Gilead Sciences Demonstrates Commitment to Scientific Innovation In HIV With New Prevention, Treatment and Cure Research Data Presented At AIDS 2020: Virtual

Gilead Sciences, Inc. (Nasdaq:GILD) today announced that new data from the company's HIV research and development program will be presented at the 23rd International AIDS Conference (AIDS 2020: Virtual) from July 6-10. The breadth of data presented at the meeting, along with Gilead-led symposia and workshops, reflect the company's commitment to advancing the scientific understanding of HIV prevention, treatment and cure strategies.

"Continued scientific innovation is essential to better understanding and addressing the evolving needs of people living with or at risk for HIV," said Diana Brainard, MD, Senior Vice President and Virology Therapeutic Area Head, Gilead Sciences. "Gilead is actively pursuing innovative cure and long-term viral suppression strategies, while seeking to optimize antiretroviral and prevention therapies for all individuals impacted by HIV. Through the data presented at AIDS 2020: Virtual, we aim to advance care in a transformative way and contribute to the shared goal of ending the HIV/AIDS epidemic."

Phase 1 trial results supporting further evaluation of a six-month dosing interval for a sustained delivery formulation of Gilead's novel, investigational HIV-1 capsid inhibitor, lenacapavir (GS-6207), will be presented. Lenacapavir is an investigational agent that is being developed as a component of a long-acting regimen in combination with other antiretroviral agents. Lenacapavir disrupts HIV capsid, a multimeric shell that is essential to viral replication, at multiple stages throughout the viral life cycle. In May 2019, the FDA granted Breakthrough Therapy Designation for the development of lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance in combination with other antiretroviral drugs.

HIV treatment data to be presented includes a pooled analysis of four international trials evaluating the safety and efficacy of Biktarvy^® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg; B/F/TAF) in adults aged 65 or older. Additionally, data evaluating the safety and efficacy of an investigational low-dose formulation of E/C/F/TAF (elvitegravir 90 mg/cobicistat 90 mg/emtricitabine 120 mg/tenofovir alafenamide 6 mg) in virologically suppressed children two years or older and weighing 14 to less than 25 kg who are living with HIV will be shared in a late-breaking presentation.

Prevention data around the impact of COVID-19 shelter-in-place orders on pre-exposure prophylaxis (PrEP) access and usage and HIV risk behavior in the United States will be shared in a late-breaking presentation. Data from the ongoing DISCOVER multi-year global Phase 3 registrational clinical trial evaluating the safety and efficacy of once-daily Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg; F/TAF) for PrEP^® will also be presented.

Insights from Gilead's cure research program include an oral presentation on vesatolimod, a toll-like receptor 7 (TLR7) agonist, and dose-dependent immune responses induced in HIV controllers.

Select accepted abstracts are as follows:

Please see below for U.S. Indications and Important Safety Information, including Boxed Warnings, for Biktarvy^® and Descovy for PrEP^®.

Lenacapavir (GS-6207), vesatolimod, and the low-dose formulation of E/C/F/TAF are investigational compounds and are not approved by the U.S. Food and Drug Administration or any other regulatory authority. Their safety and efficacy have not been established. In May 2019, FDA granted Breakthrough Therapy Designation for the development of lenacapavir (GS-6207) for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance.

Biktarvy and Descovy do not prevent other sexually transmitted infections or cure HIV or AIDS.

U.S. Important Safety Information and Indication for Biktarvy

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

• Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.

Contraindications

• Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

Warnings and precautions

• Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions.
• Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
• New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of BIKTARVY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
  Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus.
• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse reactions

• Most common adverse reactions (incidence ?5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).

Drug interactions

• Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
• Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1.
• Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

Dosage and administration

• Dosage: Patients weighing ?25 kg: 1 tablet taken once daily with or without food.
• Renal impairment: Not recommended in patients with CrCl <30 mL/min.
• Hepatic impairment: Not recommended in patients with severe hepatic impairment.
• Prior to or when initiating: Test patients for HBV infection.
• Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.

Pregnancy and lactation

• Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
• Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

U.S. Indication for Biktarvy

Biktarvy is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Biktarvy.

U.S. Important Safety Information and Indication for Descovy for PrEP

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF DESCOVY FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

• Descovy for PrEP must be prescribed only to patients confirmed to be HIV negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed.
• Severe acute exacerbations of hepatitis B have been reported in patients infected with hepatitis B virus (HBV) who discontinued products containing FTC and/or TDF and may occur with discontinuation of Descovy. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients with HBV who discontinue Descovy. If appropriate, anti-hepatitis B therapy may be warranted.

