AZD4320 / AstraZeneca - LARVOL DELTA

SINGLE CELL RNA SEQUENCING PROFILING OF ADULT T-CELL LEUKEMIA AND MOLECULAR MECHANISM OF GENE RGS13 INVOLVING IN DEVELOPMENT OF ATLL (EHA 2024) - "Single-cell sequencing data from 9 samples yielded 82,977 high-quality cells, divided into three groups: patientgroup, HTLV-1 carrier group, and healthy donor group. Using the Seurat method for clustering anddimensionality reduction, a total of 35 cell clusters were identified for each sample. Analysis revealed significantenrichment of CD4+ central memory T-cell subgroups (clusters 4, 8, 10, 11, 13, and 15) in the patient group,with higher proportions than HTLV-1 carriers and healthy donors, suggesting tumor-associated CD4+ T cells."

Clinical • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD4

AZD0466 in patients with advanced non-Hodgkin lymphoma: Efficacy and safety in an open-label phase 1 trial (AACR 2024) - P1/2 | "AZD0466 is a drug-dendrimer conjugate consisting of the dual Bcl-2/Bcl-xL inhibitor AZD4320 covalently conjugated to a pegylated poly-L-lysine dendrimer, which allows for gradual release by hydrolysis. The study was terminated due to similar findings in a concurrent trial (D8241C00001; NIMBLE). With an objective response observed at the 1200 mg dose level, further development of agents targeting Bcl-2/xL in NHL is warranted with efforts to reduce the cardiotoxicity profile."

Clinical • IO biomarker • Metastases • P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL2L1 • CASP3

Pre-Clinical Study on the Dual BCL2/BCL-XL Inhibitor AZD0466 for the Treatment of Chronic Lymphocytic Leukemia (ASH 2023) - "To evaluate if combination treatment of AZD0466 with BTK inhibitors would improve efficacy, we transplanted murine Eµ-TCL1 tumors into syngeneic recipient mice and randomized them for treatment with vehicle, ibrutinib (30mg/kg in drinking water), acalabrutinib (25mg/kg, p.o. QD), AZD0466 (70mg/kg, i.v., QW) and combination of AZD0466 with ibrutinib or acalabrutinib. Moreover, AZD4320 was highly efficacious in MAVER-1 and MINO cell line models where resistance to venetoclax mediated by BCL-XL upregulation was modelled by an in vitro dose escalation method. In summary, our pre-clinical study shows that the dual BCL2/BCL-XL inhibitor could represent an important treatment option for venetoclax resistance mediated by specific BCL2 mutations or BCL-XL upregulation and that its efficacy could be further improved upon combination treatment with BTKi."

IO biomarker • Preclinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • Transplantation • ANXA5 • BCL2 • BCL2L1 • CD5 • IGH

Safety and Tolerability of AZD0466 As Monotherapy for Patients with Advanced Hematologic Malignancies. Results from a Phase I/II Trial (ASH 2023) - P1, P1/2 | "BCL-2 inhibition by venetoclax (VEN) is beneficial in many patients (pts) with acute myeloid leukemia (AML), but resistance is common due to upregulation of other pro-survival proteins such as BCL-extra-large (BCL-xL) and myeloid cell leukemia-1...Preclinically, AZD4320 showed greater inhibition of tumor growth than VEN and navitoclax in VEN-resistant xenograft models (Balachander et al... Given the observed DLTs of asymptomatic increase in troponin levels, and the lack of significant clinical benefit, the study was terminated."

Clinical • IO biomarker • Metastases • Monotherapy • P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cerebral Hemorrhage • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Transplantation • BCL2L1 • MCL1

Identification of vulnerabilities for targeting BCL-2 family members in T-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "Venetoclax is a selective BCL-2 inhibitor and is successfully used in CLL and AML, but heterogeneous sensitivity to venetoclax has been described in ALL and inhibitors of other BCL-2 family members including BCL-XL-selective A-1331852 and MCL-1 selective AZD5991 have been developed. Moreover, a dual inhibitor of the anti-apoptotic BCL-2 family members BCL-2 and BCL-XL (AZD4320) with its dendrimer conjugate (AZD0466) has recently shown anti-tumor activity in hematologic cancer models with manageable toxicity...Taken together, we found vulnerabilities of T-ALL to BCL-2 family inhibition, particularly to dual BCL-2/BCL-XL inhibition by AZD4320, and we demonstrated on-target activities. Using BH3-profiling, we identified BAD-priming as a marker of response for AZD4320 and MCL-1 dependence as a resistance mechanism that can be targeted by combination treatment, suggesting further clinical evaluation."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • BCL2 • BCL2L1

