On November 4, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, reported that investigators involved with the Phase 1/2a study of PBCAR0191 in Relapsed/Refractory (R/R) non-Hodgkin’s lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL), will present new data during two oral presentations at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 11-14, 2021 (Press release, Precision Biosciences, NOV 4, 2021, View Source [SID1234594365]).

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"We are encouraged by the response rates seen in this heavily pre-treated patient population, and that a treatment strategy with enhanced lymphodepletion mitigated PBCAR0191 rejection and improved peak CAR T cell expansion and persistence, compared to standard lymphodepletion, with predictable toxicity," said Alan List, MD, Chief Medical Officer of Precision BioSciences. "We look forward to sharing additional patient outcome, durability, and safety data for PBCAR0191 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting."

The abstracts accepted by the ASH (Free ASH Whitepaper) are now available at www.hematology.org, and will be presented during the following oral presentation sessions:

Session Name: 626, Abstract #302. Aggressive Lymphomas Prospective Therapeutic Trials: Challenging Populations
Oral Presentation Title: Allogeneic CAR-T PBCAR0191 with Intensified Lymphodepletion is Highly Active in Subjects with Relapsed/Refractory B-cell Malignancies
Presenting Author: Bijal Shah, M.D., Moffitt Cancer Center
Date/Time: Saturday, December 11, 2021 at 4:15 PM ET
Location: Georgia World Congress Center, B401-B402

Session Name: 704, Abstract #650 Cellular Immunotherapies: Allogeneic CARs and CARs for T Cell Lymphomas
Oral Presentation Title: Preliminary Safety and Efficacy of PBCAR0191, an Allogeneic ‘Off-the-Shelf’ CD19-Directed CAR-T for Patients with Relapsed/Refractory (R/R) CD19+ B-ALL
Presenting Author: Nitin Jain, M.D., The University of Texas MD Anderson Cancer Center
Date/Time: Monday, December 13, 2021 at 10:45 AM ET
Location: Georgia World Congress Center, Sidney Marcus Auditorium

Published abstracts report on key interim clinical evaluations of CD19+ NHL or B-ALL subjects treated with PBCAR0191.

Abstract #302: For 21 subjects with Relapsed/Refractory (R/R) B-cell malignancies (16 NHL, 5 B-ALL) who received PBCAR0191 following enhanced lymphodepletion1 as of July 1, 2021:

PBCAR0191 demonstrated a safety profile with no Grade 3 CRS, one Grade 3 self-limited ICANS, no evidence of GvHD, and one infectious death at Day 54, deemed possibly related to treatment.
83% (15/18) of evaluable subjects experienced a complete response (CR) rate or complete remission with incomplete marrow recovery (CRi); 62% (8/13) of NHL subjects and 80% (4/5) of B-ALL subjects, respectively.
20% (3/15) of responders demonstrated durability of response greater than 6 months, with 3 additional responders not yet having reached a 6-month evaluation threshold.
Compared to standard lymphodepletion2, enhanced lymphodepletion mitigated PBCAR0191 rejection to markedly improve peak CAR T cell expansion and persistence with area under the curve increasing 80-fold.
Among 6 subjects who progressed following prior CD19 CAR therapy (5 NHL, 1 B-ALL), the overall response rate was 83% (5/6) with 67% (4/6) achieving a CR, including an ongoing MRD negative CR in a B-ALL subject of >6 months.
Abstract #650: For 15 subjects with R/R B-cell acute lymphoblastic leukemia including 11 subjects who received PBCAR0191 Dose Level 3/4a3 and 4 subjects who received PBCAR0191 Dose Level 4b4 as of August 2, 2021:

PBCAR0191 demonstrated a safety profile with no cases of GvHD, no Grade ≥3 CRS, and one case of Grade 3 ICANS, which resolved within 48 hours.
For subjects who received either Dose Level 3/4a following enhanced lymphodepletion or Dose Level 4b following standard lymphodepletion, 78% (7/9) achieved a high CR or CRi rate; 56% (5/9) maintained the CR at day 28 or later potentially securing an adequate window to bridge to allogeneic stem cell transplant.
Use of enhanced lymphodepletion or higher doses of PBCAR0191 resulted in substantial improvements in peak CAR T cell expansion and area under the curve.

On November 4, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported that two abstracts related to the Company’s selective PTEFb/CDK9 inhibitor, VIP152, program have been accepted for presentation at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, to be held December 11-14, 2021 in Atlanta, GA (Press release, Vincerx Pharma, NOV 4, 2021, View Source [SID1234594364]). The following abstracts were published today and are now available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

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VIP152, a selective CDK9 inhibitor, induces complete regression of high-grade B-cell lymphoma (HGBL) models and depletion of short-lived oncogenic driver transcripts, MYC and MCL1, with a once weekly schedule. (Abstract #1192)

Session Name: Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms

Date: Saturday, December 11, 2021

Time: Poster viewing 9:00am-7:30pm; presenters available 5:30-7:30pm ET

Location: Hall B5

VIP152 Is a Novel CDK9 Inhibitor with Efficacy in Chronic Lymphocytic Leukemia (Abstract #270)

