Thrombocythemia, Essential

JBI-802 is a first-in-class, orally administered, inhibitor of CoREST complex JBI-778 is a potential best-in-class, orally administered, brain penetrant inhibitor of PRMT5 MORRISVILLE, N.C., Oct. 25, 2024 /PRNewswire/ -- Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule precision therapeutics to address unmet medical needs in oncology and autoimmune diseases, today announced the dosing of first patients in global clinical trials involving two pipeline programs: Phase I/II clinical trial of JBI-802 in heme-oncology and Phase I clinical trial for JBI-778 in solid tumors. "We are excited to take this significant step forward in our mission to transform the lives of patients through the development of easy to administer precision oral medicines with enhanced safety and therapeutic efficacy," said Hari S Bhartia, Chairman, Jubilant Therapeutics Inc. JBI-802 is a first-in-class, orally administered, small-molecule dual inhibitor of LSD1 (Lysine-specific histone demethylase 1A) and HDAC6 (Histone deacetylase 6) within the CoREST (Co-repressor of Repressor Element-1 Silencing Transcription) complex. In the earlier Phase I study conducted in advanced solid tumor patients, JBI-802 showed a dose-proportional increase in exposure across cohorts and a strong correlation between exposure and the on-target effect of platelet decrease. There were no reports of Dysgeusia and Anemia, typical adverse events seen with LSD1only inhibitors. The Phase I trial also showed anti-tumor activity in Non-Small Cell Lung Cancer (NSCLC) patients including a confirmed partial response. Overall, the study results provided human proof-of-principle for expanding the development of JBI-802 in Essential Thrombocythemia and Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPN) with thrombocytosis. Essential Thrombocythemia is a chronic disease of excessive platelets with over 100,000 patients in the United States for whom the primary treatment is hydroxyurea, a therapy that poses severe limitations for patients in terms of both safety and efficacy. The second clinical trial is to assess both safety and the recommended Phase II dose for JBI-778, an oral brain-penetrant inhibitor of PRMT5 (Protein arginine N-methyltransferase 5) in mEGFR Tyrosine Kinase Inhibitor (TKI) resistant NSCLC, IDH+ high-grade glioma (HGG) and Adenoid Cystic Carcinoma (ACC). PRMT5, although a proven pathway for multiple cancers, has produced mixed results in terms of drug development due to safety concerns surrounding SAM competitive approach to PRMT5 inhibition and patient segment limitations of MTAP null tumor-focused approach PRMT5 inhibition. JBI-778 is a unique substrate competitive brain penetrant PRMT5 inhibitor that has shown no adverse effects in preclinical setting and can address both MTAP null and wild type tumors as well as brain tumors, catering to a larger patient segment including those with brain metastases. "The two most advanced novel drug candidates at Jubilant Therapeutics Inc. were discovered in-house using our TIBEO (Therapeutic Index and Brain Exposure Optimization) Discovery Engine. It is our unique approach of structure-based drug design to generate novel pharmacophores with improved therapeutic index compared to existing agents. We are excited to advance both JBI-802 and JBI-778 in genetically-defined subsets of patients with select hematological and solid tumor indications with high unmet medical needs. Initial clinical data are expected to read out in 2025," said Syed Kazmi, Chief Executive officer, Jubilant Therapeutics Inc. About JBI-802 JBI-802 is novel, oral, potent and selective dual inhibitor of two epigenetic targets of the CoREST complex: LSD1 and HDAC6. It targets stem cell modulation by inhibiting LSD1 and modulates immune suppression with isoform selective HDAC6 inhibition. Preclinical research has demonstrated its synergistic anti-tumor activity, which is superior compared to either target alone and with a favorable safety profile. JBI-802 is under evaluation in both hematological cancers such as acute myeloid leukemia, myelodysplastic syndrome and other myeloproliferative cancers as well as solid tumors, such as non-small cell lung cancer and small cell lung cancer. About JBI-778 JBI-778 is novel, oral, potent and brain penetrant inhibitor of PRMT5. JBI-778 targets the substrate site and stabilizes SAM bound to PRMT5, providing high biological selectivity and has shown a superior safety profile as seen in animals. Preclinical research has demonstrated significant activity in Tyrokinase-Inhibitor resistant cell lines, brain tumor and NSCLC. JBI-778 is under evaluation in solid tumors such as NSCLC, High Grade Glioma and Adenoid Cystic Carcinoma. About Jubilant Therapeutics Inc. Jubilant Therapeutics Inc. is a clinical stage biopharmaceutical company developing precision oral medicines with enhanced therapeutic index to address unmet medical needs in oncology and autoimmune diseases for genetically defined patients. Its advanced structure-based discovery engine, TIBEO (Therapeutic Index and Brain Exposure Optimization), has been validated through successful partnerships. The Company's clinical pipeline consists of a first-in-class dual CoREST modifier, JBI-802, currently in a Phase I/II clinical trial in multiple tumors and a novel brain-penetrant modulator of PRMT5, currently in Phase I clinical trial. Additional pre-clinical programs include brain penetrant and gut restrictive PDL1 inhibitors, as well as PAD4 inhibitors for oncology and inflammatory indications. The Company is headquartered in Pennsylvania and guided by globally renowned scientific advisors. For more information, please visit or follow us on Twitter @JubilantTx and LinkedIn. Logo: SOURCE Jubilant Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

BURLINGTON, Mass.--( BUSINESS WIRE )--PharmaEssentia Corporation (TWSE: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that it has entered into an exclusive licensing agreement with FORUS Therapeutics Inc (“FORUS”) for the registration and distribution of BESREMi ® (ropeginterferon alfa-2b-njft) for the treatment of polycythemia vera (PV), in Canada. FORUS focuses on the hematology and oncology market in Canada, with extensive experience in local drug registration and commercialization. Under the terms of the agreement, PharmaEssentia is licensing BESREMi for PV to FORUS in Canada, with potential expansion to other investigational myeloproliferative neoplasms (MPN) indications in the future. FORUS will oversee the drug registration and commercialization of BESREMi in Canada, with potential milestone payments of up to $107 million USD – including for securing approval of BESREMi in PV and meeting sales milestones. FORUS will make a portion of the milestone payments within 2024 and pay PharmaEssentia double-digit percentage royalties on sales. “FORUS and PharmaEssentia are aligned in our missions to bring new treatments to patients with hematologic and oncologic conditions that may meaningfully enhance their lives,” said Ko-Chung Lin, Ph.D., Founder and CEO of PharmaEssentia. “We continue to expand scientific data to demonstrate the clinical value of BESREMi for patients with MPNs such as PV, and we look forward to collaborating with FORUS to introduce BESREMi in Canada, to expand our footprint in North America and to benefit even more patients with PV.” “Strategic partnerships pave the way to unlocking innovation and advancing healthcare solutions,” said Kevin Leshuk, President and CEO of FORUS. “We are extremely pleased and honored to be partnering with PharmaEssentia so that we can deliver potentially transformative outcomes for those living with PV and hopefully other hematologic conditions in the future.” BESREMi has been approved for the treatment of PV in approximately 40 countries and regions, including the United States, Japan, China, and the European Union. About PharmaEssentia PharmaEssentia (TWSE: 6446), headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology, oncology, and immunology with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan. For more information about PharmaEssentia USA, visit the website , LinkedIn or Twitter . About FORUS Therapeutics FORUS Therapeutics is a Canadian biopharmaceutical company dedicated to advancing differentiated, novel medicines for hematologic malignancies and other forms of cancer. Our mission is to bring solutions to cancer patients, caregivers, physicians and our partners by accelerating unique and important treatments that meaningfully enhance life. www.forustherapeutics.com About Polycythemia Vera (PV) Polycythemia vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2. 1 About BESREMi ® (ropeginterferon alfa-2b-njft) BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients. BESREMi has orphan drug designation for the treatment of polycythemia vera (PV) in adults in the United States. BESREMi has been approved in more than 40 countries, with approval from the European Medicines Agency (EMA) in 2019, by the US Food and Drug Administration (FDA) in 2021, and by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan in 2023. It was invented by PharmaEssentia and is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders. Please see full Prescribing Information , including Boxed Warning. Indication BESREMi is indicated for the treatment of adults with polycythemia vera. Important Safety Information WARNING: RISK OF SERIOUS DISORDERS Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy. CONTRAINDICATIONS Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated autoimmune disease Immunosuppressed transplant recipients WARNINGS AND PRECAUTIONS Depression and Suicide: Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa-2b products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products. Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy. Endocrine Toxicity: These toxicities may include worsening hypothyroidism and hyperthyroidism. Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease. Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during BESREMi therapy. Discontinue BESREMi in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi. Cardiovascular Toxicity: Toxicities may include cardiomyopathy, myocardial infarction, atrial fibrillation and coronary artery ischemia. Patients with a history of cardiovascular disorders should be closely monitored for cardiovascular toxicity during BESREMi therapy. Avoid use of BESREMi in patients with severe or unstable cardiovascular disease, (e.g., uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction. Decreased Peripheral Blood Counts: These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of infection or bleeding. Hypersensitivity Reactions: Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis). If such reactions occur, discontinue BESREMi and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment. Pancreatitis: Pancreatitis has occurred in 2.2% of patients receiving BESREMi. Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever. Patients may experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. Interrupt BESREMi treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation of BESREMi in patients with confirmed pancreatitis. Colitis: Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa products, some cases starting as early as 12 weeks after start of treatment. Symptoms may include abdominal pain, bloody diarrhea, and fever. Discontinue BESREMi in patients who develop these signs or symptoms. Colitis may resolve within 1 to 3 weeks of stopping treatment. Pulmonary Toxicity: Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis. Some events have resulted in respiratory failure or death. Discontinue BESREMi in patients who develop pulmonary infiltrates or pulmonary function impairment. Ophthalmologic Toxicity: These toxicities may include severe eye disorders such as retinopathy, retinal hemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion which may result in blindness. During BESREMi therapy, 23% of patients were identified with an eye disorder. Eyes disorders ≥5% included cataract (6%) and dry eye (5%). Advise patients to have eye examinations before and during BESREMi therapy, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension. Evaluate eye symptoms promptly. Discontinue BESREMi in patients who develop new or worsening eye disorders. Hyperlipidemia: Elevated triglycerides may result in pancreatitis. Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated. Consider discontinuation of BESREMi in patients with persistently, markedly elevated triglycerides. Hepatotoxicity: These toxicities may include increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and bilirubin. Liver enzyme elevations have also been reported in patients after long-term BESREMi therapy. Monitor liver enzymes and hepatic function at baseline and during BESREMi treatment. Discontinue BESREMi in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage) during treatment. Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Avoid use of BESREMi in patients with eGFR <30 mL/min. Discontinue BESREMi if severe renal impairment develops during treatment. Dental and Periodontal Toxicity: These toxicities may include dental and periodontal disorders, which may lead to loss of teeth. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with BESREMi. Patients should have good oral hygiene and regular dental examinations. Dermatologic Toxicity: These toxicities have included skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, and hyperhidrosis. Consider discontinuation of BESREMi if clinically significant dermatologic toxicity occurs. Driving and Operating Machinery: BESREMi may impact the ability to drive and use machinery. Patients should not drive or use heavy machinery until they know how BESREMi affects their abilities. Patients who experience dizziness, somnolence or hallucination during BESREMi therapy should avoid driving or using machinery. Embryo-Fetal Toxicity: Based on the mechanism of action, BESREMi can cause fetal harm when administered to a pregnant woman. Pregnancy testing is recommended in females of reproductive potential prior to treatment with BESREMi. Advise females of reproductive potential to use an effective method of contraception during treatment with BESREMi and for at least 8 weeks after the final dose. ADVERSE REACTIONS The most common adverse reactions reported in > 40% of patients in the PEGINVERA study (n=51) were influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. In the pooled safety population (n=178), the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%). DRUG INTERACTIONS Patients on BESREMi who are receiving concomitant drugs which are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs. Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression. Avoid use with narcotics, hypnotics or sedatives and monitor patients receiving the combination for effects of excessive CNS toxicity. USE IN SPECIFIC POPULATIONS Pregnancy: Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy. Advise pregnant women of the potential risk to a fetus. Lactation: There are no data on the presence of BESREMi in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from BESREMi, advise women not to breastfeed during treatment and for 8 weeks after the final dose. Females of Reproductive Potential: BESREMi may cause embryo-fetal harm when administered to a pregnant woman. Pregnancy testing prior to BESREMi treatment is recommended for females of reproductive potential. Advise female patients of reproductive potential to use effective contraception during treatment with BESREMi and for at least 8 weeks after the final dose. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Geriatric Use: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. Forward Looking Statement This press release may contain forward looking statements, including statements regarding the clinical benefits to be derived from ropeginterferon alfa-2b, the commercial opportunity and competitive positioning, new indications or labeling for ropeginterferon alfa-2b, and business prospects for ropeginterferon alfa-2b. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and similar legislation and regulations under Taiwanese law. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward looking statements as a result of various factors. These factors include whether BESREMi is successfully commercialized and adopted by physicians and patients, the extent to which reimbursement is available for BESREMi, and the ability to receive FDA and other regulatory approvals for additional indications for BESREMi. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. © 2024 PharmaEssentia Corporation. All rights reserved. PharmaEssentia, the PharmaEssentia logo, and BESREMi are trademarks or registered trademarks of PharmaEssentia Corporation. 1 Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J . 2015;5, e366; DOI:10.1038/bcj.2015.95

RAHWAY, N.J.--( BUSINESS WIRE )--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of Shorespan-007, a pivotal Phase 3 clinical trial evaluating bomedemstat, an investigational orally available lysine-specific demethylase 1 (LSD1) inhibitor, for the treatment of patients with essential thrombocythemia (ET) who have previously not received cytoreductive therapy. Essential thrombocythemia is a chronic, rare blood disorder and is the most common type of myeloproliferative neoplasm. Global recruitment of the Shorespan-007 trial has begun, with patients now enrolling. “ The standard of care in essential thrombocythemia has remained unchanged for decades, and patients are in need of new options that have the potential to not only improve disease control, but also improve their quality of life,” said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. “ We are rapidly advancing our clinical development programs with the goal of helping to address these unmet needs and bring more options to patients living with myeloproliferative neoplasms.” Shorespan-007 is a Phase 3, randomized, double-blind, active comparator-controlled clinical trial ( NCT06456346 ) evaluating bomedemstat compared to the current standard of care chemotherapy, hydroxyurea, for treatment of patients with ET who have previously not received cytoreductive therapy. The trial will enroll approximately 300 patients globally. The primary endpoint of the study is durable clinicohematologic response rate (CHR). Key secondary endpoints include Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) individual fatigue symptom item score, Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a total fatigue score and MFSAF v4.0 total symptom score. Additional secondary endpoints include duration of hematologic remission, event-free survival and disease progression rate. As previously announced , in addition to Shorespan-007, bomedemstat is also being investigated in Shorespan-006, a Phase 3, global, randomized, open-label, active comparator-controlled clinical trial ( NCT06079879 ), evaluating bomedemstat compared to best available therapy as treatment in approximately 300 patients with ET who have an inadequate response to or are intolerant of hydroxyurea. Bomedemstat has U.S. Food and Drug Administration Orphan Drug and Fast Track Designations for the treatment of ET and myelofibrosis (MF), Orphan Drug Designation for the treatment of acute myeloid leukemia and Priority Medicines scheme designation by the European Medicines Agency for the treatment of MF. Merck presented updated data from the Phase 2b Shorespan-003 trial, including first time genomic data, at the American Society of Hematology (ASH) Annual Meeting in December 2023. The Shorespan-003 trial is one of multiple Phase 2 clinical trials where bomedemstat is being evaluated alone and in combination for the treatment of MPNs such as ET, MF and polycythemia vera (PV). About essential thrombocythemia Essential thrombocythemia is a chronic, rare blood disorder that is the most common type of myeloproliferative neoplasm. Essential thrombocythemia is most often caused by genetic mutations that cause the bone marrow to produce too many platelets, which can obstruct blood flow and cause a stroke, heart attack or pulmonary embolism. The disease is more common in women than men and in people ages 50 to 70. It is estimated that fewer than 200,000 people in the U.S. have essential thrombocythemia, which can significantly impact quality of life due to burdensome symptoms. The most common symptoms are fatigue (reported in 90% of patients), insomnia, migraines, headache and dizziness. About bomedemstat Bomedemstat (MK-3543) is an investigational small molecule, irreversible LSD1 inhibitor being developed by Merck. LSD1 regulates the proliferation of hematopoietic stem cells, playing an essential role in cell differentiation and maturation. Bomedemstat is being evaluated in a wide range of MPNs, including ET, MF and PV. Merck’s focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovation products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ).