Chronic human papillomavirus (HPV) infection

– Phase 1/2 pivotal study met the primary safety and efficacy endpoints – – 51% (18 out of 35) of patients achieved Complete Response, requiring no surgeries after treatment with PRGN-2012; complete responses have been durable beyond 12 months with median duration of follow up of 20 months as of data cutoff –– 86% of patients (30 out of 35) had a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment; RRP surgeries reduced from a median of 4 pre-treatment to 0 post-treatment – – PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2 –– PRGN-2012 treatment induced HPV 6/11-specific T cell responses in RRP patients with a significantly greater expansion of peripheral HPV-specific T cells in responders compared with non-responders – – PRGN-2012 significantly (p < 0.0001) improved Derkay and quality of life scores in complete responders – – RRP is a rare, devastating HPV-mediated chronic disease characterized by growth of benign tumors for which the current standard-of-care is repeated surgeries; if approved, PRGN-2012 has the potential to be the first FDA-approved therapeutic for the treatment of RRP –– Clinical data associated with favorable safety, strong efficacy, ease of administration, and immunological responses, position PRGN-2012 to potentially be the preferred treatment-of-choice for RRP –– PRGN-2012 rolling BLA submission, under an accelerated approval pathway, is anticipated in the second half of 2024 –– Precigen to host webcast event today at 6:00 PM CT / 7:00 PM ET – GERMANTOWN, Md., June 3, 2024 /PRNewswire/ -- Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today released positive Phase 1/2 pivotal study results for the investigational PRGN-2012 off-the-shelf (OTS) AdenoVerse ® gene therapy in patients with recurrent respiratory papillomatosis (RRP). Results were presented in a late-breaking oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting by Scott M. Norberg, DO, Associate Research Physician, Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute and a lead investigator for the PRGN-2012 clinical study. The Company will host a webcast event today at 6:00 PM CT / 7:00 PM ET to detail the results presented at ASCO. Continue Reading "We are thrilled with the results of the Phase 1/2 pivotal study showing more than half of patients were surgery free–Complete Response–and 86% of patients had a significant reduction in the need for surgeries after PRGN-2012 treatment. Based on the efficacy, safety, and ease of administration, we believe PRGN-2012 is a game-changer for RRP patients and has the potential to be the preferred treatment-of-choice for RRP," said Helen Sabzevari, PhD, President and CEO of Precigen. "We look forward to sharing these results with the FDA as part of a rolling Biologics License Application submission under an accelerated approval pathway. We have ramped up our commercial readiness efforts in anticipation of a potential launch in 2025 and are excited by the potential to bring a long overdue new treatment option to the RRP community." Pivotal Study Design and Endpoints The Phase 1/2 clinical study (clinical trial identifier: NCT04724980) evaluated safety and efficacy of PRGN-2012. The study design included an initial 3+3 dose escalation cohort to identify the recommended Phase 2 dose (RP2D). Adult RRP patients who had three or more surgeries in the prior 12 months were eligible for the study. The Phase 1/2 study enrolled a total of 38 patients. Of these, 3 patients received four administrations of PRGN-2012 at 1x 1011 particle units (PU)/dose and 35 patients received four administrations of PRGN-2012 at RP2D (5 x 1011 PU/dose) over a 12 week treatment period via subcutaneous injection. Primary endpoints included safety and Complete Response rate defined as the percentage of patients who require no RRP surgeries in the 12-month period after PRGN-2012 treatment completion. Key secondary endpoints included HPV-specific immune responses, extent of papilloma growth as measured by Derkay scoring, and quality of life measurement as measured by Vocal Handicap Index-10 (VHI-10). Patient Characteristics Baseline patient characteristics of the 35 adult patients included a median age of 49 years (range: 20-88); 20 of the patients were male and 15 were female. Patients had a median of 4 surgeries (range: 3-10) in the 12 months before PRGN-2012 treatment initiation. Average years since RRP diagnosis was 20 (range: 1-65) with 12 and 23 patients with juvenile and adult onset RRP, respectively. Clinical Efficacy Primary efficacy endpoint analysis demonstrated that 51% (18 out of 35) (95% CI: 34-69) patients achieved Complete Response, defined as no need for RRP surgeries in the 12-month period following completion of PRGN-2012 treatment. The Complete Response rate was 50% (6 out of 12) and 52% (12 out of 23) in the Phase 1 and Phase 2 portions of the study, respectively (TABLE 1). Complete Responses were durable. Median durability of response has not yet been reached with median follow up of 20 months as of the data cutoff date of May 20, 2024. PRGN-2012 treatment significantly (p < 0.0001) reduced the need for surgeries in RRP patients compared to pre-treatment history (FIGURE 1). PRGN-2012 treatment reduced the need for RRP surgeries in 86% (30 out of 35) of patients compared to their pre-treatment history. RRP surgeries were reduced from a median of 4 (range: 3-10) in the 12 months pre-treatment to 0 (range: 0-7) in the 12 months post PRGN-2012 treatment completion. PRGN-2012 treatment showed significant (p < 0.0001) improvement in anatomical Derkay scores, a tool used for research purposes to quantify RRP severity based on involvement of laryngeal structures, with mean Derkay scores reducing from 9 (range: 5-19) at baseline to 1 (range: 0-5) at 24 weeks post-treatment in patients with Complete Response. Quality of life, as evaluated using the validated VHI-10, significantly (p < 0.0001) improved from a mean of 25 (range: 12-38) at baseline to 7 (range: 0-30) at 24 weeks post PRGN-2012 treatment in patients with Complete Response. PRGN-2012 treatment induced HPV 6/11-specific T cell responses in RRP patients with a significantly greater expansion of peripheral HPV-specific T cells observed in responders compared with non-responders. Safety PRGN-2012 treatment was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events (TRAEs) greater than Grade 2 (TABLE 2). All patients received four administrations of PRGN-2012 at the intended dose levels. TRAEs were mostly mild with no treatment-related serious adverse events reported. The most common TRAE was injection site reaction. Other common TRAEs occurring in more than one subject were fatigue, chills, and fever. There was no meaningful anti-drug antibody response with repeat administrations of PRGN-2012. SOURCE Precigen, Inc.

Efficacy and Safety Pro Once-Daily Vemlidy Demonstrated in Children Six Years of Age (Weighing at Least 25kg) and Older FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Vemlidy® (tenofovir alafenamide) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease. Vemlidy is a targeted prodrug of tenofovir that was approved by the FDA in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease. In 2022, the FDA approved Vemlidy for the treatment of chronic HBV infection in pediatric patients 12 years of age and older with compensated liver disease. Vemlidy is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines. “Chronic hepatitis B can have a significant and lasting impact on the health of children. If left untreated, hepatitis B can lead to liver cirrhosis and liver cancer,” said Chaun-Hao Lin, MD, Associate Professor of Clinical Pediatrics Krek School of Medicine of USC. “As a clinician, I am well aware of the critical importance of promptly treating this disease to avoid possible complications and liver damage. The clinical trial demonstrated that tenofovir alafenamide may represent an effective treatment option for children as young as six years old affected by this chronic disease.” Vemlidy’s approval in this pediatric patient population is supported by Week 96 data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 18 treatment-naïve and treatment-experienced patients aged 6 to less than 12 years weighing at least 25 kg (Cohort 2, Group 1). Participants in the Vemlidy group and in the placebo group who switched to open-label Vemlidy after Week 24 demonstrated progressive increases in the rates of virological suppression through Week 96 overall and within both study cohorts (children and adolescents). “The expanded indication for Vemlidy for the treatment of children as young as six years old is a testament to the safety, tolerability and efficacy pro this therapy,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Effective and tolerable options for children require our best science and a dedicated focus. The work of our Gilead Pediatric Center of Excellence is responsible for coordinating pediatric clinical trials for treatments for cancer, HIV, hepatitis B, and COVID-19 and we will continue our research to help address unmet treatment needs for children.” Vemlidy has a boxed warning in its product label regarding post-treatment severe acute exacerbation of hepatitis B. See below for important safety information. U.S. IMPORTANT SAFETY INFORMATION AND INDICATION FOR THE USE OF VEMLIDY BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted. Warnings and Precautions Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used. New Onset or Worsening Renal Impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome, have been reported with TAF-containing products. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY 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. Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY 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 events in the week 96 pediatric population reported in ≥5% were: nasopharyngitis, headache, COVID-19, pyrexia, diarrhea, upper respiratory tract infection, cough, respiratory tract infection viral, abdominal pain upper. Overall, abdominal pain upper and metabolic nephropathy were the only study drug–related adverse events, which occurred in > 1 participant, reported in 2.3% (2/88 participants) each. Drug Interactions Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions. Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption. Coadministration of VEMLIDY with carbamazepine, the tenofovir alafenamide dose should be increased to two tablets once daily. Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments. Dosage and Administration Testing Prior to Initiation: HIV infection. Prior to or When Initiating, and During Treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Dosage: 1 tablet taken once daily with food. Renal Impairment: Not recommended in patients with end-stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment. No data are available to make dose recommendations in pediatric patients with renal impairment. Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment. Indication VEMLIDY is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease. About the 1092 Study Study 1092 is an ongoing Phase 2 clinical trial that randomized 88 treatment-naïve and treatment-experienced patients with chronic hepatitis B infection between the ages of 12 to less than 18 years weighing at least 35 kg to receive either Vemlidy 25 mg (N=47) or placebo (N=23) and 6 to less than 12 years weighing at least 25 kg to receive either Vemlidy 25 mg (N = 12) or placebo (N=6) once daily. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 19% (11/59) of patients treated with Vemlidy 25 mg achieved HBV DNA < 20 IU/mL at Week 24 compared to 0% (0/23) of patients treated with placebo. The overall percentage of patients with HBV DNA < 20 IU/mL progressively increased in the Vemlidy 25 mg group relative to the Week 24 time point at both Week 48 (37% [22/59 subjects]) and Week 96 (61.0% [36/59 subjects]). The overall median change from baseline in ALT values for the Vemlidy and placebo-Vemlidy treatment groups, respectively, was -39.5 U/L and -46.5 U/L at Week 96. At 96 weeks, ALT normalization (AASLD criteria) was achieved for 54% of Vemlidy-treated patients and 57% of patients who switched from placebo to Vemlidy. Serum ALT is an enzyme used to monitor liver damage. Importantly, the mean percent changes in bone mineral density from baseline to Week 24 were similar for Vemlidy-treated patients and placebo-treated patients (1.6% (N=48) and 1.9% (N=23) for lumbar spine, and 1.9% (N=50) and 2.0% (N=23) for whole body, respectively). At Week 24, mean changes from baseline BMD Z-scores were 0.01 and -0.07 for the lumbar spine, and -0.04 and -0.04 for whole body, for Vemlidy and placebo groups, respectively. About Hepatitis B Hepatitis B (HBV) is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer, and death in up to a third of patients. Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use, or perinatally from mother to child. Early symptoms may include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives), and joint pain. The disease is often asymptomatic, which may lead to undiagnosed individuals. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes), and right-sided abdominal pain (especially with external pressure or palpitation). About Gilead Sciences in Liver Disease For more than 20 years, Gilead has sought to address some of the biggest challenges in liver disease. The company has transformed the trajectory of multiple liver diseases through a relentless pursuit of innovation and pioneering access programs to bring meaningful therapies to people around the world. More work is required, and Gilead is committed to advancing innovative therapeutics to address the most pressing unmet needs in liver disease and overcoming barriers to better care. 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 and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. 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 or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Vemlidy; the risk that physicians may not see the benefits of prescribing Vemlidy for the treatment of chronic HBV in pediatric patients; and any assumptions underlying any of the foregoing. 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 is cautioned not to place undue reliance on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2023, 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 and disclaims any intent to update any such forward-looking statement. U.S. Prescribing Information for Vemlidy, including BOXED WARNINGS, is available at Vemlidy, Gilead, and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@GileadSciences), or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. View source version on businesswire.com: Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com Source: Gilead Sciences, Inc. View this news release online at:

– Approval Expands on Previous FDA Approval of Vemlidy in Adults Living With This Chronic Liver Disease – –Efficacy and Safety of Once-Daily Vemlidy Demonstrated in Individuals 12 Years of Age and Older – FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Vemlidy® (tenofovir alafenamide) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in pediatric patients 12 years of age and older with compensated liver disease. Vemlidy is a novel, targeted prodrug of tenofovir that was previously approved by the FDA in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease. It is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease in guidelines from the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL).1,2 Vemlidy’s approval in this pediatric patient population is supported by 24-week data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 70 treatment-naïve and treatment-experienced patients aged 12 to less than 18 years weighing at least 35 kg. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 21% (10/47) of subjects treated with Vemlidy 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% (0/23) of subjects treated with placebo. “Chronic hepatitis B can have a significant long-term health impact on children, including the development of liver cancer later in life if the disease is left untreated, which is compounded by treatment challenges in this population,” said Kathleen Schwarz, MD, Pediatric Gastroenterologist, Rady Children’s Hospital-San Diego, an investigator in the Vemlidy clinical trial. “As a clinician, I recognize the critical importance of treating this disease as quickly as possible to help avoid complications and potential damage to the liver. In the clinical trial, we saw that tenofovir alafenamide may represent an effective treatment option for people as young as 12 years of age living with this chronic disease.” “While pediatric hepatitis B prevalence has dropped significantly in the U.S., children who develop chronic hepatitis B following an acute infection can experience lifelong health impact,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “Gilead is focused on meeting the biggest challenges in liver disease and impacting the course of disease. With an established safety pro once-daily dosing, Vemlidy provides physicians a new option to address the treatment needs of pediatric patients living with hepatitis B.” Vemlidy has a boxed warning in its product label regarding post-treatment severe acute exacerbation of hepatitis B. See below for important safety information. U.S. IMPORTANT SAFETY INFORMATION AND INDICATION FOR THE USE OF VEMLIDY BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted. Warnings and Precautions Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used. New Onset or Worsening Renal Impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY 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. Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY 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 all clinical studies through Week 144 were headache, upper respiratory tract infection, abdominal pain, cough, back pain, arthralgia, fatigue, nausea, diarrhea, dyspepsia, and pyrexia. Drug Interactions Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions. Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption. Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments. Dosage and Administration Testing Prior to Initiation: HIV infection. Prior to or When Initiating, and During Treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Dosage: 1 tablet taken once daily with food. Renal Impairment: Not recommended in patients with end stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment. No data are available to make dose recommendations in pediatric patients with renal impairment. Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment. Indication VEMLIDY is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients 12 years of age and older with compensated liver disease. About the 1092 Study Trial 1092 was a Phase 2 clinical trial that randomized 70 treatment-naïve and treatment-experienced patients between the ages of 12 to less than 18 years weighing at least 35 kg to receive either Vemlidy 25 mg (N=47) or placebo (N=23) once daily. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 21% (10/47) of subjects treated with Vemlidy 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% (0/23) of subjects treated with placebo. Investigators also observed higher rates of serum alanine aminotransferase (ALT) normalization based on AASLD criteria at 24 weeks; 44% of Vemlidy-treated patients and 0% of placebo-treated patients achieved ALT normalization, with median (Q1, Q3) changes from baseline in ALT of -32.0 U/L (-63.0, -13.0 U/L) and 1.0 U/L (-10.0, 25.0 U/mL). Serum ALT is an enzyme used to monitor liver damage. Importantly, the mean percent changes in bone mineral density from baseline to Week 24 were numerically similar for Vemlidy- treated patients and placebo-treated patients (2.4% (N=37) and 1.9% (N=18) for lumbar spine, and 1.5% (N=39) and 1.9% (N=18) for whole body, respectively). At Week 24, mean changes from baseline BMD Z-scores were -0.03 and -0.09 for lumbar spine, and -0.05 and -0.01 for whole body, for the Cohort 1 VEMLIDY and placebo groups, respectively. About Hepatitis B Hepatitis B (HBV) is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer and death in up to a third of patients. Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use or perinatally from mother to child. Early symptoms may include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives) and joint pain. The disease is often asymptomatic which may lead to undiagnosed individuals. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes) and right-sided abdominal pain (especially with external pressure or palpitation). About Gilead Sciences in Liver Disease For more than 20 years, Gilead has sought to address some of the biggest challenges in liver disease. The company has transformed the trajectory of multiple liver diseases through a relentless pursuit of innovation and pioneering access programs to bring meaningful therapies to people around the world. More work is required, and Gilead is committed to advancing innovative therapeutics to address the most pressing unmet needs in liver disease and overcoming barriers to better care. 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 and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. 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 the risk that physicians may not see the benefits of prescribing Vemlidy for the treatment of chronic HBV and the possibility of unfavorable results from ongoing and additional clinical studies involving Vemlidy. 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 is cautioned not to place undue reliance 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 June 30, 2022, 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 and disclaims any intent to update any such forward-looking statement. U.S. Prescribing Information for Vemlidy, including BOXED WARNINGS, is available at Vemlidy, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. 1 Terrault NA, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. 2 European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021.