Granulocyte colony-stimulating factor(Shire Pharmaceuticals Services Ltd.)

4WARD Phase 3 chronic neutropenia trial in full swing; full enrollment on track for 3Q or 4Q 2025 and top-line data in 2H 2026 Additional analyses of mavorixafor clinical trial data increase confidence in successful outcome of 4WARD trial XOLREMDI® net U.S. revenues $3.5 million since May 2024 launch Conference call and webcast today at 8:30 am ET BOSTON, May 01, 2025 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today reported financial results for the first quarter ended March 31, 2025, and highlighted key recent events and expected upcoming milestones. “The first quarter of 2025 was an extremely productive and value-adding period for X4,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “Not only did we make significant progress in activating sites and enrolling participants in our ongoing mavorixafor Phase 3 trial in chronic neutropenia, but we also continued to support U.S. commercialization of XOLREMDI (mavorixafor) in WHIM syndrome, while also significantly expanding our global potential following acceptance of our EU regulatory submission in WHIM and the announcement of two international commercialization partnerships. We look forward to continuing to deliver on our milestones in the coming year toward our goal of maximizing the potential of mavorixafor to benefit patients with rare immunodeficiencies.” Key First-Quarter 2025 and Recent Corporate Highlights Advancing Mavorixafor in Chronic Neutropenia (CN) 4WARD Trial Updates. X4 continues to enroll participants in its ongoing global, pivotal Phase 3 clinical trial (NCT06056297), evaluating oral, once-daily mavorixafor in people with congenital, acquired primary autoimmune, or idiopathic CN who are experiencing recurrent and/or serious infections. As previously reported, an amendment to the 4WARD protocol has been implemented, focusing enrollment on those with the highest unmet needs and refining the definition of ANC response, making it consistent across all trial participants. Overall, the trial seeks to demonstrate statistically significant increases in ANC response and corresponding decreases in annualized infection rate between those on mavorixafor versus placebo.To date, the demographics of the enrolled population are balanced and representative of the targeted commercial CN patient populations; baseline absolute neutrophil counts (ANC) and historical infection rates are consistent with this high unmet need population.X4 continues to expect full enrollment in the trial in the third or fourth quarter of 2025, and disclosure of top-line data in the second half of 2026. Further Data Analyses Continue to Increase Confidence in Potential 4WARD Success. X4 recently applied the 4WARD trial ANC response criteria to individual participant results in the completed mavorixafor Phase 3 4WHIM trial and the Phase 2 CN trial to further assess the likelihood of 4WARD trial success. The company believes that the results of these analyses (details of which are available in the company’s updated investor presentation) further support the potential of mavorixafor to not only elevate ANC in the 4WARD trial participants, but that these ANC elevations should correspond with significant reductions in annualized infection rates in the mavorixafor treated trial population.Mavorixafor Patent Update: In March 2025, X4 received a Notice of Allowance from the U.S. Patent and Trademark Office on its application 17/941,509, which claims include the use of mavorixafor in treating severe chronic, idiopathic, and autoimmune neutropenia in patients without a CXCR4 genetic variation. The patent is expected to expire in the U.S. in March of 2041; similar patent applications are pending in Europe, China, Japan, and Canada. Commercializing XOLREMDI® (mavorixafor) in WHIM Syndrome, a Rare Primary Immunodeficiency Revenue Update: X4 has now generated $3.5 million in U.S. sales of XOLREMDI (mavorixafor) from its mid-May 2024 launch through March 2025. The company also disclosed that newly identified patients on treatment are increasing in share of the overall current population on XOLREMDI, demonstrating the positive impact of ongoing WHIM education and awareness.Upcoming WHIM Clinical and Survey Data Presentations: Published abstracts accepted for poster presentation at the upcoming meeting of the Clinical Immunology Society (CIS) summarize the following results: Phase 3 Open Label Extension (OLE) Wart Data: Two-year data from the OLE phase of the 4WHIM Phase 3 clinical trial evaluating once-daily oral mavorixafor in people with WHIM syndrome revealed marked clinical improvement in wart severity as assessed by Clinical Global Impression of Severity across 70 defined wart areas.First-Ever WHIM Infection Burden Survey Results: Of the 20 WHIM patient respondents, 60% of those <18 years and 73% of those ≥18 years reported experiencing at least one infection in the previous 3 months, with 25% requiring overnight hospitalization due to infection. The study concludes that “the frequency and severity of infections requiring medical care and