SRSF2

Preliminary data supports BMF-500’s potential as a transformative therapy for patients with FLT3 mutated relapsed or refractory (R/R) acute leukemiaBMF-500 showed a favorable safety and tolerability profile, with no dose-limiting toxicities observed across all dose levelsPharmacokinetic and pharmacodynamic data confirmed on-target FMS-like tyrosine kinase 3 (FLT3) inhibition, demonstrating dose-proportional activity and good compartmental penetrationPreliminary Phase I data for BMF-500 in R/R acute leukemia patients with FLT3 gene mutations having failed gilteritinib indicated clinical activity with evidence of responses, including a first complete response with incomplete hematologic recovery (CRi) and reductions in bone marrow blasts in 5 of 6 of the evaluable FLT3 mutated patients REDWOOD CITY, Calif., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea” or “the company”) (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, today announced preliminary data from the ongoing Phase I COVALENT-103 study evaluating BMF-500, the company’s investigational covalent FLT3 inhibitor developed using the proprietary FUSION™ System. “These early findings from the COVALENT-103 study announced today highlight the potential of BMF-500 to deliver meaningful clinical benefits for patients with acute leukemia harboring a FLT3 mutation. BMF-500 is an exceptionally potent molecule and the second covalent inhibitor we have developed in-house and advanced to the clinic and has shown high target selectivity and inhibition,” said Thomas Butler, CEO of Biomea Fusion. “Our early results are particularly exciting as FLT3 gene mutations are common in AML patients and are associated with a very poor prognosis. Patients with such mutations who have failed gilteritinib have a median overall survival of less than 2 months. We hope to provide a significant improvement in the outcome for these patients with BMF-500. Given the safety profile demonstrated to date, and the lack of myelosuppression, we think BMF-500 could be an excellent combination partner used in standard of care.” As of the data cut off, November 20, 2024, 20 patients with R/R acute leukemia had been enrolled in the dose-escalation portion of the study, all of whom received at least one dose of BMF-500. Among these, the study enrolled 13 patients with confirmed FLT3-mutations, of which 10 harbored FLT3-ITD mutations and 3 had FLT3-TKD mutations. All patients with FLT3-mutations had progressed following treatment with gilteritinib, and 5 had received at least 2 prior FLT3 inhibitors. The study enrolled 5 patients with wild-type FLT3 and 2 patients with an unknown FLT3 mutation status. The median number of prior lines of therapies among the enrolled patients was 4. No QT prolongations or related cytopenias were observed and no dose-limiting toxicities (DLTs) were reported as of the data cut off. BMF-500 was generally well tolerated, and dose escalation is continuing per protocol. Pharmacokinetic/pharmacodynamic data confirmed on-target FLT3 inhibition, as BMF-500 and its metabolites showed bone marrow penetration and near complete FLT3 inhibition as early as Day 1 of dosing, as well as dose-proportional FLT3 inhibition. Preliminary data supports BMF-500’s potential as a transformative therapy for patients with FLT3 mutated R/R acute leukemia. During dose escalation, BMF-500 achieved a first CRi at the end of Cycle 2, in 1 of 2 (50%) FLT3 mutated patients dosed at 100 mg twice daily (BID), while the other patient experienced a clearance of peripheral blasts, greater than 50% reduction in bone marrow blasts and reduced transfusion frequency. The majority (5 of 6) of efficacy evaluable FLT3-mutated patients experienced a reduction of their bone marrow blasts. Other evidence of clinical activity such as: clearance or reduction of peripheral blasts, reduction of transfusion frequency, reduction in use of hydroxyurea were observed. Case Study Highlights of Patient with Complete Response (CRi) 61-year-old patient with R/R AML, post allogenic transplant, with six co-occurring mutations (FLT3-ITD, ASXL1, IDH2, PHF6, RUNX1, SRSF2)4 prior treatment regimens including venetoclax and gilteritinibConfirmed CRi at 100 mg BID dosingProgressive improvement in normal white blood cells, neutrophils, and monocytes despite ongoing transfusion needs Webcast and Conference Call Details Biomea Fusion will host a webcast and conference call today, Monday, December 9 at 4:30 pm EST. Interested parties will be able to join the webcast and view the related presentation under the Investors and Media section of the company’s website at https://investors.biomeafusion.com/news-events/events. A replay of the webcast and conference call will be archived on Biomea’s website following the event. About COVALENT-103 COVALENT-103 is a multicenter, open-label, non-randomized trial seeking to evaluate the