Chronic lymphocytic leukaemia refractory

Presentations will summarize new preclinical data from brain-penetrant, pan-mutant B-Raf degrader program and recent clinical data from NX-5948 BTK degrader program Members of the Nurix management team also to participate in several expert panel discussions SAN FRANCISCO, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today announced that members of the Nurix team will make oral presentations on Nurix programs and participate in several industry panel discussions at the 7th Annual TPD & Induced Proximity Summit, being held October 28–31, 2024, in Boston, MA. “The growing interest in the targeted protein degradation field underscores the immense therapeutic potential of this approach,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “As an early leader in this space, Nurix has developed a broad pipeline and established numerous successful collaborations. We are excited to share preclinical data from our previously undisclosed pan-mutant B-Raf selective degrader with CNS exposure along with a review of clinical data from our NX-5948 selective BTK degrader with updated case reports.” Presentation and Panel Participation Details: Presentations Title: An Orally Bioavailable, Brain Penetrant Pan-Mutant B-RAF Degrader for the Treatment of Primary & Treatment-Resistant Solid Tumors Presenting author: Ya-Wen Lu, Ph.D. Session: Track B: Preclinical : Unearthing Brand New Bifunctional Modes of Action & Achieving Potent, Selective ADME Preclinically Date and time: Tuesday, October 29th, at 11:30 AM ET Description: Nurix has developed a potent, selective, and orally bioavailable mutant-specific B-RAF degrader for use in oncology Potent anti-tumor activity observed in multiple CDX and PDX disease models representing Class I, Class II and Class III B-RAF mutations. Anti-tumor activity was also observed in the setting of CNS disease and treatment-resistance, suggesting the potential for utility across a broad range of solid tumor types Title: Clinical Activity of NX-5948 in CLL & NHL: A First-in-Class BTK Degrader Presenting author: Paula G. O’Connor, M.D., Chief Medical Officer, Nurix Morning Keynote Plenary Session: Advancing Bifunctionals Towards the First Approval with Clinical Data from Leaders in the Clinic Date and time: Wednesday, October 30th, at 9:00 AM ET. Description: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in relapsed or refractory B-cell malignancies and recently advanced into Phase 1b expansion cohorts. Emerging data continues to support the utility of BTK degradation in patients with relapsed or refractory CLL including those with CNS involvement and with tumors harboring BTK inhibitor resistance mutations Recent data demonstrates clinical activity in Waldenstrom’s macroglobulinemia (WM) Updated case reports will be presented The slides for these presentations may be accessed following their presentation at the 7th Annual TPD & Induced Proximity Summit, via links in the Scientific Resources section of the Nurix website. Panel Discussions CEO Think Tank: A Strategic Look at Targeted Protein Degradation & Induced Proximity Field Panelist: Arthur T. Sands, M.D., Ph.D., President and CEO Morning Keynote Plenary Session: Visions for the Future of TPD & Beyond: The CEO Perspective Date and time: Tuesday, October 29th at 9:30 AM ET Lessons Learned from a Major Strategic Partnership Deal for a Platform Panelist: Jason Kantor Ph.D., Chief Business Officer Closing Keynote Plenary Session: Preparing for the Future: Accelerating Strategy, Partnering & Investment for TPD & Beyond Date and time: Wednesday, October 30th at 4:10 PM ET Lessons Learned from a Major Strategic Partnership Deal for an Asset Panelist: Jason Kantor Ph.D., Chief Business Officer Closing Keynote Plenary Session: Preparing for the Future: Accelerating Strategy, Partnering & Investment for TPD & Beyond Date and time: Wednesday, October 30th at 4:55 PM ET About NX-5948 NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the Phase 1a/b clinical trial can be accessed at ( NCT05131022 ). About Nurix Therapeutics, Inc. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that do not describe historical facts, including, but not limited to, statements regarding the planned timing for the provision of updates and findings from preclinical studies and clinical trials, including Nurix’s intention to present preclinical data and updated clinical reports at the 7th Annual TPD & Induced Proximity Summit, are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements. Such risks and uncertainties include, among others, the risks described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the period ended August 31, 2024, and subsequent filings with the SEC. Any of these risks and uncertainties could materially and adversely affect Nurix’s business and results of operations, which could, in turn, have a significant and adverse impact on Nurix’s stock price. Nurix cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Nurix undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date they were made or to reflect the occurrence of unanticipated events. Contacts: Investors Jason Kantor, Ph.D. Nurix Therapeutics, Inc. ir@nurixtx.com Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors lwolffe@wheelhouselsa.com Media Aljanae Reynolds Wheelhouse Life Science Advisors areynolds@wheelhouselsa.com

WILMINGTON, Del.--( BUSINESS WIRE )--Positive high-level results from an interim analysis of the AMPLIFY Phase III trial showed a fixed duration of AstraZeneca’s CALQUENCE ® (acalabrutinib) in combination with venetoclax, with or without obinutuzumab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemoimmunotherapy in previously untreated adult patients with chronic lymphocytic leukemia (CLL). For the secondary endpoint of overall survival (OS), a trend was observed in favor of CALQUENCE in combination with venetoclax, with or without obinutuzumab, versus standard-of-care chemoimmunotherapy. The OS data were not mature at the time of this analysis and the trial will continue to assess OS as a key secondary endpoint. CLL is caused by the abnormal production of white blood cells and is the most prevalent type of leukemia in adults worldwide, with numbers anticipated to grow. 1-3 In the first-line setting, approximately 40,000 patients are treated with the current standard of care. 4 Although CLL is considered an incurable cancer, patients often live with the disease for many years, and may remain on continuous treatment. 5 Jennifer R. Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School, and principal investigator of the trial, said: “ The AMPLIFY results demonstrate the potential of acalabrutinib and venetoclax with or without obinutuzumab to be effective and well-tolerated fixed-duration treatment options for patients with chronic lymphocytic leukemia. This is an important advance in this setting as fixed-duration regimens allow those living with this chronic disease to take breaks from their treatment, thereby decreasing the possibility of long-term adverse events and drug resistance and improving quality of life.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ The progression-free survival and overall survival results from the AMPLIFY Phase III trial demonstrate the potential of including a BTK inhibitor in a fixed-duration regimen and reinforce our leadership in advancing science for patients with chronic lymphocytic leukemia. If approved, CALQUENCE would become the only second-generation BTK inhibitor available as both a treat-to-progression and fixed-duration treatment, providing more options for patients and their healthcare providers.” The safety and tolerability were consistent with the known safety profile of each medicine. No new safety signals were identified, with low rates of cardiac toxicity observed. The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. INDICATIONS AND USAGE CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE ® (acalabrutinib) tablets Serious and Opportunistic Infections Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE. Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly. Hemorrhage Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients. Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding. Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. Cytopenias Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted. Second Primary Malignancies Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure. Cardiac Arrhythmias Serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.9% of patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate. Hepatotoxicity, Including Drug-Induced Liver Injury Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE. Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE. ADVERSE REACTIONS The most common adverse reactions (≥20%) of any grade in patients with relapsed or refractory MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%). *Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions. Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine to 1.5 to 3 times the upper limit of normal (ULN) occurred in 4.8% of patients. The most common adverse reactions (≥30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea. *Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions. In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively). Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine to 1.5 to 3 times ULN occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively. In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in >5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection. Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE. DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE. Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor. Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours. SPECIFIC POPULATIONS Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE. It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose. Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. Please see full Prescribing Information , including Patient Information . Notes CLL In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow and in blood and lymph nodes. 