hospitalization underscores the urgency to proactively treat patients with WHIM syndrome.” Maximizing the Global Opportunity for Mavorixafor in WHIM Syndrome: MAA Acceptance. In January 2025, X4 announced that its submitted Marketing Authorization Application (MAA) for mavorixafor in the treatment of WHIM syndrome was validated for review by the European Medicines Agency (EMA), enabling possible approval in the first half of 2026.Ex-US Partnerships. In the first quarter of 2025, the company announced that it had entered into two ex-U.S. partnerships for the commercialization of mavorixafor: the first, an exclusive licensing and supply agreement under which Norgine Pharma UK will commercialize mavorixafor in Europe, Australia, and New Zealand and the second, with taiba rare to distribute and commercialize XOLREMDI for the treatment of WHIM syndrome in Saudi Arabia, United Arab Emirates, Qatar, Oman, Kuwait, Bahrain, and Egypt following the necessary regulatory approvals in those countries and/or regions. Strategic RestructuringIn February 2025, X4 announced a strategic restructuring to sharpen focus and maximize the opportunity for mavorixafor in chronic neutropenia while also optimizing its U.S. promotion of XOLREMDI. X4 continues to expect that these efforts will decrease spending by $30-35 million annually. Reverse Stock SplitOn April 24, 2025, X4 announced a one-for-thirty reverse stock split of the company’s common stock. The reverse stock split took effect at 12:01 a.m. ET on April 28, 2025, and the company’s common stock began trading on a split-adjusted basis on The Nasdaq Capital Market as of the opening of trading the same day under a new CUSIP number (98420X202). The reverse split reduced the number of outstanding shares of the company’s Common Stock from approximately 173.6 million shares to approximately 5.8 million shares. First-Quarter 2025 Financial Results Cash position: X4 had $87.7 million in cash, cash equivalents, restricted cash, and marketable securities as of March 31, 2025. The company continues to believe it has sufficient funds to support operations into the first half of 2026.Revenue and Cost of Revenue: For the first quarter ended March 31, 2025, X4 reported net revenue of $28.8 million and cost of revenue of $4.7 million. Revenue in the quarter included license and other revenues of $27.9 million associated with the completed Norgine agreement and XOLREMDI product revenue of $0.9 million. Cost of revenue included $4.5 million of sublicense royalties associated with the Norgine agreement.Research and Development (R&D) Expenses were $18.5 million for the first quarter ended March 31, 2025, as compared to $19.9 million for the comparable period in 2024. R&D expenses included $0.3 million of certain non-cash expenses for the first quarter ended March 31, 2025.Selling, General, and Administrative (SG&A) Expenses were $15.0 million for the first quarter ended March 31, 2025, as compared to $17.4 million for the comparable period in 2024. SG&A expenses included $0.3 million of certain non-cash expenses for the first quarter ended March 31, 2025.Net Income (Loss): X4 reported net income of $0.3 million for the first quarter ended March 31, 2025, as compared to a net loss of $51.8 million for the comparable period in 2024. Net income included $0.5 million of stock-based compensation expenses for the first quarter ended March 31, 2025. Conference Call and Webcast X4 will host a conference call and webcast today at 8:30 am ET to discuss these financial results and business highlights. The conference call can be accessed by dialing 1-800-343-4849 from the United States or 1-203-518-9848 internationally, followed by the conference ID: X4PHARMA. The live webcast will be accessible through the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the conclusion of the call, a webcast replay will be available on the website. About WHIM SyndromeWHIM syndrome is a rare, combined primary immunodeficiency and chronic neutropenic disorder caused by CXCR4 receptor dysfunction that results in impaired mobilization of white blood cells from the bone marrow into peripheral circulation. WHIM syndrome is named for its four classic manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, although only a minority of patients experience all four manifestations in the acronym. People with WHIM syndrome characteristically have low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), and as a result, experience serious and/or frequent infections. About XOLREMDI® (mavorixafor)XOLREMDI (mavorixafor) is a selective CXCR4 receptor antagonist approved in the U.S. as a once-daily oral treatment for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. XOLREMDI is the only treatment specifically approved for patients with WHIM syndrome in the U.S. About Chronic Neutropenia and MavorixaforChronic neutropenia is a primary, rare blood condition lasting more than three months, persistently or intermittently, and characterized by low levels of circulating neutrophils and increased risk of infections and reduced quality of life due to abnormally low levels of neutrophils circulating in the blood. Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis, creating a reserve of cells. Downregulation of the CXCR4 receptor by mavorixafor, an orally active CXCR4 antagonist, has been shown to mobilize functional neutrophils from the bone marrow into the peripheral blood across multiple disease states. The level of circulating neutrophils is typically measured by drawing blood to determine the absolute neutrophil count (ANC). About the 4WARD Clinical TrialThe 4WARD trial is a global, pivotal Phase 3 clinical trial (NCT06056297) evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without G-CSF) in people with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants with confirmed trough ANC levels less than 1,000 cells per microliter at baseline screening and histories of two or more serious and/or recurrent infections in the prior year. The primary endpoint of the trial is based on two outcome measures: annualized infection rate and positive ANC response. About X4 PharmaceuticalsX4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging expertise in CXCR4 and immune system biology, X4 has successfully developed mavorixafor, an orally available CXCR4 antagonist that is currently being marketed in the U.S. as XOLREMDI® in its first indication. The company is also evaluating additional uses of mavorixafor and is conducting a global, pivotal Phase 3 clinical trial (4WARD) in people with certain chronic neutropenic disorders. X4 is headquartered in Boston, Massachusetts. For more information, please visit www.x4pharma.com. X4 Forward Looking Statements This press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target,” or other similar terms or expressions that concern X4’s expectations, strategy, plans, or intentions. Forward-looking statements include, without limitation, implied or express statements regarding the initiation, timing, progress, and results of our current and future preclinical studies and clinical trial; the timing and period during which the results of the trials will become available and reported, as well as our research and development programs; market opportunities for X4’s product candidates, including potential benefits from partnerships; expectations regarding the commercial potential of mavorixafor and ongoing engagement and feedback from regulatory authorities; and the sufficiency of X4’s cash resources and pro forma cash resources, including the potential impact of the 2025 strategic restructuring, and expectations regarding X4’s cash runway. Any forward-looking statements in this press release are based on management’s current expectations and beliefs. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond X4’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements, including the risks that: X4’s restructuring activities may be more costly or time-consuming than expected or may not achieve their intended results and savings; X4’s future financial performance and position may not improve resulting in difficulties in implementing X4’s business strategy, and plans and objectives for future operations; the expected decrease in annual spending could negatively impact X4’s commercial plans and strategy for mavorixafor; the expected sufficiency of X4’s existing cash resources and runway may not be accurate resulting in the need for additional financing sooner than anticipated or unexpected liquidity constraints; the internal and external costs required for X4’s ongoing and planned activities, and the resulting impact on expense and use of cash, may be higher than expected, which may cause the company to use cash more quickly than expected or to change or curtail some of X4’s plans or both; the expected availability, content, and timing of clinical data from X4’s ongoing clinical trials of mavorixafor may be delayed or unavailable, including the ongoing Phase 3 clinical trial; trials, studies and research programs may be delayed and may not have satisfactory outcomes, additionally earlier trials and studies may not be predictive of later trials and studies; the design and rate of enrollment for current clinical trials may not enable successful completion of the trial(s); the commercial opportunity for mavorixafor may be smaller than anticipated; X4 may be unable to obtain and maintain regulatory approvals; adverse safety effects may arise from the testing or use of X4’s product and product candidates; the need to align with collaborators may hamper or delay development and commercialization efforts or increase costs; business may be adversely affected and costs may increase if any of the company’s key collaborators fails to perform its obligations or terminates the collaboration; X4’s may be unable to advance and commercialize and increase sales in mavorixafor to treat chronic neutropenia or to optimize the U.S. promotion of XOLREMDI® (mavorixafor), approved for the treatment of WHIM; and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s most recent Annual Report on X4’s Form 10-K , as well as in other filings X4 makes with the Securities and Exchange Commission, including