Chromosome 5q Deletion Syndrome

FOSTER CITY, Calif.--( BUSINESS WIRE )--Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced new analyses presented at the 66 th American Society of Hematology (ASH) Annual Meeting from the IMerge clinical trial in patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia suggesting clinical activity of first-in-class telomerase inhibitor RYTELO™ (imetelstat) regardless of type or number of prior therapies, as well as favorable patient-reported outcomes (PROs). “ These latest IMerge analyses presented at ASH contribute to a growing body of clinical evidence that support RYTELO as a second-line option in red blood cell transfusion-dependent lower-risk MDS, regardless of prior treatments,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. “ Additionally, the sustained improvement in fatigue observed in the IMerge Phase 3 patient-reported outcomes population is meaningful for this progressive disease that is characterized by fatigue.” “ Patients with red blood cell transfusion-dependent lower-risk MDS often cycle through limited available therapies. The IMerge data presented at ASH suggesting clinical activity of imetelstat regardless of prior therapies, offers physicians important clinical evidence while assessing sequencing of treatments,” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, an investigator of the IMerge clinical trial, who presented IMerge results at ASH. “ Further, anemia and fatigue remain two of the most burdensome symptoms of lower-risk MDS, and patient-reported outcomes such as improvement in fatigue and maintenance of quality of life and anemia symptoms may inform treatment choices as we aim to improve outcomes for our patients.” “ Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes” This oral presentation reported findings from analyses investigating the effects of prior therapies on the clinical activity of imetelstat using pooled data from IMerge Phase 2, Phase 3, and the QTc substudy. Of the 226 total imetelstat-treated LR-MDS patients included in this analysis, 90% had prior treatment with an erythropoiesis-stimulating agent (ESA), 12% had prior treatment with lenalidomide, 16% had prior treatment with luspatercept and 10% had prior treatment with a hypomethylating agent (HMA). Across this pooled population, median imetelstat treatment duration was 33.6 weeks (range: 0.1-260.1 weeks). Imetelstat clinical activity was observed in the pooled patient population consistent with that of the IMerge Phase 3 pivotal trial with regards to safety and critical efficacy measures that include ≥8-week red blood cell transfusion independence (RBC-TI), ≥24-week RBC-TI, RBC transfusion reduction ≥4 U/8 weeks and hemoglobin rise ≥1.5 g/dL/8 weeks. The results suggest that patients who were ESA ineligible, patients who had prior treatment with luspatercept or lenalidomide, or patients who had prior treatment with ESAs followed by luspatercept or lenalidomide experienced clinical benefit from imetelstat treatment similar to that demonstrated in the IMerge Phase 3 pivotal trial. Patients who had prior treatment with HMAs, or with ESAs followed by HMAs, showed modest clinical activity with imetelstat. Overall, while these analyses were limited by the small number of patients in each group, imetelstat showed clinical activity regardless of prior ESA response status and regardless of the number of prior lines of therapy. “ Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents” This poster presentation reports initial results from the ventricular repolarization (QTc) substudy of IMerge conducted per FDA guidance. This substudy differed from the IMerge Phase 3 trial in its crossover design, the inclusion of patients with del(5q) MDS, and by allowing prior lenalidomide and HMA therapy besides ESAs. The QTc substudy population comprised 53 treated patients (n=35 imetelstat, n=18 placebo). As of the data cutoff on May 10, 2024, 16 of 18 placebo recipients crossed over to receive imetelstat. Median treatment duration on imetelstat, including crossover (n=51) was 29.3 weeks; median duration in the imetelstat group (n=35) was 37.0 weeks and median duration in the crossover group (n=16) was 27.9 weeks. In the total imetelstat population (n=51), 41% of patients (n=21) achieved ≥8-week RBC-TI, 25% of patients (n=13) achieved ≥24-week RBC-TI, 41% of patients (n=21) achieved hematologic improvement-erythroid (HI-E) per IWG 2018 criteria, 35% of patients (n=18) had hemoglobin rises ≥1.5 g/dL lasting ≥8 weeks and 75% of patients (n=38) had RBC transfusion reductions ≥4 U/8 weeks. In patients with prior luspatercept, lenalidomide or HMA (azacitidine or decitabine) treatment, 30% (7/23), 38% (5/13), and 21% (3/14) of patients achieved ≥8-week RBC-TI, and 22% (5/23) 15% (2/13), and 14% (2/14) achieved ≥24-week RBC-TI, respectively. Patients treated with imetelstat showed no treatment-related changes in absolute and change in QTcF nor clinically meaningful effects on cardiac repolarization compared with placebo. The poster concludes that in this QTc substudy, imetelstat was associated with an absence of proarrhythmic risk, durable RBC-TI, transfusion reduction, clinically meaningful increases in hemoglobin, and a safety profile comparable to the overall population of the pivotal Phase 3 IMerge trial. RBC-TI was attained in imetelstat-treated patients who received prior therapies with HMA, luspatercept and lenalidomide, supporting the use of imetelstat in patients with relapsed or refractory LR-MDS regardless of prior therapies. “ Correlation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial” This poster reports on the exploratory PRO analysis from IMerge Phase 3, with a data cutoff of October 2022. PROs were assessed with validated using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Functional Assessment of Cancer Therapy-Anemia (FACT-An), and Quality of Life in Myelodysplasia Scale (QUALMS) questionnaires. Sustained meaningful improvement in fatigue was defined as a ≥3-point increase in FACIT-Fatigue score for ≥2 consecutive assessments. The PRO population (n=175) included all patients in the intent-to-treat population who had FACIT-Fatigue data at baseline and consisted of 118 imetelstat-treated patients and 57 patients who received placebo. In the subgroup analysis, more patients treated with imetelstat than placebo reported sustained improvement in fatigue regardless of ring sideroblast (RS) status, prior transfusion burden and baseline serum EPO levels. Additionally, improvement in fatigue was seen in more patients who responded to imetelstat versus those who did not across measures of response including RBC-TI, hemoglobin rise and transfusion reduction. The QUALMS and FACT-An analyses suggested that imetelstat maintained QOL and anemia symptoms, while placebo recipients experienced worsening QOL and anemia symptoms. The poster concludes that data from the pivotal IMerge phase 3 trial showed that improvement in fatigue with imetelstat was associated with reduced transfusion burden and a rise in hemoglobin and that imetelstat appears to offer the advantage of sustained RBC-TI benefit while maintaining QOL in patients with LR-MDS with TD anemia. The ASH presentations are available on Geron’s website in the investor section under publications . About RYTELO™ (imetelstat) RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks. RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO. Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended. Neutropenia RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO. Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended. Infusion-Related Reactions RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion. Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended. Embryo-Fetal Toxicity RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose. ADVERSE REACTIONS Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%). Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf . About Geron Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO™ (imetelstat) is approved in the United States for the treatment of certain adult patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or follow us on LinkedIn . Use of Forward-Looking Statements Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) that the IMerge analyses presented at ASH contribute to a growing body of clinical evidence that support RYTELO as a second-line option in red blood cell transfusion-dependent lower-risk MDS, regardless of prior treatments; (ii) that sustained improvement in fatigue observed in the IMerge Phase 3 patient-reported outcomes population is meaningful for this progressive disease that is characterized by fatigue; (iii) that the IMerge data presented at ASH suggests clinical activity of imetelstat regardless of prior therapies, offering physicians important clinical evidence while assessing sequencing of treatments; (iv) that patient-reported outcomes such as improvement in fatigue and maintenance of quality of life and anemia symptoms may inform treatment choices for patients with lower-risk MDS; and (v) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron is successful in commercializing RYTELO (imetelstat) for the treatment of certain patients with LR-MDS with transfusion dependent anemia; (b) whether Geron overcomes potential delays and other adverse impacts caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for and meet expected timelines and planned milestones; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether any future safety or efficacy results of imetelstat treatment cause the benefit-risk profile of imetelstat to become unacceptable; (e) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (f) that Geron may seek to raise substantial additional capital in order to continue the development and commercialization of imetelstat; (g) whether Geron meets its post-marketing requirements and commitments in the U.S. for RYTELO for the treatment of certain patients with LR-MDS with transfusion dependent anemia; (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of imetelstat or other clinical trial materials that impact commercialization of RYTELO for the treatment of certain patients with LR-MDS with transfusion dependent anemia or the continuation of the IMpactMF trial; (i) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; (j) whether Geron stays in compliance with and satisfies its obligations under its debt and royalty financing agreements; and (k) whether the EMA will approve RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia and whether the FDA and EMA will approve imetelstat for other indications on the timelines expected, or at all. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended September 30, 2024, and subsequent filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances.

PARSIPPANY, N.J. & TEL AVIV, Israel & HYDERABAD, India--(BUSINESS WIRE)-- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), andNatco Pharma Limited (NSE: NATCOPHARM; BSE: 524816), announced today the launch of additional strengths for the generic version of Revlimid®1 (lenalidomide capsules), in 2.5 mg, and 20 mg strengths, in the United States. The companies have launched four other strengths of the product in March 2022 in the US market. With today’s launch the companies made available all the strengths of lenalidomide in the US market. Teva’s lenalidomide capsules are a prescription medicine used in adults for the treatment of (i) multiple myeloma in combination with the medicine dexamethasone, (ii) certain myelodysplastic syndromes, and (iii) mantle cell lymphoma following specific prior treatment. Please see the below “What are lenalidomide capsules?” section for more information. “The launch of additional strengths for the generic version of Revlimid® in the U.S. enhances access to an important treatment option for patients, and further demonstrates Teva’s commitment to making generic drugs available to the patients who need them,” said Christine Baeder, SVP, Chief Operating Officer, US Generics and Biosimilars, at Teva USA. With nearly 500 generic medicines available, Teva has the largest portfolio of FDA-approved generic products on the market, and holds the leading position in first-to- with approximately 100 pending first-to-files in the U.S. Currently, 1 in 12 generic prescriptions dispensed in the U.S. is filled with a Teva generic product. Revlimid® had annual sales of $2.9 billion as of January, 2023, according to IQVIA data. What are lenalidomide capsules? Lenalidomide capsules are a prescription medicine, used to treat adults with: multiple myeloma (MM) in combination with the medicine dexamethasone a condition called myelodysplastic syndromes (MDS). Lenalidomide capsules are for the type of MDS with a chromosome problem where part of chromosome 5 is missing. This type of MDS is known as deletion 5q MDS. People with this type of MDS may have low red blood cell counts that require treatment with blood transfusions. mantle cell lymphoma (MCL) when the disease comes back or becomes worse after treatment with 2 prior medicines, one of which included bortezomib. MCL is a cancer of a type of white blood cell called lymphocytes that are in the lymph nodes. Lenalidomide capsules should not be used to treat people who have chronic lymphocytic leukemia (CLL) unless they are participants in a controlled clinical trial. It is not known if lenalidomide capsules are safe and effective in children. IMPORTANT SAFETY INFORMATION What is the most important information I should know about lenalidomide capsules? Before you begin taking lenalidomide capsules, you must read and agree to all of the instructions in the Lenalidomide REMS program. Before prescribing lenalidomide capsules, your healthcare provider will explain the Lenalidomide REMS program to you and have you sign the Patient-Physician Agreement Form. Lenalidomide capsules may cause serious side effects including: Possible birth defects (deformed babies) or death of an unborn baby. Females who are pregnant or who plan to become pregnant must not take lenalidomide capsules. Lenalidomide is similar to the medicine thalidomide. We know thalidomide can cause severe life-threatening birth defects. Lenalidomide capsules have not been tested in pregnant females. Lenalidomide capsules have harmed unborn animals in animal testing. Females must not get pregnant: For at least 4 weeks before starting lenalidomide capsules While taking lenalidomide capsules During any breaks (interruptions) in your treatment with lenalidomide capsules For at least 4 weeks after stopping lenalidomide capsules Females who can become pregnant: Will have pregnancy tests weekly for 4 weeks, then every 4 weeks if your menstrual cycle is regular, or every 2 weeks if your menstrual cycle is irregular. If you miss your period or have unusual bleeding, you will need to have a pregnancy test and receive counseling. Must agree to use two acceptable forms of birth control at the same time, for at least 4 weeks before, while taking, during any breaks (interruptions) in your treatment, and for at least 4 weeks after stopping lenalidomide capsules. Talk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with lenalidomide capsules. If you had unprotected sex or if you think your birth control has failed, stop taking lenalidomide capsules immediately and call your healthcare provider right away. If you become pregnant while taking lenalidomide capsules, stop taking it right away and call your healthcare provider. If your healthcare provider is not available, you can call the REMS Call Center at 1‐888‐423‐5436. Healthcare providers and patients should report all cases of pregnancy to: FDA MedWatch at 1-800-FDA-1088, and The Lenalidomide REMS program at 1‐888‐423‐5436 There is a pregnancy exposure registry that monitors the outcomes of females who take lenalidomide capsules during pregnancy, or if their male partner takes lenalidomide capsules and they are exposed during pregnancy. You can enroll in this registry by calling the Lenalidomide REMS program at the phone number listed above. Lenalidomide can pass into human semen: Males, including those who have had a vasectomy, must always use a latex or synthetic condom during any sexual contact with a pregnant female or a female that can become pregnant while taking lenalidomide capsules, during any breaks (interruptions) in your treatment with lenalidomide capsules, and for up to 4 weeks after stopping lenalidomide capsules. Do not have unprotected sexual contact with a female who is or could become pregnant. Tell your healthcare provider if you do have unprotected sexual contact with a female who is or could become pregnant. Do not donate sperm while taking lenalidomide capsules, during any breaks (interruptions) in your treatment, and for up to 4 weeks after stopping lenalidomide capsules. If a female becomes pregnant with your sperm, the baby may be exposed to lenalidomide and may be born with birth defects. Men, if your female partner becomes pregnant, you should call your healthcare provider right away. Low white blood cells (neutropenia) and low platelets (thrombocytopenia). Lenalidomide capsules cause low white blood cells and low platelets in most people. You may need a blood transfusion or certain medicines if your blood counts drop too low. Your healthcare provider should check your blood counts often especially during the first several months of treatment with lenalidomide capsules, and then at least monthly. Tell your healthcare provider if you develop any bleeding or bruising, during treatment with lenalidomide capsules. Blood clots. Blood clots in the arteries, veins, and lungs happen more often in people who take lenalidomide capsules. This risk is even higher for people with multiple myeloma who take the medicine dexamethasone with lenalidomide capsules. Heart attacks and strokes also happen more often in people who take lenalidomide capsules with dexamethasone. To reduce this increased risk, most people who take lenalidomide capsules will also take a blood thinner medicine. Before taking lenalidomide capsules, tell your healthcare provider: If you have had a blood clot in the past If you have high blood pressure, smoke, or if you have been told you have a high level of fat in your blood (hyperlipidemia) About all the medicines you take. Certain other medicines can also increase your risk for blood clots. Call your healthcare provider or get medical help right away if you get any of the following during treatment with lenalidomide capsules: Signs or symptoms of a blood clot in the lung, arm, or leg may include: shortness of breath, chest pain, or arm or leg swelling Signs or symptoms of a heart attack may include: chest pain that may spread to the arms, neck, jaw, back, or stomach area (abdomen), feeling sweaty, shortness of breath, feeling sick or vomiting Signs or symptoms of stroke may include: sudden numbness or weakness, especially on one side of the body, severe headache or confusion, or problems with vision, speech, or balance Who should not take lenalidomide capsules? Do not take lenalidomide capsules if you: are pregnant, plan to become pregnant, or become pregnant during treatment with lenalidomide capsules. See “What is the most important information I should know about lenalidomide capsules?” are allergic to lenalidomide or any of the ingredients in lenalidomide capsules. See the end of the Medication Guide for a complete list of ingredients in lenalidomide capsules. What should I tell my healthcare provider before taking lenalidomide capsules? Before you take lenalidomide capsules, tell your healthcare provider about all of your medical conditions, including if you: have liver problems have kidney problems or receive kidney dialysis treatment have thyroid problems have had a serious skin rash with thalidomide treatment. You should not take lenalidomide capsules. are lactose intolerant. Lenalidomide capsules contain lactose. are breastfeeding. Do not breastfeed during treatment with lenalidomide capsules. It is not known if lenalidomide passes into your breast milk and can harm your baby. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Lenalidomide capsules and other medicines may affect each other, causing serious side effects. Talk with your healthcare provider before taking any new medicines. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist. What should I avoid while taking lenalidomide capsules? See “What is the most important information I should know about lenalidomide capsules?” Females: Do not get pregnant and do not breastfeed while taking lenalidomide capsules. Males: Do not donate sperm while taking lenalidomide capsules, during any breaks (interruptions) in your treatment, and for up to 4 weeks after stopping lenalidomide capsules. Do not share lenalidomide capsules with other people. It may cause birth defects and other serious problems. Do not donate blood while you take lenalidomide capsules, during any breaks (interruptions) in your treatment, and for 4 weeks after stopping lenalidomide capsules. If someone who is pregnant gets your donated blood, her baby may be exposed to lenalidomide and may be born with birth defects. What are the possible side effects of lenalidomide capsules? Lenalidomide capsules can cause serious side effects, including: See “What is the most important information I should know about lenalidomide capsules?” Increased risk of death in people who have chronic lymphocytic leukemia (CLL). People with CLL who take lenalidomide capsules have an increased risk of death compared with people who take the medicine chlorambucil. Lenalidomide capsules may cause you to have serious heart problems that can lead to death, including atrial fibrillation, heart attack, or heart failure. You should not take lenalidomide capsules if you have CLL unless you are participating in a controlled clinical trial. Risk of new cancers (malignancies). An increase in new (second) cancers has happened in patients who received lenalidomide capsules and melphalan, or a blood stem cell transplant, including certain blood cancers, such as acute myelogenous leukemia (AML), and myelodysplastic syndrome (MDS) and certain other types of cancers of the skin and other organs. Talk with your healthcare provider about your risk of developing new cancers if you take lenalidomide capsules. Your healthcare provider will check you for new cancers during your treatment with lenalidomide capsules. Severe liver problems, including liver failure and death. Your healthcare provider should do blood tests to check your liver function during your treatment with lenalidomide capsules. Tell your healthcare provider right away if you develop any of the following symptoms of liver problems: yellowing of your skin or the white part of your eyes (jaundice) dark or brown (tea-colored) urine pain on the upper right side of your stomach area (abdomen) bleeding or bruising more easily than normal feeling very tired Severe skin reactions and severe allergic reactions can happen with lenalidomide capsules and may cause death. Call your healthcare provider right away if you develop any of the following signs or symptoms during treatment with lenalidomide capsules: a red, itchy, skin rash peeling of your skin or blisters severe itching fever Get emergency medical help right away if you develop any of the following signs or symptoms during treatment with lenalidomide capsules: swelling of your lips, mouth, tongue, or throat trouble breathing or swallowing raised red areas on your skin (hives) a very fast heartbeat you feel dizzy or faint Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure and sometimes death. Your healthcare provider may do blood tests to check you for TLS. Worsening of your tumor (tumor flare reaction) can happen with lenalidomide capsules and may cause death. Tell your healthcare provider if you get any of these symptoms of tumor flare reaction during treatment with lenalidomide capsules: tender swollen lymph nodes, low grade fever, pain, or rash. Your healthcare provider may tell you to decrease your dose, temporarily stop or permanently stop taking lenalidomide capsules if you develop certain serious side effects during treatment with lenalidomide capsules. Thyroid problems. Your