1 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain. 6 As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets. This could result in anemia, infection and bleeding. 1 B-cell receptor signaling through BTK is one of the essential survival pathways for CLL. AMPLIFY AMPLIFY is a randomized, global, multi-center, open-label Phase III trial evaluating the efficacy and safety of CALQUENCE in combination with venetoclax with and without obinutuzumab compared to investigator's choice of chemoimmunotherapy in adult patients with previously untreated CLL without del(17p) or TP53 mutation. 7 Patients were randomized 1:1:1 to receive either CALQUENCE in combination with venetoclax, CALQUENCE in combination with venetoclax plus obinutuzumab for a fixed duration or standard-of-care chemoimmunotherapy. 7 The primary endpoint is PFS in the CALQUENCE and venetoclax arm as assessed by an Independent Review Committee (IRC) and PFS in this arm assessed by investigators (INV) is a key secondary endpoint. IRC and INV assessed PFS in the CALQUENCE , venetoclax and obinutuzumab arm as a key secondary endpoint. Other key secondary endpoints include OS, event-free survival, overall response rate, duration of response and time to next treatment. 7 The trial includes 27 countries across North and South America, Europe, Asia and Oceania. 7 The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the COVID-19 pandemic. 7 Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalization and death compared to the general population. 8 CALQUENCE CALQUENCE (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity. 9 In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion. CALQUENCE has been used to treat more than 80,000 patients worldwide 10 and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. CALQUENCE is also approved in the US, China and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. CALQUENCE is not currently approved for the treatment of MCL in Japan or the EU. As part of an extensive clinical development program, CALQUENCE is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma. AstraZeneca in hematology AstraZeneca is pushing the boundaries of science to redefine care in hematology. Our goal is to help transform the lives of patients living with malignant, rare and other related hematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians. In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across six scientific platforms. Our recent acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., focused on cell therapies for hematologic malignancies, expand our hematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end development and delivery of novel therapies. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version: General Information About Chronic Lymphocytic Leukemia. Available online. Accessed July 2024. American Cancer Society. What is Chronic Lymphocytic Leukemia? Available online. Accessed July 2024. Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126(23):871. Cerner CancerMPact and DRG databases. Reflects epidemiology estimates across G8 countries (Cerner CancerMPact for G7: US, EU, Japan; DRG database for China). Accessed July 2024. American Cancer Society. After Chronic Lymphocytic Leukemia Treatment. Available at: https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/after-treatment/follow-up . Accessed July 2024. American Cancer Society. Signs and Symptoms of Chronic Lymphocytic Leukemia. Available online. Accessed July 2024. ClinicalTrials.gov. Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL (AMPLIFY). Available at: https://clinicaltrials.gov/study/NCT03836261 . Accessed July 2024. Dube S, et al. Continued Increased Risk of COVID-19 Hospitalisation and Death in Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses: Updated 2023 Results from INFORM, a Retrospective Health Database Study in England. Poster P0409 at ECCMID 2024. Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol . 2016;9(21). Data on File, REF-236261. AstraZeneca Pharmaceuticals LP. US-92135 Last Updated 7/24

Cell and gene therapy (CGT) is an emerging treatment strategy that stands out for its potential "one-time treatment, permanent cure" capability, offering many patients the possibility of long-term relief from their medical conditions. Data shows that in the first half of 2024, a total of 8 CGT therapies were approved globally:  1. Sarepta Therapeutics' Elevidy Receives Full FDA Approval: On June 20th, Sarepta announced the label expansion of its gene therapy Elevidys for Duchenne muscular dystrophy (DMD), now approved for patients aged 4 and above. For ambulatory patients, the FDA granted regular approval, while for non-ambulatory patients, it received accelerated approval. Sarepta has committed to conducting and submitting the results of a randomized controlled trial to verify and confirm the clinical benefit of Elevidys in non-ambulatory DMD patients, which is the ongoing ENVISION (SRP-9001-303) study. Elevidys was previously granted accelerated approval in June 2023 for pediatric DMD patients aged 4-5 years, and the expansion to ≥4 years old patients, regardless of their ambulatory status, marks a significant milestone in the