Syros Pharmaceuticals announced that it has "discovered and validated" a novel fetal hemoglobin repressor, Nuclear Factor I X, using its gene control platform. "The finding sheds light on how the gamma-globin gene, which leads to the production of fetal hemoglobin, is controlled and points to new potential targets for therapeutic intervention in sickle cell disease," according to the company. These data will be presented in an oral presentation tomorrow at the American Society of Hematology Annual Meeting. The data showed: Increases in expression of gamma-globin mRNA comparable to known fetal hemoglobin repressors; Detectable levels of fetal hemoglobin in nearly 100% of cells, compared to 16% of cells when the NFIX gene was not knocked down; Increases in total fetal hemoglobin levels to 40%, exceeding levels that are associated with a functional cure in sickle cell patients with HPFH, according to Syros.

Genentech, a member of Roche Group, announced updated data from two pivotal Phase III Venclexta studies that highlight Venclexta combination treatments as chemotherapy-free, fixed-duration options that achieve minimal residual disease negativity, in people with chronic lymphocytic leukemia. The pivotal Phase III CLL14 study evaluated the combination of Venclexta plus Gazyva in people with previously untreated CLL, who had co-existing medical conditions. At a median follow-up of more than three years, when all patients had been off therapy for a minimum of two years, Venclexta plus Gazyva showed high response rates, including MRD-negativity. The company said higher rates of MRD-negativity in peripheral blood and bone marrow were observed at the end of treatment in people treated with Venclexta plus Gazyva versus Gazyva plus chlorambucil, respectively. MRD-negativity indicates that no cancer can be detected using a specific, highly sensitive test, and was defined as less than one CLL cell in 10,000 white blood cells, it added. MRD-negativity was observed in 42% of people treated with Venclexta plus Gazyva who achieved a complete response in the peripheral blood, and 14% of people treated with Gazyva plus chlorambucil. Further, the pivotal Phase III Murano study evaluated the combination of Venclexta plus Rituxan in relapsed or refractory CLL. Results showed that Venclexta plus Rituxan significantly reduced the risk of disease progression or death by 81%, Genentech reported. Venclexta plus Rituxan also reduced the risk of death by 59%.

Magenta Therapeutics announced that new results from its MGTA-145 stem cell mobilization program were presented at the Annual Meeting of the American Society of Hematology. These results showed that MGTA-145 in combination with plerixafor met all the endpoints in the study, and safely mobilized a large number of high-quality stem cells in a single day, the company said. The cells were then shown to engraft in a humanized mouse model. Magenta is developing MGTA-145 as the new first-line standard of care for stem cell mobilization in a broad range of diseases, including autoimmune diseases and genetic diseases. MGTA-145, a CXCR2 agonist, works in combination with plerixafor, a CXCR4 antagonist, to harness the physiological mechanism of stem cell mobilization. MGTA-145 was safe and well-tolerated as a single agent and in combination with plerixafor and showed the expected target pharmacology, Magenta said. Five of six subjects who received a single dose of the combination of MGTA-145 at the .03 dose level and plerixafor mobilized more than 20 CD34+ cells/microliter, the clinically accepted threshold for successful mobilization, in a single day. The median percentage of CD34+CD90+ cells was 33%, compared to approximately 10% with G-CSF-mobilized peripheral blood.

The Bristol-Myers Squibb-Pfizer Alliance announced results from retrospective real-world data analyses reporting outcomes on the safety and effectiveness of Eliquis compared to low molecular weight heparin or warfarin for the treatment of venous thromboembolism in patients with active cancer. The real-world data analyses were highlighted during oral presentations at the American Society of Hematology Annual Meeting. Results from the primary analysis showed that Eliquis use was associated with lower rates of major bleeding, clinically-relevant non-major bleeding and recurrent VTE compared to LMWH. Eliquis was also associated with a lower rate of recurrent VTE and similar rates of major bleeding and CRNM bleeding compared to warfarin, the Alliance said. Outcomes were defined based on diagnosis codes and setting of care. In a second oral presentation, results from a sub-group analysis of the primary study were highlighted based on different levels of risk for developing recurrent VTE, a blood clot most often found in the legs or lungs. Study findings were generally consistent with the primary analysis, it said.

Unum Therapeutics announced Phase 1 clinical updates for its Antibody-Coupled T cell Receptor engineered T-cell therapies, ACTR707 and ACTR087, in patients with relapsed or refractory CD20+ non-Hodgkin lymphoma. "The clinical data presented at this year's ASH include updates from the ongoing Phase 1 trial of ACTR707 in combination with rituximab and the completed Phase 1 trial of ACTR087 in combination with rituximab, both conducted in patients with relapsed or refractory CD20+ NHL," said Jessica Sachs, M.D., Chief Medical Officer of Unum. "The data with ACTR707 at this year's ASH continue to support further dose-escalation in this Phase 1 trial and provide proof-of-mechanism for the ACTR platform that we are also applying in our lead program, a Phase 1 trial with ACTR707 in combination with trastuzumab in HER2+ solid tumor cancers. Safety data from the Phase 1 trial with ACTR087 presented at this year's ASH provide learnings that are being applied to ongoing clinical trials with ACTR T cell products. A complete response was achieved in 40% of patients in Cohorts 1 through 4. Of the eight complete responders, four remained in complete response at six months of follow-up, two remain in complete response but have not yet reached the six-month timepoint for evaluation, and two progressed before the six-month timepoint.

Autolus Therapeutics announced new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia and adults with relapsed/refractory diffuse large B cell lymphoma. Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie. The trial is designed to assess the primary endpoints of safety and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden, who were considered high-risk for experiencing cytokine release syndrome. Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply. As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 or greater CRS, and 3 of 16 patients, who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Of 15 patients evaluable for efficacy, 13 achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Bristol-Myers Squibb announced the pivotal study of lisocabtagene maraleucel, an investigational CD19-directed CAR T-cell therapy with a defined composition of purified CD8+ and CD4+ CAR T cells in relapsed/refractory large B-cell lymphomas met its primary and secondary endpoints while demonstrating durable responses. In the study, 344 patients were leukapheresed and 269 patients received liso-cel at one of three dose levels. There were 25 patients that received nonconforming product and there were two instances where product could not be manufactured. Patients were heavily pretreated and had aggressive disease with a median of three prior therapies including 35% with prior autologous or allogeneic hematopoietic stem cell transplant and 67% with chemotherapy-refractory disease. Bridging therapy was administered to 59% of patients. Among patients evaluable for efficacy, the overall response rate was 73% with 53% of patients achieving a complete response. Responses were similar across all patient subgroups, the company added. The median duration of response for all patients was not reached at a median follow-up of 12 months. Median progression-free survival was 6.8 months and median overall survival was 21.1 months. The median PFS and OS for patients who achieved a CR was not reached with 65.1% of patients progression free and 85.5% of patients alive at 12 months, respectively, Bristol added.