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20:28 EST Fly Intel: Top five weekend stock stories - Catch up on the weekend's top five stories with this list compiled by The Fly: 1. Chick-fil-A, the largest U.S. chicken-restaurant chain, sued Tyson Foods (TSN) and several other top American poultry producers, accusing them of illegally coordinating with one another to keep prices high, Bloomberg's Michael Hirtzer reported. Chick-fil-A is the latest to join in the years-long antitrust litigation accusing poultry companies of fixing prices beginning in 2008 and continuing for about a decade, the author notes. Target (TGT) filed also filed a lawsuit this month, joining others including grocer Fresh Market and convenience-store chain Wawa. Named in the latest complaint are the top three U.S. chicken makers - Tyson, Pilgrim's Pride (PPC) and Sanderson Farms (SAFM) - as well as others, the publication added. 2. Pfizer India has applied to India's drug regulator for emergency-use authorization for its COVID-19 vaccine, after the company's parent received clearance for the treatment from Britain and Bahrain, Bloomberg's Baiju Kalesh wrote, citing Press Trust of India. Pfizer (PFE) is the first drugmaker to seek the approval in India and submitted the application on Dec. 4, the report said. 3. Airbnb (ABNB) could be one of the hottest initial public offerings of the year, Andrew Bary wrote in this week's edition of Barron's. With its asset-light business model and global presence, the company is poised to benefit from a rebound in travel, the author noted. While the proposed market value of Airbnb - around $30B at the top of the proposed pricing range of $44-$50 a share - isn't cheap, valuation looks reasonable given the company's market position, scarcity value, brand power, and global opportunity at a time when investors regularly value exciting growth companies at considerably more than 10 times annual sales, Bary added. 4. JD.com (JD), China's second-biggest online retailer, will become the country's first virtual mall to use digital yuan, the cryptocurrency backed by the central bank, according to Bloomberg. JD Digits, the e-commerce giant's fintech affiliate, will launch a pilot program this month, and customers will pay for certain items with digital yuan, it said on its official WeChat account. 5. DoorDash (DASH) was mentioned cautiously in this week's edition of Barron's.

19:54 EST Antengene announces IND acceptance in China for ATG-010 in combo with R-GDP - Antengene announced that the National Medical Products Administration has accepted the Investigational New Drug application for ATG-010 combined with R-GDP for the treatment of relapsed/refractory diffuse large B-cell lymphoma. The trial is a global Phase 2/3, multicenter, randomized study aiming to evaluate the safety and efficacy of ATG-010 in combination with R-GDP in patients with rrDLBCL. ATG-010 is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics. In July 2019, the U.S. Food and Drug Administration approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma. After its initial approval of rrMM, FDA approved ATG-010 as a single-agent for the treatment of rrDLBCL in June 2020. In China, Antengene is conducting a registrational Phase 2 clinical trial to evaluate the efficacy and safety of ATG-010 in the treatment of patients with rrDLBCL who have received at least 2 but no more than 5 previous systemic regimens and the first patient was dosed in April 2020. The Phase 2 part of the study aims to identify the optimal dose of ATG-010 in combination with R-GDP and will also evaluate the SR-GDP regimen against an active R-GDP comparator arm. The Phase 3 part of the study contains three arms and aims to evaluate the selected optimal dose of ATG-010 in combination with R-GDP for up to 6 cycles followed by continuous ATG-010 until disease progression versus the selected optimal dose of ATG-010 in combination with R-GDP for up to 6 cycles followed by placebo until disease progression and versus standard R-GDP with matching placebo for up to 6 cycles followed by placebo until disease progression. The study will be conducted at multiple international centers across 11 countries, including China, U.S., Europe, Australia and other countries. Up to 501 patients will be enrolled and treated in the Phase 2/3 study.

19:48 EST Xencor presents updated data from Phase 1 study Vibecotamab in AML - Xencor announced updated data from its ongoing Phase 1 dose-escalation study of vibecotamab, a CD123 x CD3 bispecific antibody, in patients with relapsed or refractory acute myeloid leukemia. The data were presented in an oral session at the 62nd American Society of Hematology Annual Meeting. At data cut off on October 28, 2020, 112 patients with relapsed or refractory AML had received vibecotamab. Patients were a median of 64 years old and were heavily pretreated, having had a median of three prior therapies and 30% with a history of allogeneic hematopoietic stem cell transplantation. 86% of patients were refractory to their last therapy, and 62% were categorized as adverse risk at diagnosis by the European LeukemiaNet system. The study is ongoing, and additional patients are being enrolled. Cytokine release syndrome was the most common toxicity occurring in 61% of patients, and 9% of patients experienced CRS at Grade 3 or higher. The majority of CRS was observed in the first dose and was generally manageable with premedication. Additional mitigation measures included selecting a lower priming dose, avoiding weekly dose step-up, and more frequent dosing in the first week to allow a higher cumulative exposure and to avoid the potential CD123 antigen sink. There was no evidence of drug related myelosuppression. Neurological events were infrequent and primarily Grade 1 and Grade 2 headaches. The efficacy analysis included 54 evaluable patients who received a dose of at least 0.75 mcg/kg, completed at least the first cycle of treatment and had at least one post-treatment disease assessment. Two patients achieved complete remission, and three patients achieved a CR with incomplete hematologic recovery. Additionally, two patients reached a morphologic leukemia-free state, and one patient experienced partial remission, as assessed by the investigator. The overall response rate was 15%. Biomarker analyses suggest that low baseline leukemic burden and low PD-1 expression on CD4+ and CD8+ T cells are independent predictors of response. Seven responders had a baseline blast count less than or equal to 25% blasts in bone marrow. The ORR increased to 26% when using this threshold to define the population with low disease burden for the analyses.

19:43 EST Protagonist announces updated results from ongoing Phase 2 study of PTG-300 - Protagonist Therapeutics announced additional updated results from the ongoing Phase 2 study of PTG-300 in patients with polycythemia vera, demonstrating dramatic decreases in the need for therapeutic phlebotomy in patients with PV, while maintaining control over blood hematocrit levels. The data were presented in an oral presentation today at the 62nd American Academy of Hematology annual meeting, being held December 5-8, 2020. Of the 18 PV patients treated with PTG-300, the vast majority were able to eliminate therapeutic phlebotomies and maintain a target hematocrit level of less than 45%. Treatment with PTG-300 was also shown to reverse iron deficiency, a serious side effect of regular therapeutic phlebotomies as a treatment for PV. Early observations suggest a decreased symptom burden over time, including overall burden, as well as measurements specific to mental function, fatigue and itching. Administration of PTG-300 was well tolerated, with injection site reactions and bruise as the only observed adverse events. The ongoing Phase 2 PTG-300 polycythemia vera study is designed to monitor the safety profile and obtain evidence of efficacy in approximately 50 patients requiring frequent phlebotomies. The study design consists of three stages: a 16-week open-label stage with dose escalation, reduction, or maintenance every four weeks from 10 mg to 80 mg by subcutaneous administration at weekly intervals, a 12-week maintenance period at doses that generate desired hematocrit levels, and then a randomized and blinded withdrawal stage for up to 12 weeks. The study also has an open-label extension for up to one year to monitor long-term safety and other effects. The primary endpoint is the control of hematocrit below 45 percent during the blinded randomized withdrawal period. Other endpoints of this clinical proof-of-concept study include measurement of blood parameters, reductions or delay in phlebotomy requirements, and symptoms related to quality of life.