SAFETY AND TOLERABILITY OF AZD0466 AS MONOTHERAPY FOR PATIENTS WITH ADVANCED HEMATOLOGICAL MALIGNANCIES - PRELIMINARY RESULTS FROM AN ONGOING PHASE I/II TRIAL (EHA 2023) - P1/2 | "Background: The BCL2 family of proteins induce apoptosis via caspase activation and are being increasingly targeted in hematologic malignancies by small molecules such as venetoclax (VEN)...Preclinically, AZD4320 showed activity in patient (pt)-derived AML xenografts and superior tumor growth inhibition to VEN and navitoclax in VEN-resistant xenograft models (Balachander et al...Module 2 investigates drug-drug interactions between AZD0466 and voriconazole... Treatment with AZD0466 is well tolerated in pts with R/R acute leukemia, with AEs matching expected toxicity from preclinical data. Preclinical efficacy modeling and clinical PK data suggest further dose escalation is warranted to explore clinical activity."

Clinical • IO biomarker • Metastases • Monotherapy • P1/2 data • Acute Myelogenous Leukemia • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • BCL2 • BCL2L1

Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR. (PubMed, J Ovarian Res) - "In a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC."

Journal • Endometriosis • Gynecology • Oncology • Ovarian Cancer • Solid Tumor • Women's Health • ARID1A

AZD0466, a dual BCL-2/XL targeting nanomedicine, is active in small cell lung cancer models (AACR 2023) - P1, P1/2 | "The active moiety, AZD4320, is a potent dual inhibitor of BCL-2 and BCL-XL...AZD0466 outperformed the selective BCL-2 inhibitor venetoclax in 6/10 models. Notably, AZD0466 was active in models resistant to platinum/etoposide chemotherapy, the standard-of-care for SCLC...AZD0466 exhibits linear PK, consistent across solid tumor and leukemia patients. The doses tested are in line with preclinical studies in SCLC."

IO biomarker • Preclinical • Hematological Malignancies • Leukemia • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • BCL2 • BCL2L1 • CASP3 • NEUROD1 • NEUROD1 • YAP1

[VIRTUAL] New Targetable Pathways in Chronic Lymphocytic Leukemia (CLL) (SOHO 2021) - P1/2 | "AZD5991 is a highly selective BH3-mimetic that demonstrates high in vitro potency in MCL1-dependent cell lines with an IC50 <1 nM.7 We have demonstrated that direct MCL1 inhibition with AZD5991 disrupts survival of neoplastic B-cells in lymph-node mimicking conditions, induces mitochondrial dysfunction and cooperates with BCL2/X inhibitors in vitro and in vivo.8 A phase 1 clinical trial of AZD5991 alone or in combination with venetoclax in hematologic malignancies is ongoing (NCT03218683)...AMG-176 demonstrated synergy with venetoclax in AML models; however, it also caused cytopenias.9 AMG-176 was shown to induce apoptosis of CLL cells independent of prognostic markers and overcame the protective effect of stromal microenvironment.10 However, suppressive effects on hematopoiesis will likely become the dose- limiting factor in clinical trials of MCL1-targeting agents. The effect of MCL1 inhibition on cord blood-derived CD34+ cells was studied using a..."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2 • BCL2L1 • BCL2L2 • CD19 • CD34 • CDK7 • ROR1 • SYK

Novel Agents in Chronic Lymphocytic Leukemia (CLL) (SOHO 2022) - "The subsequent key areas hold promise: Alternative Inhibitors of BTK Here, non-covalent BTK inhibitors, such as pirtobrutinib (LOXO- 305) and nemtabrutinib (ARQ-531), have shown effi cacy in CLL resistant to covalent BTK inhibitors...AZD5991 is a highly selective BH3-mimetic that demonstrates high potency in MCL1-dependent cell lines.9 Our group has shown that selective targeting Mcl-1 induced metabolic dysfunction and abrogated survival of lymphoid cells in vitro and in vivo.10 Other BH3- mimetics targeting Mcl-1 include AMG-176 and S63845.11,12 However, Mcl-1 targeting agents may be associated with toxicities, including against the hematopoietic stem and progenitor cells, potentially leading to cytopenias in the clinic.13 The therapeutic window for these agents needs to be defi ned. BH3-mimetics which target Bcl-xL, such as navitoclax, are not being developed in CLL due to concerns of thrombocytopenia.14 However, AZD4320, an alternative Bcl-2/xL inhibitor, is being..."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2L1 • CD19 • ROR1 • TP53

