Publicly-traded Company Research Articles

Gilteritinib (GILT) Monotherapy with Addition of Decitabine (DEC) in Non-Responders in Older Newly Diagnosed (ND) FLT3 Mutated Acute Myeloid Leukemia (AML) Patients Having High and Low Variant Allele Frequency (VAF): A Phase 2/1b Sub-Study of the Beat AML Master Trial

Gilteritinib (GILT) Monotherapy with Addition of Decitabine (DEC) in Non-Responders in Older Newly Diagnosed (ND) FLT3 Mutated Acute Myeloid Leukemia (AML) Patients Having High and Low Variant Allele Frequency (VAF): A Phase 2/1b Sub-Study of the Beat AML Master Trial

A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or without Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL)

A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or without Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL)

Donor-Derived Adoptive T-Cell Therapy Targeting Multiple Tumor Associated Antigens to Prevent Post-Transplant Relapse in Patients with ALL

Donor-Derived Adoptive T-Cell Therapy Targeting Multiple Tumor Associated Antigens to Prevent Post-Transplant Relapse in Patients with ALL

A Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Interim Results

▪Background: Leukocyte Adhesion Deficiency-I (LAD-I) is a rare disorder of neutrophil adhesion resulting from ITGB2 mutations encoding for the β2-integrin component, CD18. Severe LAD-I (CD18 <2% of polymorphonuclear [PMN] cells) is characterized by severe infections, impaired wound healing, and childhood mortality. Allogeneic hematopoietic stem cell transplant (alloHSCT) is potentially curative; however, its efficacy is limited by donor availability and risk of graft-versus-host disease (GVHD) and graft failure. RP-L201-0318 (NCT03812263), a phase 1/2 open-label trial currently underway, employs autologous CD34+ cells transduced with a lentiviral vector (LV) carrying the ITGB2 gene (cDNA)Methods: Pediatric patients ≥ 3 months old with severe LAD-I are eligible. HSCs are collected via apheresis after mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor and transduced with Chim-CD18-WPRE-LV. Myeloablative therapeutic drug monitoring (TDM) busulfan conditioning precedes RP-L201 infusion. Patients are followed for safety and efficacy (i.e., survival to age 2 and at least 1-year post-infusion, increase in PMN leukocyte CD18 expression to at least 10%, peripheral blood [PB] vector copy number [VCN], decrease in infections/hospitalizations, and resolution of skin or periodontal abnormalities).Results: Seven patients (ages 5mos-9yrs) have received RP-L201; all with follow-up ≥3 to 18 months. RP-L201 cell doses ranged from 2.8x106 to 6.5x106 CD34+ cells/kg with VCN from 1.8-3.8 copies/cell. No serious RP-L201 related treatment-emergent adverse events were reported. PB PMN CD18 expression in Patient 1 at 18-months post-treatment was 40% (vs. < 1% at baseline), with PB VCN of 1.44. Baseline skin lesions resolved with no new lesions reported. CD18 expression in the subsequent 6 patients has been 25-80% in neutrophils and stable for each patient from 3 to up to 18 months post-treatment. No new infections have been reported in patients post-infusion. The safety profile of RP-L102 remains highly favorable with no serious adverse events (SAEs) attributed to the investigational product (IP).Conclusion: RP-L201 leads to durable neutrophil CD18 expression and improved clinical course. Additional patient treatment is ongoing in 2021. DisclosuresKohn: UC Regents: Patents & Royalties; Pluto Immunotherapeutics: Membership on an entity's Board of Directors or advisory committees; Allogene: Membership on an entity's Board of Directors or advisory committees; ImmunoVec: Membership on an entity's Board of Directors or advisory committees; Lyrik Therapeutics: Membership on an entity's Board of Directors or advisory committees; MyoGene Bio: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Sangamo Biosciences: Membership on an entity's Board of Directors or advisory committees. Booth: GSK: Honoraria; Takeda: Honoraria; SOBI: Consultancy, Honoraria; Orchard Therapeutics: Consultancy, Honoraria; Rocket Pharmaceuticals, Inc.: Consultancy. Sevilla: Miltenyi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Rocket Pharmaceuticals, Inc.: Consultancy, Other: J.Sevilla is an inventor on patents on lentiviral vectors filed by CIEMAT, CIBERER and Fundación Jiménez Díaz, and may be entitled to receive financial benefits from the licensing of such patents.; SOBI: Consultancy. Rao: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Almarza: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Nicoletti: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. de Oliveira: Orchard Therapeutics: Research Funding; Bluebird Bio: Research Funding. Law: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Beard: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Choi: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zeini: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Thrasher: Orchard Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Generation bio: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; 4Bio Capital: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rocket Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bueren: Rocket Pharmaceuticals, Inc.: Consultancy, Other: J.Bueren is an inventor on patents on lentiviral vectors filed by CIEMAT, CIBERER and Fundación Jiménez Díaz, may be entitled to receive financial benefits from the licensing of such patents and receives funding for research., Patents & Royalties, Research Funding. Schwartz: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company.