healthcare provider may check your thyroid function before you start taking lenalidomide capsules and during treatment with lenalidomide capsules. Risk of Early Death in MCL. In people who have Mantle Cell Lymphoma (MCL), there may be a risk of dying sooner (early death) when taking lenalidomide capsules. Talk with your healthcare provider about any concerns and possible risk factors. The most common side effects of lenalidomide capsules include: diarrhea rash nausea constipation tiredness or weakness fever itching swelling of your arms, hands, legs, feet and skin sleep problems (insomnia) headache muscle cramps or spasms shortness of breath cough, sore throat, and other symptoms of a cold upper respiratory tract infection or bronchitis inflammation of the stomach and intestine (“stomach flu”) nose bleed shaking or trembling (tremor) joint aches pain in your back or stomach-area (abdomen) These are not all the possible side effects of lenalidomide capsules. Call your doctor for medical advice about side effects. You are encouraged to report side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. Please read the Medication Guide in the full Prescribing Information including Boxed Warning. About Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic and innovative medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of innovative and biopharmaceutical products. Learn more at . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to the development and commercial success of our generic version of Revlimid® (lenalidomide capsules); our ability to successfully compete in the marketplace, including, that we are substantially dependent on our generic products, concentration of our customer base and commercial alliances among our customers, delays in launches of new generic products and the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; our substantial indebtedness; our business and operations in general, including, the impact of global economic conditions and other macroeconomic developments and the governmental and societal responses thereto, and costs and delays resulting from the extensive pharmaceutical regulation to which we are subject; compliance, regulatory and litigation matters, including failure to comply with complex legal and regulatory environments; other financial and economic risks; and other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2022, including in the section captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. 1 Revlimid® is a registered trademark of Celgene Corporation, a Bristol-Myers Squibb Company

Perseverance is the foundation of impactful scientific discoveries, and is a core value that Precision BioSciences’ newly-appointed chief medical officer, oncology giant Alan List, shares. Precision BioSciences’ newly-appointed chief medical officer, Alan List. Perseverance is the foundation of impactful scientific discoveries, and is a core value that Precision BioSciences ’ newly-appointed chief medical officer, oncology giant Alan List , shares. “Anyone involved in scientific research knows that success only occurs when one perseveres and adapts to unexpected results,” he told BioSpace. List, known as the father of Revlimid®, pegged his career on improving cancer therapies in ways that are meaningful to patients. The story of Revlimid is an example: “My laboratory at the Arizona Cancer Center identified an angiogenic circuit that was important in the self-renewal of malignant stem and progenitor cells in a disease called myelodysplastic syndromes (MDS). We screened many different compounds and biologics that targeted the pathway…and one compound stood out. Celgene called this an immunomodulatory imide drug (IMiD), specifically CC-5013.” Safety and efficacy studies involving MDS patients showed that, “Shockingly, a subset of patients with the most common chromosome abnormality in that disease – chromosome 5q deletion [del(5q)] – was profoundly sensitive. In the vast majority of patients who experienced complete remissions, the chromosome abnormality disappeared. “Celgene quickly launched an international multicenter trial and confirmed that 75 percent of patients experienced major hematological improvement. Two-thirds became transfusion-free and normalized their blood counts with remissions that lasted more than two-and-a-half years. The FDA approved Revlimid® for Del(5q) MDS in 2005. It now is used to treat many different hematologic malignancies, including myeloma and lymphoma. Its 