– Zero HIV Acquisitions Occurred Among Participants Receiving Twice-Yearly Lenacapavir During the 52-Week Study Period –

– PURPOSE 5 Study Findings Highlight the Potential of Long-Acting HIV Prevention Option to Address Persistence Challenges with Up to a Full Year of Protection After Second Dose –

Company Website: https://www.gilead.com/
FOSTER CITY, Calif. -- (Business Wire)

GileadSciences, Inc. (Nasdaq: GILD) today announced results from the PURPOSE 5 trial showing significantly higher persistence—defined as consistent and continuous on-time use—among people starting twice-yearly injectable lenacapavir for HIV prevention as pre-exposure prophylaxis (PrEP), compared with those starting daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF). The trial included people in the United Kingdom (UK) and France who would benefit from PrEP. These data will be presented at HIV Glasgow 2026.

Key Highlights:

• Twice-yearly lenacapavir achieved significantly higher one-year PrEP persistence than daily oral F/TDF, with 85.6% of participants receiving twice-yearly lenacapavir remaining persistent through Week 52 compared with 46.3% for participants taking once-daily F/TDF (p<0.0001).
• PURPOSE 5 is the first randomized study specifically designed to compare persistence between a long-acting HIV prevention option and daily oral PrEP among individuals not currently taking PrEP.
• Zero HIV acquisitions occurred among participants receiving twice-yearly lenacapavir during the 52-week study period.
• Results highlight the potential of twice-yearly lenacapavir to address persistence challenges that can limit the effectiveness of HIV prevention efforts.

Despite substantial progress in HIV prevention, approximately 1.2 million people acquired HIV globally in 2025, according to UNAIDS, underscoring the need for prevention options that better support long-term use and protection. Persistence on PrEP remains one of the most important determinants of real-world prevention effectiveness. Daily oral F/TDF is currently the most commonly used oral PrEP medication globally.

“While starting on PrEP is important, persisting on PrEP is critical to preventing HIV acquisition,” said Professor Chloe Orkin, MBE, Clinical Professor of Infection and Inequities, Queen Mary University of London. “In PURPOSE 5, people in France and the United Kingdom receiving twice-yearly lenacapavir injections were much more likely to keep taking PrEP effectively compared with those receiving daily PrEP tablets. These findings suggest long-acting injections for PrEP may help address a very important barrier to sustained HIV prevention for people who need it. It is notable that the study was able to reach a high proportion of new PrEP users.”

“This study was designed specifically to evaluate one of the most important challenges in HIV prevention today: helping people remain on PrEP for as long as they need protection,” said Jared Baeten, MD, PhD, Senior Vice President, Clinical Development, Virology Therapeutic Area Head, Gilead Sciences. “These results demonstrate that twice-yearly lenacapavir has the potential to help close the gap between starting PrEP and staying on PrEP which can have an important impact on our efforts to end the HIV epidemic in Europe and around the world.”

PURPOSE 5 Results

PURPOSE 5 is an ongoing Phase 2, randomized, open-label study evaluating PrEP persistence among individuals with HIV prevention needs in the United Kingdom and France who were not taking PrEP at the time of enrollment. Participants were randomized 2:1 to receive either twice-yearly lenacapavir or daily oral F/TDF and were followed for 52 weeks.

A total of 267 participants enrolled in the study, including cisgender men (72.3%), cisgender women (7.1%) and gender-diverse individuals (20.6%). 37.8% were PrEP-naïve at baseline.

At Week 52:

• 85.6% (154/180) of participants receiving twice-yearly lenacapavir remained persistent on PrEP
• 46.3% (37/80) of participants receiving daily oral F/TDF remained persistent on PrEP
• The difference of 39.3 (95% CI: 26.66% - 51.41%) was statistically significant (p<0.0001)

Zero HIV acquisitions occurred among participants receiving lenacapavir. One HIV acquisition was reported in the F/TDF group; drug-level analysis at the time of diagnosis was consistent with fewer than two doses of F/TDF per week. Participant retention across both groups remained high throughout the study, with 89.4% of participants in the lenacapavir group and 83.9% of participants in the F/TDF group attending the Week 52 study visit.