Phase 2 Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)

Phase 2 Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): One-Year Follow-up of ZUMA-1 Cohort 6 (C6)

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): One-Year Follow-up of ZUMA-1 Cohort 6 (C6)

Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: Interim Results of a Global Phase 1 Study for Adult and Pediatric Patients

▪Background: Pyruvate kinase deficiency (PKD) is a rare inherited hemolytic anemia caused by mutations in the PKLR gene resulting in decreased red cell pyruvate kinase activity and impaired erythrocyte metabolism. Manifestations include anemia, reticulocytosis, splenomegaly and iron overload, and may be life-threatening in severely affected individuals. PKD represents a significant unmet medical need as current treatments are palliative and limited to blood transfusions, chelation therapy, and splenectomy which are associated with significant side effects. Preclinical studies in a clinically relevant PKD murine model have demonstrated that infusion of gene-modified Lin− bone marrow (BM) cells may ameliorate PKD phenotype. Based on compelling preclinical data, a global Phase 1 clinical trial RP-L301-0119 (NCT04105166) is underway to evaluate the feasibility and safety of lentiviral mediated gene therapy in adult and pediatric subjects with severe PKD.Methods: Six adult and pediatric patients with severe PKD (defined as severe and/or transfusion-dependent anemia despite prior splenectomy) will be enrolled. Peripheral blood (PB) hematopoietic stem cells (HSCs) are collected on 2 consecutive days via apheresis after mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor. HSCs are enriched, transduced with PGK-coRPK-WPRE lentiviral vector (LV), and cryopreserved. Following release testing of the investigational product (IP), RP-L301, myeloablative therapeutic drug monitoring (TDM) busulfan is administered over 4 days. RP-L301 is then thawed and infused. Patients are followed for safety assessments, including replication competent lentivirus (RCL) and insertion site analysis (ISA), and for efficacy parameters including PB and BM genetic correction, decrease in transfusion requirements, clinically significant improvement in anemia, and reduction of hemolysis for 2 years post-infusion.Results: As of May 2021, 2 adult patients with severe anemia have received RP-L301. Patient 1 (age 31 years) received 3.9x106 CD34+ cells/kg with mean vector copy number (VCN) of 2.73. Patient 2 (age 47 years) received 2.4x106 CD34+ cells/kg with mean VCN of 2.08. Despite baseline hemoglobin (Hb) levels in the 7.0-7.5 g/dL range, both patients displayed normal-range hemoglobin (Hb), improved hemolysis markers, and have required no red blood cell transfusions post-engraftment at 9- and 6- months follow-up. Both report improved quality of life. PB mononuclear cell VCNs for both patients were >2.0 at last evaluated timepoint (6- and 3-months post-treatment, respectively). No serious adverse events have been attributed to RP-L301. Updated safety and efficacy data will be presented.Conclusions: Hematopoietic stem cell mobilization using G-CSF and plerixafor is feasible and effective in adult PKD patients. RP-L301 was successfully manufactured to meet the required specifications for the Phase 1 clinical study and administered without short-term infusion related complications. Efficacy was demonstrated by normalized Hb associated with engraftment confirmed by PB and BM VCN. DisclosuresShah: OrchardTherapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Dr. Shah currently serves on the medical advisory board for Orchard Therapeutics . Navarro: Rocket Pharmaceuticals, Inc.: Current equity holder in publicly-traded company, Other: Dr. Navarro has licensed medicinal products and receives research funding and equity from Rocket Pharmaceuticals, Inc., Patents & Royalties, Research Funding. Sevilla: Miltenyi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Rocket Pharmaceuticals, Inc.: Consultancy, Other: J.Sevilla is an inventor on patents on lentiviral vectors filed by CIEMAT, CIBERER and Fundación Jiménez Díaz, and may be entitled to receive financial benefits from the licensing of such patents.; SOBI: Consultancy. Glader: Agios: Consultancy. Quintana Bustamante: Rocket Pharmaceuticals, Inc.: Current equity holder in publicly-traded company. Beard: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Law: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zeini: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Choi: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Nicoletti: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Rao: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Bueren: Rocket Pharmaceuticals, Inc.: Consultancy, Other: J.Bueren is an inventor on patents on lentiviral vectors filed by CIEMAT, CIBERER and Fundación Jiménez Díaz, may be entitled to receive financial benefits from the licensing of such patents and receives funding for research., Patents & Royalties, Research Funding. Schwartz: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Segovia: Rocket Pharmaceuticals, Inc.: Consultancy, Research Funding.