safety and efficacy of BMF-500, a twice daily oral treatment, in adult patients with relapsed or refractory acute leukemia with FMS-like tyrosine kinase 3 (FLT3) wild-type and FLT3 mutations. The Phase I COVALENT-103 study aims to evaluate the safety and tolerability of BMF-500, determine the optimal biologic dose and recommended Phase II dose. Additional information about the Phase I clinical trial of BMF-500 can be found at ClinicalTrials.gov using the identifier, NCT05918692. About BMF-500 BMF-500, an investigational, novel, orally bioavailable, highly potent and selective covalent small molecule inhibitor of FLT3, was discovered and developed in-house at Biomea using the company’s proprietary FUSION™ System and has demonstrated encouraging potential based on extensive preclinical studies. The kinase inhibitory profile of BMF-500 showed high target selectivity, suggesting the potential for reduced off-target liabilities. BMF-500 was designed to have a therapeutic profile to allow for combinations with standard of care and/or novel targeted agents like icovamenib, Biomea’s investigational covalent menin inhibitor currently in clinical development for solid and liquid tumors as well as diabetes. Previous data presented at the 2022 American Society of Hematology Annual Meeting showed BMF-500’s picomolar affinity for inhibition of activating FLT3 mutations, including FLT3-ITD and various tyrosine kinase domain (TKD) mutations. BMF-500 demonstrated multi-fold higher potency and increased cytotoxicity as compared to the commercially available non-covalent FLT3 inhibitor gilteritinib. These data also showed complete tumor regression in mouse models of FLT3-ITD acute myeloid leukemia (AML), with no tumor regrowth even after treatment cessation. Data presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting demonstrated the potential utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of BMF-500 and icovamenib. Additionally, Biomea has shown the potential of combinatorial approaches of BMF-500 and icovamenib with MEK and BCL2 blockade in other preclinical studies. These data provide preclinical evidence for combining pathway-specific inhibitors as a potential therapeutic strategy for further investigation in acute leukemia. About FLT3 in AML FLT3 is a receptor tyrosine kinase (RTK) that plays a central role in the survival, proliferation, and differentiation of immature blood cells. FLT3 gene mutations are common in patients with AML and are associated with a poor prognosis. Nearly 40% of AML patients have a FLT3 mutation, representing more than 7,000 incident patients in the U.S. each year. Once failing the only approved agent in the R/R setting, gilteritinib, patients typically have a poor prognosis and very short survival (median overall survival ~1.8 months). Academic literature suggests that up to 50% of AML patients with an NPM1 mutation also harbor a FLT3 mutation. While FLT3-specific and pan-tyrosine kinase inhibitors are approved by the FDA across various lines of therapy in AML, these agents have produced relatively low rates of durable responses and overall survival remains an unmet need. About Biomea Fusion Biomea Fusion is a clinical-stage biopharmaceutical company focused on the discovery and development of oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. We are utilizing our proprietary FUSION™ System to discover, design, and develop a pipeline of next-generation covalent-binding small-molecule medicines designed to maximize clinical benefit for patients. We aim to have an outsized impact on the treatment of disease for the patients we serve. We aim to cure. Visit us at biomeafusion.com and follow us on LinkedIn, X, and Facebook. Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our product candidates and development programs, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in preclinical or clinical development, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research and development activities, and the risk that preliminary or interim data from our clinical trials will not be predictive of future results of such trials. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact:Investor and Media Relations:Ramses ErdtmannCOO & President of Biomea Fusionre@biomeafusion.com