For the purpose of this study Gilead used strict protocol definitions of persistence. For lenacapavir persistence was defined as receipt of on-time LEN injection at Day 1/baseline and week 26 (+/- 2 weeks) and on-time follow-up visit at week 52. For F/TDF persistence was defined as dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations consistent with ≥ 4 doses/week (≥ 700 fmol/punch) at Weeks 13, 26, 39, and 52.

Safety

The safety profile observed in PURPOSE 5 was generally consistent with previous studies of lenacapavir for HIV prevention. Serious adverse events were uncommon and occurred in 3.9% of participants receiving lenacapavir and 3.4% of participants receiving F/TDF. Investigators determined that no serious adverse events were related to study treatment. No participants discontinued treatment due to adverse events with lenacapavir. The most common treatment-related events were mild or moderate injection-site reactions (ISRs) associated with subcutaneous lenacapavir administration, and included nodules (67.8%), pain (60.0%), induration (20.6%), and erythema (17.8%).

Addressing a Critical HIV Prevention Challenge

Although awareness and availability of PrEP have increased, persistence remains a challenge across many settings. Daily oral PrEP is highly effective when taken as prescribed, but real-world studies have consistently shown that many individuals discontinue PrEP within the first year of use. By reducing dosing frequency to one dose every six months, twice-yearly lenacapavir has the potential to offer a discreet and convenient HIV prevention option that may better align with the needs and preferences of some individuals more vulnerable to HIV acquisition.

About PURPOSE 5

PURPOSE 5 is the first randomized study designed specifically to compare persistence between a long-acting injectable HIV prevention option and daily oral PrEP among individuals who would benefit from PrEP and were not currently taking oral PrEP. The Phase 2 study conducted in the United Kingdom and France evaluates whether twice-yearly lenacapavir can improve persistence compared with daily oral F/TDF over 52 weeks.

PURPOSE 5 is part of Gilead’s broader PURPOSE clinical development program evaluating lenacapavir across diverse populations and settings with the goal of expanding HIV prevention choice through long-acting prevention options.

About the PURPOSE Program

Gilead’s landmark PURPOSE program is the most comprehensive and diverse HIV prevention trial program ever conducted. The program comprises five HIV prevention trials around the world that are focused on innovation in science, trial design, community engagement, and health equity.

The PURPOSE 1 and PURPOSE 2 trials evaluated the safety and efficacy of twice-yearly injectable lenacapavir to reduce the chance of getting HIV. The ongoing Phase 2 and 3 program, consisting of PURPOSE 1-5 studies, is assessing the potential of lenacapavir to help a diverse range of people around the world who could benefit from PrEP.

More information about the PURPOSE program, including individual trial descriptions, populations and locations, can be found at www.purposestudies.com.

About Lenacapavir

Twice-yearly lenacapavir is approved in multiple countries as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV in adults and adolescents who are at risk of HIV acquisition. Lenacapavir is also approved in multiple countries for the treatment of multi-drug-resistant HIV in adults, in combination with other antiretrovirals.

The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes.

Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program, including a once-yearly injection for HIV prevention. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. The journal Science named lenacapavir its 2024 “Breakthrough of the Year.”

Indication for Yeytuo^® (lenacapavir)

Yeytuo injection is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents with increased HIV-1 acquisition risk weighing at least 35kg.

Indication for Yeztugo^® (lenacapavir)

Yeztugo is indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35kg) who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating Yeztugo.

Important Safety Information for Yeztugo

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF YEZTUGO IN UNDIAGNOSED HIV-1 INFECTION

• Individuals must be tested for HIV-1 infection prior to initiating Yeztugo, and with each subsequent injection of Yeztugo, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of Yeztugo by individuals with undiagnosed HIV-1 infection. Do not initiate Yeztugo unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving Yeztugo must transition to a complete HIV-1 treatment regimen.

Contraindications

• Yeztugo is contraindicated in individuals with unknown or positive HIV-1 status.