Safety and Tolerability of AZD0466 As Monotherapy for Patients with Advanced Hematological Malignancies. Preliminary Results from an Ongoing Phase I/II Trial (ASH 2022) - P1, P1/2 | "Specific Bcl-2 inhibition using venetoclax is beneficial in patients with acute myeloid leukemia (AML), but resistance often develops due to upregulation of anti-apoptotic proteins such as Bcl-xL and Mcl-1...Following IV infusion, released AZD4320 exhibited a dose-proportional increase in area under the concentration time curve (AUC) and maximum serum concentration (Cmax), moderate PK variability (≈50% coefficient of variation), and a half-life of ≈18 hours. AZD0466 has been well tolerated, with no DLTs to date and no discontinuations due to treatment-related AEs. The trial continues to enroll, further dose escalation is planned, and updated data will be presented."

Clinical • Monotherapy • P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • BCL2L1

Combined Inhibition of MCL1 By AZD5991 and BCL2/Bclxl By AZD4320 As Promising Strategies to Overcome Acute Leukemia Tumor Burden and Niche Chemoresistance (ASH 2022) - "To investigate the in vitro, ex vivo and in vivo effects of AZD5991 (AstraZeneca), a novel MCL1 inhibitor compound, alone or in combination with AZD4320 (BCL-2/BCL-XL inhibitor compound), venetoclax, cytarabine and doxorubicin. MCL1 overexpression in mononuclear cells from patients with acute leukemia and that present or not resistance to venetoclax treatment, is associated with poor prognosis and relapse disease. Our results demonstrated that co-targeting MCL-1, BCL-2 and BCL-xL, through the AZD5991 and AZD4320 compounds in the treatment of acute leukemias, may enhance therapeutic specificity, overcome chemoresistance and contribute with the cure of these aggressive malignant disorders."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • ANXA5 • BCL2 • BCL2L1 • CD34

BCL-XL Blockage with A1155463 Significantly Increases Efficacy of Venetoclax in Mantle Cell Lymphoma in Vitro and In Vivo (ASH 2022) - "Mantle cell lymphoma (MCL) is a rare chronically relapsing subtype of aggressive B-cell non-Hodgkin lymphoma characterized by the canonical chromosomal translocation t (11; 14) and other molecular cytogenetic aberrations including overexpression of BCL2 protein. We demonstrated that the thrombocytopenia associated with continued therapy with A1155463 could be managed by 4 days on / 3 days off treatment strategy, which cannot be applied in case of fixed dual BCL2/BCL-XL inhibitors like navitoclax, or AZD4320. In summary, the combined inhibition of BCL2 and BCL-XL with VEN and A1155463 is a highly effective experimental treatment strategy for R/R MCL with a potential translation to the clinical grounds."

IO biomarker • Preclinical • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • Transplantation • BCL2L1 • CD40 • MCL1

NIMBLE: A Phase I/II Study of AZD0466 Monotherapy or in Combination in Patients with Advanced Hematological Malignancies (ASH 2021) - P1, P1/2 | "Dual BCL2/xL inhibition with AZD4320 has potential for broader activity than BCL2-specific inhibition with venetoclax (Balachander et al, Clinical Cancer Research 2020)...Treatment with hydroxyurea during screening and cycle 1 is permitted to control white blood cell count...Module 2 is a drug-drug interaction (DDI) study that will investigate the safety and establish the sensitivity of AZD0466 to voriconazole, a strong inhibitor of CYP3A4...This study is actively enrolling patients at sites in the USA, and will be opening at multiple sites in Australia, Europe and South Korea. An update of preliminary safety and pharmacokinetics will be presented."