18:22 EST MacroGenics presents flotetuzumab data in patients with refractory AML - MacroGenics announced updated results from a single-arm, registrational study of flotetuzumab, an investigational, bispecific CD123 CD3 DART molecule, in patients with primary induction failure and early relapsed acute myeloid leukemia. The data were presented at the 62nd Annual Meeting of the American Society of Hematology taking place December 5-8, 2020. In the open label study of flotetuzumab, 44 AML patients had disease classified as either PIF or ER6. Of these patients, 72.7% had adverse risk cytogenetics by ELN Risk Stratification. Patients were treated with flotetuzumab at the recommended Phase 2 dose of 500 ng/kg/day by continuous infusion. Data were reported as of the cut-off date of November 10, 2020. The study is currently ongoing, with a total of up to 200 patients planned for enrollment for registrational purposes. The median time to achieve a response to flotetuzumab was one cycle. The most common treatment-related adverse event was infusion-related reaction/cytokine release syndrome, which occurred in all patients. However, most CRS events observed were of short duration and mild to moderate in severity, with only a single Grade 3 event reported.

18:17 EST CTI presents data on Pacritinib potential benefit in preventing acute GVHD - CTI BioPharma announced an oral presentation supporting the company's pacritinib development program in the prevention of acute graft versus host disease at the 62nd American Society of Hematology Annual Meeting & Exposition, being held virtually December 5-8, 2020. The results are from an investigator-sponsored Phase 1/2 study conducted at the Mayo Clinic and Moffit Cancer Center. Results from an investigator-sponsored Phase 1/2 study of GVHD prophylaxis for allogeneic hematopoietic cell transplantation using pacritinib, sirolimus, low-dose tacrolimus were being presented Sunday in an oral presentation session. This single-arm Phase 1/2 study tested the safety, pharmacodynamics and efficacy of pacritinib when administered with sirolimus plus low-dose tacrolimus after alloHCT. A 3+3 dose escalation design was planned using three doses of pacritinib in combination with standard sirolimus and low-dose tacrolimus immunosuppressive therapy. Efficacy endpoints included acute GVHD rate at day 100. PAC 100 mg twice daily, dose level 2, was selected as the recommended Phase 2 dose based on its biological activity and safety profile. Preliminary evidence of the benefit of adding pacritinib to standard immunosuppressive therapy in reducing the rates of aGVHD was reported, with a 25% rate of grade 2-4 aGVHD across all dose cohorts, and 17% at the recommended Phase 2 dose of 100 mg BID, as compared to grade 2-4 aGVHD incidence rate of 43% expected with sirolimus plus low-dose tacrolimus administered alone1. No compromise in alloHCT outcome or major safety concerns were observed. Futher, there was no evidence of cytopenias, impaired immune reconstitution, or cytomegalovirus reactivation. A Phase 2 clinical trial to fully evaluate efficacy in GVHD prevention is ongoing.

18:05 EST Gilead announces updated results from magrolimab Phase 1b trial - Gilead Sciences announced updated results from the magrolimab Phase 1b trial. Magrolimab is an investigational, potential first-in-class, anti-CD47 monoclonal antibody being studied in previously untreated acute myeloid leukemia patients who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML. The study continues to demonstrate high response rates with magrolimab in combination with azacitidine, with an overall response rate of 63% among the total patient population and 69% in TP53-mutant patients. The data were presented at the 62nd American Society of Hematology Annual Meeting and Exposition. In the study, 64 patients were treated with magrolimab plus azacitidine, including 47 patients with the TP53 mutation, a treatment-refractory and poor-prognosis population. As of November 2020, 63% of patients evaluable for efficacy achieved an objective response per European LeukemiaNet 2017 criteria, 42% achieved a complete remission, and 12% achieved a CR with an incomplete count recovery. The median duration of response was 9.6 months and the median time to response was 1.95 months. For patients with the TP53 mutation, 69% achieved a response, 45% achieved a CR and 14% achieved a CRi. The median DOR was 7.6 months and the minimum residual disease negativity in patients with a CR/CRi was 29%. Preliminary median overall survival for TP53-wild-type patients was 18.9 months and for TP53-mutant patients was 12.9 months. The median follow-up for TP53-wild-type and TP53-mutant patients was 12.5 months and 4.7 months, respectively. Additional patients and longer follow-up in a comparative trial are needed to further characterize the survival benefit. Treatment-related adverse events observed with over 15% incidence included anemia, fatigue, blood bilirubin increased, infusion related reaction, neutropenia, thrombocytopenia and ALT increase. Most patients were cytopenic at baseline, and no significant increased cytopenias, infections or immune-related adverse events were observed in the study. Thirty-day all-cause mortality was 4.7%, and 60-day mortality was 7.8%. Treatment discontinuation due to drug-related AE occurred in 4.7% of all patients.

17:57 EST Fate presents patient case study from Phase 1 clinical trial of FT596 - Fate Therapeutics presented a patient case study from the company's Phase 1 clinical trial of FT596, its universal, off-the-shelf, CD19-targeted chimeric antigen receptor natural killer cell product candidate, at the 62nd Annual Society of Hematology Annual Meeting and Exposition. The case study described a heavily pre-treated patient with diffuse large B-cell lymphoma who achieved a partial response following administration of a single-dose treatment cycle of FT596 as a monotherapy in the first dose cohort of 30 million cells. The patient subsequently received a second single-dose treatment cycle of FT596, which resulted in a deepening response as evidenced by further decrease in both tumor size and metabolic activity. No dose-limiting toxicities, no FT596-related serious adverse events, and no events of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by the investigator. The patient had previously received seven prior treatment regimens, including five rituximab-containing regimens as well as autologous stem cell transplantation, and was most recently refractory to an experimental cellular therapy. The open-label, multi-center Phase 1 clinical trial is designed to assess the safety and activity of a single-dose treatment cycle of FT596 in up to four dose cohorts as a monotherapy and in combination with CD20-targeted monoclonal antibody therapy for the treatment of relapsed / refractory B-cell malignancies. Under the clinical protocol, the company may seek consent of the U.S. Food and Drug Administration for administration of a second single-dose treatment cycle. The patient, a 76 year old woman with refractory DLBCL, had received seven prior lines of therapy, which included five rituximab-containing regimens, autologous stem cell transplantation, and two experimental cellular therapies. Of note, the patient was most recently refractory to an experimental NK cell therapy regimen comprised of fludarabine and cyclophosphamide lympho-conditioning followed by ex vivo expanded, donor-derived NK cells (greater than or equal to1 billion cells), IL-2, and rituximab. Approximately 3.5 months from last prior therapy, the patient enrolled into the first dose cohort of FT596 as a monotherapy at 30 million cells.The patient underwent fludarabine and cyclophosphamide lympho-conditioning and was administered a single dose of FT596 as a monotherapy at 30 million cells. Following FDA consent for continued treatment based on review of the clinical data from the first FT596 treatment cycle, the patient underwent another round of lympho-conditioning and was administered a second dose of FT596 as a monotherapy at 30 million cells. No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. No FT596-related serious adverse events were reported, and the only Grade greater than or equal to 3 adverse events deemed possibly related to FT596 were neutrophil count decreased, white blood cell count decreased, and lymphocyte count decreased. All other Grade greater than or equal to3 adverse events were consistent with lympho-conditioning chemotherapy and prior treatment regimens. No evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected. The patient achieved a partial response as of the Day 29 protocol-defined response assessment, with a greater than 50% reduction in tumor size and a substantial reduction in metabolic activity as assessed by PET-CT scan per Lugano 2014 criteria. The protocol-defined response assessment following the second FT596 treatment cycle showed a deepening response, with an additional 33% reduction in tumor size and further reduction in metabolic activity. The duration of response, which was not aided by further therapeutic intervention, was 3.8 months and is comparable to that of FDA-approved autologous CD19 CAR-T cell therapy among patients who achieve partial response as best overall response. The pharmacokinetic profile of both FT596 treatment cycles was consistent and indicative of cell expansion, with peak peripheral blood exposure observed on the eighth day following administration of FT596, which further validates that retreatment with FT596 conferred additional clinical benefit. Dose escalation in the FT596 Phase 1 study is currently ongoing in the second dose cohort of 90 million cells as monotherapy and in combination with CD20-targeted monoclonal antibody therapy for patients with relapsed / refractory B-cell lymphoma. In addition, for patients with relapsed / refractory chronic lymphocytic leukemia, the company has initiated enrollment in the first dose cohort of 30 million cells as monotherapy and plans to begin enrollment in combination with obinutuzumab upon dose-limiting toxicity clearance of monotherapy in the first dose cohort. FT596 is also currently being evaluated in an investigator-initiated Phase 1 clinical trial sponsored by investigators from the Masonic Cancer Center, University of Minnesota for patients with B-cell lymphoma who have undergone autologous hematopoietic stem cell transplant and are considered high risk for early relapse. Up to three dose cohorts of FT596, beginning at 90 million cells per dose, in combination with CD20-targeted monoclonal antibody will be assessed.