Warnings and precautions

• Comprehensive risk management:
  • Use Yeztugo to reduce the risk of HIV-1 acquisition as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).
  • HIV-1 acquisition risk includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or present STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network. Counsel individuals on the use of other prevention methods to help reduce their risk.
  • Use Yeztugo only in individuals confirmed to be HIV-1 negative. Evaluate for current or recent signs or symptoms consistent with HIV-1 infection. Confirm HIV-1 negative status prior to initiating, prior to each subsequent injection, and as clinically appropriate.
• Potential risk of resistance:
  • There is a potential risk of developing resistance to Yeztugo if an individual acquires HIV-1 before or when receiving Yeztugo, or following discontinuation. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection taking only Yeztugo, because Yeztugo alone is not a complete regimen for HIV-1 treatment.
  • To minimize this risk, it is essential to test before each injection and additionally as clinically appropriate. Individuals confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen.
  • Alternative forms of PrEP should be considered after discontinuation of Yeztugo for those who are at continuing risk of HIV-1 acquisition and should be initiated within 28 weeks of the last Yeztugo injection.
• Long-acting properties and potential associated risks:
  • Residual concentrations of Yeztugo may remain in systemic circulation for up to 12 months or longer after the last injection.
  • Select individuals who agree to the required injection dosing schedule because nonadherence or missed doses could lead to HIV-1 acquisition and development of resistance.
• Serious injection site reactions: Improper administration (intradermal injection) has been associated with serious injection site reactions, including necrosis and ulcer. Only administer Yeztugo subcutaneously.

Adverse reactions

• Most common adverse reactions (≥5%) in Yeztugo clinical trials were injection site reactions, headache, and nausea.

Drug interactions

• Strong or moderate CYP3A inducers may significantly decrease Yeztugo concentrations. Dosage modifications are recommended when initiating these inducers.
• It is not recommended to use Yeztugo with combined P-gp, UGT1A1, and strong CYP3A inhibitors.
• Coadministration of Yeztugo with sensitive substrates of CYP3A or P-gp may increase their concentrations and result in the increased risk of their adverse events. Yeztugo may increase the exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last injection of Yeztugo.

Dosage and administration

• HIV screening: Test for HIV-1 infection prior to initiating, prior to each subsequent injection, and as clinically appropriate using an approved or cleared test for the diagnosis of acute or primary HIV-1 infection.
• Dosage: Initiation dosing (injections and tablets) followed by once-every-6-months continuation injection dosing. Tablets may be taken with or without food.
  • Initiation: Day 1: 927 mg by subcutaneous injection (2 x 1.5-mL injections) and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally.
  • Continuation: 927 mg by subcutaneous injection every 6 months (26 weeks) from date of last injection ±2 weeks.
• Anticipated delayed injections: If scheduled 6-month injection is anticipated to be delayed by more than 2 weeks, Yeztugo tablets may be taken on an interim basis (for up to 6 months) until injections resume. Dosage is 300 mg orally (1 x 300-mg tablet) once every 7 days. Resume continuation injections within 7 days of the last oral dose.
• Missed injections: If more than 28 weeks have elapsed since the last injection and Yeztugo tablets have not been taken, restart with initiation dosing if clinically appropriate.
• Dosage modifications of Yeztugo are recommended when initiating with strong or moderate CYP3A inducers. Consult the full Prescribing Information for recommendations.

About Gilead HIV

For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 14 HIV medications, including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people.

Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships, collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic worldwide. Gilead has been repeatedly recognized as one of the top two leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS.

Discover more about Gilead’s unique collaborations worldwide and the work to help end the HIV epidemic.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. In 2025, Gilead announced a $32 billion investment to further strengthen its U.S. footprint to power the next era of discovery, job creation and public health preparedness – while continuing to invest globally to ensure patients everywhere benefit from its scientific innovation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress and complete clinical trials in the anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials, including those involving lenacapavir (such as PURPOSE 5); uncertainties relating to regulatory applications and related filing and approval timelines, including regulatory applications for lenacapavir for PrEP, and the risk that any regulatory approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of lenacapavir for indications currently under evaluation and, as a result, lenacapavir may never be successfully commercialized for such indications; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2026, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.

U.S. full Prescribing Information for Truvada (F/TDF) and Yeztugo, including Boxed Warning, are available at www.gilead.com.

Gilead and the Gilead logo, Truvada, Yeztugo and Yeytugo are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).

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investor_relations@gilead.com

Source: Gilead Sciences, Inc.