Merck Investor update

Good morning, everyone, and thank you for joining us for Merck's HIV Investor event following the 26th International AIDS Conference that took place in Rio de Janeiro, Brazil last week. Before we get started, I'd 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 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 2025 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 & Co., Inc., Rahway, New Jersey, U.S.A., 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 and our SEC filings are posted to the investor relations section of our company's website. Joining me today are Dr. Eliav Barr, Senior Vice President and Chief Medical Officer, Dr. Liz Ray, Vice President of Clinical Research for Infectious Diseases, and Brian Foard, Executive Vice President and President, Specialty Pharma and Infectious Diseases Business Unit. Now moving to the agenda. Eliav will begin with an overview of the HIV landscape and our strategy.

Liz will then discuss the data that was presented at AIDS 2024, and Brian will finish by discussing the commercial opportunity associated with our portfolio before we then move to Q&A. During Q&A, we will be joined by Gregg Szabo, head of our global HIV franchise. With that, let me turn it over to Eliav.

Thank you, Peter. Good morning, everyone, and thank you for joining us today. We are meeting at an exciting time for our HIV development program. At AIDS 2024, we presented important updates across several programs that have the potential to improve outcomes for individuals living with or at risk of HIV infection. Most notably, we shared positive phase III results from the ISLAND-1 and ISLAND-2 studies, evaluating once-weekly islatravir plus lenacapavir while continuing to advance our broader efforts in both treatment and prevention. Now, before discussing our strategy and the data presented at the AIDS Conference, I wanted to step back and frame how we think about HIV today. For more than four decades, Merck has remained committed to HIV research innovation. Over that period, the HIV epidemic has transformed from a uniformly fatal disease into a chronic, manageable condition for many people around the world.

At the same time, we are far from ending the damage caused by this epidemic. Despite the availability of active antiretroviral regimens and prophylaxis options, we are far from meeting the 2030 goals public health authorities have set some years ago. Progress has slowed for many reasons, the most important of which are the known limitations of current HIV treatment and prevention regimens and the evolving nature of the epidemic. Now, putting a real dent into the HIV epidemic will require a diverse set of highly efficacious treatment and prevention strategies that reduce the burden on people and practitioners and fit seamlessly into the fabric of the communities impacted by HIV. Now, many of the medical tools needed to further reduce the impact of the HIV epidemic are already within reach in our pipeline.

We have focused on developing simple, easy-to-use pills that can be highly effective oral treatment and prevention regimens. Now, we've made tremendous progress over the past year in our clinical development program. Now, we now have a new approved daily treatment option, positive phase III data supporting a potentially first once-weekly oral treatment regimen, continued advancement of another weekly oral program to provide more choice, and ongoing phase III development of a monthly oral PrEP pill. Today, we're excited to share with you our innovative weekly oral approach to treatment and monthly approach to prevention. With that, let me turn it over to Liz.

Thank you, Eliav. Good morning, everyone. I'm so pleased to be here this morning to share with you the data we presented at AIDS 2024 across both of our weekly oral treatment programs. I'll begin with the phase III results for islatravir lenacapavir and then discuss the phase II data for islatravir rilpivirine and the path forward into phase III. This slide highlights how dramatically HIV treatment has evolved over the past decades. It has progressed from the early days, when complex regimens required as many as 16 pills per day, or more than 5,800 pills per year, to the modern single-tablet regimens that are taken daily.

Today, we are evaluating the potential for once-weekly oral treatment, reducing the floor for pill burden from 365 tablets per year to just 52. The data we presented at AIDS on our two weekly oral treatment programs that are given weekly support that next step in HIV treatment evolution. We'll start with ISLAND-1, which was a global phase III double-blinded study evaluating islatravir/lenacapavir, once-weekly two-drug combination given orally against the daily three-drug treatment of bictegravir FTC TAF, studied in virologically suppressed adults. In this trial, a total of 607 participants were randomized one to one to each treatment group. The primary endpoint was HIV RNA greater than or equal to 50 copies per milliliter at week 48 by the FDA snapshot analysis. Secondary endpoints included rates of viral suppression, CD4 cell count changes, and treatment discontinuations.

Results in ISLAND-1 for islatravir/lenacapavir show that non-inferior efficacy was achieved against the comparator bictegravir FTC TAF. The regimen demonstrated efficacy as well in terms of rates of viral suppression, which were above 90% through week 48, and importantly, there was no treatment-emergent resistance to either islatravir or lenacapavir in this trial. These strong efficacy results support the potential for islatravir/lenacapavir as the first complete once-weekly oral treatment regimen for HIV. In ISLAND-2, the second phase III trial, we also evaluated islatravir/lenacapavir. In this study, the design was open label, and the comparator was a variety of daily oral treatment regimens. In this study, we enrolled 626 participants who were randomized to these two regimens. Similar to ISLAND-2, islatravir/lenacapavir also demonstrated non-inferior efficacy. Rates of viral suppression as well in this study remained high at approximately 95%.

Importantly, in ISLAND-2, because of the open label study design, we had the opportunity to examine participant satisfaction with weekly oral treatment. Participants reported being more satisfied with islatravir/lenacapavir than with their standard of care therapies that they had come in on. As well, found islatravir/lenacapavir to be less of a burden compared with daily orals. We were very pleased to see these satisfaction rates. In addition, safety across ISLAND-1 and ISLAND-2 were consistent. Islatravir/lenacapavir was well-tolerated with a safety profile comparable to bictegravir FTC TAF and standard of care regimens. There were no clinically meaningful changes in lymphocytes, CD4 counts, or body weight that were observed, and there were no participants discontinued due to declines in CD4 or absolute lymphocyte counts. Taken together, these data support the potential for islatravir/lenacapavir to become the first once-weekly oral single tablet regimen for the treatment of HIV.

Across both phase III studies, we observed high rates of viral suppression, no resistance signals, and safety and tolerability comparable with the control arms. We look forward to submitting islatravir/lenacapavir to global regulatory authorities and working to bring this innovative weekly option to appropriate people living with HIV as quickly as possible. I'll now turn to our wholly owned investigational once-weekly oral treatment regimen containing islatravir and ulonivirine. As we've discussed in the past, the once-weekly two-drug combination of islatravir and ulonivirine has the potential to be the smallest weekly pill approved, with no loading dose and a favorable DDI profile. In addition, this is being evaluated not just in virologically suppressed, but also in treatment-naive participants.

At AIDS 2024, we presented data from the phase II-B trial of islatravir and ulonivirine with week 24 results demonstrating that the combination maintained viral suppression and demonstrated efficacy comparable to continuing daily bictegravir FTC TAF. There were no participants on the islatravir/ulonivirine group with an HIV RNA greater than or equal to 50 copies per mL, and viral suppression rates were high at over 94% of participants remaining suppressed. Importantly, there were no treatment-emergent resistance cases detected. In the trial, islatravir/ulonivirine was generally well-tolerated. There were no new safety concerns identified. In addition, the adverse event profile was comparable to bictegravir FTC TAF, and we observed no meaningful effect on lymphocyte counts or CD4 counts. Based on these results, we plan to advance islatravir ulonivirine into a comprehensive phase III program.

The SYMPHORIA studies will evaluate this combination in both virologically suppressed adults switching from daily therapy and in adults with HIV without prior treatment experience. The phase III trials in virologically suppressed adults, SYMPHORIA number one and number two, are anticipated to open in the first half of 2027. SYMPHORIA number three, the study in treatment-naive participants, is a phase II/III trial. The phase II component has been completely enrolled, and we anticipate results in the first half of 2027. With that, I'll turn it over to Brian.