Gilead's Livdelzi® (Seladelpar) Delivers Statistically Significant Composite ALP Normalization in Phase 3 IDEAL Trial in Primary Biliary Cholangitis (PBC)

– IDEAL Evaluated Livdelzi in People Living with PBC with Elevated ALP Levels (1-1.67xULN) on or Intolerant to UDCA –

– 52-Week Results Demonstrate High and Sustained ALP Normalization and Generally Well-Tolerated Safety Profile –

– Findings Add to Growing Evidence Supporting ALP Normalization as an Achievable Treatment Goal in PBC –

Gilead Sciences, Inc. (NASDAQ:GILD) today announced positive results from a Phase 3 study in people with primary biliary cholangitis (PBC), showing that treatment with Livdelzi^® (seladelpar) led to significantly more patients achieving normalization of alkaline phosphatase (ALP), a key liver marker of disease progression, compared with placebo after 52 weeks. The primary endpoint was defined as a composite of ALP ≤ 1.0× upper limit of normal (ULN) and a ≥ 15% decrease from baseline.

These findings were observed in people with inadequately controlled disease, defined as having ALP levels above the ULN and below 1.67×ULN, with an incomplete response or intolerance to ursodeoxycholic acid (UDCA). This population has been underrepresented in prior randomized trials despite being commonly seen in clinical practice.

The safety profile of seladelpar observed in IDEAL was consistent with previously reported Livdelzi studies, with no new safety concerns identified.

"Together with prior pivotal Phase 3 RESPONSE data, which established Livdelzi as the first and only PBC treatment to demonstrate statistically significant reductions in both disease markers and pruritus versus placebo, IDEAL further strengthens support for the efficacy and safety profile of Livdelzi," said Cynthia Levy, MD, Professor of Clinical Medicine and Hepatology, University of Miami Miller School of Medicine. "These results extend the evidence base for Livdelzi to a broader population of people living with PBC and support ALP normalization as an achievable therapeutic goal in patients with ALP between 1 to 1.67xULN."

In PBC, ALP is a key disease marker associated with disease activity and long‑term outcomes. ALP levels above normal, including in the 1.0 to 1.67×ULN range, are associated with increased risk of progression to liver transplant or death compared with normalized ALP levels.

"Advancing and leading in liver disease requires a sustained commitment to addressing areas of persistent unmet need," said Swati Tole, MD, MS, Senior Vice President, Clinical Development, Inflammation, Gilead Sciences. "As the field moves toward ALP normalization as an important treatment goal in PBC, we are focused on generating robust, clinically meaningful evidence to better understand treatment response and inform care—translating scientific progress into meaningful patient impact."

Full data will be presented at an upcoming medical congress, and Gilead will engage with global regulatory authorities to discuss these results.

About IDEAL (NCT06060665)

The IDEAL study is a Phase 3, double‑blind, placebo‑controlled trial designed to evaluate Livdelzi in adults living with primary biliary cholangitis (PBC) who have inadequately controlled disease, defined as having alkaline phosphatase (ALP) levels above normal but less than 1.67× ULN despite treatment with ursodeoxycholic acid (UDCA) or with UDCA intolerance. Its primary objective is to evaluate the effect of Livdelzi treatment at Week 52 compared to placebo, assessing rates of ALP normalization, defined as a composite of ALP ≤ 1.0× upper limit of normal (ULN) and ≥ 15% decrease from baseline in PBC participants with an ALP value greater than ULN but less than 1.67× ULN. A composite was used for the primary endpoint to ensure rigorous evaluation of ALP normalization over time. The study enrolled 96 adults aged 18–75 years.

About PBC

PBC is a chronic, autoimmune disease of the bile ducts that affects approximately 130,000 Americans. PBC is more common in women and causes liver damage that can progress to liver failure and result in the need for liver transplant, if left untreated. The most common symptoms of PBC are pruritus (chronic itch) and fatigue, which up to 80% of people living with PBC can experience and can profoundly compromise quality of life. Symptoms of PBC are often invisible to others and the journey to a PBC diagnosis can be long and challenging.

There is currently no cure for PBC, and treatment goals include reducing the risk of disease progression and reducing the symptoms related to cholestasis (impaired bile flow), such as cholestatic itch. The effect is primarily measured by an improvement in liver biochemical tests, including the improvement and normalization of alkaline phosphatase (ALP) levels, an important marker associated with long‑term outcomes in PBC.

About Livdelzi

Livdelzi (seladelpar) is an oral PPAR‑delta agonist, or delpar, for the treatment of primary biliary cholangitis (PBC). PPAR‑delta is known to regulate key metabolic and liver disease pathways. Preclinical and clinical data indicate that Livdelzi has anticholestatic, anti‑inflammatory, antipruritic, and antifibrotic effects.

Clinical trial data have shown that Livdelzi can support meaningful improvements in key markers of disease activity, including biochemical response and alkaline phosphatase (ALP) normalization, with durable effects observed over long‑term follow‑up in multiple studies.

Livdelzi has the potential to help address ongoing unmet needs for people living with PBC, including those who remain inadequately controlled on existing therapies. Pruritus is a common symptom of PBC that can significantly impair quality of life, and prior studies have demonstrated improvements in pruritus with Livdelzi compared with placebo.

U.S. Indication for Livdelzi

Livdelzi is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. The FDA approved this indication under accelerated approval based on a reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Limitations of Use:

Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

U.S. Important Safety Information for LIVDELZI

Warnings and Precautions

• Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care.
• Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (e.g., jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI.
• Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.

Adverse Reactions

• The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).

Drug Interactions

• OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure.
• Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI.
• Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (e.g., cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure.
• CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions.
• Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.

Pregnancy and Lactation

• Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235.
• Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI.

About Gilead Sciences in Liver Disease

For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. The company has helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For individuals living with hepatitis B or D, Gilead's focus on advancing medicines drives hope that today's research will turn into tomorrow's cures. Beyond viral hepatitis, Gilead is working to deliver advanced treatments for people living with PBC. The commitment of Gilead doesn't stop there. Through ground-breaking science and collaborative partnerships, the company strives to create healthier futures for everyone living with liver disease. Gilead remains devoted to a future without liver disease.

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. 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 within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving seladelpar (such as the IDEAL, ASSURE and any confirmatory studies); uncertainties relating to regulatory applications and related filing and approval timelines, including additional pending and potential applications for seladelpar, 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 clinical programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; 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 March 31, 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.

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

U.S. full Prescribing Information for Livdelzi is available at www.gilead.com.

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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Priscilla White, Media

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Jacquie Ross, Investors

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