Personalized Therapy Biosimulation Uncovers a Spectrum of Genomic Aberrations that Predict Response to HMA in Myelodysplastic Syndrome Patients SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Cellworks Group Inc., a leader in Precision Drug Development and Personalized Therapy Biosimulation, today announced results from a study that examined how Differentiation Scoring (DS) derived from key myeloid biomarkers in individual Myelodysplastic Syndrome (MDS) patients using the Cellworks Platform and Computational Biology Model (CBM) can predict response to Hypomethylating Agents (HMA). In the study, DS predicted HMA response in MDS patients and showed a strong correlation to the treatment efficacy score (ES). Non-responders had lower DS and survival than patients with high DS. Conclusions from the study suggest that DS-low MDS patients should be considered for novel combination therapy at the time of diagnosis. Results from the study were featured in a poster presentation as Abstract 2171 at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition on December 10, 2022 and have been published online at Blood®. “Given that 50% of MDS patients who are treated with HMA as a single agent will have unsatisfactory outcomes, we need to be able to predict therapy response for individual patients prior to treatment,” said Dr. Guido Marcucci, MD, Chair and Professor, Department of Hematologic Malignancies Translational Science, Director, Gehr; Family Center for Leukemia Research, Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope; and Co-Principal Investigator of the study. “This study demonstrates the power of using Cellworks personalized therapy biosimulation to gain insight into individual patient mutanome, drug resistance pathways and novel biomarkers that determine their drug response and resistance to better inform treatment decisions for MDS patients.” “MDS patients typically have multiple molecular aberrations which impact how they respond to treatment,” said Dr. Scott Howard, MD, MSc, Professor at University of Tennessee Health Science Center and Co-Principal Investigator of the study. “This study showcases the complexity of MDS-related aberrations and provides a metric for identifying beforehand which patients will benefit from HMA as a single agent. By identifying which patients will not respond to HMA, clinicians can consider other options such as a combination therapy or a clinical trial.” “Biosimulation of MDS using differentiation scoring was able to identify patients with minimal benefits from HMA for whom an alternative strategy at the outset of treatment could offer a very meaningful chance to enhance outcomes,” said Dr. Michael Castro, MD, Neuro-oncologist, Medical Oncologist at Beverly Hills Cancer Center; Chief Medical Officer at Cellworks, Group Inc. and Co-Principal Investigator of the study. Cellworks Personalized Therapy Biosimulation The Cellworks Platform biosimulates how a patient's personalized genomic disease model will respond to therapies prior to treatment and can also identify novel drug combinations for treatment-refractory patients. The platform is powered by the groundbreaking Cellworks CBM, a highly curated mechanistic network of 6,000+ human genes, 30,000 molecular species and 600,000+ molecular interactions. As part of the biosimulation process, personalized disease models are created for each patient using their cytogenetic and molecular data as input to the Cellworks CBM. The Cellworks Platform analyzes the impact of specific therapies on the patient’s personalized disease model and predicts the efficacy of specific chemotherapies. Study: ASH Abstract 2171 The purpose of the study was to examine how Differentiation Scoring derived from the Cellworks Platform, Computational Biology Model, and each Myelodysplastic Syndrome patient’s genomic aberrations could serve as a biomarker to predict response to Hypomethylating Agents. Background Differentiation arrest resulting from aberrant methylation represents a key pathogenic and phenotypic feature of MDS. Hypomethylating agents (HMA) can reverse epigenetic dysregulation, but single agents fail to control the disease in approximately 50% of patients, many of whom progress to AML and carry a dismal prognosis. Methods The study included 169 MDS patients treated with azacytidine (n = 86) or decitabine (n = 83) whose genomic aberrations and clinical outcomes were available from public databases. Biosimulation of the disease state was computationally derived from pathways that were up- or down-regulated by individual genomic aberrations. DS was defined as the ratio of the quantified impact of key differentiation biomarkers in myeloid malignancies (CEBPA, GATA1, SPI1 and ITGAM) divided by the impact of HOXA9 transcription, a known repressor of differentiation, and normalized on a log2 scale. The Cellworks Platform and CBM were used to determine the change in DS attributable to HMA to define an efficacy score (ES) as a parameter of drug response. A Pearson correlation coefficient was obtained using the two variables. DS in clinical responders (R) and non-responders (NR) was evaluated with the Student t-test. DS was defined with DS > 1.5 as DS-high and < 1.5 as DS-low. Survival data were available for 101 patients and correlated with DS-high (n=49) and DS-low (n=52) groups using a KM-curve. Results Regarding HMA response, 62 patients were responders, while 107 were non-responders. Prior to therapy, 86 patients had DS-high and 83 had DS-low