Healthcare Resource Utilization and Costs of Patients with Relapsed/Refractory Follicular Lymphoma Receiving 3 or More Lines of Therapy

Healthcare Resource Utilization and Costs of Patients with Relapsed/Refractory Follicular Lymphoma Receiving 3 or More Lines of Therapy

Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Completed Induction Phase Analysis of Magnify: Phase 3b Study of Lenalidomide + Rituximab (R 2) Followed By Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

Completed Induction Phase Analysis of Magnify: Phase 3b Study of Lenalidomide + Rituximab (R 2) Followed By Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

CC-99282 is a Novel Cereblon (CRBN) E3 Ligase Modulator (CELMoD) Agent with Enhanced Tumoricidal Activity in Preclinical Models of Lymphoma

CC-99282 is a novel, oral CELMoD ® agent currently under investigation in phase 1 clinical studies in patients with relapsed or refractory (R/R) non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Mechanistically, CC-99282 interacts with the CRL4 CRBN E3 ubiquitin ligase substrate receptor CRBN to induce recruitment and ubiquitin-mediated proteasomal degradation of transcription factors Ikaros and Aiolos. The design intent for CC-99282 included efficient absorption, deep tissue distribution, and prolonged exposure to optimize activity in bulky lymphoma lesions. Recently, we reported that CC-99282 shows potent antitumor activity in different preclinical models of diffuse large B cell lymphoma (DLBCL; Lopez-Girona, et al. Hematol Oncol. 2021). Here, we provide an expanded analysis of CC-99282 activity as a monotherapy, as well as examine its synergistic activity with anti-CD20 antibody treatment, in preclinical models of NHL including DLBCL and follicular lymphoma (FL).Compared with existing agents targeting Ikaros/Aiolos that show activity in hematologic malignancies, such as lenalidomide, avadomide, and iberdomide (CC-220), CC-99282 induced a more rapid, deep, and sustained degradation of Ikaros/Aiolos, causing derepression of cyclin-dependent kinase (CDK) inhibitors and interferon-stimulated genes (IRF7, IFIT3, and DDX58), and the reduction of the highly critical oncogenic factors c-Myc and IRF4. These molecular changes were followed by potent, 10- to 100-fold enhanced, autonomous cell killing and induction of apoptosis (Figure). Our results show that these effects were independent of the cell of origin (activated B cell [ABC; TMD8 cell line], germinal center B cell [GCB; WSU-DLCL2 cell line], or primary mediastinal B cell lymphoma [PMBL] subtypes of DLBCL) or presence of high-risk chromosomal translocations (MYC, BCL2, and/or BCL6), as observed in a panel of 36 lymphoma cell lines that included DLBCL and FL cell lines. In vivo, CC-99282 demonstrated robust tissue distribution that favored target tissues and exhibited antitumor activity resulting in improved tumor regression and tumor-free animals in several lymphoma xenograft models, including an intracranial xenograft model. This strong antitumor activity was observed using various continuous and intermittent dosing paradigms.The potent, direct autonomous cell-killing activity of CC-99282 was augmented when CC-99282 was combined with the anti-CD20 antibody rituximab. In vitro combination studies of CC-99282 with rituximab in lymphoma cell lines demonstrated enhanced cell killing by human natural killer (NK) cells, macrophage-mediated phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). In FL and DLBCL cell lines, we showed that the combination of CC-99282 with rituximab resulted in increases in both NK-mediated ADCC and macrophage-mediated ADCP of up to 20% compared with rituximab treatment alone. In vivo, combination treatment with CC-99282 and rituximab induced dose-dependent tumor growth inhibition in WSU-DLCL2 and RL (FL) xenograft models. In the WSU-DLCL2 model, CC-99282 (1 mg/kg) or rituximab (10 mg/kg) monotherapy resulted in modest tumor growth inhibition, whereas the combination of CC-99282 (1 mg/kg) and rituximab (10 mg/kg) resulted in tumor regression in 100% of animals. Similar results were obtained in FL xenograft models using the RL cell line, where combinations of CC-99282 (1 mg/kg) with rituximab (25 mg/kg) induced complete tumor regression in 100% of animals.In conclusion, CC-99282 is a novel CELMoD agent with an improved substrate degradation profile compared with existing Ikaros/Aiolos-degrading agents. CC-99282 demonstrated enhanced antiproliferative and apoptotic activities across a broad range of lymphoma cells and a robust distribution profile that favors target tissues such as lymphoid organs. In addition, CC-99282 acts synergistically in combination with anti-CD20 monoclonal antibody treatment. Collectively, these data support the clinical investigation of CC-99282 as monotherapy and in combination with rituximab in patients with R/R NHL. [Display omitted] DisclosuresCarrancio: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Groocock: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Janardhanan: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Jankeel: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Galasso: Ryan Galasso: Current Employment, Current equity holder in publicly-traded company. Guarinos: Bristol Myers Squibb: Current Employment. Narla: Bristol Myers Squibb: Current Employment. Groza: Bristol Myers Squibb: Current Employment. Leisten: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Pierce: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rolfe: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Lopez-Girona: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Glofitamab Step-up Dosing Induces High Response Rates in Patients (pts) with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL), Most of Whom Had Failed Prior Bruton's Tyrosine Kinase Inhibitor (BTKi) Therapy

Glofitamab Step-up Dosing Induces High Response Rates in Patients (pts) with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL), Most of Whom Had Failed Prior Bruton's Tyrosine Kinase Inhibitor (BTKi) Therapy

Bone Mineral Density Remains Stable in Pyruvate Kinase Deficiency Patients Receiving Long-Term Treatment with Mitapivat

Bone Mineral Density Remains Stable in Pyruvate Kinase Deficiency Patients Receiving Long-Term Treatment with Mitapivat

Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study

Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study

Bispecific Vγ9Vδ2-T and Type 1 NKT Cell Engager Lava-051 As First-in-Class Clinical Candidate to Target CD1d Expressing CLL, MM and AML

Bispecific Vγ9Vδ2-T and Type 1 NKT Cell Engager Lava-051 As First-in-Class Clinical Candidate to Target CD1d Expressing CLL, MM and AML

SY5609, a Potent and Selective CDK7 Inhibitor, Potentiates BTK Inhibitor Activity in Mantle Cell Lymphoma Preclinical Models

Introduction: CDK7 is a key regulator of transcription and cell cycle progression and has been implicated in multiple tumor types driven by aberrant transcriptional (e.g., MYC-, ESR1-activation) and/or aberrant cell cycle control (e.g., loss of RB pathway checkpoint function) mechanisms. SY-5609 is a potent and selective CDK7 inhibitor currently in development in patients with solid tumors (NCT04247126). To assess the potential for SY-5609 development in heme malignancies, we evaluated SY-5609 activity in preclinical models of mantle cell lymphoma (MCL). MCL is an aggressive B cell lymphoma driven by genetic alterations in RB pathway genes (e.g. CCND1, RB1, CDKN2A) and by hyper-activation of B-cell receptor (BCR) signaling leading to activation of NF-kB-dependent transcriptional programs that drive cell proliferation and survival. Our results support evaluation of SY-5609 in MCL patients and highlight the potential for combining SY-5609 with Bruton's Tyrosine Kinase (BTK) inhibitors, inhibitors of BCR signal transduction approved for treatment of MCL.Methods: SY-5609 in vitro antiproliferative activity was assessed in a panel of 7 MCL cell lines by evaluating growth rate inhibition (GR) curve metrics GR 50 (drug concentration at which growth rate is inhibited by 50%) and GR max (maximum depth of response) after 5-days of treatment. SY-5609 pharmacodynamic (PD) responses and combination activity with the BTK inhibitor acalabrutinib were further assessed in MCL cell line Mino-1. PD activity was assessed by measuring transcriptional changes in POLR2A using a NanoString-based PD assay from the SY-5609 solid tumor trial. Combination activity in vitro was assessed by comparing GR curve metrics between acalabrutinib, SY-5609, and acalabrutinib in combination with SY-5609. Expression of CCND1 and E2F1, a key transcriptional regulator of DNA replication commitment and progression, were assayed via western blot. Combination activity in vivo was assessed in mice bearing Mino-1 xenograft tumors by comparing tumor growth rate inhibition (GRI) and body weight change in mice treated with acalabrutinib (15mg/kg, QD) and/or SY-5609 (0.5mg/kg, BID, days 1-7 and 15-21) over 25 days.Results: SY-5609, as a single agent, potently inhibited proliferation of all 7 MCL cell lines tested with a GR 50 geometric-mean of 7 nM (range: 2 to 20 nM) and a GR max geometric-mean of -0.2 (range: -0.6 to 0.2). In MCL cell line Mino-1, SY-5609 induced a dose-dependent increase in POLR2A expression to levels associated with SY-5609 antiproliferative activity