Clinical • IO biomarker • Monotherapy • P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • BCL2L1 • CYP3A4 • TP53

"https://t.co/LUzvPliMKs #ASH22 Combined Inhibition of MCL1 By AZD5991 and BCL2/Bclxl By AZD4320 As Promising Strategies to Overcome Acute Leukemia Tumor Burden and Niche Chemoresistance." (@TalhaBadarMD)

Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1

THE DUAL BCL-2 AND BCL-XL INHIBITOR AZD4320 SHOWS ON-TARGET ACTIVITY IN ALL AND ACTS SYNERGISTICALLY WITH MCL-1 INHIBITION (EHA 2022) - "AZD4320 was developed as a dual inhibitor of BCL-2 and BCL-XL, and its dendrimer conjugate (AZD0466) was recently reported to demonstrate anti-tumor activity in hematological cancer models, while showing only a transient thrombocytopenia. Aims In this study, the anti-leukemia activities of the dual BCL-2 and BCL-XL inhibitor AZD4320 and of MCL-1-selective AZD5991 were evaluated and compared to the effects of other BH3-mimetics (BCL-2-selective venetoclax, BCL-XL-selective A-1331852 and MCL-1-selective S63845)...Importantly, the highest synergism was found at low concentrations of both inhibitors, suggesting efficacy at moderate concentrations, which could potentially be achieved in vivo . Conclusion In summary, our study demonstrates sensitivity, on-target activity and synergism of the dual BCL-2 and BCL-XL inhibitor AZD4320 with inhibition of MCL-1, thereby providing strong evidence for further clinical evaluation in ALL."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia • BCL2 • BCL2L1

Combination Therapy of Bcl-2/XL dual Inhibitor AZD0466 with Acalabrutinib to Overcome Therapeutic Resistance in Aggressive R/R Mantle Cell Lymphoma (ASH 2021) - "This is largely due to frequent relapses after therapies including paradigm shifting therapies BTK inhibitors (BTKi), such as ibrutinib and acalabrutinib, and Bcl-2 inhibitor (Bcl-2i) venetoclax after long-term treatment in the clinic. Conclusion Compared to AZD4320/AZD0466 and acalabrutinib, combination therapy demonstrated anti-MCL synergy both in vitro and in vivo . These findings suggest that targeting Bcl-2/X L and BTK is promising to overcome multiple acquired resistance phenotypes, including CD19 CAR T-cell therapy."

Combination therapy • IO biomarker • Cardiovascular • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL2L1 • CASP3 • CD19

ASPP2k, a Dominant-Negative Splicing Variant of the Apoptosis-Stimulating Protein of p53-2 (ASPP2), Modulates Treatment Response Towards BCL-Signaling Inhibitors in Acute Myeloid Leukemia (ASH 2021) - "Several compounds targeting BCL-2 signaling, which are under clinical investigation, were tested (BCL-2: venetoclax, BCL-2/Xl: AZD4320, MCL-1: AZD5991 and CDK9: AZD4573)...Priming with a hypomethylating agent (HMA, decitabine) resulted in additive (CI close to 1) to synergistic (CI 0.25 – 0.7) proapoptotic effects in isobologram analysis and led to a release of drug resistance in primary resistant cell lines...attenuation thereof after forcely expressing the dominant-negative splicing variant). To summarize, we show that inhibition of BCL-2 signaling is a promising approach to target acute leukemia – as a monoagent as well as in combination with HMA: Further, we provide a path for exploration of ASPP2k as a predictive tool as well as a therapeutic sensitizer of pro-apoptotic drugs, which will be addressed in future studies."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

[VIRTUAL] Pharmacologic targeting Mcl-1 with AZD5991 induces apoptosis, suppresses mitochondrial respiration and overcomes ibrutinib resistance in non-Hodgkin lymphoma cells (AACR 2021) - "Co-treatment of DLBCL cells with Bcl-2/xL inhibitors AZD4320, venetoclax and navitoclax overcame resistance to AZD5991. Mcl-1 inhibition leads to mitochondrial dysfunction and inhibition of cellular respiration. Resistance to Mcl-1 inhibition may be overcome by concurrent targeting of alternative anti-apoptotic proteins (Bcl-2/xL) in NHL."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2L1 • CD40LG