17:47 EST Rocket announces preliminary data from Phase 1 Trial of RP-L301 - Rocket Pharmaceuticals announces preliminary clinical data from its Phase 1 clinical trial of RP-L301 for the treatment of Pyruvate Kinase Deficiency, showing significant improvement in hemoglobin levels and transfusion independence over the initial 3-months following therapy. These results were presented virtually at the 62nd American Society of Hematology Annual Meeting in a poster presentation. The data presented in the poster presentation are from two adult patients with significant anemia and transfusion requirement. Patient L301-006-1001 was treated with RP-L301, Rocket's ex vivo lentiviral gene therapy candidate for PKD. Patient L301-006-1001 was 31-years old at the time of enrollment and had been followed for 3-months post treatment at the time of data cutoff. Patient L301-001-1002 was 47-years old at the time of enrollment and was recently treated. Key highlights from the presentation include: RP-L301 was well tolerated, with no serious safety issues or infusion-related complications observed 3-months post treatment; Patient L301-006-1001 received a cell dose of 3.9x106 cells/kilogram with a drug product mean vector copy number of 2.73; Hematopoietic reconstitution in less than 2 weeks; Peripheral blood VCN of 2.21 at 1-month, normalized hemoglobin and hemolysis markers; No red blood cell transfusion requirements following engraftment; In the two years prior to enrollment, the patient underwent approximately 14 transfusion episodes; Normalization of bilirubin, lactate dehydrogenase and erythropoietin levels at 3-months post treatment, each of which had been substantially elevated prior to study enrollment; Patient L301-006-1002 was recently treated with RP-L301; The patient received a cell dose of 2.4x106 cells/kg with a mean drug product VCN of 2.08 Aspects of the RP-L301 pre-clinical data package, including phenotypic reversal in the murine PKD knockout model, were also reviewed.

17:41 EST Corvus presents new data on Investigational ITK Inhibitor CPI-818 - Corvus Pharmaceuticals announced that new data on CPI-818, the company's ITK inhibitor, were presented at the 62nd American Society of Hematology Annual Meeting & Exposition, which is taking place as an all-virtual event from December 5-8, 2020. The data include a poster presentation covering updated data from the Phase 1/1b clinical trial for T cell lymphoma and an oral presentation covering pre-clinical data demonstrating its potential for the treatment of autoimmune lymphoproliferative syndrome, a rare genetic disease. CPI-818 is an investigational, orally bioavailable, covalent inhibitor of ITK designed to have low nanomolar affinity. In vitro studies have shown that it potently inhibited T cell receptor signal transduction. CPI-818 is currently being studied in a Phase 1/1b clinical trial that was designed to select the optimal dose of CPI-818 and evaluate its safety, pharmacokinetics, target occupancy, biomarkers and efficacy. The study employed an adaptive, expansion cohort design, with an initial phase that evaluated escalating doses in successive cohorts of patients, followed by a second phase that is designed to evaluate safety and tumor response to the recommended dose of CPI-818 in disease-specific patient cohorts. By protocol design, treatment is discontinued after one year or upon disease progression. The study enrolled 25 patients from the United States, Australia and South Korea with several types of advanced, refractory T cell lymphomas, including nine patients with peripheral T-cell lymphoma, 12 patients with cutaneous T-cell lymphoma, four patients with other T-cell lymphomas. All patients had failed multiple prior therapies.

17:36 EST Global Blood presents data on new sickle cell disease pipeline therapies - Global Blood Therapeutics announced new preclinical data on its sickle cell disease pipeline therapies - inclacumab, a novel P-selectin inhibitor in development to reduce the frequency of vaso-occlusive crises in patients with SCD, and GBT021601, a next-generation hemoglobin S polymerization inhibitor. These data were presented at the all-virtual 62nd American Society of Hematology Annual Meeting and Exposition. In vitro study results demonstrated that inclacumab has the potential to be a best-in-class P-selectin inhibitor for reducing the frequency of VOCs in patients with SCD. When characterized alongside crizanlizumab, an FDA-approved P-selectin inhibitor for treatment of VOCs, inclacumab: Binds P-selectin at the natural ligand binding site and has an affinity similar to crizanlizumab, demonstrated rapid binding kinetics to P-selectin and remained bound for longer, and inhibited platelet-leukocyte aggregation to a greater extent than crizanlizumab. Additionally, prior clinical experience with inclacumab in more than 700 non-SCD participants demonstrated the potential for a substantially longer duration of exposure and near complete inhibition of platelet-leukocyte aggregation over a 12-week period. Taken together, the company believes these characteristics will translate into quarterly dosing, improved patient adherence, and the potential to expand use to a broader patient population. In 2021, GBT plans to initiate two global, randomized, placebo-controlled pivotal Phase 3 trials evaluating safety and efficacy of inclacumab. These trials are designed to enhance understanding of how P-selectin inhibitors could provide clinical benefit for patients with SCD and reduce overall healthcare utilization. One study is designed to reduce the frequency of VOCs over one year in patients with SCD when treated with inclacumab or placebo every 12 weeks. The second study will evaluate inclacumab based on a primary endpoint of 90-day hospital readmission rates following a VOC hospitalization. Participants in that trial will receive either a single dose of inclacumab or placebo, peri-discharge following a VOC hospitalization. Approximately 50% of U.S. SCD patients with least two annual VOC events are re-admitted within 90 days following a VOC hospitalization.1 Initiation of both trials is expected in the first half of 2021. Preclinical data on GBT021601, a molecule discovered and designed by scientists at GBT, demonstrated its potential as a potent next-generation HbS polymerization inhibitor. GBT021601 has the same mechanism of action as Oxbryta tablets, but with the potential for greater efficacy by achieving higher hemoglobin occupancy at significantly lower doses. The study showed that GBT021601 normalized Hb levels in Townes sickle cell mice. In addition, in this study GBT021601 was highly effective in: Reducing hemolysis, Prolonging red blood cell lifespan, Improving RBC health, and Potentially improving organ function. Following treatment with GBT021601, levels of erythropoietin (EPO), a hormone that plays a key role in the production of RBCs, did not change - indicating that the observed increase in Hb levels was safe and was not due to hypoxic response. A Phase 1 clinical study on the safety and tolerability of GBT021601 in SCD patients is expected to begin by mid-2021.

17:23 EST BioCryst announces preclinical data on BCX9930 - BioCryst Pharmaceuticals announced that preclinical data on BCX9930, an oral Factor D inhibitor under development as monotherapy for paroxysmal nocturnal hemoglobinuria and other complement-mediated diseases, showed complete in vitro blockade of both hemolysis of PNH erythrocytes and accumulation of C3 fragments on PNH erythrocytes, indicating that BCX9930 monotherapy has the potential to inhibit both intravascular and extravascular hemolysis. In the study, BCX9930 was highly specific for the alternative pathway and, after oral dosing of BCX9930 in primates, alternative pathway activity was completely suppressed. The data were presented at the 62nd American Society of Hematology Annual Meeting being held as a virtual event, December 5-8, 2020.

17:16 EST 'Durable benefits' induced by IMV T Cell, Keytruda combo presented at ASH - IMV Inc. (IMV) announces that durable clinical benefits induced by combination treatment of IMV's T cell therapy with Merck's (MRK) Keytruda in subjects with PD-L1 positive recurrent/refractory Diffuse Large B Cell Lymphoma have been presented at the American Society of Hematology Annual Meeting. In the PD-L1+ population, subjects have significantly higher median Progression Free Survival of 230 days, compared to the PD-L1 negative subjects with a p-value of 0.007, suggestive of a strong predictive biomarker for this treatment combination; demonstrated an objective response in six subjects, including three subjects who have completed one-year of study treatment; demonstrated an ORR and a DCR at both 85.7%. Peripheral blood was assessed for survivin-specific ELISpot responses in 15 subjects with available samples. All 3 subjects with a CR, and 3 of 4 subjects with a PR had positive ELISpot responses while only 1 subject with SD and 1 subject with PD demonstrated survivin-specific ELISpot response, suggestive of an association between the clinical responses with the mechanism of action of DPX-Survivac. Treatment was well tolerated. The majority of treatment-related adverse events were grade 1 and 2 severity. A majority of these were injection site reactions associated with the subcutaneous administration of DPX-Survivac.

16:33 EST GlycoMimetics presents Uproleselan, Venetoclax/HMA combo data - GlycoMimetics said that its product candidate uproleselan - when added to a combination therapy of venetoclax and a hypomethylating agent - was shown in an oral presentation to break chemoresistance by "dramatically and significantly" reducing tumor burden as detected by circulating human AML cells after three weeks of treatment, and by significantly increasing survival in an animal model engrafted with AML from a patient with acquired resistance to venetoclax/HMA combination therapy. The oral presentation at the 62nd ASH Annual Meeting and Exposition supports the need for further clinical investigation to potentially extend the use of uproleselan, an investigational, first-in-class, targeted E-selectin antagonist, to other drug combinations and, in particular, to venetoclax/HMA. GlycoMimetics previously presented preclinical data showing that hypomethylating agents up-regulate the expression of E-selectin ligand on AML cells. The company believes E-selectin upregulation increases the binding affinity of the blasts to the vascular endothelium, where E-selectin is expressed, and as a result, contributes to increased chemoresistance. By antagonizing E-selectin's role in this cascade, GlycoMimetics believes uproleselan may be able to play a key role in deepening patient responses to or enhancing the duration of efficacy of venetoclax/HMA combinations.

16:24 EST Cellectis reports preliminary results from Phase 1 BALLI-01 study of UCART22 - Cellectis announced preliminary results from Cellectis' dose escalation Phase 1 BALLI-01 study of UCART22 product candidate in relapsed/refractory B-cell Acute Lymphoblastic Leukemia were presented at the American Society of Hematology Annual Meeting. This is the first publicly released data from Cellectis' BALLI-01 clinical trial. As of the November 2, 2020 data cutoff, 7 patients were enrolled and 5 patients received UCART22 cells. One patient failed screening and one patient was discontinued prior to the administration of UCART22 cells due to an adverse event related to the lymphodepletion. No patient experienced a DLT, ICANS, GvHD, AESI1, nor UCART22-related Grade greater than or equal to3 adverse event nor serious adverse event. No patient discontinued treatment due to a UCART22-related treatment-emergent adverse event. Two patients in Dose Level 1 achieved an objective response of complete remission with incomplete hematologic recovery at Day 28, one of which attained a complete remission at Day 42 and received a transplant after subsequent therapy with inotuzumab. One patient in Dose Level 2 with refractory disease did achieve a noteworthy reduction in bone marrow blasts after treatment with UCART22 product candidate and then progressed. Host lymphocyte reconstitution was observed in all patients within the DLT period. Correlative analysis of UCART cell expansion and persistence is ongoing. UCART22 demonstrated preliminary signs of activity at low dose levels with fludarabine/cyclophosphamide lymphodepletion regimen, without unexpected nor significant treatment-related toxicities. Host immune recovery was observed early, supporting the addition of alemtuzumab to the FC lymphodepletion regimen which is expected to result in a deeper and more sustained T-cell depletion and thereby promote expansion and persistence of UCART22 cells. Enrollment into the Dose Level 2 cohorts with alemtuzumab is ongoing.

16:09 EST ImmunoGen presents updated findings from Phase 1/2 study of IMGN632 - ImmunoGen announced that new safety and efficacy findings from the expansion phase of the Phase 1/2 study of IMGN632 in patients with relapsed/refractory blastic plasmacytoid dendritic cell neoplasm were presented during an oral session at the 62nd American Society of Hematology Annual Meeting. IMGN632 demonstrated a favorable safety profile in 29 patients who received 0.045 mg/kg once every 3 weeks via a short intravenous infusion, with limited grade greater than or equal to3 treatment-related adverse events and no treatment-related deaths. The most common grade greater than or equal to 3 AEs were febrile neutropenia, hyperglycemia, and thrombocytopenia. Grade greater than or equal to 3 liver function test elevations were seen in one patient. No capillary leak syndrome was reported. In all relapsed/refractory BPDCN patients, the overall response rate was 29% with a composite complete remission rate of 18%. In patients with prior SL-401 exposure, the ORR was 31% with a CCR of 15%. Among patients with bone marrow response assessment, 60% achieved a bone marrow complete response. Durable responses were seen in multiple patients, up to 9.2 months without hematopoietic stem cell transplant. Two patients have been successfully bridged to hematopoietic stem cell transplant.

16:03 EST Legend Biotech announces Phase 1b/2 data of Cilta-cel - Legend Biotech has announced the latest data results from the combined Phase 1b/2 CARTITUDE-1 study of ciltacabtagene autoleucel, an investigational B-cell maturation antigen directed chimeric antigen receptor T cell therapy, for the treatment of patients with relapsed or refractory multiple myeloma, sponsored by Janssen Research & Development. The data continued to show a very high overall response rate that deepened over time, with 97% of patients achieving a response and 67% of patients achieving a stringent complete response at a median follow-up of 12.4 months. The data were presented at the 62nd American Society of Hematology Annual Meeting and Exposition. The trial included 97 patients treated with cilta-cel who received a median of six prior lines of therapy; 88% were triple-refractory, 42% were penta-refractory and 99% were refractory to the last line of therapy. The median administered dose was 0.71x106 CAR+ viable T cells/kg and manufacturing of cilta-cel was successful for all patients. ORR per independent review was 97%, which included a sCR rate of 67%, very good partial response rate of 26% and partial response rate of 4%. Median time to first response was 1 month and responses were ongoing in 72% of patients. Of 57 minimal residual disease evaluable patients, 93% were MRD negative at 10-5.1 Median progression-free survival was not reached at median follow-up of 12.4 months. The 12-month PFS rate was 77% and the 12-month OS rate was 89%. The study also demonstrated a manageable safety profile for cilta-cel at the recommended Phase 2 dose. In the combined results, the most common hematologic adverse events observed in the CARTITUDE-1 study were neutropenia; anemia; thrombocytopenia; leukopenia, and lymphopenia. Cytokine release syndrome of any grade was observed in 95 percent of patients, with a median duration of four days, and 99% of which resolved within 14 days of onset. Of the 92 patients with CRS, most were Grade 1/2, 3% were Grade 3, 1% was Grade 4 and 1% was Grade 5. The median onset of CRS was seven days post-infusion, with 89% of patients experiencing CRS onset at day four or later, which is supportive of potential outpatient administration for cilta-cel. Total CAR-T cell neurotoxicity of any grade was observed in 21% of patients, with Grade greater than or equal to 3 neurotoxicity observed in 10% of patients.1 Of these, Immune effector Cell-Associated Neurotoxicity Syndrome was observed in 16 patients and generally occurred concurrently with CRS; other neurotoxicities were observed in 12 patients and generally occurred after resolution of CRS and/or ICANS. ICANS events were resolved in all patients with a median time to recovery of four days. Other neurotoxicities were resolved in six patients at a median time of 75 days and were not resolved in six patients. Fourteen deaths were reported during the study: five due to disease progression, three due to adverse events unrelated to treatment and six due to adverse events related to treatment.

15:51 EST Poseida Therapeutics provides update on Phase 1 trial of P-BCMA-101 - Poseida Therapeutics reported results of an ongoing Phase 1 clinical trial of P-BCMA-101, an autologous chimeric antigen receptor T-cell product candidate in relapsed/refractory multiple myeloma, during an oral presentation at the 2020 American Society of Hematology Annual Meeting. The results show that patients treated with equivalent doses of product manufactured with a modified nanoplasmid process in the expanded Phase 1 trial achieved deeper responses while maintaining a similar safety profile compared to product manufactured with the company's legacy plasmid. The Phase 1 dose escalation trial initially included five cohorts with a product candidate created using a standard plasmid process. The trial was expanded in 2020 to include cohorts utilizing a new nanoplasmid manufacturing process. The nanoplasmid technology allows for a reduction in the plasmid backbone size, enhancing the transposition efficiency during manufacturing and improving the final CAR-T product performance. The expansion part of the trial is also evaluating several novel dosing strategies with 19 patients treated as of the data cutoff with a variety of dosing regimens, including single administration, cyclic dosing, combination with rituximab, and combination with lenalidomide. Using the new manufacturing process, a dose of 0.75 x 106 cells/kg was administered to eight patients in the initial P-BCMA-101 nanoplasmid expansion cohorts. Patients treated in this cohort and evaluable by International Myeloma Working Group criteria showed a higher response rate, with an ORR of 67% as compared to an ORR of 50% for the same dosing cohort using the standard P-BCMA-101 plasmid. Additionally, as of the cutoff date, three patients achieved deeper responses of either very good partial response or complete response in the nanoplasmid expansion cohort as compared to no patients reaching a VGPR or CR in the standard plasmid group at the Cohort 1 dose. As of the data cutoff date, two of the three nanoplasmid patients who reached VGPR or CR remained in durable responses at approximately 6 months. At the 0.75 x 106 cells/kg dose, cytokine release syndrome was seen in just one, or 12.5%, of evaluable Phase 1 nanoplasmid patients and neurotoxicity was not seen in any patients, demonstrating the preservation of the product safety profile within the expansion cohort. There have been no patient deaths, dose limiting toxicities or unexpected/off-target toxicities related to P-BCMA-101. The most common adverse events were cytopenias and infections generally attributable to lymphodepleting chemotherapy regimens. Based on the safety results, the protocol was amended to allow fully outpatient CAR-T cell administration. The median patient age was 60, with a median time since diagnosis of approximately five years. Patients were heavily pre-treated, with a median of eight prior lines of therapy. All patients had received a protease inhibitor or at least one IMid, and nearly all patients had been previously treated with a CD38 monoclonal antibody. Sixty percent of the patients were refractory to all three drug classes, and four patients had previously received an anti-BCMA targeted therapy. This open label, multicenter Phase 1 study is designed to assess the safety of P-BCMA-101 in subjects with relapsed and/or refractory multiple myeloma and includes multiple exploratory cohorts to evaluate the administration of P-BCMA-101 CAR-T within the framework of moving from the standard plasmid CAR-T product to the nanoplasmid product. The primary objective of this study is to determine the safety and maximum-tolerated dose of P-BCMA-101. Secondary objectives include anti-myeloma effect of P-BCMA-101.

15:43 EST GeneTx, Ultragenyx announce presentation of Phase 1/2 data on GTX-102 - GeneTx Biotherapeutics and Ultragenyx Pharmaceutical announced the presentation of data from the Phase 1/2 study of GTX-102 at the Foundation for Angelman Syndrome Therapeutics Global Summit. Details regarding the scientific basis for GTX-102 targeting in Angelman syndrome were presented along with additional supportive clinical data on EEG and other endpoints, along with further description of the safety events. Additional nonclinical study data were included showing substantial silencing activity at low repeat doses along with chronic nonclinical safety data at higher doses compared to dosing in the human study. Five patients in three dose cohorts were enrolled who all had deletions in the UBE3A locus as the cause of Angelman syndrome and were treated with a monthly intrathecal dose of GTX-102 that increased for each of the first four doses provided to each patient. Two patients in cohort 1 received a monthly ascending dose sequence of 3.3 mg, 10 mg, 20 mg, and 36 mg, with the first patient receiving one additional fifth dose in an extension amendment at the 36 mg level. Two patients in cohort 2 received three sequential monthly doses of 10 mg, 20 mg, and 36 mg. One patient in cohort 3 received a single dose of 20 mg. Further dosing was stopped once the first serious adverse event occurred, as previously described. Pharmacokinetic results indicate that plasma levels of GTX-102 were dose proportional. GTX-102 was not detectable in the blood or cerebrospinal fluid in samples taken one month after the last dose and prior to subsequent monthly doses, indicating that the drug did not accumulate in the blood or CSF. Previously disclosed improvements in the Clinical Global Impression of Improvement Scale for Angelman Syndrome were presented along with detailed individual results for both global scores and individual domains. The mean change was +2.4 in the CGI-I-AS global score and all patients had at least 3 domains of improvement and 2 domains of much improved or very much improved at this interim assessment. Communication was one of the most impaired functions in these five patients based on baseline scores and is the most important disease domain for families according to a recently published disease concept model. Detailed scores from the communication domain of the CGI-I-AS showed much improved or very much improved scores in four of five subjects along with supportive detailed data from other scores. In the Bayley Scales of Infant and Toddler Development, multiple patients improved on receptive or expressive communication sub-scales. In the Observed Reported Communication Ability measure of expressive, receptive, and pragmatic communication, three patients, ages 5, 10, and 15, demonstrated clinically relevant increases at day 128 and two patients did not have notable changes. At baseline, all patients had stable seizure control per protocol requirements and did not have reports of seizures as adverse events during the study. Blinded independent central electroencephalogram readings were conducted at baseline and day 128 for four of five treated patients to assess delta waves and epileptiform discharges among other findings common in Angelman syndrome. Qualitative readings of the EEGs indicate decreases in the prevalence of notched delta waves in three of the four evaluated patients with patient 1 showing minimal change or a slight increase. Decreases in the prevalence of epileptiform discharges were also observed in three of the four evaluated patients with patient 5 showing minimal change or a slight increase. Quantitative analysis of the EEGs completed to date in the first two patients showed decreases in relative delta power in both evaluated patients after beginning GTX-102. These are preliminary findings and, due to normal variability in EEG tracings, the assessments will be repeated after longer-term treatment with GTX-102. Preliminary readings from the ActiMyo device that measures hourly distance walked, stride length, and stride speed, support the utility of this functional measure. One patient, who initially had a decrease in distance walked due to the lower extremity weakness SAE, later was able to exhibit a meaningful increase from baseline as the SAE resolved. Other improvements in fine motor function previously disclosed were presented. The clinical changes observed appear to last at least 3 to 5 months from the last dose. To date, most of the subjects have retained many caregiver-reported clinical changes observed but some patients are observed to be experiencing some loss of effect. The long period of observed clinical response post-dose would support use of a maintenance dosing regimen of every 3 months, if an appropriate and safe dosing regimen is identified. As previously reported, all patients had a grade 1 or 2 serious adverse event of lower extremity weakness associated with local inflammation in the region of intrathecal administration in the lower back at the higher doses of GTX-102. The SAE has fully resolved in all five patients. The SAE occurred between 6 and 30 days after the last infusion of 36 mg in four patients and 20 mg in one patient. In patient 1, the SAE was not observed until after the second dose at the 36 mg level. Clinical improvements observed in the study have been sustained beyond resolution of the SAE and the negative impact of the SAE on gross motor function in certain patients has recovered with resolution of the SAE. No new adverse events have been reported since the last update. No patients have withdrawn from the study.

15:34 EST Genentech announces new data from pivotal Phase III MURANO, CLL14 studies - Genentech, a member of the Roche Group (RHHBY), announced that new data from the pivotal Phase III MURANO and CLL14 studies support the efficacy of fixed-duration, chemotherapy-free Venclexta-based combinations in certain people with chronic lymphocytic leukemia and provide more evidence on the potential value of minimal residual disease. Data were presented at the all-virtual 62nd American Society of Hematology Annual Meeting and Exposition on Saturday, December 5, 2020. Five-year data from the pivotal Phase III MURANO trial continue to show sustained investigator-assessed progression-free survival with Venclexta plus Rituxan. Data, presented in an oral session, showed: Venclexta plus Rituxan reduced the risk of disease progression or death by 81% compared to bendamustine plus Rituxan in people with relapsed or refractory CLL. At the time of analysis, median overall survival had not been reached in either arm, however, five-year OS was 82.1% in the Venclexta plus Rituxan arm, compared to 62.2% in the BR arm. In the Venclexta arm, among the 130 patients who completed two years of treatment without progressive disease, 63.8% had undetectable MRD levels at the end of treatment. In an analysis of this patient subgroup, uMRD was associated with improved progression-free survival. Undetectable MRD, sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes. No new safety events were reported in the study. Data from the Phase III CLL14 study contributes to growing evidence regarding the potential of MRD measurements to predict future outcomes for certain people with previously untreated CLL who were treated with fixed-duration Venclexta plus Gazyva:Patients with uMRD and a partial response had longer PFS than patients with detectable MRD and a complete response. In collaboration with Adaptive Biotechnologies, clonal growth rate, a measure for how quickly cancer cells grow, was analyzed using the next-generation sequencing Adaptive clonoSEQ Assay and insights were used to better understand the potential role of MRD in predicting outcomes. In this analysis, after treatment with fixed-duration Venclexta plus Gazyva, the estimated clonal growth rate was slower and lower, suggesting more effective MRD eradication in these patients compared to those treated with Gazyva plus chlorambucil. Early data suggest a correlation between MRD responses and PFS, which will be further evaluated by the study authors. Exploring novel endpoints, such as MRD, is an important area of development for Genentech, which continues to investigate Venclexta in a robust clinical development program. This includes the Phase III CRISTALLO trial in previously untreated CLL, which uses MRD as a primary endpoint. Venclexta is being developed by AbbVie (ABBV) and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

15:18 EST Syros Pharmaceuticals presents new data from Phase 2 trial of SY-1425 - Syros Pharmaceuticals has announced new clinical data from its Phase 2 trial evaluating SY-1425, its first-in-class selective retinoic acid receptor alpha agonist, in combination with azacitidine in two acute myeloid leukemia patient populations. The data is being presented in oral presentations at the 62nd American Society of Hematology Annual Meeting. In a separate poster presentation on Monday, Syros will present translational data highlighting the potential of SY-1425 to benefit newly diagnosed unfit AML patients who may be resistant to the standard-of-care combination of venetoclax plus azacitidine. Syros presented new data from its fully enrolled Phase 2 trial evaluating the safety and efficacy of SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy, as well as in RARA-positive relapsed or refractory AML patients. As of October 1st, 51 newly diagnosed unfit AML patients, including both RARA-positive and RARA-negative patients, were eligible for a safety analysis. Eighteen RARA-positive were evaluable for clinical response. In those patients, the data showed that: Overall response rate was 67%, with a composite CR rate of 61%, including nine patients achieving a complete response, two patients achieving a complete response with incomplete blood count recovery. 89% of CRs were deep molecular or cytogenetic CRs. Responses were seen across AML risk groups, including patients with mutations that are typically associated with poor outcomes. Median time to initial response was 1.2 months. Median duration of response was 10.8 months, and median overall survival among patients who achieved a CR or CRi was 18 months. 86% of patients who were transfusion dependent at baseline became transfusion independent, and 67% of patients achieved or maintained transfusion independence. SY-1425 in combination with azacitidine was generally well-tolerated with no evidence of increased toxicity relative to either as a single agent, including rates of myelosuppression that were comparable to single-agent azacitidine. Syros will also present new translational data demonstrating that most RARA-positive newly diagnosed unfit AML patients have a monocytic disease phenotype that is highly correlated with resistance to upfront treatment with venetoclax and azacitidine. These data suggest that the RARA biomarker not only selects for patients who are more likely to respond to treatment with SY-1425 but also for patients who are less likely to respond to treatment with venetoclax and azacitidine. As of October 1st, 28 RARA-positive R/R AML patients were eligible for safety analysis and 21 were evaluable for clinical response. In those patients, the data showed: ORR was 19%, consisting of one CRc, two CRi and one MLFS. In HMA and venetoclax naive patients, the ORR was 43%. Median OS was 5.9 months. 30% achieved or maintained transfusion independence, including 27% of patients who were transfusion dependent at baseline. SY-1425 in combination with azacitidine was also generally well-tolerated in this patient population. Syros plans to advance SY-1425 in combination with azacitidine into a registration-enabling Phase 3 trial in RARA-positive newly diagnosed higher-risk myelodysplastic syndrome patients. HR-MDS is a hematologic malignancy that is closely related to AML, and as in AML, about 30 percent of HR-MDS patients are RARA-positive. Based on feedback from the U.S. Food and Drug Administration, Syros plans to enroll approximately 190 RARA-positive newly diagnosed HR-MDS patients in the double-blind placebo-controlled trial, randomized 2:1 to receive SY-1425 in combination with azacitidine or placebo with azacitidine, respectively. The primary endpoint of the trial will be the CR rate, which, depending on the data outcome, could support accelerated or full approval in this patient population. Syros expects to initiate the Phase 3 trial in the first quarter of 2021. In addition, Syros plans to advance SY-1425 in combination with venetoclax and azacitidine in RARA-positive newly diagnosed unfit AML patients. The trial is designed with a single-arm safety lead-in to confirm the dosing regimen of the triplet to be used in the randomized portion of the Phase 2 trial, which will evaluate the safety and efficacy of SY-1425 in combination with venetoclax and azacitidine compared to venetoclax and azacitidine in approximately 80 patients randomized 1:1. The trial will also evaluate the triplet as a salvage therapy in patients who don't respond to venetoclax and azacitidine. Syros expects to initiate the Phase 2 trial in the second half of 2021.

12:17 EST AbbVie announces new data from Phase 2 CAPTIVATE trial evaluating IMBRUVICA - AbbVie has announced new data from the Phase 2 CAPTIVATE clinical trial evaluating IMBRUVICA in combination with VENCLEXTA/VENCLYXTO in previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma during an oral presentation session at the virtual 2020 American Society of Hematology Annual Meeting. The one-year disease-free survival rate in patients randomized to placebo or ibrutinib after completing the combination regimen provides data to support a fixed-duration treatment that can offer CLL/SLL patients remission and time off treatment. These findings build on the previously reported results showing that this first-line combination regimen for CLL resulted in high rates of undetectable minimal residual disease in both peripheral blood and in bone marrow. Undetectable MRD is defined as little to no cancer cells found after treatment. In the Confirmed uMRD group, one-year DFS rate was not significantly different for patients randomized to placebo versus ibrutinib. During the overall study period across all-treated patients, most common grade 3/4 adverse events were neutropenia, hypertension, thrombocytopenia, and diarrhea. The safety profile of the combination was consistent with known adverse events for ibrutinib and venetoclax individually and no new safety signals emerged.

12:11 EST Allogene reports initial results from Phase 1 UNIVERSAL study of ALLO-715 - Allogene Therapeutics has announced initial results from the Phase 1 UNIVERSAL study of ALLO-715 in relapsed/refractory multiple myeloma. Data were presented at an oral session of the American Society of Hematology annual meeting. This study utilizes ALLO-647, Allogene's anti-CD52 monoclonal antibody, as a part of its differentiated lymphodepletion regimen. As of the October 30, 2020 data cutoff, 35 patients were enrolled with 31 patients evaluable for safety and 26 patients evaluable for efficacy. Patients were refractory to their last line of myeloma therapy, had a median of five prior lines of therapy, and 94% were penta-exposed. Four patients became ineligible for treatment due to rapidly progressing disease. The median time from enrollment to the start of therapy was five days. In the initial dose escalation phase of the UNIVERSAL trial, patients received lymphodepletion followed by ALLO-715 at one of three dose levels in a 3+3 dose escalation design. DL4 was added in a subsequent cohort. As of the data cutoff, the overall median follow-up for efficacy was 3.2 months and six out of the nine patients treated with DL3 or DL4 with a response remain in response. The longest response was ongoing at six months from the DL3 cohort with FCA lymphodepletion. As part of the company's three-pronged anti-BCMA strategy, the Phase 1 UNIVERSAL study continues to enroll patients at higher doses of ALLO-715 and ALLO-647 in an effort to optimize the therapy. The UNIVERSAL study is expected to begin enrolling patients in the first half of 2021 to evaluate ALLO-715 in combination with SpringWorks Therapeutics' investigational gamma secretase inhibitor, nirogacestat. An investigational new drug application is expected to be submitted in the first half of 2021 for the Company's first TurboCAR candidate, ALLO-605, an investigational BCMA-directed AlloCAR T therapy for MM. TurboCAR technology allows cytokine activation signaling to be engineered selectively into CAR T cells and has shown the ability to improve the potency and persistence of allogeneic cells in preclinical models.

12:00 EST Bristol, Bluebird announced updated data evaluating Anti-BCMA CAR T cell therapy - Bristol Myers Squibb (BMY) and Bluebird Bio (BLUE) announced updated data evaluating the companies' investigational B-cell maturation antigen directed chimeric antigen receptor T cell therapy, idecabtagene vicleucel, were presented at the 62nd American Society of Hematology Annual Meeting and Exposition. The data include longer-term updated results from the original Phase 1 CRB-401 study of ide-cel in relapsed and refractory multiple myeloma, including the primary endpoint of safety and exploratory endpoints of progression-free survival and overall survival. Analyses of the pivotal registrational KarMMa trial will also be presented at the ASH meeting, including an analysis of health-related quality of life in patients with RRMM treated with ide-cel, and a subgroup analysis of outcomes for patients with high-risk RRMM. A subgroup analysis of elderly patients with RRMM treated with ide-cel in the KarMMa study were also presented. In addition, data from the ongoing Phase 1 CRB-402 study of bb21217, an investigational BCMA-directed CAR T cell therapy, were presented at the meeting. In the Phase 1 CRB-401 study, 62 patients with heavily pretreated relapsed and refractory multiple myeloma were treated with ide-cel across dose levels of 50, 150, 450, or 800 106 CAR positive T cells. The primary endpoint was safety, and secondary and exploratory endpoints included response rates, PFS, OS, and minimal residual disease. Safety remained consistent with previously reported results from CRB-401. The most frequent adverse events were neutropenia, cytokine release syndrome, anemia, and thrombocytopenia. The most frequent Grade 3/4 AEs were neutropenia, leukopenia, anemia, and thrombocytopenia. Most CRS events were Grade 1 or 2. Four patients had Grade 3 CRS; there were no Grade 4 or 5 CRS events reported. Among 62 patients treated with ide-cel in this study, the overall response rate was 76%, including 24 patients who achieved a complete response. The median duration of response was 10.3 months. Median PFS was 8.8 months and median OS was 34.2 months, with a median follow-up of 14.7 months. Ide-cel demonstrated deep and durable responses in the pivotal Phase 2 KarMMa study of patients with triple-class exposed relapsed and refractory multiple myeloma. A subgroup analysis was conducted to assess outcomes of treatment with ide-cel across target dose levels of 150 to 450 106 CAR positive T cells in patients with poor prognosis, including those with extramedullary disease, high-risk cytogenetics, and high tumor burden. In the analysis of 128 patients, ide-cel demonstrated deep and durable responses across the majority of subgroups, including those with the highest risk. The ORR and CR rate were greater than or equal to65% and greater than or equal to20%, respectively, for the majority of high-risk subgroups. Additionally, in the majority of the high-risk subgroups, the median DoR was greater than9.2 months and the median PFS was greater than7.5 months. A separate subgroup analysis was conducted to evaluate the outcomes of treatment with ide-cel in elderly patients. Multiple myeloma occurs most commonly among the older population, with a median age of 69 at diagnosis. Advanced age has been shown to negatively affect prognosis and limit treatment options. Of the 128 patients treated with ide-cel in the KarMMa study, 45 patients were aged greater than or equal to65 years and 20 patients were aged greater than or equal to 70 years. Response rates for both age groups were comparable and consistent with the overall ide-cel treated population, across all target dose levels, with ORRs of 84% to 90% and CR rates of 31% to 35%. Likewise, median DoR among responders in both age groups was similar to that of the overall ide-cel treated population. Median PFS was 8.6 months in patients aged greater than or equal to 65 years and 10.2 months in patients aged greater than or equal to 70 years. Additionally, no new safety signals were observed. In an analysis of the impact of ide-cel treatment on health-related quality of life measures in patients with relapsed and refractory multiple myeloma from the KarMMa study, ide-cel was associated with clinically meaningful QoL benefits without compromising any HRQoL domains. Patients demonstrated a clinically meaningful improvement in most functioning and symptom scores from baseline to Month 3 through 15, with statistical significance reached at various time points for different subscales throughout the follow-up period. Updated safety and efficacy results from the ongoing Phase 1 study of bb21217, an investigational BCMA-directed CAR T cell therapy being studied in patients with relapsed and refractory multiple myeloma, were also presented in an oral presentation. bb21217 uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor to enrich for T cells displaying a memory-like phenotype with the intention of increasing the in vivo persistence of CAR T cells. As of the September 1, 2020 cutoff date, 69 patients were treated with bb21217 and updated results include new data following the introduction of a manufacturing process change. The study has completed enrollment and follow-up is ongoing as data continue to mature and the durability of response at the RP2D is assessed.

11:13 EST Preclinical data demonstrate anti-viral activity of AlloVir's ALVR109 - AlloVir announced that preclinical data presented in an oral presentation at the 62nd American Society of Hematology Annual Meeting, demonstrates selective antiviral activity of ALVR109 -the company's virus-specific T cell therapy designed to combat SARS-CoV-2, the virus responsible for COVID-19. The data presented found that the SARS-CoV-2 virus-specific T cell therapy, ALVR109, was able to produce effector molecules and selectively kill viral antigen-expressing targets, while leaving non-infected targets intact. These data suggest the potential for using these cells to treat COVID-19 in hospitalized high-risk patients in order to prevent the development of severe disease. These data were featured in the ASH Annual Meeting press program. A clinical trial evaluating ALVR109 has recently been initiated at the Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital. Researchers at BCM and AlloVir developed a bank of off-the-shelf, SARS-CoV-2 specific T cells that are ready to be administered to patients enrolled in the study.

10:34 EST Gamida Cell presents updated, expanded results from Phase 1 study of GDA-201 - Gamida Cell announced in an oral presentation the updated and expanded results from a Phase 1 clinical study of GDA-201, an investigational, natural killer cell-based cancer immunotherapy for the treatment of patients with non-Hodgkin lymphoma and multiple myeloma, at the 62nd American Society of Hematology Annual Meeting & Exposition, which is being held virtually December 5-8. GDA-201 was well-tolerated and no dose-limiting toxicities were observed in 35 patients. The data show that therapy using GDA-201 with monoclonal antibodies demonstrated significant clinical activity in heavily pretreated patients with advanced NHL. Of the 19 patients with NHL, 13 complete responses and one partial response were observed, with an overall response rate of 74% and a complete response rate of 68%. The maximum tolerated dose was not achieved, as no dose limiting toxicities were observed in patients who received the maximum target dose.

09:50 EST Editas announces preclinical data/large-scale manufacturing process for EDIT-301 - Editas Medicine announced preclinical data and successful development of a large-scale manufacturing process for EDIT-301, a potentially best-in-class, one-time, durable, autologous cell therapy medicine to treat sickle cell disease and beta-thalassemia. EDIT-301 is the first experimental medicine in development generated using CRISPR/Cas12a gene editing. The company reported these data at the 62nd Annual Meeting and Exposition of the American Society of Hematology being held virtually. The data showed that high levels of editing in CD34+ cells from normal donors and sickle cell patients were achieved with CRISPR/Cas12a at the HBG1 and HBG2 promoters, leading to robust fetal hemoglobin induction in their erythroid progeny in a pan-cellular fashion. Red blood cells derived from edited sickle cell patient CD34+ cells showed remarkable correction of sickle cell disease phenotypes, including a reduction in sickling and improved rheological properties when deoxygenated. In addition, the company's large-scale manufacturing process was shown to be consistent and robust. When infused into immunodeficient mice, edited CD34+ cells from normal donors manufactured at large-scale led to long term multi-lineage hematopoietic reconstitution that was comparable to unedited control cells. The engraftment was stable and highly polyclonal with high levels of editing detected throughout the course of the study. Editas Medicine continues to prepare for a Phase 1/2 clinical trial evaluating EDIT-301 for the treatment of sickle cell disease. The Company has completed preclinical toxicology studies, identified a lead principal investigator, and engaged a contract research organization. Clinical trial materials are being manufactured by Editas Medicine. The company remains on track to file an IND for the treatment of sickle cell disease by the end of 2020.

09:40 EST Kite announces four-year follow-up data from ZUMA-1 trial of Yescarta in LBCL - Kite, a Gilead company, announced four-year follow-up data from the pivotal ZUMA-1 trial of Yescarta in adult patients with refractory large B-cell lymphoma. Among Yescarta-treated patients with a minimum follow-up of four years after a single infusion of Yescarta, the Kaplan-Meier estimate of the four-year overall survival rate was 44%. The data were presented at the 62nd American Society of Hematology Annual Meeting and Exposition. Of 111 patients enrolled in the ZUMA-1 Phase 2 cohorts, Yescarta was administered to 101 patients with refractory LBCL, and the median time from leukapheresis to complete response was less than two months. There have been no Yescarta-related secondary malignancies reported. Blood sample analyses provided by 21 patients who were treated with Yescarta and showed an ongoing response at a minimum of three years follow-up also demonstrated that 67% had detectable CAR gene-marked cells and polyclonal B cells in blood. Additionally, normal B-cells were present in 91 percent of evaluable patients. These results suggest that persistence of functional CAR T cells is not necessary for durable remissions in patients with refractory LBCL and may support long-term safety of the therapy. Kite has presented four-year survival data for Yescarta in the ZUMA-1 study of patients with refractory large B-cell lymphoma. Based on these data and other data presented at ASH, Kite believes that Yescarta could bring the hope of survival to patients with a number of other hematological malignancies. 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, including diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of cytokine release syndrome and neurologic toxicities, and Yescarta is approved with a risk evaluation and mitigation strategy due to these risks.

09:26 EST Beam presents updated data from base editing programs for Sickle Cell Disease - Beam Therapeutics has announced that updated data from the company's complementary base editing approaches to treat hemoglobinopathies were presented during poster sessions at the 62nd American Society of Hematology Annual Meeting and Exposition. "Base editing is ideally suited to precisely edit the genetic mutations that cause disease without disrupting any other part of the genome," said Giuseppe Ciaramella, president and chief scientific officer of Beam. "The new data for BEAM-101 highlight the precise targeting of our base editor with no off-target editing observed and will support our planned Investigational New Drug application submission in the second half of 2021. In addition, the in vivo proof of concept data presented from an early version of our Makassar base editor demonstrate robust engraftment after 16 weeks. Our final editor from this program, BEAM-102, has achieved even higher levels of editing of the sickle mutation. In aggregate, today's data support the opportunity for our base editors to offer potentially disease-modifying treatments for people with sickle cell disease, which affects nearly 100,000 Americans and millions worldwide." According to the company, BEAM-101 reproduces single base changes seen in individuals with hereditary persistence of fetal hemoglobin, or HPFH. Individuals with sickle cell disease or beta-thalassemia, who also have HPFH, typically experience a milder form of the disease or may be asymptomatic. Using adenine base editors, BEAM-101 recreates HPFH by installing base edits in the gamma globin gene promoters, HBG1 and HBG2, that disrupt repressor binding and lead to increased expression of gamma globin. Two theoretical types of off-target events that are possible as a consequence of these edits are guide-dependent and guide-independent deamination. To determine the potential for guide-dependent off-target editing, Beam evaluated BEAM-101 in a homology-dependent biochemical assay. In the findings presented, no guide-dependent off-target effects were observed in CD34+ hematopoietic stem and progenitor cells edited at a supra-saturating dose of BEAM-101. Beam assessed guide-independent off-target effects using single-clone whole genome sequencing, which revealed that no significant fold change of guide-independent A-to-G DNA mutations occurred in edited cells compared to unedited controls. Further, whole transcriptome sequencing and somatic variant calling showed no guide-independent RNA deamination in CD34+ HSPCs edited at a supra-saturating dose of BEAM-101. Together, the findings support precision editing with BEAM-101 with a very low risk for potential off-target toxicities. Beam's Makassar base editing program aims to treat SCD by directly editing the causative HbS point mutation to recreate a naturally occurring normal human hemoglobin variant, HbG-Makassar. The Makassar variant has been reported to have the same function as the wild-type variant and does not cause SCD. In the presentation, Beam showed new long-term in vivo data generated using an early version of the Makassar base editor, which yielded approximately 50% conversion of the sickle allele to a Makassar allele. At 16 weeks post-transplant of CD34+ cells containing the sickle trait, Beam observed equivalent human chimerism between unedited and edited cells and evidence of multi-lineage reconstitution in mouse models. Levels of editing were sustained after long-term hematopoietic engraftment. Further, editing of the sickle allele led to the expression of the Makassar globin protein in vivo. Additional data presented by Beam showed that the final optimized editor used in BEAM-102 has achieved greater than 90% bi- and mono-allelic Makassar editing in SCD CD34+ HSPCs in vitro. Beam expects that these improvements will lead to even greater editing levels and higher Makassar globin conversion in future in vivo studies.

09:21 EST Novo Nordisk announces FDA approval of Saxenda in obesity in adolescents - Novo Nordisk today announced that the U.S. Food and Drug Administration approved an updated label for Saxenda injection 3 mg for use in the treatment of obesity in adolescents aged 12-17 with a body weight above 60 kg and an initial body mass index corresponding to 30 kg/m2 or greater for adults, as an adjunct to reduced-calorie meals and increased physical activity. Saxenda was approved in 2014 for chronic weight management in adults with a BMI greater than or equal to 30 kg/m2, or greater than or equal to 27 kg/m2 with at least one weight-related comorbidity, as an adjunct to a reduced calorie meal plan and increased physical activity. The safety and efficacy of Saxenda as a treatment for adolescents with obesity is supported by data from a phase 3a trial published earlier this year in the New England Journal of Medicine. The 56-week clinical trial investigated the effects of Saxenda compared to placebo for weight management in 251 patients aged 12-17 living with obesity as an adjunct to lifestyle therapy, defined as counselling in healthy nutrition and physical activity for weight loss. In the trial, the primary endpoint was change from baseline in Body Mass Index Standard Deviation Score at week 56.6. The data demonstrated a significant reduction in BMI-SDS, as well as reductions in BMI, mean body weight, and other weight-related endpoints versus placebo in adolescents with obesity when using Saxenda as an adjunct to lifestyle therapy. Adverse events seen in an adolescent population were similar to those observed in adults. The most common adverse reactions were gastrointestinal events, including nausea, vomiting and diarrhea.