treatment of DMD.   2. Geron's Rytelo Becomes the First FDA-Approved Oligonucleotide Telomerase Inhibitor: On June 6th, Geron announced that Rytelo was approved for the treatment of transfusion-dependent anemia in lower-risk myelodysplastic syndromes (LR-MDS) patients. The approval of Rytelo was based on the positive results of the Phase 3 IMerge trial published in The Lancet, which met its primary and key secondary endpoints, showing Rytelo's significant advantage over placebo in reducing the need for red blood cell transfusions, with durable and sustained responses in responders. This approval marks the fulfillment of a nearly 40-year-long pursuit of a telomerase-targeted therapy, and is viewed as one of the important therapies of the year. With the approval of Rytelo, Geron's stock price surged by 22%. Evaluate predicts that Rytelo's sales could reach $737 million by 2028, reflecting the market's recognition of the therapy's potential. Geron has set a clear pricing strategy for Rytelo, with a wholesale acquisition cost of $2,471 for a 47 mg single dose and $9,884 for a 188 mg single dose. The dosage will be adjusted based on the patient's weight.  3. Moderna's mRESVIA Vaccine: Moderna, Inc. (NASDAQ: MRNA) announced on May 31st that its mRNA respiratory syncytial virus (RSV) vaccine, mRESVIA (mRNA-1345), has been approved by the U.S. Food and Drug Administration (FDA) to protect adults aged 60 and above from RSV-associated lower respiratory tract disease. This vaccine, being the only RSV vaccine administered via a pre-filled syringe, marks the first approval of an mRNA vaccine for a non-COVID-19 disease. The approval was based on the positive results of the global Phase 3 ConquerRSV trial conducted in approximately 37,000 adults aged 60 or older across 22 countries. The primary analysis with a median follow-up of 3.7 months showed the vaccine had an efficacy of 83.7% (95.88% CI 66.0%, 92.2%) against RSV lower respiratory tract disease (LRTD). These results have been published in the New England Journal of Medicine. A longer-term analysis also showed the vaccine's protective effect against RSV LRTD persisted over a median follow-up of 8.6 months. No serious safety concerns were observed in the Phase 3 trial, with the most common adverse reactions including injection site pain, fatigue, headache, muscle pain, and joint pain.  4. Pfizer and its BEQVEZ gene therapy： On April 26, 2024, Pfizer announced that its adeno-associated virus (AAV) vector-based gene therapy BEQVEZ (fidanacogene elaparvovec-DZKT) has been approved by the US FDA for the treatment of adults (18 years and older) with moderate to severe hemophilia B who test negative for neutralizing antibodies to AAV serotype Rh74. The therapy is priced at $3.5 million, comparable to the price of UniQure's hemophilia B gene therapy Hemgenix. This approval was primarily based on the positive data from the Phase III BENEGENE-2 study (n=45), which showed that patients receiving a single dose of BEQVEZ had a significantly reduced annualized bleeding rate (ABR) compared to the standard preventive treatment group (1.3 vs. 4.43, P<0.0001) within 12 months, meeting non-inferiority and superiority endpoints. Currently, BEQVEZ is under review by the European Medicines Agency (EMA) and has been approved by the Canadian regulatory authorities. In addition to BEQVEZ, Pfizer is also investigating two phase III gene therapy programs for hemophilia A and Duchenne muscular dystrophy, as well as a novel anti-tissue factor pathway inhibitor marstacimab for the treatment of hemophilia A or B patients with factor VIII (FVIII) or factor IX (FIX) inhibitors. The FDA and EMA are currently reviewing the Biologics License Application and Marketing Authorization Application for marstacimab, respectively.  5. Orchard Therapeutics：  On March 18, the FDA approved Orchard Therapeutics' gene therapy Lenmeldy for the treatment of metachromatic leukodystrophy (MLD) in pediatric patients. The therapy is priced at $42.5 million, making it the most expensive drug in history. Lenmeldy is the only FDA-approved therapy for the treatment of early-onset MLD in children and has also been approved in the EU and UK. Lenmeldy (atidarsagene autotemcel, formerly OTL-200) utilizes Orchard's core technology, which involves ex vivo modification of autologous stem cells with a lentiviral vector encoding the arylsulfatase-A (ARSA) gene, with the aim of restoring ARSA expression in a single treatment to halt or slow disease progression. The FDA approval was based on data from 37 children, with a median follow-up of 6.76 years, which showed significantly improved overall survival and reduced incidence of motor dysfunction or death in patients receiving Lenmeldy. In terms of safety, Lenmeldy demonstrated good tolerability, with no treatment-related serious adverse events or deaths.  6. BMS's Breyanzi： On March 14, Bristol Myers Squibb (BMS) announced that the US Food and Drug Administration (FDA) has granted accelerated approval for its CD19-targeted CAR-T cell therapy Breyanzi (lisocabtagene maraleucel; liso-cel). This therapy is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior therapies, including a Bruton's tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor. According to the company's press release, Breyanzi is the first CAR-T cell therapy approved for adult patients with R/R CLL or SLL.  