Stockwinners Market Radar for December 12, 2021 - Earnings, Upgrades downgrades, option trades, Best Stock Advisory Service

19:46 EST Dollar Tree responds to Mantle Ridge's Notice of Nomination of Directors - Dollar Tree has issued a statement regarding recent interactions with Mantle Ridge and its notice seeking to nominate a full slate of 11 directors to the company's Board of Directors at its 2022 Annual Meeting saying that, "Dollar Tree's Board of Directors and management team maintain an ongoing dialogue with shareholders and welcome input about the Company's strategy and performance. We are however disappointed that Mantle Ridge has been unwilling to engage with us constructively and has instead chosen to proceed in such an unwarrantedly aggressive and hostile manner. Mantle Ridge's overreach in seeking to replace our full Board with its own hand-picked slate -- despite having no ideas or plans to improve on our business or operations -- is not justified nor would it be in the best interests of Dollar Tree shareholders. Dollar Tree first heard from Mantle Ridge when it filed a Schedule 13D on November 12 reflecting a significant economic interest in the Company (almost entirely through derivative instruments) and sent a letter to the Dollar Tree Board. In its letter, Mantle Ridge expressed its support of the Company's multi-price strategy and applauded the Company's 'steady resistance' to calls to dispose of or dismantle Family Dollar, which it agreed 'would have been a grave error and enormously value destructive'. Within days, Dollar Tree invited Mantle Ridge to present its ideas for business improvement to the Dollar Tree Board. Mantle Ridge, however, declined all invitations to meet with Dollar Tree unless with the entire Board in person and so waited until the regularly scheduled in-person Board meeting three weeks later. On December 2, the entire Dollar Tree Board met in person for several hours with Mr. Paul Hilal, Mr. Richard Dreiling and three other Mantle Ridge representatives. At that meeting, despite repeated requests both in advance of and during the meeting, Mantle Ridge offered no new ideas for how to improve the Company's performance or operations. The only operational suggestion made - that the Company should sell Dollar Tree merchandise at Family Dollar stores - is something Dollar Tree has already been doing for several years. Instead, Mantle Ridge simply expressed that it wanted a majority of the Board to be replaced, Mr. Dreiling to be named Executive Chairman, and other control rights. Taken together, in the view of the Board, these demands amounted to handing control of the Company to Mr. Hilal and Mantle Ridge. After deliberating on that meeting, the Dollar Tree Board sent a letter to Mantle Ridge in which, among other things, it offered to explore a settlement in which Mr. Dreiling would be added to the Dollar Tree Board (and potentially be engaged as a meaningful consultant) and also offered Mantle Ridge a role in the Company's ongoing Board refreshment program. Continuing Mantle Ridge's pattern, the Company never heard back from Mantle Ridge until it received the letter nominating its slate to replace the entire Board. [...] Regardless, the Dollar Tree Board stands ready to engage constructively with Mantle Ridge, even though it is disappointed that, rather than pursuing constructive engagement, Mantle Ridge has chosen to embark on an unwarranted and potentially disruptive proxy contest to replace the entire Board. While the Company would like to avoid an expensive and distracting proxy fight, the Board does not believe that handing control of the Company to Mr. Hilal and Mantle Ridge as it demands is in the best interests of Dollar Tree, its shareholders or other stakeholders."

18:21 EST Editas Medicine reports preclinical data demonstrating tumor reduction - Editas Medicine reported in vitro and in vivo preclinical data on the enhanced tumor killing capacity of two modified induced pluripotent stem cell-derived natural killer cell therapies using Editas Medicine's proprietary AsCas12a gene editing. The research evaluated two strategies to generate engineered iPSC clones, which were then differentiated into iNK cells and evaluated in vitro and in vivo to determine anti-tumor activity. These approaches have the potential to create allogeneic, investigational NK cell therapy medicines with enhanced activity against solid tumors. IPSC's were edited at the GAPDH locus using the company's proprietary SLEEK technology and engineered AsCas12a nuclease to knock-in both CD16 and membrane-bound IL-15. CD16+/+/mbIL-15+/+ edits were designed to increase antibody-dependent cellular cytotoxicity when combined with tumor-targeting antibodies and prolong iNK cell persistence. DKI iNK cells, as monotherapy or in combination with trastuzumab, showed significantly enhanced tumor killing compared with wild type iNKs in an in vitro 3D SKOV-3 ovarian tumor spheroid assay. Evaluation in an in vivo mouse SKOV-3 cancer model confirmed that DKI iNKs combined with trastuzumab exerted greater anti-tumor activity compared to WT iNKs with trastuzumab, or trastuzumab alone. A single dose of DKI iNKs combined with three doses of trastuzumab induced complete tumor clearance in 50 percent of mice. Importantly, DKI iNKs were detected in the peritoneum of the treated mice for greater than three months, demonstrating that the mbIL-15 maintained iNK survival for a prolonged period in the absence of exogenous cytokine support. In a separate study, iPSCs were edited with Editas-engineered AsCas12a to knock out both the CISH and TGFbeta-receptor 2 genes. CISH-/-/TGFbetaR2-/- edits were designed to improve iNK cell effector function and provide resistance to TGFbeta-mediated NK suppression in the tumor microenvironment. DKO iNKs induced enhanced tumor killing against in vitro 3D SKOV-3 ovarian tumor spheroids compared to WT iNKs. Following stimulation, DKO iNKs produced elevated levels of inflammatory cytokines, including IFN-gamma and TNF-alpha. The DKO iNK cells also induced significant reduction in tumor burden compared with WT iNK treatment when tested in vivo in a SKOV-3 ovarian cancer mouse model. At ASH, the company also presented preclinical data on EDIT-301 supporting its differentiated approach to develop a transformative medicine for people living with transfusion-dependent beta-thalassemia. AsCas12a edited TDT erythroid cells had improved maturation, health, and higher total hemoglobin content per cell when compared to unedited controls. The EDIT-301 Phase 1/2 RUBY trial for the treatment of sickle cell disease is currently enrolling study participants and the Company expects to begin dosing in the first half of 2022.

18:15 EST Pfizer, Sangamo announce updated results from Phase 1/2 Alta study - Pfizer (PFE) and Sangamo Therapeutics (SGMO) announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A. At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII activity of 25.4% via chromogenic clotting assay. In this cohort, mean annualized bleeding rate was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up as of the October 1, 2021 cutoff date. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII. No participants in the highest dose cohort have resumed prophylaxis. Giroctocogene fitelparvovec was generally well-tolerated in this Phase 1/2 study. Among the five patients in the highest dose cohort, four received corticosteroids for liver enzyme elevations. All elevations fully resolved with oral corticosteroids. As previously reported, one patient in the highest dose cohort had a treatment-related serious adverse event of hypotension and fever, with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec and resolved approximately 12 hours post-infusion. Across all four cohorts, 26 treatment-related adverse events occurred in six patients as of the October 1, 2021 cutoff date. No other treatment-related serious adverse events were reported as of the cutoff date. Additionally, no confirmed FVIII inhibitor development occurred, and no thrombotic events were reported. The Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec in patients with hemophilia A has started and is over 50% enrolled. Following the observation of FVIII levels greater than 150% in some treated patients, Pfizer voluntarily paused screening and dosing of additional patients in the trial to implement a protocol amendment to provide clinical management guidance for elevated FVIII levels. Subsequently, on November 3, 2021, the U.S. Food and Drug Administration informed Pfizer that this trial has been placed on clinical hold while the protocol amendment and associated documents are reviewed.

