH patients would likely Part D and a third commercial. Perhaps can you expand on the free assistance program that you're hoping to initiate? And what proportion of those Part D patients do you think could be receiving free product this year?

Yes, I appreciate the question. We are very focused on ensuring that patients get access to the medicine and are committed to this goal. In addition to our usual programs, we also have an independent access program that operates separately from our commercial operations. We do not report data from this program as it is managed through a different foundation, primarily aimed at ensuring that patients receive their medicines. This program is available on our website, and we are dedicated to making sure patients can access the medication. However, we won't go into specifics on that.

Maybe on your personalized cancer vaccine with Moderna, as the Phase III sort of nears completion of enrollment, it of course begs the question around the potential to sort of file based on the existing data you have. Can you maybe just update us on your thoughts there and whether you think you still need Phase III data or manufacturing would preclude an early filing? Any help there would be appreciated.

Yes, I'll take that. I don't want to speculate on the FDA's actions. However, I want to highlight the exciting aspects of our I&T program and our collaboration with Moderna. We are inducing and coaxing immunity and combining it with a well-known drug that enhances pre-existing immunity, which is KEYTRUDA. We have a randomized, early-stage immune-oncology sensitive trial that clearly demonstrates the contribution of components of the INT, not just in terms of immunogenicity but in clinical benefit. I want to emphasize this when comparing our data with that of others. We have also started to advance into Phase III for adjuvant melanoma and adjuvant non-small cell lung cancer, and our ability to expedite this process and successfully enroll patients is crucial, as we will need Phase III data regardless of the FDA’s decision on accelerated approval. Moreover, we are exploring other immune-oncology sensitive tumors like renal cell carcinoma. The strength of our data concerning durability is being addressed, and we are making progress in opening these trials successfully. We acknowledge the significant work done by our colleagues in manufacturing, especially regarding mRNA vaccines, as this will be vital for developing a meaningful treatment. The FDA will ultimately decide how they view this opportunity.

Just a couple of GARDASIL questions. You're pointing to a more evenly distributed China sales this year, and it seems like a tougher 2Q comp. But can you just directionally talk about growth for GARDASIL more broadly for the year? I guess the heart of it is still a healthy growth asset for you this year. And the second one on GARDASIL is if we were to move to a single dose of GARDASIL-9, what does that mean commercially and from a sales perspective for the franchise?

Chris, it's Caroline. So in terms of the phasing of GARDASIL, as you pointed out, during 2023, we saw in China an acceleration of the shipment from the second half of the year to the first half of the year, specifically to the second quarter. What that's done is it's provided an actual tailwind to revenue growth in the first quarter for China, but it will provide a headwind more significant in the second quarter. And that's what we've called out. As we look at overall growth for GARDASIL, given where we are with the level of vaccinations across the world, given the manufacturing that we have been scaling up, we're confident in our ability to continue to drive growth during 2024. And in 2025, we will see our manufacturing capacity unconstrained so enabling us to further supply and support the market. As we've talked in the past, our opportunities for growth are significant as we look to continue to improve on adolescent vaccination rates, as we look to improve upon gender-neutral vaccinations, as we look to really activate the mid-adult segment, but increasingly get to the lower-income and middle-income markets, which will come at a different price point. As we sit here today, continue to be confident in the outlook for GARDASIL over both the near and the long term. As we look at the possibility of a single dose of GARDASIL, the study that we are conducting will be a comprehensive study and will take some time to unfold. What we're seeing in the marketplace currently is where certain low-income markets are implementing a single-dose regimen, they are also increasing the numbers of people they are vaccinating by broadening the age cohort or also opting to vaccinate males at this stage. We'll have to be long term how the data plays out with regards to a single dose to ensure that we will price our vaccine based on the benefit that we're bringing and we vaccinate as many people in the world that we can.

I also have questions on the WINREVAIR launch. I just wanted to check how straightforward the subcutaneous administration is and when you might expect to launch an auto-injector. Also, should we actually expect the Part D access to come online at a similar pace as commercial? I'm just not sure whether that's something that's maybe sitting more into next year. And if I can, just another question on that with Part D is that you price for the Part D restructure next year. How do you expect payers to behave when this happens? I can see that the payer will take on a greater burden for higher-priced oral therapies. Do you expect some pushback within the actual drug that you would have higher rebates at that point? Or do you think that incremental burden for the payers might be spread more broadly across all products? It's a kind of bigger-picture question that WINREVAIR brings it into focus.

So this is Dean. I'll answer your questions in terms of delivery of WINREVAIR. We have it in a vial, and we have it in a situation where both a health care provider or self-administration is both feasible, possible and will be used. We believe that the vast majority with time that people will use it as self-administration. This is a patient population that's quite used to doing injection. So we think that, that will be able to navigate and that the patients will get access. But as you point out, further innovation will be demanded for, and an auto-injector will be critically important. We are doing the studies right now to evaluate how do we provide such an option, and we hope to have those options and those plans more public in the near future. But we agree with you totally in the fact that a future auto-injector will be important.

And Luisa, this is Caroline. At this stage, we are seeing a real acceptance of the value proposition of WINREVAIR in the United States. We're seeing policy for coverage equally across both the Medicare and Medicaid patient population as well as the commercial segment. So as we move forward, we'll look forward to just helping as many patients as we can across all of those segments, irrelevant of their coverage.

Wanted to ask actually about your RSV-targeted antibody, how you're thinking about that, the optionality for it and the market size and Merck's potential participation in this market as it relates to the competitors' global supply constraints at this point in time. It seems like coming to market more aggressively or as aggressively as possible could actually make for a meaningful market opportunity for Merck.

We are excited about clesrovimab. As many may know, it's a monoclonal antibody that provides passive immunity to infants, which we believe is crucial based on recent observations. Our formulation involves a single fixed dose that lasts throughout the entire RSV season, which we think is critically important. Moreover, this can be administered to infants at any time, unlike alternative strategies like maternal vaccination. We also believe our monoclonal antibody stands out due to its high resistance barrier. We are eager to advance this and analyze the data swiftly and rigorously to bring it to market, as we see it being a vital contributor, especially in light of what we observed in the recent RSV season. Additionally, I want to highlight that we are also enthusiastic about our dengue V181, a live attenuated tetravalent vaccine, which is gaining attention in the media. We are equally committed to progressing it into Phase III, having already received positive data from our colleagues at Institute Butantan regarding its effectiveness and efficacy.