A novel BH3-mimetic, AZD0466, targeting BCL-XL and BCL-2 is effective in pre-clinical models of malignant pleural mesothelioma. (PubMed, Cell Death Discov) - "Malignant pleural mesothelioma (MPM) is an aggressive cancer with treatment limited to Cisplatin and Pemetrexed chemotherapy...In this study we show another inhibitor, AZD4320 that targets BCL-XL (and BCL-2), can also potently kill MPM tumor cells in vitro (EC values in the 200 nM range) and this effect is enhanced by co-inhibition of MCL-1 using AZD5991...Critically, the degree of thrombocytopenia, an on-target toxicity associated with BCL-XL inhibition, was significantly reduced throughout the treatment period compared to other BCL-XL-targeting BH3-mimetics. These pre-clinical findings provide a rationale for the future clinical evaluation for novel BH3-mimetic formulations in MPM, and indeed, other solid tumor types dependent on BCL-XL."

IO biomarker • Journal • Preclinical • Hematological Disorders • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • Thrombocytopenia • BCL2 • BCL2L1

Design and optimisation of dendrimer-conjugated Bcl-2/x inhibitor, AZD0466, with improved therapeutic index for cancer therapy. (PubMed, Commun Biol) - "The optimised candidate is shown to be efficacious and better tolerated in preclinical models compared with AZD4320 alone. The AZD4320-dendrimer conjugate (AZD0466) identified, through mathematical modelling, has resulted in an improved therapeutic index and thus enabled progression of this promising dual Bcl-2/Bcl-x inhibitor into clinical development."

Journal • Cardiovascular • Oncology • Solid Tumor • BCL2 • BCL2L1

AstraZeneca Demonstrates Strength in Hematology With Robust Data at ASH 2020 (Businesswire) - “AstraZeneca will present new research aimed at addressing key unmet needs facing patients with blood cancers at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, held virtually from 5 to 8 December 2020.The Company will present 27 abstracts spanning five medicines and potential new medicines and eight different hematology conditions that demonstrate the Company’s commitment to advancing hematology research and treatments for patients living with hematologic malignancies.”

Clinical data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Mantle Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

[VIRTUAL] Pharmacologic Inhibition of B Cell-Receptor-Associated Kinases with CG-806 Induces Apoptosis and Metabolic Reprogramming in Aggressive Non-Hodgkin Lymphoma (NHL) Models (ASH 2020) - "While targeting BTK (ibrutinib, acalabrutinib) and PI3K (idelalisib, duvelisib) has shown efficacy in CLL, clinical responses fall short in aggressive NHL, necessitating the development of novel approaches to suppress BCR signaling...Consistent with the above observations, synergy was observed between CG-806 and inhibitors of metabolic enzymes (teleglenastat, perhexiline maleate) and BH3-mimetics targeting BCL2/X proteins (venetoclax, AZD4320)...BCL2 family proteins may be implicated in resistance to CG-806. These results provide rationale for further investigation of CG-806 in aggressive NHL."

IO Biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL2L1 • CD19 • CD40LG • CD5 • PTPRC • SYK

[VIRTUAL] AZD4320 Is a Novel and Potent BCL-2/XL Dual Inhibitor in Targeting Aggressive Mantle Cell Lymphoma (ASH 2020) - "AZD0466, the nanomedicine formulation of AZD4320 (30mg/kg, weekly, IV), dramatically inhibited tumor growth and prolonged mouse survival in an ibrutinib-CAR-T dual-resistant PDX mouse model. The novel BCL-2/XL dual inhibitor AZD4320 demonstrated excellent anti-MCL activity in both ibrutinib/venetoclax-sensitive and -resistant MCL cells in vitro. This was further validated in vivo in a ibrutinib-CAR-T dual-resistant PDX model. These findings provide evidence that dual targeting of BCL-2 and BCL-XL by AZD4320 is promising as it may overcome therapeutic resistance in relapsed/refractory MCL."

IO Biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL2L1 • MCL1

AZD4320, a dual inhibitor of Bcl-2 and Bcl-xL, induces tumor regression in hematological cancer models without dose-limiting thrombocytopenia. (PubMed, Clin Cancer Res) - "AZD4320 is a potent molecule with manageable thrombocytopenia risk to explore the utility of a dual Bcl-2/Bcl-x inhibitor across a broad range of tumor types with dysregulation of Bcl-2 pro-survival proteins."

Journal • Preclinical • Hematological Disorders • Hematological Malignancies • Oncology • Thrombocytopenia • BCL2 • BCL2L1