18:11 EST NexImmune announces preliminary Phase 1/2 NEXI-002 results - NexImmune announced preliminary Phase 1/2 results from an ongoing study of NEXI-002, a patient-derived multi-antigen-specific CD8+ T cell treatment for patients with relapsed/refractory multiple myeloma who have failed greater than or equal to3 prior lines of therapy. The data on low doses of NEXI-002, presented at the 63rd American Society of Hematology Annual Meeting and Exposition, showed a promising safety and tolerability profile and evidence of immunologic and clinical activity. In this heavily pre-treated patient group, the clinical data suggests that NEXI-002 is well-tolerated without dose-limiting toxicities. Biomarker data show that the NEXI-002 product candidate contains CD8+ antigen-specific T cells with key memory phenotypes which, after administration, are detected in peripheral blood and bone marrow of treated individuals and proliferate and persist over time. Furthermore, TCR sequencing shows that the NEXI-002 product candidate contains CD8+ T cell clones that were undetectable in the peripheral blood of the patients at baseline and which expand in both blood and bone marrow over time. After receiving lymphodepleting therapy followed by NEXI-002 infusion, patients experienced rapid lymphocyte recovery with reconstitution of both CD4+ and CD8+ T cell subtypes. Despite the infusion of very low numbers of NEXI-002 T cells, these heavily pre-treated patients achieved stable disease for 2 to 3.5 months of duration. Importantly, despite receiving an average of 7.6 previous lines of therapy, the quality, functionality and in vivo persistence of all patient-derived NEXI-002 T cell products were comparable to those expanded from healthy donors. Strategies to yield higher product doses are underway, including evaluating patients with lower disease burden plasma cell dyscrasias.

18:06 EST Imago BioSciences presents data from ongoing Phase 2 study of bomedemstat - Imago BioSciences presented positive data from its ongoing global Phase 2 clinical study evaluating bomedemstat in patients with essential thrombocythemia. Of the 29 patients treated with bomedemstat for more than 6 weeks: 100% of patients experienced platelet count reduction to within normal ranges. 90% of patients achieved a platelet count of less than 400 x 109/L without thromboembolic events, the primary composite endpoint of this study. Of the 17 evaluable patients at 24 weeks: 71% showed a decrease in Total Symptom Score. 53% showed a greater than or equal to50% decrease in TSS. Patients with all genotypes identified in the study responded to bomedemstat. Bomedemstat was generally well-tolerated.

18:02 EST Loxo Oncology at Lilly announces updated data from Phase 1/2 BRUIN trial - Loxo Oncology at Lilly, a research and development group of Eli Lilly, announced updated clinical data from the pirtobrutinib global Phase 1/2 BRUIN clinical trial in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and mantle cell lymphoma. Pirtobrutinib is an investigational, highly selective, non-covalent Bruton's tyrosine kinase inhibitor. As of July 16, 2021, 618 patients were enrolled in the study, including 296 with CLL/SLL, 134 with MCL, and 188 with other B-cell malignancies. The efficacy data presented at ASH are based on investigator response assessments. Patients were considered efficacy-evaluable if they had at least one post-baseline response assessment or if they discontinued treatment prior to their first post-baseline response assessment. Among the 296 CLL/SLL patients enrolled, 261 were previously treated with a BTK inhibitor and are the subject of this analysis. The median number of prior lines of therapy was three with 100% receiving a prior BTK inhibitor, 88% an anti-CD20 antibody, 79% chemotherapy, 41% venetoclax, 20% a PI3K inhibitor, 6% CAR-T therapy and 2% stem cell transplant. In 252 efficacy-evaluable patients, 171 responded including two complete responses, 137 partial responses, 32 partial responses with ongoing lymphocytosis, and 62 stable disease, resulting in an overall response rate of 68%. Responses continue to deepen over time, with the ORR rising to 73% for those followed 12 months or more, and ORR remains consistent regardless of reason for prior BTK discontinuation, type or number of prior therapies or BTK C481 or PCLG2 mutational status. Pirtobrutinib demonstrated evidence of durable activity with a median progression-free survival not reached in patients who had received at least a prior BTK inhibitor. In patients who had received at least a BTK inhibitor and BCL2 inhibitor, the estimated median PFS was 18 months, although these data remain immature and unstable due to the small percentage of patients with progression. As of the data cut-off, 74% of BTK pre-treated patients remained on pirtobrutinib. Median follow-up for all BTK pre-treated patients was 9.4 months. In an exploratory analysis in patients with prior progression on a BTK inhibitor, the PFS with pirtobrutinib was similar in patients with BTK C481-mutated and BTK C481-wildtype CLL and SLL. The 134 patients with MCL received a median of three prior lines of therapy, with 90% receiving a prior BTK inhibitor, 97% an anti-CD20 antibody, 91% chemotherapy, 22% stem cell transplant, 17% immunomodulatory drugs, 15% venetoclax, 13% proteasome inhibitor, 5% CAR-T cell therapy, and 4% PI3K inhibitor. Of the 100 efficacy-evaluable patients with BTK pre-treated MCL, 51 responded including 25 CRs and 26 PRs resulting in an ORR of 51%. Among 11 BTK naive MCL patients, nine responded including two CRs and seven PRs resulting in an ORR of 82%. Responses in MCL were observed in patients who received prior stem cell transplant and prior CAR-T therapy. Median duration of response was 18 months. Median follow-up for all responding MCL patients was 8.2 months with 60% of responses ongoing as of the data cut-off. Safety data were presented for the entire enrolled BRUIN population. Adverse events commonly associated with covalent BTK inhibitors occurred at a low rate, with the majority being Grade 1 or 2. During the Phase 1 dose escalation, no dose limiting toxicities were reported and a maximum tolerated dose was not reached. Permanent discontinuations for drug-related adverse events were observed in 1% of patients. A real-world evidence database study on outcomes for patients with CLL previously treated with a covalent BTK inhibitor and a BCL2 inhibitor will be presented in a poster presentation on Monday, December 13. Additionally, a study on outcomes for patients with MCL following covalent BTK inhibitor therapy was published as an online-only abstract.

17:55 EST BeiGene presents results from SEQUOIA trial of BRUKINSA - BeiGene announced results from a planned interim analysis of the Phase 3 SEQUOIA trial in patients with treatment-naive chronic lymphocytic leukemia, including the randomized Cohort 1 comparing BRUKINSA to bendamustine plus rituximab and Cohort 3 of BRUKINSA in combination with venetoclax in patients with deletion of chromosome 17p and/or pathogenic TP53 variants. A total of 479 patients with TN CLL whose tumor did not exhibit del(17p) were enrolled in Cohort 1 of the SEQUOIA trial, with 241 patients randomized to receive BRUKINSA and 238 patients randomized to receive B+R. Patient characteristics were balanced between the two arms, with more than 50% with unmutated IGHV gene and 18% with del(11q) in each. Patients with del(17p) typically have poor response to chemoimmunotherapy and were assigned to receive BRUKINSA treatment in Cohort 2. Results from Cohort 2 were previously presented at the 2020 ASH Annual Meeting. The primary endpoint of the SEQUOIA trial is progression-free survival per independent review committee assessment in the randomized Cohort 1. At the interim analysis, with a median follow-up of 26.15 months, BRUKINSA demonstrated superiority in PFS over B+R, as assessed by IRC. Cohort 3 of SEQUOIA was designed to examine the hypothesis that the addition of venetoclax to BRUKINSA can drive tumors into deeper remission. Building on the demonstrated efficacy and safety of BRUKINSA in Cohort 2, Cohort 3 is planned to enroll approximately 80 patients with TN CLL whose tumor exhibits del(17p) or TP53 mutations, with key endpoints being safety, overall response rate, PFS, and duration of response. These patients will receive BRUKINSA treatment at 160 mg twice daily for three months, followed by combination treatment of BRUKINSA at the same dosing and venetoclax with a ramp-up dosing to 400 mg once daily for 12 to 24 cycles until progressive disease, unacceptable toxicity, or confirmed undetectable measurable residual disease. At the data cutoff on September 7, 2021, 49 patients were enrolled in Cohort 3, including 46 patients with centrally confirmed positive del(17p) status and three patients with a pathogenic TP53 variant alone. Patients enrolled in Cohort 3 also exhibited other markers of high risk, including 87.8% with unmutated IGHV, 91.9% with concurrent TP53 mutation, and 83.3% with complex karyotype. With a short median follow-up of 12.0 months, a high ORR was observed in the 36 patients who had at least one post-baseline response evaluation by the data cutoff date. Preliminary efficacy results per investigator assessment included: Of the 14 patients who received combination treatment for more than 12 months, five patients achieved a confirmed complete response or CR with incomplete bone marrow recovery in a bone marrow assessment and four additional patients met the criteria for CR or CRi but not confirmed in bone marrow assessment due to COVID-19 restrictions; and in all 36 patients evaluable for efficacy, the ORR was 97.2% and the CR/CRi rate was 13.9%. With a median follow-up of 7.9 months, safety results in all 49 enrolled patients included: 40 patients experienced at least one AE of any grade; 16 patients experienced at least one Grade greater than or equal to3 AE and four patients experienced at least one serious AE; AEs leading to dose interruption, dose reduction, and treatment discontinuation occurred in 10 patients, no patients, and one patient, respectively; and one patient experienced a fatal AE. With a median follow-up of 13.5 months, safety results in the 34 patients who received combination treatment included: 29 patients experienced at least one AE of any grade; 13 patients experienced at least one Grade greater than or equal to3 AE and three patients experienced at least one serious AE; and AEs leading to dose interruption occurred in 10 patients, with no AEs leading to dose reduction or treatment discontinuation.

17:46 EST Jazz Pharmaceuticals presents interim Phase 2/3 results of Rylaze in ALL, LBL - Jazz Pharmaceuticals announced initial positive results from a Phase 2/3 trial of intramuscular administration of Rylaze in adult and pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma who have developed hypersensitivity or silent inactivation to an E. coli-derived asparaginase. The study was developed and conducted in close collaboration with the Children's Oncology Group. Three cohorts with unique, IM administration dosing schedules were evaluated in the trial, demonstrating a safety profile consistent with other asparaginases. In Cohort 1c, a dosing regimen of Rylaze administered 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday demonstrated a positive benefit-to-risk profile, showing that Rylaze maintains a clinically meaningful level of nadir serum asparaginase activity greater than or equal to0.1 IU/mL at both 48 and 72 hours. Rylaze was approved by the U.S. Food and Drug Administration (FDA) on June 30, 2021 under the Real-Time Oncology Review program for use as a component of a multi-agent chemotherapeutic regimen for the treatment of ALL or LBL in adult and pediatric patients one month and older who have developed hypersensitivity to E. coli-derived asparaginase. Rylaze was approved at the dosing schedule of 25 mg/m2 every 48 hours based on data from Cohort 1a, in conjunction with data produced by a preliminary population pharmacokinetic model. These data will support additional regulatory filings for Rylaze, including a supplemental Biologics Licensing Application in early 2022 for a Monday/Wednesday/Friday IM dosing schedule that will be reviewed under the FDA RTOR program. These data will also support regulatory submissions in Europe in mid-2022, with potential for approval in 2023. Grade 3/4 treatment-emergent adverse events, regardless of causality, occurred in 78/137 patients. There were no treatment-related TEAEs leading to death. Overall, the safety profile of Rylaze was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy. Further study analyses are ongoing, and full study results will be reported at a later date.

17:41 EST Beam outlines long-term strategy for base editing programs in SCD - Beam Therapeutics shared a three-stage, long-term development strategy for its base editing approach to treat sickle cell disease. The plan, and supportive data, are being presented during a Scientific Program Session oral presentation and two poster sessions at the 63rd American Society for Hematology Annual Meeting & Exposition. To fully address SCD and support broad accessibility, Beam is deploying a stepwise strategy that includes advancements of its ex vivo programs, BEAM-101 and BEAM-102, improvements in patient conditioning regimens, and enablement of in vivo base editing with delivery directly into patients via lipid nanoparticles. During the presentations at ASH, Beam is highlighting its stepwise strategy for treating SCD and is presenting complementary data supporting several components of its approach. Beam is advancing ex vivo base editing programs, in which cells are collected from a patient, edited and then infused back into the patient following a conditioning regimen, such as treatment with busulfan, the standard of care in hematopoietic stem cell transplantation today. This approach is being deployed in the company's BEAM-101 and BEAM-102 base editing programs, and allows the company to pursue an efficient path for development using increasingly validated clinical endpoints and regulatory strategies. During ASH, Beam is presenting updated preclinical data further characterizing Makassar hemoglobin created by BEAM-102 and demonstrating biophysical and biochemical properties consistent with normal hemoglobin, as expected: Makassar globin did not polymerize in vitro; Cells co-expressing Makassar globin and sickle globin had properties similar to sickle trait cells, which are cells with one normal globin gene and one sickle globin gene and which do not sickle; Oxygen binding of Makassar globin was comparable to the most abundant normal adult hemoglobin; The crystal structures of the Makassar globin and of HbA were superimposable, suggesting no meaningful structural differences. In parallel with Wave 1 development, Beam also aims to improve the transplant conditioning regimen for SCD patients, reducing toxicity challenges associated with standard of care. Conditioning is a critical component necessary to prepare a patient's body to receive the ex vivo edited cells that must engraft in the patient's bone marrow in order to be effective. Today's conditioning regimens rely on nonspecific chemotherapy or radiation, which are associated with significant toxicities. Beam has a collaboration with Magenta Therapeutics to evaluate the potential utility of MGTA-117, Magenta's novel antibody drug conjugate that is designed to precisely target only hematopoietic stem and progenitor cells, sparing immune cells. Importantly, improved conditioning regimens could potentially be paired with BEAM-101 and BEAM-102, as well as other base editing programs in hematology. Beam is also exploring the potential for in vivo base editing programs for SCD, in which base editors would be delivered to the patient through an infusion of LNPs targeted to HSCs, eliminating the need for transplantation altogether. This approach could provide a more accessible option for patients, particularly in regions where ex vivo treatment is challenging. Building on its acquisition of Guide Therapeutics, Beam has established a DNA-barcoded LNP screening technology to enable high-throughput in vivo identification of LNPs with novel biodistribution and selectivity for target organs beyond the liver. During ASH, Beam is presenting updated preclinical data using this technology to screen more than 1,000 LNPs for potential to deliver to HSCs and identified LNP-HSC1 as the most potent, with efficient transfection in both mice and non-human primates. Updated findings in the poster showed: LNP-HSC1 was validated in vivo, leading to durable, dose-dependent mRNA transfection in HSCs and resulting in fluorescent reporter expression in more than 40% of cells, now maintained out to 16 weeks post-delivery; LNP-HSC1 efficiently transfected human CD34+ cells in vitro; LNP-HSC1 efficiently transfected nearly 20% of CD34+ HSCs in humanized mice and non-human primates at a dose of 1.0 mg/kg.

17:36 EST ALX Oncology announces initial data from ASPEN-02 study - ALX Oncology announced the presentation of initial clinical data from its ongoing trial evaluating evorpacept in combination with azacitidine for the treatment of patients with previously untreated higher-risk or relapsed or refractory myelodysplastic syndrome. The new results show that the combination of evorpacept and azacitidine is active and well tolerated. As of October 25, 2021, 22 patients with either previously untreated HR or r/r MDS have been treated with evorpacept in the Phase 1 dose escalation part of the study, administered at 20 mg/kg or 30 mg/kg once every 2 weeks or 60 mg/kg once every 4 weeks together with standard dosing of azacitidine. Median follow-up is 3.4 months, and accrual is ongoing. Evorpacept in combination with azacitidine was well tolerated with no dose limiting toxicities, no observed treatment related serious adverse events, and a maximum administered dose of 60 mg/kg Q4W. In 6 previously untreated HR MDS response-evaluable patients, 3 patients achieved an objective response, and 2 patients achieved stable disease. Two out of 4 transfusion dependent patients achieved transfusion independence on study. Among 5 previously untreated HR MDS patients with TP53 mutation and complex cytogenetic abnormalities, 3 achieved an OR. Five of 9 patients with response-evaluable relapsed or refractory MDS that had progressed upon prior hypomethylating agents achieved an OR. In addition, 2 patients achieved SD.

17:31 EST Epizyme presents updates from SYMPHONY-1 Tazemetostat + R2 combination study - Epizyme presented updated safety and activity data from the Phase 1b portion of its Phase 1b/3 confirmatory study evaluating the investigational use of TAZVERIK, a first-in-class, oral, selective inhibitor of EZH2, in combination with rituximab + lenalidomide in patients with relapsed/refractory follicular lymphoma who have been treated with at least one prior systemic therapy, including patients who are rituximab-refractory and/or POD24, at the 2021 American Society of Hematology Annual Meeting. Updated data from the Phase 1b portion of the study reported included 40 FL patients who had received treatment with tazemetostat and R2 as of the September 29, 2021 data cut-off. The findings demonstrated that the safety profile of the tazemetostat and R2 combination was consistent with the previously reported safety information in the prescribing information for both tazemetostat and R2, respectively. Additionally, there was no clear dose response for treatment-emergent adverse events or dose modifications. Thirty-five of the 40 patients were evaluable for tumor assessments as of the data cut off, with 32 patients responding to treatment. The activity findings showed an objective response rate of 91.4 percent. The duration of response data continue to mature as the study is ongoing. The Phase 1b safety run-in component evaluated tazemetostat at three dose levels in 28-day cycles with standard-dose R2 using a 3 + 3 design. Rituximab was administered at 375 mg/m2 intravenously on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2 to 5. Lenalidomide was administered at 20 mg or 10 mg orally once daily on days 1 to 21 every 28 days for 12 cycles. In the Phase 3 component, approximately 500 patients will be randomly assigned to receive the RP3D of tazemetostat + R2 or placebo + R2. The study will also include a maintenance arm with tazemetostat or placebo following the first year of treatment with tazemetostat + R2 or placebo + R2. Treatment with tazemetostat and R2 was generally well tolerated. Grade 3/4 TEAEs were observed in 17 patients; the most common grade 3/4 TEAE was neutrophil count decrease/neutropenia. Ten patients reported a total of 16 SAEs. The only SAE reported in greater than1 patient was COVID-19, reported in 2 patients; all other SAEs were reported in 1 patient each. sarcoma not eligible for complete resection. Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies. Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

17:24 EST Xencor presents data from Phase 1 dose-escalation study of plamotamab - Xencor announced updated data from its Phase 1 dose-escalation study of plamotamab, a CD20 x CD3 bispecific antibody, in patients with B-cell non-Hodgkin lymphomas. The Phase 1 study of plamotamab was originally designed in two parts: Part A to establish an initial priming dose with fixed, weight-based dosing regimens and Part B to escalate dosing on administrations after the priming dose. A third part, Part C, was added to establish a step-up dosing regimen with higher, flat and less frequent dosing. The Part C schedule, an intravenous, 50 mg flat dose every two weeks after step-up dosing during the first two cycles of treatment, was generally well tolerated and was determined to be the recommended Phase 2 dose. Expansion cohorts are actively recruiting patients with diffuse large B-cell lymphoma and follicular lymphoma and are dosing using the recommended Phase 2 regimen to further evaluate the safety and efficacy of plamotamab monotherapy. The safety population included 50 patients in Part B and 14 patients in Part C. Patients were heavily pretreated, had a median age of 61.5 years, had a median of 4 prior therapies and had been diagnosed a median of 26.5 months prior to treatment. In Part C of the study, patients had generally more advanced disease and poorer responses to prior therapy. The Part C population had a median age of 64 years, had a median of 5 prior therapies and had been diagnosed a median of 30.5 months prior to treatment. Of the 14 patients in Part C, eight patients received prior CAR-T and three patients received NK cell therapy. Two of these patients received both. All eight patients with DLBCL received prior CAR-T therapy. The efficacy analysis included 47 evaluable patients with either DLBCL or FL who were treated in Part B or in Part C. Responses were assessed based on the Lugano Classification. The objective response rate was 51%, and complete responses were observed in 12 patients. In part C of the study, the ORR was 100% for patients with follicular lymphoma, and CRs were observed in two patients. For patients with diffuse large B-cell lymphoma, the ORR was 40%, and a CR was observed in one patient. All 5 evaluable patients with DLBCL received prior CAR-T therapy, and two evaluable patients with DLBCL received prior NK cell therapy. At the data cut off, the median duration of response for weight-based dosing cohorts and Part C was 225 days for patients with DLBCL and 171 days for patients with FL, with six patients continuing to respond to plamotamab monotherapy.

17:18 EST Precision BioSciences reports program updates for Allogeneic CAR T pipeline - Precision BioSciences announced program updates across its allogeneic CAR T cell therapy pipeline, including updated data for its Phase 1/2a clinical study of PBCAR0191 with enhanced lymphodepletion 1 presented at the 63rd American Society of Hematology Annual Meeting. The updated data from the PBCAR0191 Phase 1/2a study included 22 heavily pre-treated R/R subjects with predominantly advanced or aggressive B-cell malignancies who were evaluable as of November 16, 2021. Evaluable subjects received a median 5 lines of prior treatment, including 27% who previously received a CD19-directed autologous CAR T. For patients that received treatment of PBCAR0191 following eLD as of November 16, 2021 PBCAR0191 showed no greater than or equal to Grade 3 cytokine release syndrome, one Grade 3 immune effector cell-associated neurotoxicity syndrome with resolution to less than or equal to Grade 2 in 72 hours, no evidence of graft versus host disease and one infectious death at Day 54 deemed possibly related to treatment. PBCAR0191 yielded an overall response rate of 73% and a complete response rate of 59% using a 3 x 106 cells/kg cell dose. Four responders among the 17 evaluable NHL subjects reached Day 180 durability assessment Most notably, a potential signal for PBCAR0191 was observed among six subjects that previously received an autologous CAR T: 100% of these patients responded and 66% experienced a complete response at greater than or equal to Day 28; More than half of these patients had a longer duration of response on PBCAR0191 than with the prior autologous CAR T treatment. The Phase 1 clinical study of PBCAR19B is actively enrolling subjects with R/R NHL. Flat doses of PBCAR19B CAR T cells following standard lymphodepletion (sLD)3 are administered starting at Dose Level 1. The company has dosed the first three subjects at Dose Level 1. PBCAR269A is an investigational allogeneic CAR T immunotherapy targeting B-cell maturation antigen for the treatment of R/R multiple myeloma. The following has been observed among 14 patients that have been evaluated for clinical activity and safety across four dose levels of PBCAR269A4 monotherapy following sLD: No Grade greater than or equal to 3 CRS or ICANS; Dose-dependent increase in PBCAR269A peak expansion; Overall, PBCAR269A monotherapy response observed in the Phase 1/2a trial was not comparable with autologous CAR T profiles. Therefore, Precision is continuing to enroll subjects with PBCAR269A in combination with nirogacestat, a gamma secretase inhibitor developed by SpringWorks Therapeutics, in pursuit of a potential therapeutic index comparable with or better than autologous CAR T. Initial clinical data from the combination cohort is expected to be presented in mid-2022. The company's balance of cash and cash equivalents was approximately $152 million as of November 30, 2021. The company continues to expect that existing cash and cash equivalents, expected operational receipts, and available credit will be sufficient to fund its operating expenses and capital expenditure requirements into 2023.

17:00 EST Vincerx Pharma presents data on PTEFb/CDK9 inhibitor VIP152 in DLBCL, CLL - Vincerx Pharma announced data on VIP152, the Company's PTEFb/CDK9 inhibitor, in high-grade B-cell lymphoma, formerly referred to as double-hit lymphoma, and chronic lymphocytic leukemia, in two presentations at the 63rd American Society of Hematology Annual Meeting held December 11-14, 2021 in Atlanta GA. Compared with two oral CDK9 inhibitors in development, KB-0742 and atuveciclib, at equimolar concentrations, VIP152 demonstrated more potent and durable downregulation of phospho-Serine 2 on RNA polymerase II, a key biomarker for evaluating the mechanism of action of CDK9 inhibitors. Additionally, depletion of short half-life MYC and MCL-1 transcript levels up to 48 hours was observed. VIP152 treatment conferred a shift in transcriptional program, supporting an oncogenic shock mechanism of action, and sustained robust reduction and near clearance of MYC and MCL-1 proteins in MYC overexpressing lymphoma cell lines. Once weekly VIP152 treatment showed antitumor efficacy as demonstrated by dose-dependent tumor regression and tumor-outgrowth control in the SU-DHL-10 xenograft model. The pharmacodynamic effect demonstrated in the blood of HGBL patients treated with VIP152 suggests that the effect may translate to the clinic. Tumor-based pharmacodynamic studies are planned to confirm these findings. VIP152 is currently being evaluated in HGBL patients and other MYC expressing indications in the clinic. VIP152 shows selective CDK9 inhibition with improved activity over other CDK9 inhibitors in development including dinaciclib, KB-0742 and atuveciclib. VIP152 induces apoptosis in CLL cell lines and demonstrates cytotoxic activity that overcomes stromal protection of primary CLL samples. VIP152 disrupts transcriptomics of patient samples after a two-hour treatment, alters cellular programming and disrupts binding of CDK9 to canonical binding partners, thereby inhibiting its function. VIP152 weekly dosing decreases peripheral disease in a circulating tumor CLL mouse model and improves survival. Data support the ongoing clinical trial in CLL.

16:27 EST IGM presents data from IGM-2323 in patients with Advanced B Cell Malignancies - IGM Biosciences announced the presentation of clinical results from the company's Phase 1 trial evaluating IGM-2323, a novel bispecific IgM antibody targeting CD20 x CD3, at the 63rd American Society of Hematology Annual Meeting and Exposition. The multicenter, open-label Phase 1 dose escalation trial was intended to assess the safety, pharmacokinetics and preliminary efficacy of intravenous IGM-2323 in patients with advanced B cell malignancies. As of September 10, 2021, the data cutoff date for the presentation, 40 patients were enrolled and treated at escalating dose levels of IGM-2323. All 40 patients received at least one dose and were evaluable for safety. There were no dose limiting toxicities, no neurotoxicity adverse events, a relatively low rate of cytokine release syndrome and no patients discontinued due to an AE. Of the 10 patients treated in the 100 mg cohort, 3 of 6 diffuse large B cell lymphoma patients had a complete response and 2 of 3 follicular lymphoma patients had a complete response. Additionally, the one mantle cell patient treated in the 100 mg dose cohort had a partial response. Overall, of the 38 patients evaluable for efficacy, 11 patients showed a response, 8 of which were complete responses. Based on these promising results, two Phase 2 studies are being initiated to assess the safety and efficacy of two doses of IGM-2323, 100 mg and 300 mg, in patients with DLBCL and FL. If supportive, the data from this Phase 2 multicenter, open-label study could potentially be used as the basis for accelerated review and approval of IGM-2323.

16:23 EST Imago BioSciences presents data from ongoing Phase 2 study of Bomedemstat - Imago BioSciences presented positive data from its ongoing global Phase 2 clinical study evaluating bomedemstat in patients with advanced myelofibrosis. Of the evaluable patients at 24 weeks 74% showed a decrease in Total Symptom Score. 26% showed a greater than or equal to 50% decrease in TSS. 75% showed spleen volume reductions. 81% of mutant allele frequencies were either stable or reduced, including driver and high molecular risk mutations such as ASXL1. 89% of patients who were transfusion-independent at baseline had stable or improved hemoglobin at 12 weeks. No new mutations or transformation to acute myeloid lymphoma in more than 600 days of follow-up in patients with high risk of progression. Bomedemstat was generally well-tolerated to date in patients with myelofibrosis.

16:18 EST Karyopharm presents updated Phase 2 Selinexor data - Karyopharm Therapeutics announced an oral presentation highlighting updated data from the Phase 2 ESSENTIAL study, an investigator-sponsored study evaluating single-agent selinexor, a first-in-class, oral Selective Inhibitor of Nuclear Export compound, in patients with myelofibrosis previously treated with JAK inhibition. The results were based on the open label, prospective, investigator-initiated single center ESSENTIAL study in adult patients with primary or secondary MF with resistance or intolerance to JAK inhibitor therapy. Selinexor was administered orally at a dose of 80mg or 60mg once weekly to 12 patients. The primary endpoint of the study is to assess the efficacy of selinexor on SVR. Median duration of prior JAK inhibitor therapy was 22 months and 92% patients had MF refractory to ruxolitinib. As of the data cutoff, the median duration of treatment was 11 months. Of the ten patients who were on treatment for at least 24 weeks, four patients achieved SVR of greater than or equal to35% and six patients achieved SVR of greater than or equal to25%. Of the five patients who were transfusion dependent at screening, two achieved transfusion independence. Of the three patients with hemoglobin less than10g/dL at screening, improvement was observed in two patients. Reduction in marrow reticulin fibrosis from MF grade 3 to MF grade 1 was observed in a patient who had an assessment at week 72 demonstrating disease modification potential with longer treatment. While median overall survival was not yet reached, the two-year survival probability was assessed to be 91.7%. This compares favorably with a historical survival of 13-14 months in this population. The most common grade greater than or equal to 3 treatment emergent adverse events were anemia and fatigue. These were manageable with treatment interruption and dose reduction, except in one patient who discontinued treatment.

16:13 EST Bluebird Bio presents new results for betibeglogene autotemcel - Bluebird bio presented new results for betibeglogene autotemcel, a deeply studied investigational gene therapy, that demonstrate adult and pediatric patients living with beta-thalassemia who require regular red blood cell transfusions can produce normal or near-normal levels of total hemoglobin and continue to remain transfusion-free, and achieve stable iron markers, through up to seven years of follow-up. These findings further support beti-cel as a potentially curative one-time treatment option that addresses the underlying genetic cause of beta-thal and mitigates the burdens associated with the practical management of the disease. beti-cel is a one-time gene therapy that adds functional copies of a modified form of the beta-globin gene into a patient's own hematopoietic (blood) stem cells. Once patients have the betaA-T87Q-globin gene, the HSCs have the potential to produce gene therapy-derived adult Hb at levels that can eliminate the need for transfusions. In studies of beti-cel, transfusion independence is defined as no longer needing RBC transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL. As of the data cut-off of August 18, 2021, a total of 63 pediatric, adolescent and adult patients, including 20 patients with at least five years of follow-up, 11 with at least six years and three with up to seven years across beta0/beta0 and non-beta0/beta0 genotypes, have been treated with beti-cel in the Phase 1/2 HGB-204 and HGB-205 studies and the Phase 3 HGB-207 and HGB-212 studies. Data from bluebird bio's Phase 1/2 and Phase 3 clinical studies represent more than 240 patient-years of experience with beti-cel and the longest available follow-up data in beta-thal patients requiring regular RBC transfusions treated with one-time gene therapy. Adverse reactions considered related to beti-cel were few and consisted primarily of non-serious infusion-related reactions that occurred on the day of infusion and cytopenias. Pain in extremity shortly after treatment was also documented. One of these adverse events was a serious adverse event of thrombocytopenia considered possibly related to beti-cel and has resolved. The majority of AEs and SAEs in the beti-cel clinical development program were unrelated to beti-cel and consistent with the known side effects of HSC collection and busulfan conditioning regimen. After participating in and completing the two years of follow-up in any of the Phase 1/2 or Phase 3 studies, patients treated with beti-cel were invited to enroll in a 13-year long-term follow-up study, LTF-303. As of August 18, 2021, 57 of 63 beti-cel-treated patients across age groups and genotypes spanning a broad range of the most severe beta0/beta0 and non-beta0/beta0 genotypes were enrolled in LTF-303 with a median post-infusion follow-up of 41.5 months. Twenty patients enrolled in LTF-303 have at least five years of follow-up. Of the 57 patients enrolled in LTF-303, 46 patients achieved TI: 15/22 patients treated in Phase 1/2 and 31/35 patients treated in Phase 3. All 46 patients who achieved TI maintained it through last follow-up in LTF-303, demonstrating the long-term durability of beti-cel. Phase 1/2 patients had a median duration of ongoing TI of 65.9 months and Phase 3 patients had a median ongoing TI duration of 32 months/ Weighted average Hb in patients who achieved TI reached normal or near-normal levels in the Phase 1/2 studies and in the Phase 3 studies. Patients who require regular blood transfusions need to reduce excess iron caused by chronic blood transfusions. For people living with beta-thal, iron can be removed from the body in several ways, including chelation. Prior to beti-cel infusion, all patients were on iron chelation. Importantly, the majority of patients who achieved TI that restarted iron chelation after infusion have since stopped; and 24% of those who achieved TI were able to receive phlebotomy, which is another method for iron reduction that is only possible for patients who have sufficient hemoglobin levels without RBC transfusions. This supports the potential for beti-cel to reduce the treatment burden associated with iron management. A sub-analysis of iron status in LTF-303 included 16 patients who achieved TI and stopped chelation, with at least nine months of follow-up after discontinuation of chelation. The sub-analysis showed iron reduction in response to chelation and stabilization of iron markers after chelation was discontinued. There were no deaths, no vector-derived replication-competent lentivirus, and no events of insertional oncogenesis or malignancy in LTF-303. No drug-related AEs were reported. Serious AEs unrelated to beti-cel included infertility issues, gallbladder disease, cholelithiasis, infection and low white blood cell count in the setting of a wild-type HIV, and individual events of diabetic ketoacidosis, pulmonary embolism, and major depression. Pulmonary embolism occurred concurrently with diabetic ketoacidosis in a patient with a history of thromboembolic events. Each event was reported once.

16:03 EST Kite announces updated two-year results from ZUMA-5 study - Kite, a Gilead company, announced updated two-year results from ZUMA-5, a global, multicenter, single-arm, open-label Phase 2 study evaluating Yescarta in adult patients with relapsed or refractory indolent non-Hodgkin lymphoma after at least two prior lines of therapy. At the time of data cut-off, 110 patients; 24 with marginal zone lymphoma were eligible for efficacy analyses. FL patients had at least two years of follow-up time, and the minimum requirement for MZL was four weeks. Among eligible patients with FL, median follow-up was 30.9 months. The objective response rate in FL was 94%, with a complete response rate of 79%. Fifty-seven percent of eligible FL patients had ongoing responses. The estimated median duration of response and progression-free survival was 38.6 months and 39.6 months, respectively. Among eligible FL patients, median time to next treatment was 39.6 months. Median overall survival was not reached, with an estimated 24-month OS rate of 81%. Among eligible patients with MZL, median follow-up was 23.8 months. Eighty-three percent of patients achieved ORR, including 63% with a CR. Fifty percent of patients were in ongoing response at the time of data cut-off. Median DOR and time to next treatment were not yet reached among eligible patients, and median PFS was 17.3 months. Median OS was not yet reached, with an estimated 24-month OS rate of 70%. Among all evaluable patients, safety observations were consistent with the known safety profile for Yescarta. Grade greater than or equal to 3 cytokine release syndrome and neurologic events occurred in 7% and 19% of patients, respectively. Most CRS cases and neurologic events of any grade resolved by the time of data cut-off. Yescarta received accelerated approval from the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in March 2021. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a Risk Evaluation and Mitigation Strategy due to these risks; see below for Important Safety Information. Yescarta is currently under review in the European Union for the treatment of adult patients with relapsed or refractory FL. Yescarta has not been approved by any regulatory agency for the treatment of MZL.

15:55 EST BeiGene presents updated safety, efficacy findings on BRUKINSA - BeiGene presented additional safety and efficacy results from an ongoing Phase 2 trial evaluating BRUKINSA in patients with previously treated B-cell malignancies who were intolerant to ibrutinib and/or acalabrutinib. This single-arm, open-label, multicenter Phase 2 trial in the U.S. evaluated the safety and efficacy of BRUKINSA in patients with previously treated B-cell malignancies who were intolerant to prior BTK inhibitor therapy, with preliminary results presented at the 62nd ASH Annual Meeting in December 2020. The primary endpoint of safety was assessed by the recurrence and the change in severity of adverse events compared to patients' intolerance AE profile to ibrutinib and/or acalabrutinib. Secondary endpoints included investigator-assessed disease control rate, overall response rate, investigator-assessed progression-free survival and patient-reported outcomes. A total of 67 patients were enrolled in the trial, with 57 patients intolerant to ibrutinib and 10 patients intolerant to acalabrutinib and/or ibrutinib, including 43 patients with chronic lymphocytic leukemia, 11 patients with Waldenstrom's Macroglobulinemia, seven patients with small lymphocytic lymphoma, three patients with mantle cell lymphoma, and three patients with marginal zone lymphoma. Patients were considered intolerant if they developed significant or persistent toxicities while on ibrutinib and/or acalabrutinib despite optimal care. At the data cutoff on September 8, 2021, with a median BRUKINSA exposure of 11.1 months, more than a majority of the ibrutinib and acalabrutinib intolerance events did not recur with BRUKINSA treatment and none of the intolerance events recurred at a higher severity.

15:49 EST Harpoon Therapeutics presents interim data from Phase 1/2 study for HPN217 - Harpoon Therapeutics presented a poster with interim data from the ongoing dose-escalation portion of the Phase 1/2 trial for HPN217 in patients with relapsed/refractory multiple myeloma at the 63rd American Society for Hematology Annual Meeting and Exposition. HPN217 targets B-cell maturation antigen and is based on Harpoon's proprietary Tri-specific T cell Activating Construct platform designed to recruit a patient's own immune cells to kill tumor cells. As of November 10, 2021, the data cutoff date for the interim clinical data presentation, 37 patients have been dosed across 10 cohorts at fixed doses of 5 to 2860 microgram/week and in step dosing cohorts up to 3240 microgram/week administered as an intravenous infusion. These interim data demonstrated that HPN217 is generally well tolerated with one dose limiting toxicity reported of Grade 4 AST elevation that resolved, MTD has not been reached. HPN217 is clinically active at higher dose levels with clinical benefit, disease control rate of 88%, demonstrated in 7 of 8 disease evaluable patients in the 2150 microgram/week cohort. 2 stringent complete responses have been observed, one in each of the higher dose 2150 and 2860 microgram/week cohorts. Transient and manageable cytokine release syndrome reported in 9 of 37 patients were all Grade 1 or 2 Introduction of step dose regimens has allowed for the administration of higher target doses, currently at 3240 microgram/week.

15:36 EST Kite announces five-year follow-up pivotal data from ZUMA-1 trial of Yescarta - Kite, a Gilead company, announced five-year follow-up data from the pivotal ZUMA-1 trial of Yescarta in adult patients with refractory large B-cell lymphoma. Among all patients treated with Yescarta, the five-year overall survival rate was 42.6%. Among patients who had a complete response, the five-year OS rate was 64.4% and median survival time has yet to be reached. Among treated patients alive at five years, 92% have received no additional treatment since their one-time infusion of Yescarta, suggestive of a cure for these patients. Since the four-year analysis, there has been one death in the study, which was due to secondary malignancy from prior chemotherapy and/or conditioning chemotherapy-related myelodysplastic syndrome while the patient was in complete remission for LBCL. There have been no new safety signals reported, including no Yescarta-related secondary malignancies. The presenters also reported an exploratory analysis of ZUMA-1 data showing a high degree of correlation between long-term OS and event-free survival status, which potentially supports the use of one-year and two-year EFS as surrogate endpoints for long-term OS in relapsed/refractory LBCL. Yescarta was the first CAR T-cell therapy to be approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a Risk Evaluation and Mitigation Strategy due to these risks; see below for Important Safety Information.

15:32 EST Epizyme presents preclinical data, Phase 1/1b trial design on EZM0414 - Epizyme shared preclinical data and the Phase 1/1b trial design for EZM0414, the company's novel, first-in-class, oral SETD2 inhibitor, an investigational agent being developed for the treatment of adult patients with relapsed or refractory multiple myeloma or with diffuse large B-cell lymphoma. The data and the design were presented at the 2021 American Society of Hematology Annual Meeting. The data presented from both in vitro and in vivo preclinical studies, demonstrated that targeting SETD2 with EZM0414 resulted in significantly reduced growth of t(4;14) MM cell lines, as well as non-t(4;14) MM and DLBCL cell lines. Additionally, in in vitro studies, EZM0414 showed synergy with MM and DLBCL standard of care and emerging therapies, which supports the potential for the study of EZM0414 in combination with current MM and DLBCL treatments. Epigenetic mutations and dependencies have been identified in B cell malignancies, including MM and DLBCL, providing therapeutic rationale for epigenetic inhibitors in these tumor types. Previous data demonstrated that there is broad sensitivity of MM cell lines to SETD2 inhibition, and in particular, t(4;14) MM cell lines, which are dependent on SETD2 due to overexpression of MMSET by the high-risk t(4;14) translocation. These preclinical data form the basis for SET-101, the company's Phase 1/1b clinical study, which is designed to evaluate the safety and determine the optimal dose of EZM0414. Under the trial protocol, following the Phase 1 dose ranging portion of the trial, the study will be expanded to evaluate EZM0414 in three patient cohorts: t(4;14) MM, non-t(4;14) MM, and DLBCL. In the Phase 1 portion of the study, adult patients with relapsed or refractory MM and DLBCL will be enrolled and treated in a Bayesian optimal interval design to evaluate the safety, tolerability, and pharmacokinetics of EZM0414 at six dose levels. Up to 36 patients will be enrolled, and at least nine patients will be evaluated for maximum tolerated dose. At least eight patients, each with t(4;14) MM, non-t(4;14) MM, or DLBCL will be included. The primary endpoints include the safety and tolerability of EZM0414 and the maximum tolerated dose. The Phase 1b dose expansion portion of the study will include three cohorts, t(4;14) MM, non-t(4;14) MM, and DLBCL, of up to 20 patients each. There will be two interim assessments when clinical data from the first 10 and 15 patients enrolled in each expansion cohort are available. Futility assessments will also be conducted at that time. The final analysis will be performed when all data from the 20 patients in each expansion cohort are available. Primary endpoints include the recommended Phase 2 dose, and secondary endpoints include efficacy and response rates. The trial is currently enrolling patients in the United States and has been screening patients for enrollment.

15:23 EST Kite announces results from primary analysis of ZUMA-7 trial - Kite, a Gilead company, announced results from the primary analysis of ZUMA-7, a global Phase 3 study evaluating Yescarta as a one-time infusion, in a head-to-head study against standard of care for adults with large B-cell lymphoma who relapsed or were refractory to first-line treatment. Yescarta was evaluated against the current SOC which is a multi-step process intended to culminate in a stem cell transplant. ZUMA-7 was initiated in 2017 and is the first and largest Phase 3 randomized study of any CAR T-cell therapy in the second-line setting, enrolling 359 patients in 77 centers around the world. ZUMA-7 is considered a landmark trial for being the only study to reach the clinically meaningful two-year follow-up milestone. With a median follow-up of over two years, the study met the primary endpoint of event-free survival. Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years and did not require the need for additional cancer treatment or experienced cancer progression and a four-fold greater median EFS compared to SOC. These statistically significant and clinically meaningful results were not confounded by any bridging chemotherapy. Improvements in EFS with Yescarta were consistent across key patient subgroups, including the elderly, primary refractory disease, high-grade B-cell lymphoma including double-hit and triple-hit lymphoma, and double expressor lymphoma. In ZUMA-7, nearly three times as many patients randomized to Yescarta ultimately received the definitive CAR T-cell therapy treatment versus those randomized to SOC who received HDT+ASCT. Among randomized patients, overall response and complete response rates were also higher with Yescarta. Median overall survival, evaluated as a preplanned interim analysis, favored Yescarta compared to SOC. The primary analysis of OS will occur at approximately 210 deaths. In a separate ZUMA-7 analysis of patient-reported outcomes which will also be shared in an ASH oral presentation on December 12, patients receiving Yescarta and eligible for the PROs portion of the study showed significant and clinically meaningful improvements in quality of life at Day 100 compared with those who received SOC using a prespecified analysis for three PRO domains. The data also suggest faster recovery to pretreatment QoL for patients treated with Yescarta versus SOC. In the ZUMA-7 trial, Yescarta had a manageable safety profile that was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, Grade greater than or equal to 3 cytokine release syndrome and neurologic events were observed in 6% and 21% of patients, respectively. No Grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had high grade events, mostly cytopenias. Global regulatory filings to expand the indication for Yescarta to include second-line relapsed or refractory LBCL based on the ZUMA-7 data are currently underway. The U.S. Food and Drug Administration has accepted the supplemental Biologics License Application and granted Priority Review designation to Yescarta for this patient population with a target action date under the Prescription Drug User Fee Act of April 1, 2022. Regulatory submissions have also been filed with other global health authorities, including the European Medicines Agency.

09:24 EST Novartis presents updated 48-week data from Phase III ASCEMBL trial - Novartis announced new 48-week data from the Phase III ASCEMBL trial of Scemblix demonstrating that the results observed in the primary analysis versus Bosulif were maintained in longer-term follow up for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase previously treated with two or more tyrosine kinase inhibitors 1-4. In this analysis, presented at the 63rd American Society of Hematology Annual Meeting & Exposition, the major molecular response rate at 48 weeks was 29.3% for patients treated with Scemblix versus 13.2% for patients in the Bosulif arm, which is consistent with a doubling of the efficacy at 24 weeks 1-4. The proportion of patients treated with Scemblix who experienced adverse reactions leading to discontinuation was more than three times lower than those in the Bosulif arm. Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket2. This novel mechanism of action, also known in scientific literature as a STAMP inhibitor, can help address resistance to TKI therapy in patients with CML and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells2-4. Scemblix continues to be studied across multiple lines of treatment for CML-CP3-12. In this updated analysis, responses were also durable, with 60 out of 62 patients on Scemblix maintaining MMR at time of their last assessment1. Scemblix continued to deliver more favorable deep molecular responses with MR4 and MR4.5 rates at 48 weeks of 10.8% and 7.6%, compared to 3.9% and 1.3% in patients treated with Bosulif, respectively. Additionally, the cumulative proportion of patients achieving a level of BCR-ABL1IS less than or equal to1% at 48 weeks - a predictor of better long-term outcomes in this heavily pretreated patient population - was higher in the Scemblix arm than in the Bosulif arm. The most common reason for treatment discontinuation was lack of efficacy in 37 patients treated with Scemblix and 27 patients treated with Bosulif. Median duration of exposure was 15.4 months for Scemblix and 6.8 months for Bosulif. With a longer duration of exposure, the safety and tolerability profile remains consistent with the primary analysis of the ASCEMBL trial1-4. The most common adverse reactions reported in this analysis were thrombocytopenia and neutropenia in the Scemblix arm; and diarrhea, nausea, increased ALT, vomiting, rash, increased AST (21.1%) and neutropenia in the Bosulif arm. Scemblix received FDA approval in October 2021 and is currently available for physicians to prescribe to appropriate patients in the US2. Scemblix is also being evaluated in studies across multiple treatment lines and indications for CML-CP, including the ASC4FIRST Phase III study for newly diagnosed adult patients, as well as in a Phase Ib/II dose assessment study in pediatric patients with Ph+ CML-CP.

09:12 EST Roche presents data at ASH 2021 for novel cancer immunotherapy mosunetuzumab - Roche announced that new pivotal data on its CD20xCD3 T-cell engaging bispecific antibody, mosunetuzumab, will be presented for the first time at the 63rd American Society of Hematology Annual Meeting and Exposition from 11-14 December 2021. Emerging data continue to show the promising benefit-risk profile of mosunetuzumab in relapsed or refractory follicular lymphoma, a slow-growing, or indolent, form of non-Hodgkin lymphoma. Pivotal results from the phase I/II GO29781 study demonstrated that mosunetuzumab induces durable complete responses lasting at least 18 months in heavily pretreated patients with R/R FL who have received two or more prior therapies, with a 60.0% complete response rate and a median progression-free survival of 17.9 months. Median duration of response was 22.8 months among responders. The most common adverse event was cytokine release syndrome, which was generally low grade. Roche recently submitted the initial marketing authorisation application for mosunetuzumab to the European Medicines Agency, with the hope to bring this drug as soon as possible to people with NHL. Genentech plans to submit the new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL. Additionally, as part of Roche's broad pipeline of haematology immunotherapies and application of novel combinations, key data for the bispecific antibodies mosunetuzumab, glofitamab and cevostamab are being presented. Initial results from the phase Ib CO41942 study of mosunetuzumab in combination with lenalidomide in people with R/R FL who have received at least one prior line of therapy demonstrated encouraging preliminary efficacy and a tolerable safety profile. Data from the phase Ib/II GO40516 study evaluating mosunetuzumab in combination with Polivy showed promising efficacy and favorable safety in heavily pretreated patients with aggressive R/R NHL with an objective response rate of 65.0% and a CR rate of 48.3%. A phase I/Ib NP30179 dose-escalation study evaluating glofitamab as a monotherapy and in combination with Gazyva/Gazyvaro following pretreatment with Gazyva/Gazyvaro in patients with R/R B-cell NHL showed promising activity in both R/R FL and R/R mantle cell lymphoma, an uncommon but aggressive form of lymphoma with poor prognosis for those who progress. Preliminary results in heavily pretreated patients with R/R FL showed high response rates across all treatment groups, including high-risk subgroups, with an ORR of 81.0% for the glofitamab monotherapy group and an ORR of 100% for the glofitamab plus Gazyva/Gazyvaro combination therapy group.5 For patients with R/R MCL, treated with glofitamab monotherapy following Gazyva/Gazyvaro pretreatment, the ORR was 81.0%. Across both studies, the most common AE was CRS, with the majority of events being low grade. Results of the phase Ib/II NP39488 study of glofitamab in combination with Polivy demonstrated encouraging preliminary efficacy and a tolerable safety profile in people with difficult-to-treat R/R diffuse large B-cell lymphoma. With a median follow up of 3.2 months, an ORR of 73.0% was observed with a 51.5% CR rate, with patients showing durable responses at greater than or equal to6 months. No Grade 3 or higher CRS events were observed, and the safety profile of the combination was consistent with that of the individual medicines. Data from the phase I GO39775 dose-escalation and expansion study investigating cevostamab in heavily pretreated patients with R/R multiple myeloma showed the first-of-its kind FcRH5xCD3 bispecific antibody induced clinically meaningful, target dose-dependent increases in ORR without an increase in the rate of CRS, with an ORR of 54.5% in the 160 mg dose group. Results from double step-up dosing suggest this approach could help mitigate CRS and potentially improve the safety profile compared to single step-up dosing.