As an autologous CAR-T cell therapy targeting CD19, Breyanzi has a defined composition and incorporates a 4-1BB co-stimulatory domain. The FDA had previously approved Breyanzi in February 2021 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) who have received two or more lines of systemic therapy. The unique feature of Breyanzi is its controlled ratio of CD8-positive and CD4-positive T cells, which helps to better manage the potential toxicities of cell therapy. Additionally, the 4-1BB signaling domain significantly enhances the expansion and persistence of the CAR-T cells. The accelerated approval for this indication was based on response rates and duration of response, and further approval will depend on the verification of clinical efficacy in a confirmatory trial. The TRANSCEND CLL 004 trial, which served as the basis for this approval, is an open-label, single-arm, multicenter Phase 1/2 study. The data analysis showed that 20% of patients with relapsed or refractory CLL or SLL achieved complete remission (CR) after receiving Breyanzi, and the safety profile has been established.  7. Carsgen Therapeutics' Selinexor Injection：  On March 1st, Carsgen Therapeutics announced that the new drug application (NDA) for its BCMA CAR-T product Carsgencel® (Selinexor Injection) has been approved by the National Medical Products Administration (NMPA) of China. The product is mainly used to treat adult patients with relapsed or refractory multiple myeloma, who have received at least 3 prior lines of therapy (having received at least one proteasome inhibitor and one immunomodulatory agent). Selinexor Injection is the fifth CAR-T therapy approved in China.  On March 5th, Carsgen Therapeutics announced the launch price of its CAR-T cell therapy Selinexor Injection (brand name: Carsgencel) at 1.15 million RMB. In collaboration with Huadong Medicine (000963.SZ), the company estimates the peak annual sales of this product to be over 1 billion RMB.  Carsgencel® is an autologous BCMA-targeted CAR-T cell product produced through lentiviral transduction. The lentiviral vector encodes a fully human BCMA-specific single-chain variable fragment (scFv), a human CD8α hinge structure, a CD8α transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ activation domain. Carsgen Therapeutics' in-house developed new fully human scFv has demonstrated high binding affinity and stability. Currently, Carsgen Therapeutics is conducting a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of Carsgencel® in the treatment of relapsed or refractory multiple myeloma.  In January 2023, Carsgen Therapeutics and Huadong Medicine reached a commercialization collaboration agreement for Carsgencel® in mainland China. According to this agreement, Carsgen Therapeutics has granted the exclusive commercial rights of Carsgencel® in mainland China to Huadong Medicine. In this collaboration, Huadong Medicine (Hangzhou) will pay a 200 million RMB upfront payment to Carsgen Therapeutics' wholly-owned subsidiary Kaixing Life, and Huadong Medicine will be responsible for up to 1.025 billion RMB in future registration and sales milestone payments. 8. Iovance Biotherapeutics, which announced on February 16th that its tumor-infiltrating lymphocyte (TIL) therapy Amtagvi (lifileucel) has received FDA accelerated approval for the treatment of advanced melanoma, with a price tag of $515,000. It is noteworthy that lifileucel is the world's first approved TIL cell therapy.  Amtagvi is a personalized autologous T-cell immunotherapy derived from the patient's tumor tissue. In the initial treatment, the patient's tumor tissue is removed, and T cells are isolated and further expanded in vitro, before being re-infused back into the patient in a single dose. Each Amtagvi dose contains 7.5 to 72 billion active cells, and the entire process from receiving the tumor tissue to completing the product preparation takes approximately 34 days.  Phase 2 clinical trial data showed that after a median follow-up of 27.6 months, the objective response rate (ORR) was 31.4%, including 8 complete responses (CR) and 40 partial responses (PR). In Iovance's 4-year follow-up data, the longest duration of response reached 55.8 months.   Looking ahead, it is expected that 5 other cell and gene therapies (CGTs) may be approved in 2024, including Carsgen's CAR-T therapy Selinexor Injection, Adaptimmune Therapeutics' TCR T-cell therapy, BioCardia's CardiAMP, Pfizer's novel gene therapy Fidanacogene elaparvovec, and Autolus Therapeutics' CAR-T therapy Obecabtagene autoleucel. However, Rocket Pharmaceuticals' gene therapy Kresladi and Abeona Therapeutics' autologous cell therapy Prademagene zamikeracel (pz-cel) were recently rejected by the FDA in June and April, respectively, due to chemistry, manufacturing, and control (CMC) related issues, and they currently need to provide additional CMC information to complete the review.