2020 sales exceeded $11 billion.” Today, gene editing in on List’s mind. “Precision BioSciences’ ARCUS gene editing technology genuinely amazes and excites me. It’s unique in the gene editing space,” he said, because of its size and ability to make specific edits, likely with minimal off-target editing. “It’s an exciting time, overall, in this space.” As examples, List cited data presented recently at the American Society of Clinical Oncology (ASCO) annual meeting, including Precision’s allogenic CAR T cell therapy targeting CD19 for patients with non-Hodgkin’s lymphoma. “If you look at clinical trials of autologous CAR Ts, up to 30% of the patients screened to participate never received their infusions. That’s because, while waiting weeks with high grade, relapsed lymphomas, the disease doesn’t sit tight. Ultimately, many patients become too sick to participate. With allogeneic CAR Ts that are ready to go or ‘off the shelf,’ the minute you see the need, you can intervene for the patient. This is going to transform cancer care.” For List, finding better ways to treat cancer is personal. When he was growing up, “A cousin had acute lymphoblastic leukemia. She survived for years with that disease, and it was devastating to watch her suffer,” he said. That experience propelled him to study biology, and to complete his bachelor’s and master’s degrees together, in four years. Before joining Precision Biosciences, List served as CEO of the Moffitt Cancer Center in Tampa. “I’ve been advising Precision on its clinical trial programs for nearly a year and, with some exciting milestones coming up, I couldn’t pass up the opportunity to work with the team on what I feel could have a profound impact on cancer care, perhaps of a similar impact as Revlimid.” List sees his role as CMO as that of a physician- scientist. That’s a role in which he has flourished throughout much of his 40+ year career, as leader and mentor as well as physician and researcher. “We have an amazing team of researchers at Precision, and a big part of my job is to help each of them develop and reach their potential,” he said. “I feel that my background has prepared me for the role – I’ve been driving advances in cancer care for a long time. But ultimately, it is a team effort, and it is the science that will determine whether you are successful or not.” The importance of the team mustn’t be underestimated. During his residency, Phil Scheerer, M.D., a hematology attending physician, “opened my eyes to the opportunities to make an impact in hematologic malignancies,” by directly interpreting bone marrow findings (which are readily accessible for laboratory research) and making clinician managing care decisions. Sydney Salmon, M.D., founding director of the Arizona Cancer Center, was also influential. “He was a pioneer in multiple myeloma… and brought in faculty who had a foot in the clinic as well as the lab,” List said. “That was key to discovering and developing more effective therapies. His guidance solidified my career focus.” A full life involves more than career success. Weekends often find List with his wife, Kim, exploring the highways and byways of North Carolina. Until about a year ago, the soundtrack to their explorations was the distinctive growl of their Harley-Davidson motorcycles. “Kim had a beautiful denim blue Softail Deluxe, and I had a black Road King Classic. We loved riding in the country… and through the Blue Ridge Mountains. Unlike driving in a car, riding a motorcycle through the mountains is a fully immersive experience. You smell the wildflowers on the side of the road and feel the wind on your face.” Although the Lists sold those Harleys last year, they still enjoy the wind in their faces…but now from touring bicycles. “The greenway paths in the Raleigh/Durham area are just phenomenal for biking.” World War II history is another great interest. “My father served in the Battle of Anzio, which he really never spoke about,” List said. To help fill in that gap, List read Rick Atkinson’s Liberation Trilogy, which tells how the Allies liberated Europe from the Nazis. “Reading that taught me a lot about his experience and the role soldiers from York (Pennsylvania, his hometown) played as the point of the spear invading Nazi Germany, because of the local fluency in German.” It’s a lesson in determination and flexibility, and one that List knows well. Perseverance and adaptation – in science, in life, and in war – is a touchstone for great accomplishments.