Contraindication:

• Descovy for PrEP is contraindicated in patients with unknown or positive HIV status.

Comprehensive management to reduce risks:

• Use Descovy for PrEP to reduce the risk of HIV-1 infection as part of a comprehensive strategy that includes adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).
• HIV-1 risk factors: Behavioral, biological, or epidemiologic HIV-1 risk factors may include, but are not limited to: condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network.
• Reduce STI risk: Counsel on the use of STI prevention measures (e.g., consistent and correct condom use, knowledge of partner's HIV-1 viremic status, regular testing for STIs).
• Reduce potential for drug resistance: Only prescribe Descovy for PrEP to patients confirmed to be HIV negative immediately prior to initiation, at least every 3 months while taking Descovy, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in patients with undetected HIV-1 infection who are taking only Descovy because Descovy alone is not a complete regimen for treating HIV-1.
  • Some HIV tests may not detect acute HIV infection. Prior to initiating Descovy for PrEP, ask patients about potential recent exposure events. If recent (<1 month) exposures are reported or suspected, or symptoms of acute HIV infection (e.g., fever, fatigue, myalgia, skin rash) are present, confirm HIV-negative status with a test approved by the FDA for use in the diagnosis of acute HIV infection.
  • If HIV-1 infection is suspected or if symptoms of acute infection are present while taking Descovy for PrEP, convert the Descovy for PrEP regimen to a complete HIV treatment regimen until HIV-negative status is confirmed by a test approved by the FDA for use in the diagnosis of acute HIV infection.
• Counsel on adherence: Counsel patients to strictly adhere to daily dosing, as efficacy is strongly correlated with adherence. Some patients, such as adolescents, may benefit from more frequent visits and counseling.

Warnings and precautions:

• New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. Do not initiate Descovy in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue Descovy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients (see Dosage and Administration section).
• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue use if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse reactions:

• Most common adverse reactions (?2%) in the Descovy for PrEP clinical trial were diarrhea, nausea, headache, fatigue, and abdominal pain.

Drug interactions:

• Prescribing information: Consult the full Prescribing Information for Descovy for more information, warnings, and potentially significant drug interactions, including clinical comments.
• Metabolism: Drugs that inhibit P-gp can increase the concentrations of tenofovir alafenamide (TAF), a component of Descovy. Drugs that induce P-gp can decrease the concentrations of TAF, which may lead to loss of efficacy.
• Drugs affecting renal function: Coadministration of Descovy with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

Dosage and administration:

• Dosage: One tablet taken once daily with or without food.
• HIV screening: Test for HIV-1 infection immediately prior to initiating, at least every 3 months during use, and upon diagnosis of an STI (see Warnings and Precautions section).
• HBV screening: Test for HBV infection prior to or when initiating Descovy.
• Renal impairment and monitoring: Not recommended in patients with creatinine clearance (CrCl) <30 mL/min. Prior to or when initiating Descovy, and during use on a clinically appropriate schedule, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.

U.S. Indication for Descovy for PrEP

Descovy for PrEP is indicated in at-risk adults and adolescents (?35 kg) to reduce the risk of sexually acquired HIV-1 infection, excluding individuals at risk from receptive vaginal sex. HIV-1?negative status must be confirmed immediately prior to initiation.

Limitation of Use:

• Descovy for PrEP is not indicated in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.

About Gilead Sciences

Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.

For more than 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention, testing and linkage to care, and cure research. Today, it's estimated that more than 12 million people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company's manufacturing partners.

Gilead is committed to supporting the global health community to quickly and effectively respond to serious and life-threatening viral outbreaks worldwide. To that end, we are contributing our antiviral expertise and resources to help investigate potential treatments for patients with COVID-19.

Forward-Looking Statement

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 the possibility of unfavorable results from ongoing and additional clinical trials involving Biktarvy, Descovy for PrEP, the low-dose formulation of E/C/F/TAF, lenacapavir and vesatolimod, and the possibility that we are unable to complete one or more of such trials on the currently anticipated timelines or at all. In addition, it is possible that Gilead may make a strategic decision to discontinue development of the low-dose formulation of E/C/F/TAF, lenacapavir and vesatolimod, and as a result, the low-dose formulation of E/C/F/TAF, lenacapavir and vesatolimod may never be successfully commercialized. All statements other than statements of historical fact are statements that could be deemed forward-looking statements.

These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Biktarvy, and Descovy for PrEP, including BOXED WARNINGS, is available at www.gilead.com

Biktarvy, Descovy, Descovy for PrEP, Gilead and the Gilead logo are 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 Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.