scores. Post-treatment, DS were correlated with HMA ES (R = 0.58, p < 2.2e-16), and showed a favorable HMA response for DS-high patients. Biosimulation showed the incremental benefit on DS of HMA was greater for people with DS-high than DS-low scores (44% vs 16%, p = 7.51 e-17). Median DS was higher in responders than in non-responders (p=0.00232). Patients with DS-high scores had superior survival compared to those with DS-low scores (log rank p = 0.0016). Different genomic aberrations contributed to the DS scores. DS-high patients had more TP53 mutations, 17p del, 8q amp, and 5q del. On the other hand, DS-low patients more often had mutations in ASXL1, SRSF2, RUNX1, DNMT3A, EZH2, NF1, NRAS, CBL, or 7q deletion. Conclusions This study shows that Cellworks personalized therapy biosimulation, which was based on each patient’s genomic aberrations, reveals a high spectrum of DS among patients with MDS. DS strongly predicted HMA response and in general, non-responders had lower DS and survival than high-DS patients. While patients with DS-low scores might have fared even worse without HMA therapy, this study suggests that DS-low patients should be considered for novel combination therapy at the time of diagnosis given their unsatisfactory outcomes with HMA therapy as a single agent. About Cellworks Group Cellworks Group, Inc. is a leader in Precision Drug Development and Personalized Therapy Biosimulation. The Cellworks Platform predicts therapy response for individual patients and patient cohorts using a breakthrough Computational Biology Model (CBM) and biosimulation technology. Backed by Artiman Ventures, Bering Capital, Sequoia Capital, UnitedHealth Group and Agilent Ventures, Cellworks has the world’s strongest trans-disciplinary team of molecular biologists, cellular pathway modelers and software technologists working toward a common goal – attacking serious diseases to improve the lives of patients. The company is based in South San Francisco, California with a research and development facility in Bangalore, India. For more information, visit . All trademarks and registered trademarks in this document are the properties of their respective owners.

Exploratory analysis from Cohort 3 of the Phase 2 REFINE study presented in an oral session at ASH NORTH CHICAGO, Ill., Dec. 10, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new data from Cohort 3 of its Phase 2 REFINE study of investigational navitoclax in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (MF). The exploratory analysis suggests the combination of navitoclax and ruxolitinib led to reductions in bone marrow fibrosis (BMF) and variant allele frequency (VAF) for common genetic mutations found in individuals with myelofibrosis that may indicate potential disease modification.1 The findings were shared in an oral presentation (abstract #237) at the 64th American Society of Hematology Annual Meeting & Exposition (ASH). "While the current standard of care for patients with myelofibrosis can improve disease symptoms, impact on underlying disease biology is limited. It is our hope that patients have an option that goes beyond symptom control," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development, AbbVie. "Consistent with previous evidence, these results suggest navitoclax combination may have disease modifying potential, both as an anti-fibrosis agent and by reducing variant allele frequency of driver mutations." REFINE (NCT03222609) is a Phase 2 non-randomized open-label multi-cohort study evaluating the safety and efficacy of navitoclax alone or in combination with ruxolitinib in MF.2 These data build on AbbVie's history of transforming standards of care in blood cancers, including recent presentations of investigational navitoclax data from the REFINE study earlier this year at the American Association for Cancer Research (AACR) Annual Meeting and the European Hematology Association (EHA) Annual Congress. The findings presented at ASH were based on an exploratory analysis of 32 JAK inhibitor-naïve patients with MF from Cohort 3 of the Phase 2 REFINE study. The primary endpoint was spleen volume reduction of ≥35 percent (SVR35) from baseline at week 24.1 Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF and a reduction in VAF for the driver gene mutations (JAK2V617, CALR, MPL or Triple-negative), respectively.1 In this exploratory analysis, SVR35 at week 24 was observed in higher-risk groups, improving over time. The four poor prognosis subgroups were: Type (primary or secondary) of MF (primary MF, 59 percent [n = 10/17]; age (≥75 years, 50 percent [n = 4/8]); prognostic risk score, as measured by Dynamic International Prognostic Scoring System or DIPSS (intermediate-2, 63 percent [n = 12/19]; high, 33 percent [n = 1/3]); and presence of high molecular risk (HMR) mutations (47 percent [n = 9/19].1 In Cohort 3, BMF grade improvement was evaluable