in Mino-1 cells in vitro and to levels comparable with those observed in peripheral blood mononuclear cells (PBMCs) collected from SY-5609 solid tumor trial patients. In combination with acalabrutinib, SY-5609 demonstrated synergistic antiproliferative activity in Mino-1 cells in vitro, a dose-dependent decrease in acalabrutinib GR 50 (up to ~2-fold at the highest SY-5609 concentration tested, 5nM), and a dose-dependent increase in GR max (up to ~10-fold). In addition, the combination of SY-5609 and acalabrutinib caused dose-dependent decreases in CCND1 and E2F1 protein expression in vitro, which were not observed with either single agent alone. Finally, in mice bearing Mino-1 xenografts, the combination of SY-5609 and acalabrutinib significantly (p < 0.01) increased tumor GRI relative to each single agent at the doses and regimens tested and was well tolerated (no difference in body weight changes relative to vehicle treated mice).Conclusions: SY-5609 is a potent and selective CDK7 inhibitor that demonstrates antiproliferative activity in MCL cells in vitro, associated with PD changes comparable to those observed in patients enrolled in the SY-5609 solid tumor trial (ENA, 2020). The combination of SY-5609 and acalabrutinib is synergistic in MCL cells in vitro and inhibits expression of key cell cycle regulatory proteins CCND1 and E2F1 at concentrations that are preclinically subtherapeutic for either single agent alone. The combination of SY-5609 and acalabrutinib is also significantly more effective at inhibiting MCL xenograft growth in vivo than either single agent. These results support evaluation of SY-5609, including in combination with BTK inhibitors, in patients with mantle cell lymphoma. DisclosuresJohannessen: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Henry: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Sawant: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. D'Ippolito: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Ke: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lefkowitz: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Eaton: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Dworakowski: Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Rosario: Syros Pharmaceuticals: Current Employment. Hodgson: Syros Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company.

Clinical Trials of BCMA-Targeted CAR-T Cells Utilizing a Novel Non-Viral Transposon System

Clinical Trials of BCMA-Targeted CAR-T Cells Utilizing a Novel Non-Viral Transposon System

A Phase 2 Study of the LSD1 Inhibitor Img-7289 (bomedemstat) for the Treatment of Advanced Myelofibrosis

A Phase 2 Study of the LSD1 Inhibitor Img-7289 (bomedemstat) for the Treatment of Advanced Myelofibrosis

Pevonedistat (PEV) + Azacitidine (AZA) Versus AZA Alone As First-Line Treatment for Patients with Higher-Risk Myelodysplastic Syndromes (MDS)/Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML) with 20-30% Marrow Blasts: The Randomized Phase 3 PANTHER Trial (NCT03268954)

Pevonedistat (PEV) + Azacitidine (AZA) Versus AZA Alone As First-Line Treatment for Patients with Higher-Risk Myelodysplastic Syndromes (MDS)/Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML) with 20-30% Marrow Blasts: The Randomized Phase 3 PANTHER Trial (NCT03268954)

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-Risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi)

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-Risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi)