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20:29 EDT Editas announces data supporting novel approach for Sickle Cell,Beta-Thalassemia - Editas Medicine announced results from experiments to demonstrate expanded CRISPR genome editing strategies in hematopoietic stem cells for the treatment of sickle cell disease and beta-thalassemia. In these experiments, the company demonstrated HBG1/2 promoter-edited CD34+ cells robustly engrafted in mice without lineage skewing of red blood cell precursors. The company reported these data in an oral presentation at the 60th Annual Meeting of the American Society of Hematology. In these experiments, NBSGW mice received an infusion of human CD34+ cells which had been edited either at the BCL11A erythroid enhancer site or at the HBG1/2 promoter site. Analysis of bone marrow collected eight to 16 weeks post-infusion demonstrated that robust fetal hemoglobin induction was achieved when targeting HBG1/2 promoters. Notably, editing HBG1/2 promoters upregulated fetal hemoglobin with superior repopulation of red blood cell precursors as compared to editing the BCL11Ae site. The red blood cell precursors from bone marrow edited at the BCL11Ae site had lower productive editing rates compared to other lineages and showed increased level of apoptosis, or programmed cell death, in erythroid culture compared to HBG1/2 promoter-edited cells. Increased production of fetal hemoglobin can be beneficial to patients with sickle cell disease or beta-thalassemia. Editing at the HBG1/2 site is a differentiated approach for development of a human therapeutic for the treatment of sickle cell disease and beta-thalassemia as compared to other medicines currently under development that edit at the BCL11Ae site.

19:41 EDT Spark Therapeutics announces updated data on SPK-8011 - Spark Therapeutics announced updated preliminary data on the first 12 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-8011 in hemophilia A. These data were presented at the 60th American Society of Hematology Annual Meeting and Exposition. The 12 participants in the Phase 1/2 trial received a single administration of investigational SPK-8011, including two at a dose of 5x1011 vector genomes/kg body weight, three at a dose of 1x1012 vg/kg and seven at a dose of 2x1012 vg/kg. As of the Nov 2, 2018, data cutoff, no inhibitors, no thrombotic events and no persistent or unresolved transaminase elevations have been observed across a cumulative 9.7 years of data follow-up. Across all three doses, beginning four weeks after vector infusion, there has been a 94-percent reduction in bleeds and a 95-percent reduction in FVIII infusions. Participants in the 5x1011 vg/kg and 1x1012 vg/kg dose cohorts have shown dramatic reductions in bleeds and infusions as well as stable FVIII activity with up to 78 weeks of follow-up, with observation ongoing. Among the five participants treated in the 2x1012 vg/kg cohort who did not experience an immune response-associated decline in FVIII expression, beginning four weeks after vector infusion, there has been a 100-percent reduction in bleeds and a greater than 99-percent reduction in FVIII infusions, with up to 46 weeks of follow-up. Seven of the 12 participants received a tapering course of reactively administered oral steroids, including five in the 2x1012 vg/kg cohort, in response to an alanine aminotransferase elevation above the patient's baseline, declining FVIII levels and/or positive IFN-g enzyme-linked immunospots. For all participants, steroids led to rapid normalization of ALT and/or ELISPOTs. All participants responded to vector infusion with an increase in circulating levels of FVIII. As previously disclosed, two participants in the 2x1012 vg/kg cohort had a suspected capsid immune response that caused their FVIII levels to decline to less than 5%. One of these participants did not rapidly respond to reactively administered oral steroids and was electively admitted to the hospital to receive two intravenous methylprednisolone infusions. The event subsequently resolved without sustained deleterious effects other than the decrease in FVIII activity. The admission to hospital for these infusions met the criteria for a serious adverse event. Across the study through the data cutoff, the 12 participants demonstrated rapid clearance of vector from body fluids, with median time to clear vector DNA from saliva, semen and urine of two weeks. Spark Therapeutics intends to initiate a Phase 3 run-in study by the end of 2018 to collect prospective observational data on trial participants.

19:35 EDT Arthur J. Gallagher acquires IBS Re Singapore - Arthur J. Gallagher announced that it has acquired a 40% equity stake in Indonesian insurance broker and risk management services provider PT IBS Insurance Broking Service, as well as 100% of reinsurance broker, IBS Re Singapore. Other terms of the transaction were not disclosed.

18:40 EDT Miragen Therapeutics announces data from Phase 1 Cobomarsen trial - Miragen Therapeutics announced data from its Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of cobomarsen, an inhibitor of miR-155, in mycosis fungoides patients. These data was presented at the 60th American Society of Hematology Annual Meeting. The Phase 1 clinical trial investigated the safety, tolerability, PK, PD and efficacy of cobomarsen in a total of 43 MF patients. Cobomarsen was initially administered via intratumoral injection, and then via systemic administration by subcutaneous, intravenous bolus or IV infusion, at 300, 600 or 900 mg/dose with loading doses in the first week followed by weekly maintenance dosing. The patients had been in the clinical trial for up to 23 months as of the reporting of these data. Highlights from the trial observations include: 92% of the MF subjects in the systemic administration cohorts had improvement in tumor burden as assessed by modified Severity Weighted Assessment Tool score independent of concomitant therapies; 52% of patients receiving more than six doses achieved a partial response in mSWAT score; with 69% of these patients who achieved a partial response maintained the response for at least four consecutive months. For these patients, the mean duration of response was 259 days at the time of the data cutoff. Cobomarsen was generally well-tolerated at all doses tested.

18:31 EDT Pfizer presents positive 26-week data for PF-05280586 at ASH - Pfizer announced at the American Society of Hematology Annual Meeting that the REFLECTIONS B328-06 study, a comparative safety and efficacy study of PF-05280586 versus Rituxan/MabThera, met its primary endpoint of overall response rate at Week 26 of the 52-week study.1 26-week data from the ongoing 52-week REFLECTIONS B328-06 study demonstrated no clinically meaningful differences in efficacy, in terms of ORR at Week 26, between PF-05280586 and MabThera, for the first-line treatment of patients with CD20-positive, low tumor burden, follicular lymphoma. ORR at Week 26 was 75.5% versus 70.7%, and was within the pre-specified equivalence margin. ORR is defined as the percentage of patients achieving complete response or partial response, based on central review. Additionally, estimated rates of one-year progression-free survival were similar across groups. The results also show that PF-05280586 had a similar safety profile to MabThera. PF-05280586 has been accepted for review by the FDA, the BsUFA goal date for a decision by the FDA is in second-quarter 2019. Pfizer is also working towards making PF-05280586 available for patients in Europe. Further results on the safety and efficacy from this ongoing 52-week study in LTB-FL are expected to be presented next year.

18:21 EDT NewLink Genetics presents encouraging updated Phase 1 data in Frontline AML - NewLink Genetics announced that updated Phase 1 data evaluating indoximod plus standard-of-care chemotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukemia were presented at the 60th American Society of Hematology Annual Meeting. This Phase 1 trial evaluated the initial safety and preliminary evidence of clinical activity of adding indoximod to standard 7+3 induction and high-dose cytarabine consolidation chemotherapy for adult patients with newly diagnosed AML. The presentation highlighted an initial safety profile indicating that the treatment regimen was well tolerated with adverse events commensurate with chemotherapy alone. Evidence of clinical activity was observed for indoximod plus chemotherapy in newly diagnosed AML as supported by these Phase 1 data showing post-induction minimal residual disease negativity rate of 86% and post-HiDAC1 MRD negativity of 100%. Fifty-seven patients were screened, and 38 patients initiated induction therapy on protocol. Five patients never received indoximod resulting in an intent-to-treat population of 33 patients. Twenty-two patients received the pre-specified 80% of indoximod dosing required to be included in the per protocol analysis, 8 received less than 80% of the scheduled indoximod dosage, and 3 patients remained on induction treatment as of the date of data cut off. Of these 22 PP patients, 16/22 achieved complete morphological response and 6 were primary refractory. Of the patients who achieved CR, 14 had results available from MRD testing post-induction. MRD negativity was defined by a flow cytometry assay at a level of less than 0.02%. Of those tested, 12/14 were MRD-negative. Of the 14 patients, 1 patient proceeded to transplant, and 13 began HiDAC consolidation therapy. Post-HiDAC consolidation, all 13 patients were tested for MRD status with all 13/13 reported to be MRD-negative. When benchmarked against available published studies, these initial data appear encouraging. For a more precise comparison, a contemporaneous multi-institutional dataset is being aggregated to benchmark these data against data generated from patients undergoing the same chemotherapy regimen without the addition of indoximod using the same MRD assay assessed at the same reference laboratory. Safety data from this Phase 1 trial indicate that the combination therapy regimen was well tolerated. No RLTs were observed when combining indoximod with standard-of-care chemotherapy. Grade 3 or greater adverse hematologic events included febrile neutropenia, anemia, and thrombocytopenia while non-hematologic events included hypoxia, anemia, and pneumonia. The overall adverse event profile observed in this small sample size is consistent with that of 7+3 induction chemotherapy plus HiDAC consolidation alone.

18:14 EDT Apellis presents data from study of APL-2 in Paroxysmal Nocturnal Hemoglobinuria - Apellis Pharmaceuticals announced interim data from its Phase 1b study of APL-2 in treatment-naive patients with paroxysmal nocturnal hemoglobinuria. Data from the PADDOCK trial were presented in a poster session today at the 60th Annual Meeting of the American Society of Hematology. Interim results from the ongoing PADDOCK study evaluating 270mg subcutaneous APL-2 administered daily are presented. Data are presented for 19 patients at baseline, 15 patients on therapy at day 85 and 10 patients at day 169. PADDOCK is an open-label, dose-escalation trial designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple doses of APL-2, in patients with PNH, a rare and serious condition affecting the bone marrow. Data to be presented demonstrates: Broad control of hemolysis, both intravascular and extravascular, led to significant and sustained increases in hemoglobin in the absence of transfusions. The baseline Hb was 8.0 g/dL which increased to 10.8 g/dL and 12.2 g/dL at Days 29 and 85, respectively. In the 12 months prior to screening, subjects received an average of 8.7 units pRBCs. Transfusion independence was achieved while on APL-2 maintenance therapy with the exception of one patient with severe aplastic anemia at Day 364. Systemic inhibition of C3 with APL-2 controls both intravascular and extravascular hemolysis in PNH patients as demonstrated by rapid and durable normalization of LDH, total bilirubin, and reticulocytes, all markers of hemolysis.

17:50 EDT AbbVie announces results of up to 7 years of PFS of trial follow-up in CLL/SLL - AbbVie announced the results of up to seven years of clinical trial follow-up for IMBRUVICA monotherapy in chronic lymphocytic leukemia/small lymphocytic lymphoma, the longest follow-up for a Bruton's tyrosine kinase inhibitor to date. The updated Phase 1b/2 data demonstrated durable responses in CLL/SLL patients with an overall response rate of 89%. Evaluated patients included those with high-risk genomic factors such as complex karyotype and unmutated IGHV, and more than 70 patients with three to 12 prior lines of therapy. Progression-free survival rates were also sustained. The analysis also found that PFS trended better for R/R patients when treated with ibrutinib in earlier lines of therapy. High grade adverse events were reported in 74% of newly diagnosed patients and 89% of R/R patients. Hypertension, diarrhea and hyponatremia were among the most common grade 3 or higher treatment-emergent AEs. Major hemorrhage and grade 3 or higher atrial fibrillation, thrombocytopenia, anemia and arthralgia were observed in 11% or less of newly diagnosed and R/R patients. In addition, infection was more common in R/R patients. No new or unexpected AEs were observed, and the occurrence of most grade 3 or higher AEs and serious AEs decreased over time, with the exception of hypertension. Additional data presented at ASH include a sub-analysis derived from patients with R/R CLL enrolled in the RESONATE trial. The sub-analysis assessed the effects of ibrutinib versus ofatumumab on T-cell function and proliferation. CLL is a B-cell malignancy that is also characterized by profound immune dysregulation, including dysfunctional T cells.

17:41 EDT Sunesis presents preliminary data from Phase 1b/2 trial of Vecabrutinib - Sunesis Pharmaceuticals announced the presentation of results from the company's Phase 1b/2 clinical trial of its non-covalent BTK inhibitor vecabrutinib in adults with relapsed/refractory chronic lymphocytic leukemia and other B-cell malignancies. Data reported were available from 11 of 13 treated patients. These included 7 with relapsed/refractory CLL, two with mantle cell lymphoma, and two with Waldenstrom macroglobulinemia. Patients had received an average of 5 lines of prior therapy, and all had progressed on prior covalent BTK inhibitor treatment. Four of the 7 CLL patients had BTK C481 mutations. Currently, 4 patients are on study: one in Cycle 2, one in Cycle 3, and two new subjects who are in Cycle 1 and are anticipated to complete the 50 mg cohort. The most common TEAEs of any grade were anemia and neutropenia and night sweats. Grade 3 drug-related AEs were anemia, neutropenia, leukocytosis, and ALT increase. In the second cohort, one patient experienced a dose-limiting toxicity of an inadequate number of Cycle 1 doses administered due to a drug-related grade 3 ALT elevation, resulting in expansion of the cohort to 6 patients. The pharmacokinetic profile of the 50mg dose is approximately dose proportional to the 25 mg dose. The next dose levels are expected to produce plasma concentrations associated with consistently high inhibition of BTK. Vecabrutinib inhibition of BTK phosphorylation was rapid and sustained in the 5 patients who had adequate baseline signal for analysis. Decreases in serum concentrations of key cytokines associated with B-cell malignancies, CCL2, CCL3, and CCL4, were also observed in 7 patients, consistent with inhibition of BTK signaling.

17:20 EDT Kura announces Proof of Concept in Angioimmunoblastic T-Cell Lymphoma - Kura Oncology reported preliminary data in angioimmunoblastic T-cell lymphoma and CXCL12+ peripheral T-cell lymphoma, the two expansion cohorts in its Phase 2 clinical trial of its lead drug candidate tipifarnib in patients with relapsed or refractory PTCL. The data, presented at the American Society of Hematology Annual Meeting, showed encouraging activity with tipifarnib in late-stage PTCL patients, including a significant association between CXCL12 expression and clinical benefit, and proof of concept in AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression. As of November 21, 2018, a total of 39 patients were enrolled in the ongoing Phase 2 trial, including 19 patients with AITL. Six of the 16 AITL patients were not evaluable as of the data cutoff date, including two who were pending initial efficacy assessments. Of the 13 evaluable AITL patients, two achieved a complete response (CR) and four achieved a partial response, for an objective response rate of 46%. According to the study protocol, the AITL cohort is considered positive when four or more responses are observed.The study also identified a particularly responsive subset within AITL and non-AITL patients. Specifically, patients with a high ratio of expression of CXCL12 to its receptor CXCR4 experienced a 50% ORR (five of 10) and a 90% clinical benefit rate with tipifarnib. Patients in this Phase 2 trial had a median of three prior lines of therapy. The high CXCL12/CXCR4 expression ratio had 90% sensitivity and 93% specificity to identify PTCL patients likely to benefit from tipifarnib.In addition to the Phase 2 clinical data, the results from two ancillary, non-clinical studies were also reported at ASH. In the first, the expression of CXCL12 and CXCR4 was investigated using tumor bank samples of PTCL patients treated with standard-of-care agents. Worse prognosis was observed in PTCL patients with high CXCL12/CXCR4 expression ratio, indicating that CXCL12 is a negative prognostic factor for standard PTCL therapy. In the second study, the effect of the incubation of stroma cells with tipifarnib on CXCL12 secretion was investigated in a mouse model of bone marrow culture. Tipifarnib reduced secretion of the CXCL12 chemokine from the stromal cells, providing a potential mechanism of action for the observed clinical activity. The Phase 2 study was designed to investigate the anti-tumor activity of tipifarnib in patients with relapsed or refractory PTCL. After preliminary data suggested that CXCL12 expression was associated with tipifarnib's clinical activity, two expansion cohorts were added to enroll patients with tumors expected to overexpress CXCL12: AITL tumors, and those non-AITL tumors that lack a single nucleotide variation in the 3'-untranslated region of the CXCL12 gene. CXCL12 is a stroma-derived chemokine that promotes the progression of lymphoma and other hematological and solid tumors carrying the CXCR4 receptor, and our previous results had suggested an association between CXCL12 expression and the most common form of the 3'-UTR CXCL12 variant. In the expansion cohorts, both the presence or absence of this variant and the expression levels of CXCL12 and CXCR4 were assessed. In the expansion cohorts in the Phase 2 trial tipifarnib was dosed at 300 mg twice daily on days 1-21 of a 28-day cycle. The reported data indicated that tipifarnib was generally well-tolerated, with adverse events consistent with its known safety profile. The most common treatment-related adverse events were hematology-related, including neutropenia, thrombocytopenia, leukopenia, febrile neutropenia and anemia. Last week, the U.S. Patent and Trademark Office issued a new patent for tipifarnib as a method of treating patients with AITL. In May 2018, the USPTO issued a patent for tipifarnib as a method of treating patients with certain CXCL12-expressing cancers, including PTCL. Both patents expand protection for tipifarnib, providing exclusivity in the U.S. to 2037.

17:13 EDT Seattle Genetics highlights additional analyses from ECHELON-1 Phase 3 trial - Seattle Genetics highlighted data from the ECHELON-1 phase 3 clinical trial evaluating ADCETRIS in combination with AVD in newly diagnosed stage III or IV classical Hodgkin lymphoma at the 60th American Society of Hematology Annual Meeting and Exposition. Three poster presentations highlight analyses from the ECHELON-1 phase 3 clinical trial evaluating ADCETRIS in combination with AVD compared to ABVD in stage III or IV frontline classical HL patients. As previously reported, the ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by independent review facility. Modified PFS was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy per IRF followed by subsequent anticancer therapy. An analysis was conducted to examine PFS outcomes at three-years and evaluate how the inclusion of subsequent therapy as modified events affected efficacy outcomes in the ECHELON-1 study. After a median follow-up time of 37.1 months, the three-year PFS rate per investigator for patients in the ADCETRIS plus AVD arm was 83.1% compared to 76.0% in the control arm. After a median follow-up time of 24.7 months, the assessment of two-year PFS per investigator, including subsequent chemotherapy in patients who were not in a complete response at the end of frontline treatment, in the ADCETRIS plus AVD arm was 84.0% compared to 77.3% in the control arm. After a median follow-up time of 24.7 months, the assessment of two-year traditional PFS per investigator in the ADCETRIS plus AVD arm was 84.2% compared to 78.0% in the control arm. The safety profile of ADCETRIS plus AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen. Per IRF, AYA treated with ADCETRIS plus AVD showed a positive trend towards improved modified PFS and consistent benefit across all age subgroups compared with patients in the ABVD arm. The two-year modified PFS per IRF for patients age 40 or less who received ADCETRIS plus AVD was 84.6% compared to 78.6% who received ABVD. Patients age 30 or less who received ADCETRIS plus AVD had improved modified PFS compared with patients treated with ABVD. Traditional PFS by investigator was consistent with the modified PFS outcomes across all age subgroups. The rate of adverse events in patients receiving ADCETRIS plus AVD or ABVD was similar across age groups and consistent with the previously reported rate of adverse events for the ECHELON-1 intent to treat population. As previously reported in the ECHELON-1 study, the incidence of peripheral neuropathy of any grade was 67% and 43% in the ADCETRIS plus AVD and ABVD arms of the study, respectively. At the time of primary analysis and with a median follow-up time of approximately 21 months, 67% of patients treated with ADCETRIS plus AVD had either complete resolution or improvement of peripheral neuropathy events by at least one grade at the time of last follow-up. An updated analysis of peripheral neuropathy outcomes from the ECHELON-1 study at a median follow-up time of 30 months include: After continued follow-up at a median of 30 months, peripheral neuropathy was either completely resolved or improved in 335 out of 442 patients in the ADCETRIS plus AVD arm and 234 out of 286 patients in the ABVD arm. For patients whose peripheral neuropathy had not resolved by end of treatment, the median time to resolution of all peripheral neuropathy events was 28 weeks for ADCETRIS plus AVD arm and 14 weeks for the ABVD arm. In the patients who experienced peripheral neuropathy, 10% and 4% discontinued treatment due to peripheral neuropathy in the ADCETRIS plus AVD arm and ABVD arm, respectively. For both study arms, peripheral neuropathy was generally manageable and reversible, and the majority of ongoing peripheral neuropathy was Grade 1/2.

17:00 EDT Celgene announces initial Phase 1/2 liso-cel data in Relapsed/Refractory CLL - Celgene announced initial data from the dose-escalation part of an ongoing, open-label multicenter phase 1/2 study of investigational lisocabtagene maraleucel in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, including patients with cytogenetic features of high-risk disease, who were previously treated with ibrutinib. Data presented from TRANSCEND CLL-004 include 16 patients from the ongoing phase 1 monotherapy dose-escalation part of the study. The median number of lines of prior therapy was 4.5, and 75% of patients had high-risk cytogenetic features. All patients had previously received treatment with ibrutinib, 81% had relapse/refractory disease on ibrutinib and 50% received prior treatment with ibrutinib and venetoclax. Following lymphodepletion with fludarabine and cyclophosphamide for three days, patients received liso-cel at dose level 1 or dose level 2. The overall response rate, which was an exploratory objective, was 81%, with 43% of patients demonstrating a complete response. As of September 2018, five patients have six-month follow-up and all have maintained a response and undetectable minimal residual disease in the blood as measured by flow cytometry. The median time-to-peak expansion was 16 days, and CAR+ T cells remained detectable in patients at three months. The most common treatment-emergent adverse events reported included anemia, thrombocytopenia, cytokine release syndrome, neutropenia, leukopenia, hypokalemia, pyrexia, lymphopenia, nausea, diarrhea, febrile neutropenia, headache, insomnia, and tremor. One patient experienced grade 3 cytokine release syndrome and three patients experienced grade 3 neurologic events. No patients experienced grade 4 cytokine release syndrome or neurologic events. Liso-cel is not approved in any country.

16:48 EDT Zogenix presents positive findings on impact of treatment with FINTEPLA - Zogenix announced results from a post-hoc analysis of its investigational drug, FINTEPLA, on caregiver-reported everyday executive function in children and young adults with Dravet syndrome, who participated in the company's first pivotal Phase 3 clinical trial, Study 1. In Study 1, of the 119 total patients in the trial, 77 patients, aged 5-18 years, were assessed using the Behavior Rating Inventory of Executive Function scale. The BRIEF scale was developed to assess everyday executive function in the home and school environments for children and young adults from 5-18 years of age. The data from Study 1 were mapped to the BRIEF2 scale, which is a more current, validated version with more stable and sensitive scales for assessing changes related to everyday executive function. Patients were randomized to one of three treatment groups: FINTEPLA 0.8 mg/kg/day, FINTEPLA 0.2 mg/kg/day or placebo. Using the BRIEF2 scale, Reliable Change Index scores were calculated to evaluate whether changes from baseline to end of study in individual scores were clinically meaningful or were changes greater than expected due to measurement error, practice effects, and other factors, such as age. Following 14 weeks of treatment, patients treated with FINTEPLA experienced clinically meaningful improvement on the Behavior Regulation and Emotion Regulation Indexes compared with those in the placebo group. A significantly greater proportion of patients in the pooled FINTEPLA treatment group also showed benefit on the Plan/Organize scale of the Cognitive Regulation Index compared with the placebo group. No significant, clinically meaningful differences were observed among the treatment groups for worsening of everyday executive function. Two other presentations at AES include new analyses of data from the Sibling Voices Survey, which was developed by Zogenix to assess the emotional impact of growing up with a sibling with severe childhood epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Both analyses involved anonymous sibling and parent respondents representing 107 families of patients with EE, and these new findings again underscore the need to address disease burden on the family in addition to the patient. The first analysis evaluated the psychosocial concerns of siblings growing up with a brother or sister with a severe EE. Young siblings reported feelings of guilt, resentment, and jealousy toward their sibling. Most adult siblings expressed concern over the psychological/emotional toll of caring for their affected sibling should care transition from their parents to themselves. A second analysis compared parental perception to that of siblings on quality of life and mood symptoms. There was a more than two-fold difference between parental perception and siblings' responses on items regarding "sadness about the sibling's diagnosis," "not getting enough attention from mom and dad," and "how stressed are you over your sibling's diagnosis." As previously reported, Study 1 met its primary objective demonstrating that FINTEPLA, at a dose of 0.8 mg/kg/day, was superior to placebo as adjunctive therapy in the treatment of Dravet syndrome in children and young adults based on change in the frequency of convulsive seizures.

16:19 EDT Autolus Therapeutics announces update on novel CAR T cell program for PTCL - Autolus Therapeutics announced that the first patient has been dosed in its Phase 1/2 LibrA T1 clinical trial of AUTO4, a developmental therapy for the treatment of relapsed or refractory TRBC1-positive peripheral T cell lymphoma. In addition, the company also announced that data on the preclinical sister program, AUTO5 targeting TRBC2-positive lymphoma, were presented at the 60th American Society of Hematology Annual Meeting. Autolus' T cell program comprises a companion diagnostic to determine whether the PTCL is TRBC1- or TRBC2-positive and two novel CAR T cell product candidates AUTO4 and AUTO5. On December 2 at the 60th ASH Annual Meeting in San Diego, the company presented data from preclinical studies of AUTO5 targeting TRBC2. TRBC1 and TRBC2 are virtually identical in sequence, and antibody binders had to be designed to differentiate TRBC1 from TRBC2 extracellular domains by selectively recognizing a single inversion of two amino acids. Employing a structural biology approach and molecular modelling techniques, a binder was generated that could bind TRBC2 without binding to TRBC1, and when included in a CAR T approach, selectively eliminated TRBC2-positive cells. The LibrA T1 trial is a single-arm, open label, multi-center, Phase 1/2 trial evaluating the safety and efficacy of AUTO4, a single dose intravenous CAR T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1-positive selected PTCL. The trial will consist of a Phase 1 portion, or dose escalation phase, and a Phase 2 portion, or expansion phase. The Phase 1 portion of the trial, which is expected to enroll up to 25 patients, is designed to evaluate up to three dose levels, beginning with a low dose of 25 million AUTO4 cells in cohorts of three to six patients. If no dose limiting toxicities are observed, the dose escalation phase of the trial will continue to higher doses of 75 million AUTO4 cells and 225 million AUTO4 cells. Once a recommended dose has been identified in the Phase 1 portion of the trial, up to 30 patients will be enrolled and treated in the Phase 2 portion. AUTO4 is a programmed T cell therapy product candidate being developed to leverage a new targeting approach based on the mutually exclusive expression of two subtypes of the T cell receptor beta chain: AUTO4 targets TRBC1, while another of the company's product candidates in development, AUTO5, targets TRBC2. Normal T cells contain both TRBC1 and TRBC2 compartments, whereas T cell lymphoma cells are derived from mature cells and express only TRBC1 or TRBC2. A companion diagnostic is used to identify if the T cell lymphoma is TRBC1 or TRBC2 positive. Unlike non-selective approaches targeting the entire T cell population that can lead to severe immunosuppression, this approach has the potential to eradicate a portion of T cells containing the malignancy, while preserving a healthy T cell sub-population to preserve cellular immunity.

13:41 EDT BeiGene announces results of Zanubrutinib in Mantle Cell Lymphoma - BeiGene announced the presentation of clinical data from two ongoing trials of its investigational Bruton's tyrosine kinase inhibitor, zanubrutinib, in patients with mantle cell lymphoma. The presentations were made at the 60th Annual Meeting of the American Society of Hematology. Results from the pivotal Phase 2 trial of zanubrutinib in Chinese patients with relapsed or refractory MCL were featured in an oral presentation, while updated results from the global Phase 1 trial of zanubrutinib in patients with multiple subtypes of B-cell malignancies, including treatment naive and R/R MCL, were featured in a poster presentation. Zanubrutinib is being studied in several clinical trials as part of a broad development program and was granted Fast Track Designation by the U.S. Food and Drug Administration for the treatment of patients with Waldenstrom macroglobulinemia. BeiGene plans to submit an initial NDA to the FDA for zanubrutinib in 2019 or early 2020. The NDAs in China for R/R MCL and R/R chronic lymphocytic leukemia/small lymphocytic lymphoma have been accepted by the National Medical Products Administration and the MCL filing has been granted priority review. The single arm, open-label, multi-center, pivotal Phase 2 trial of zanubrutinib as a monotherapy in Chinese patients with R/R MCL enrolled 86 patients who had received a median of two prior lines of therapy. Patients were treated with zanubrutinib, dosed at 160 mg orally twice-daily. The primary endpoint of the trial was overall response rate assessed by independent review committee using PET-based imaging according to the Lugano Classification 2014. As of March 27, 2018, 85 patients with R/R MCL were evaluable for efficacy and 65 patients remained on study treatment. The median follow-up time for patients enrolled in the trial was 35.9 weeks. Results included: The ORR by IRC was 83.5%; the complete response rate was 58.8% and the partial response rate was 24.7%; The 24-week progression-free survival was estimated at 82%. The median PFS had not yet been reached; With 24.1 weeks median follow-up, the median duration of response had not yet been reached and 90% of responders were still in response at 24 weeks; Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and the majority of adverse events were grade 1 or 2 in severity. The most frequent AEs of any attribution were neutrophil count decreased, rash, upper respiratory tract infection, and platelet count decreased; The most frequently reported grade 3 or higher AEs were neutrophil count decreased and lung infection; Four patients had treatment emergent adverse events leading to death; and among events of special interest for BTK inhibitors, diarrhea was observed in nine patients, all grade 1-2. Major hemorrhage was observed in 1 patient with blastoid variant of MCL who had intra-parenchymal CNS bleeding. No cases of atrial fibrillation/flutter were reported in this trial. Meanwhile, the open-label Phase 1 trial of zanubrutinib as a monotherapy in patients with different subtypes of B-cell malignancies, including MCL, is being conducted in Australia, New Zealand, the U.S, Italy, and South Korea. As of July 24, 2018, 48 patients with TN or R/R MCL have been enrolled in the trial and the median follow-up time was 12.7 months. 45 patients including six with TN and 39 with R/R MCL, were evaluable for efficacy in this analysis, per the Lugano 2014 classification. At the time of the data cutoff, 26 patients remained on study treatment. Updated results included: The ORR by investigator was 88.9%; the CR rate was 26.7% and the PR rate was 62.2%. The majority of patients were assessed via CT-scan; PET scans were optional per trial protocol; The median DOR was 16.2 months and the median PFS for R/R patients was 18.0 months; Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and the majority of AEs were grade 1 or 2 in severity. Grade 3-5 AEs occurred in 56.3% of patients. Grade 3-5 AEs of any attribution reported in greater than three patients included anemia, major hemorrhage, cellulitis, myalgia, neutropenia, pneumonia; and thrombocytopenia; Discontinuation due to AEs occurred in 18.8% of patients with all but one event determined to be unrelated to study drug; and there were four deaths due to AEs, which were all determined by the investigators to be unrelated to zanubrutinib treatment.

13:00 EDT Bluebird Bio presents updated data from clinical studies of LentiGlobin - Bluebird Bio announced new long-term data from the completed Phase 1/2 Northstar study of investigational LentiGlobin gene therapy in patients with transfusion-dependent beta-thalassemia and from the ongoing Phase 1/2 HGB-206 study of LentiGlobin in patients with sickle cell disease at the 60th Annual Meeting of the American Society of Hematology. The results reported for the completed Phase 1/2 Northstar study reflect data as of September 14, 2018. After treatment with LentiGlobin, patients are monitored for production of HbAT87Q, which is gene therapy derived-hemoglobin. The production of HbAT87Q increases the overall hemoglobin level in patients with the goal of reducing or eliminating the need for transfusions. Data showed that eight of 10 patients with TDT and a non-beta0/beta0 genotype who were treated with LentiGlobin in the Northstar study achieved transfusion independence, meaning they had not received a transfusion for at least 12 months and maintained hemoglobin greater than9 g/dL. These eight patients have maintained transfusion independence for a median duration of 38 months as of September 14, 2018. Total hemoglobin levels for the eight transfusion-independent non-beta0/beta0 genotype patients were stable and ranged from 9.7 - 14.1 g/dL at the last study visit. HbAT87Q remained stable in these patients over time, for up to four years as of the time of data cut-off. Three of the eight patients with TDT and a beta0/beta0 genotype who were treated with LentiGlobin achieved transfusion independence. Two of these patients had follow-up for more than 3.5 years and one had more than two years of follow up. All three maintained transfusion independence through their last follow up with hemoglobin ranging from 9.1 - 10.9 g/dL. An exploratory assessment was conducted to assess liver iron concentration in the 11 patients who have become transfusion independent in the Northstar study. Increased iron levels are a consequence of frequent transfusions. High iron levels can cause organ damage, which many TDT patients are at risk for and must manage through chelation regimens. Liver iron concentrations were measured at baseline and then at every 12 months after treatment. Over time, iron concentrations began to decrease in the 11 patients, with the largest decrease observed in patients who had 48 months of data available. The safety profile of LentiGlobin treatment in adults and adolescents with TDT in the Northstar study was generally consistent with myeloablative conditioning. The median time to platelet engraftment was 39.5 days. In the Phase 3 Northstar-2 and Northstar-3 studies, a refined manufacturing process was used to produce LentiGlobin to further improve the clinical results observed in the Northstar study. The Phase 1/2 HGB-206 study is an ongoing, open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for the treatment of adults with SCD. A total of nine patients were treated with LentiGlobin in Groups A and B in the HGB-206 study. As of the data cut-off date of September 14, 2018, there was up to 39 months of follow-up for the seven patients in Group A and up to 17 months of follow-up for the two patients in Group B. In Group A patients, consistent HbAT87Q production was observed ranging from 0.7 - 2.8 g/dL at last visit and patients maintained stable total hemoglobin levels ranging from 7.6 - 11.8 g/dL at last visit. HbAT87Q production was higher in Group B patients, ranging from 3.4 - 6.5 g/dL and total hemoglobin levels were stable at 11.0 - 12.3 g/dL at the last visit. These higher rates of total hemoglobin and HbAT87Q production in Group B are attributed to the implementation of a refined drug product manufacturing process and protocol modifications to improve engraftment of genetically modified stem cells. In all patients who received LentiGlobin treatment, frequency of VOEs was reduced. The safety profile of LentiGlobin remains generally consistent with underlying SCD and myeloablative conditioning. A serious adverse event of myelodysplasia syndrome was reported in a patient who received LentiGlobin approximately three years ago in Group A of the Phase 1/2 HGB-206 study. Analysis of the patient's cells showed no evidence of vector mediated insertional oncogenesis, and the independent data monitoring committees, along with the treating physician, agreed the SAE was unlikely related to LentiGlobin gene therapy. In order to further improve the clinical results observed in Groups A and B, in addition to the refined manufacturing process introduced in Group B, plerixafor mobilization and apheresis-derived hematopoietic stem cells were used to produce LentiGlobin for Group C of the Phase 1/2 HGB-206 study.

12:48 EDT Tegna, Dish reach multi-year carriage agreement - Tegna (TGNA) said it has reached a multi-year carriage agreement with Dish (DISH). All Tegna stations will return to the Dish lineup effective immediately.

12:43 EDT Regeneron presents positive data at for REGN1979 CD20xCD3 bispecific antibody - Regeneron Pharmaceuticals presented new data for REGN1979 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including promising clinical results in follicular lymphoma and diffuse large B-cell lymphoma which are the two most common types of NHL. In this Phase 1 proof-of-concept trial, REGN1979 demonstrated an acceptable safety and tolerability profile with no observed dose-limiting toxicities. There were no clinically-significant neurotoxicities, including no occurence of seizures or encephalopathy. REGN1979 is a wholly-owned, investigational, full-length bispecific monoclonal antibody designed to trigger tumor killing by binding CD3 on immune system T-cells and CD20 on B-cell malignancies. In the data presented at the 2018 American Society of Hematology Annual Meeting, heavily pre-treated patients with R/R FL grades 1 to 3a who received REGN1979 doses of 5 mg to 40 mg, experienced a 100% overall response rate; 90% of responders maintained a response during treatment. Based on these data, Regeneron plans to initiate in 2019 a potentially registrational Phase 2 trial investigating REGN1979 in R/R FL. REGN1979 also showed encouraging dose-dependent clinical activity in heavily pre-treated patients with R/R DLBCL. Among patients receiving doses between 5 mg and 12 mg, the ORR was 18%. At doses of 18 mg to 40 mg, the ORR increased to 60%. Regeneron plans to continue dose-escalation in DLBCL. The objectives for this ongoing Phase 1 proof-of-concept trial are to assess safety, tolerability and efficacy of REGN1979 monotherapy. The data presented at ASH included a total of 68 patients with R/R B-NHL who were treated with REGN1979. These patients had received a median of three prior therapies, including an anti-CD20 therapy. As of September 2018, 14 patients had completed treatment, 13 patients remained on treatment and 41 had discontinued treatment. The most common reason for treatment discontinuation was progressive disease. Two patients discontinued treatment due to a treatment-emergent adverse event. In the trial, the most common TEAEs occurring in at least 25% of patients were pyrexia, chills, cytokine release syndrome, fatigue, increased C-reactive protein, anemia, hypotension, infusion-related reaction and nausea. IRR and CRS events were generally mild to moderate in severity, and neither resulted in trial discontinuations. Three patients in the trial died due to adverse events. Of these, one death, in a patient with a tumor involving the gastric lining who experienced a gastric perforation, was attributed to REGN1979.

12:35 EDT Bellicum announces favorable interim event-free survival data for rivo-cel - Bellicum Pharmaceuticals announced late interim results from its BP-004 European registration trial, suggesting that adding rivo-cel to stem cell transplants in patients who lack a matched donor may deliver comparable outcomes to matched unrelated donor transplants. The data were reviewed in a presentation at the 60th Annual Meeting of the American Society of Hematology. The interim data show a 90.9% event-free survival rate at 180 days for patients treated with rivo-cel after a stem cell transplant from a haploidentical, or partially matched, donor. These results appear comparable to an interim evaluation of patients who received a MUD transplant in the concurrently-run observational study, demonstrating an 87.7% EFS rate at 180 days. The company expects to report final comparison results from both study populations and file for approval in Europe in 2019. Demonstrating non-inferiority to MUD transplantation is the primary study objective required for rivo-cel product registration in Europe.

12:29 EDT Catalyst announces positive data from Phase 2/3 study of Marzeptacog Alfa - Catalyst Biosciences announced additional positive interim data from its Phase 2/3 study of subcutaneous prophylactic Factor VIIa variant marzeptacog alfa, currently being developed for the treatment of hemophilia A or B with inhibitors. The data were presented in a poster at the 60th American Society of Hematology Annual Meeting and Exposition. The updated results included the new data from two additional subjects who have completed the Phase 2/3 MarzAA trial. The first subject, who had an annualized bleed rate of 15.2, had no bleeds during 50 days of treatment with 30 microg/kg MarzAA. The second subject, who had an ABR of 22.2, experienced a bleed on Day 4 that did not require treatment. The subject continued on the 30 microg/kg dose level, as the bleed occurred within the first five days of dosing when FVIIa levels are still increasing to therapeutic levels and completed the trial with no additional bleeds during the treatment period. To date, 13 subjects have consented and five have completed dosing in the Phase 2/3 MarzAA trial. These five subjects had an ABR range of 15.2-26.7 before MarzAA treatment. Three participants experienced no bleeds with individualized dosing of either 30 microg/kg or 60 microg/kg MarzAA and two others had clinically significant reductions in ABR. The median proportion of days with bleeding during the pre-study period was 11.9% and this was significantly reduced to a median of 0.5% during the treatment period. Through a total of more than 300 days of subcutaneous dosing, no injection site reactions or anti-drug antibodies to MarzAA have been detected. In one subject, two subcutaneous injections resulted in a mild localized hematoma that resolved without sequelae or treatment. Final data from the study are expected in the first half of 2019.