in 81 percent (26/32) of patients.1 Of these study participants, 35 percent (9/26) achieved ≥ 1 grade improvement at any time during treatment with a median time-to-improvement of 12.3 weeks.1 Complete resolution of BMF was observed in 22 percent (2/9) of patients.1 Reduction in driver gene mutation VAF > 20% from baseline at week 12 or 24 was observed in 50 percent (14/28) of patients, while 18 percent (5/28) of patients achieved > 50% VAF reduction from baseline. There were no differences in > 20% VAF reductions from baseline to week 12 or 24 between those with or without HMR mutations (47 percent [7/15] versus 54 percent [7/13], respectively). Preliminary safety analysis identified no new safety signals. Twenty-five (78 percent) patients reported one or more adverse events (AE). The most common grade ≥3 AEs were thrombocytopenia (47 percent), anemia (34 percent), and neutropenia (25 percent). 9.4 percent of patients discontinued therapy due to an AE.3 "These results are promising for patients who need a treatment option that goes beyond just symptom control," said Francesco Passamonti, full professor of hematology, University of Insubria and chief, hematology, Varese Hospital, Italy. "The suggestion of disease modification in this analysis from combination therapy with navitoclax is encouraging, particularly when combined with clinical efficacy in terms of SVR35 rates in the higher risk groups that improved over time." About Navitoclax Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. Navitoclax is not approved by any health authority worldwide at this time. Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies. AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently enrolling. Please visit us here for more information about enrolling in a clinical trial. About the REFINE Study REFINE is a multi-cohort, Phase 2, randomized, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis (MF).2 The primary outcome measure is the percentage of patients who achieve spleen volume reduction of greater than or equal to 35 percent (SVR35) from baseline to week 24.2 Secondary outcomes measures include percentage of participants achieving 50 percent reduction in total symptom score from baseline to week 24; anemia response every 12 weeks up to approximately 96 weeks, measured according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria; and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System.2 Data presented at ASH 2022 include safety and efficacy results from Cohort 3 of REFINE (n=32). Patients in Cohort 3 had primary or secondary MF with splenomegaly (DIPSS ≥ intermediate-1) and had not received JAK-2 therapy or bromodomain and extra terminal motif (BET) inhibitors prior to enrollment. The primary endpoint of SVR35 was assessed by MRI conducted by central review. Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF obtained from BM biopsies by local evaluation and a reduction in VAF for the driver gene mutations (JAK2V617, CALR, or MPL), respectively. Studied HMR mutations included ASXL1, EZH2, SRSF2, IDH1/2, and U2AF1 p.Q157. Driver gene VAF and HMR mutations were determined in whole blood with a 50-gene focus myeloid next-generation sequencing panel. The findings presented at ASH 2022 are representative of data from Cohort 3 of the REFINE study as of February 7, 2022. More information about the REFINE study can be found at (NCT03222609). About Myelofibrosis Myelofibrosis (MF) is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Patients living with MF experience symptoms such as an enlarged spleen, fatigue, weakness, and severe anemia which are often debilitating and greatly impact quality of life. MF also carries a risk of transformation to more aggressive disease such as acute myeloid leukemia.4 About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit and our Blood Cancer Press Kit page. About AbbVie AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2021 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. References: Passamonti F, Foran J, Tandra A, et al. The Combination of Navitoclax and Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Mediates Responses Suggestive of Disease Modification. [Oral Presentation #237]. Presented at 2022 American Society of Hematology (ASH) Annual Meeting and Exhibition, December 10-13, 2022. ClinicalTrials.gov. A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis (REFINE). NCT03222609. Available at . Last accessed October 2022. Navitoclax plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: Preliminary safety and efficacy in a multicenter, open-label Phase 2 study. [Oral Presentation S197]. Presented at European Hematology Association 2022 Congress (EHA 2022), June 9-12, 2022. Tsujimoto Y. (1998). Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria?. Genes to cells: devoted to molecular & cellular mechanisms, 3(11), 697–707. SOURCE AbbVie