its quarterly report on Form 10-Q, from time to time. X4 undertakes no obligation to update the information contained in this press release to reflect new events or circumstances, except as required by law. (Tables Follow) X4 PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except per share amounts)(unaudited) Three Months Ended March 31, 2025 2024 License and other revenue $27,865 $— Product revenue, net 942 — Total revenue 28,807 — Costs and operating expenses: Cost of revenue 4,716 — Research and development 18,513 19,854 Selling, general and administrative 15,021 17,435 Total operating expenses 38,250 37,289 Loss from operations (9,443) (37,289)Other income (expense), net 9,759 (14,458)Income (loss) before provision for income taxes 316 (51,747)Provision for income taxes 34 19 Net income (loss) $282 $(51,766)Net income (loss) per share- basic $0.04 $(7.77)Weighted average common shares outstanding- basic 6,840 6,666 Net income (loss) per share- diluted $0.04 $(7.77)Weighted average common shares outstanding- diluted 6,869 6,666 X4 PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands)(unaudited) March 31,2025 December 31,2024Current assets: Cash and cash equivalents $40,257 $55,699 Accounts receivable 509 1,070 Marketable securities 46,694 46,361 Research and development incentive receivable 665 640 Inventory 3,089 2,817 Prepaid expenses and other current assets 4,483 5,588 Total current assets 95,697 112,175 Property and equipment, net 487 776 Goodwill 17,351 17,351 Intangible asset, net 9,813 10,000 Right-of-use assets 3,652 4,065 Other assets 3,013 2,080 Total assets $130,013 $146,447 Current liabilities: Accounts payable $11,115 $8,621 Accrued expenses 12,611 23,005 Deferred revenue 855 — Current portion of lease liability 1,303 1,251 Total current liabilities 25,884 32,877 Long-term debt, including accretion, net of discount 75,629 75,425 Lease liabilities 1,109 1,410 Warrant liability 2,925 13,755 Deferred revenue and other liabilities 1,522 831 Total liabilities 107,069 124,298 Total stockholders' equity 22,944 22,149 Total liabilities and stockholders' equity $130,013 $146,447 X4 Investor Contact:X4 Media Contact:Daniel FerryLifeSci Advisorsdaniel@lifesciadvisors.com(617) 430-7576Rhiannon JeselonisTen Bridge Communicationsrhiannon@tenbridgecommunications.com

FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive topline results from the Phase 3 ASCENT-04/KEYNOTE-D19 study, demonstrating that Trodelvy® (sacituzumab govitecan-hziy) plus Keytruda® (pembrolizumab) significantly improved progression-free survival (PFS) compared to Keytruda and chemotherapy in patients with inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1 (CPS ≥ 10). The study met its primary endpoint, showing a statistically significant and clinically meaningful improvement in PFS. The safety profile of Trodelvy plus Keytruda in the ASCENT-04 study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination. “These findings are the first to show the transformative potential of an antibody-drug conjugate combined with an immuno-oncology agent in early treatment lines of metastatic breast cancer,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “For patients with this difficult to treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options.” “For patients with metastatic triple-negative breast cancer, there is a critical need for more effective treatment options,” said Dr. Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04 study. “These data suggest that the combination of sacituzumab govitecan-hziy and pembrolizumab may offer a new treatment approach—bringing together a potent antibody drug conjugate with immunotherapy to improve outcomes for patients.” Overall survival (OS) is a key secondary endpoint and was not mature at the time of the PFS primary analysis. However, in the ASCENT-04 study, there was an early trend in improvement for OS with Trodelvy plus Keytruda. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analyses planned. Detailed results from the study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy plus Keytruda in patients with previously untreated PD-L1+ metastatic TNBC is investigational, and the safety and efficacy of this use have not been established. The significant and meaningful improvement in PFS demonstrated in ASCENT-04 further reinforces the potential of Trodelvy plus Keytruda as a much-needed new treatment option for patients with previously untreated inoperable (unresectable) PD-L1+ locally advanced or mTNBC. Trodelvy is the only approved Trop-2-directed antibody-drug conjugate (ADC) that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers: 2L+ mTNBC and pre-treated HR+/HER2- mBC. It is a Category 1 preferred treatment for both indications per the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelinesi) and the only ADC with an ESMO Magnitude of Clinical Benefit Scale (MCBS) rating of 5 for mTNBC. Trodelvy also has an MCBS rating of 4 for women with HR+/HER2- mBC. With established healthcare professional experience, Trodelvy has shown consistent outcomes across clinical trials and real-world studies in 50,000+ patients across ~50 countries over ~5 years. It has now demonstrated improved outcomes in three Phase 3 breast cancer trials and is being studied in several ongoing clinical trials, aiming to extend survival across diverse tumor types and disease stages. Currently, Gilead has three ongoing Phase 3 studies investigating Trodelvy across HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) mBC, including the upcoming ASCENT-03 pivotal trial in 1L mTNBC patients who are not candidates for PD-L1 based therapy, the ASCENT-05 pivotal trial in patients with early-stage TNBC (eTNBC), and the ASCENT-07 pivotal trial in patients with HR+/HER2- mBC who have received endocrine therapy. Trodelvy is also being investigated in additional Phase 3 studies in other disease settings, including in lung and gynecological cancers. Gilead would like to thank the patients, families, investigators and advocates who have contributed and continue to contribute to this important research. We remain committed to advancing care to address the unmet needs for the breast cancer community. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Triple-Negative Breast Cancer with PD-L1+ Tumors TNBC is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC is diagnosed more frequently in younger and premenopausal women and is more prevalent in Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with mTNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC. Despite progress in treatment, first-line mTNBC has seen limited new approvals in recent years for tumors that express PD-L1+, and additional options are urgently needed. Despite recent advances, over 50% of patients do not receive treatment beyond first-line, reinforcing the urgent need for new options to help improve patient outcomes. Breast cancers expressing PD-L1 are overall more aggressive and associated with reduced survival time. About the ASCENT-04/KEYNOTE-D19 Study In 2021, Gilead entered a collaboration with Merck & Co. to investigate sacituzumab govitecan in combination with pembrolizumab in the Phase 3 trial, ASCENT-04/KEYNOTE-D19. The ASCENT-04/KEYNOTE-D19 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan in combination with pembrolizumab compared with treatment of chemotherapy plus pembrolizumab in patients with previously untreated, inoperable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1. The study enrolled 443 patients across multiple study sites. Patients were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg intravenously on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab. The chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression. The primary endpoint of the study is progression-free survival (PFS) as determined by BICR using RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety. More information about ASCENT-04/KEYNOTE-D19 is available at ClinicalTrials.gov: NCT05382286. About Trodelvy Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect. Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer. Trodelvy is being investigated for use in other TNBC and HR+/HER2- breast cancer populations, as well as a range of tumor types where Trop-2 is highly expressed, including extensive-stage small cell lung cancer and first-line metastatic non-small cell lung cancer where Trodelvy has shown clinical activity through the TROPiCS-03 proof-of-concept study and the EVOKE-02 proof-of-concept study, respectively. INDICATIONS TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. IMPORTANT SAFETY INFORMATION BOXED WARNING: NEUTROPENIA AND DIARRHEA CONTRAINDICATIONS Severe hypersensitivity reaction to TRODELVY. WARNINGS AND PRECAUTIONS Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI. Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments. Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions. Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting. Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function. Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose. ADVERSE REACTIONS In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes. In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. DRUG INTERACTIONS UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY. UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY. Please see full Prescribing Information, including BOXED WARNING. 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 Trodelvy (such as ASCENT-03, ASCENT-04 and ASCENT-05); uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for programs and/or indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these 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 Annual Report on Form 10-K for the year ended December 31, 2024, 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. Prescribing Information for Trodelvy, including BOXED WARNING, is available at www.gilead.com. Trodelvy, 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 X/Twitter ( @Gilead Sciences ) and LinkedIn, or contact Gilead Public Affairs at public_affairs@gilead.com, 1-800-GILEAD-5 or 1-650-574-3000. i NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.