Session Name: Chemical Biology and Experimental Therapeutics

Date: Saturday, December 11, 2021

Time: Oral Presentation at 3:15 ET

Location: Georgia World Congress Center, C108-C109

On November 4, 2021 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies to block the CD47 checkpoint pathway, reported the Company will be presenting early clinical data from ASPEN-02, its ongoing Phase 1/2 study evaluating evorpacept in combination with azacitidine for the treatment of myelodysplastic syndromes ("MDS") in a poster presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting held December 11-14, 2021 in Atlanta, Georgia (Press release, ALX Oncology, NOV 4, 2021, View Source [SID1234594363]).

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Key Abstract Data

As of July 15, 2021, 13 subjects with newly diagnosed ("ND") higher risk or relapsed/refractory ("R/R") MDS were enrolled into phase 1 cohorts receiving escalating doses of evorpacept (20 mg/kg Q2W, 30 mg/kg Q2W, and 60 mg/kg Q4W) combined with standard doses of azacitidine. Of the 7 ND subjects, 4 had therapy-related MDS, and 5 had TP53 mutation with complex cytogenetics. Of the 6 R/R subjects, all had received at least one hypomethylating agent-based regimen.

Among the 5 ND subjects evaluable for response (all with TP53 mutation), there were 2 subjects with cytogenetic response who met criteria for complete response ("CR") subsequent to the date of this abstract, 1 subject with a best response of marrow complete response ("mCR") with hematologic improvement ("HI"), and 1 subject each with stable disease ("SD") and progressive disease ("PD"). Of the 4 ND subjects who were transfusion dependent at baseline, 2 achieved transfusion independence. Among the 5 R/R subjects evaluable for response, there were 2 subjects with a best response of mCR, 2 with SD, and 1 with PD. No dose-limiting toxicities were observed in any cohort and no maximum tolerated dose was reached. Additional results will be presented at the conference.

Poster Presentation Details

Title: Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint Inhibitor, in Combination with Azacitidine: A Phase 1/2 Study in Patients with Myelodysplastic Syndrome (ASPEN-02)

Session Name: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster II

Presentation Date and Location: December 12, 2021, 6:00pm – 8:00pm ET, Georgia World Congress Center, Hall B5

Publication Number: 2601

On November 4, 2021 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that clinical data for HM43239, a myeloid kinome inhibitor in-licensed by Aptose (announced separately today – link) is being presented in an oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held Saturday, December 11 – Monday, December 14, 2021 in Atlanta, GA and virtually (Press release, Aptose Biosciences, NOV 4, 2021, View Source [SID1234594362]). In addition, clinical data for luxeptinib, a dual lymphoid and myeloid inhibitor, and for APTO-253, a small molecule MYC oncogene repressor, have been accepted for poster presentation.

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The abstracts accepted for presentation are listed below and can be viewed online at the ASH (Free ASH Whitepaper) conference website. Note that the presentations will include additional data not found in the abstracts. Aptose also will be holding an investor event during the ASH (Free ASH Whitepaper) timeframe to provide up-to-date data. Details will be forthcoming.

Oral Presentation Details

Publication #702: First in Human FLT3 and SYK Inhibitor HM43239 Shows Single Agent Activity in Patients with Relapsed or Refractory FLT3 Mutated and Wild-Type Acute Myeloid Leukemia (AML)
Oral Presentation Session Date & Time: Monday, December 13, 2021, 4:00 PM ET
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Targeted Therapies and Novel Therapies
Location: Georgia World Congress Center, Georgia Ballroom 1-3

Poster Presentation Details

Publication #1355: A Phase 1 a/b Dose Escalation Study of the Mutation Agnostic BTK/FLT3 Inhibitor Luxeptinib (CG-806) in Patients with Relapsed or Refractory B-Cell Malignancies
Poster Session Date & Time: Saturday, December 11, 2021, 5:30 – 7:30 PM ET
Session Name: 623. Mantle Cell, Follicular, and other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Location: Georgia World Congress Center, Hall B5

Publication #1272: A Phase 1 a/b Dose Escalation Study of the Mutation Agnostic FLT3/BTK Inhibitor Luxeptinib (CG-806) in Patients with Relapsed or Refractory Acute Myeloid Leukemia
Poster Session Date & Time: Saturday, December 11, 2021, 5:30 – 7:30 PM ET
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster I
Location: Georgia World Congress Center, Hall B5

Publication #3411: A Phase 1 a/b Dose Escalation Study of the MYC Repressor Apto-253 in Patients with Relapsed or Refractory AML or High-Risk MDS
Poster Session Date & Time: Monday, December 13, 2021, 6:00 – 8:00 PM ET
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Location: Georgia World Congress Center, Hall B5

The poster abstracts also will be published in the November supplemental issue of Blood, an ASH (Free ASH Whitepaper) journal, available online.

On November 4, 2021 bluebird bio, Inc. (Nasdaq: BLUE) reported that new data from its lentiviral vector (LVV) gene addition programs for patients with β-thalassemia (beta-thal) who require regular red blood cell (RBC) transfusions and sickle cell disease will be presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 11-14, 2021, at the Georgia World Congress Center in Atlanta, Georgia, and virtually (Press release, bluebird bio, NOV 4, 2021, View Source [SID1234594360]).

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bluebird bio will present updated efficacy and safety results from its clinical programs, including long-term follow-up results of betibeglogene autotemcel (beti-cel) that demonstrate iron level stabilization in adult and pediatric patients living with beta-thal who require regular RBC transfusions followed for up to seven years; the oral presentation will also be featured in the ASH (Free ASH Whitepaper) press program. Additional beti-cel data include improvement in health-related quality of life among adult and pediatric patients in the HGB-207 and HGB-212 Phase 3 studies.

Updated results from the Phase 1/2 HGB-206 study of LentiGlobin for sickle cell disease gene therapy (bb1111) will also be presented, including new analyses demonstrating improvements in clinical and biologic outcomes, as well as updated and longer-term data from HGB-206 Group C that show sustained improvements in quality of life.

β-Thalassemia Data
Oral Presentation [#573]: Restoring Iron Homeostasis in Patients who Achieved Transfusion Independence After Treatment with Betibeglogene Autotemcel Gene Therapy: Results from up to 7 Years of Follow-up
Presenting Author: Alexis A. Thompson, MD, MPH, Hematology Section Head, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
Date/Time: Monday, December 13, 2021, 11:00 am ET

Poster [#3085]: Improvement in Health-Related Quality of Life Following Treatment with Betibeglogene Autotemcel in Patients with Transfusion-Dependent β-Thalassemia Enrolled in Phase 3 Studies
Presenting Author: Janet L. Kwiatkowski, MD, MSCE, Director, Thalassemia Center at Children’s Hospital of Philadelphia, Philadelphia, PA
Date/Time: Monday, December 13, 2021, 6:00 – 8:00 pm ET

Sickle Cell Disease Data
Oral Presentation [#7]: Sustained Improvements in Patient Reported Quality of Life up to 24 Months Post-treatment with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Presenting Author: Mark C. Walters, MD, Medical Director, Jordan Family Center for BMT & Cellular Therapies Research, UCSF Benioff Children’s Hospital Oakland, Oakland, CA
Date/Time: Saturday, December 11, 2021, 9:30 am ET

Oral Presentation [#561]: Polyclonality Strongly Correlates with Biological Outcomes and is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy
Presenting Author: John F. Tisdale, MD, Chief, Cellular and Molecular Therapeutics Branch, NHLBI, Bethesda, MD
Date/Time: Sunday, December 12, 2021, 5:00 pm ET

Poster [#3093]: Severe Acute Complications of Sickle Cell Disease in two Expert Referral Centers (UK and Italy): Natural History Studies Highlight Ongoing Unmet Need for Effective Disease Modifying or Curative Therapies
Presenting Author: Raffaella Colombatti, MD, PhD, Pediatric Hematologist, University of Padova, Padua, Italy
Date/Time: Monday, December 13, 2021, 6:00 – 8:00 pm ET

Abstracts outlining bluebird bio’s accepted data at ASH (Free ASH Whitepaper) are available on the ASH (Free ASH Whitepaper) conference website.

About betibeglogene autotemcel (beti-cel)
betibeglogene autotemcel (beti-cel) (pronounced beh TEE cell) is a one-time gene therapy custom-designed to treat the underlying cause of beta-thalassemia in patients who require regular transfusions. In order to correct the deficiency of adult hemoglobin that is the hallmark of beta-thalassemia, beti-cel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is beti-cel-derived adult hemoglobin (Hb) at levels that may eliminate or significantly reduce the need for transfusions. In beti-cel studies, transfusion independence (TI) is defined as no longer needing RBC transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL. Across Phase 3 studies, 89% (32/36) of evaluable patients across ages and genotypes, including pediatric patients as young as four years of age and those with the most severe β0/β0 genotypes, achieved TI.

beti-cel is manufactured using the BB305 lentiviral vector (LVV), a third-generation, self-inactivating LVV that has been studied for more than a decade.

Adverse reactions considered related to beti-cel were uncommon and consisted primarily of infusion-related reactions (abdominal pain, hot flush, dyspnea, tachycardia and non-cardiac chest pain) and cytopenias (thrombocytopenia, leukopenia and neutropenia). Pain in extremity shortly after treatment was also documented. One of these adverse events (AE) was a serious adverse event (SAE) of thrombocytopenia considered possibly related to beti-cel.

The majority of AEs and SAEs unrelated to beti-cel were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan (including several SAEs of veno-occlusive disease). The Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies evaluating beti-cel are ongoing; enrollment is complete, and all patients have been treated. bluebird bio is also conducting a long-term follow-up study, LTF-303, to monitor safety and efficacy for people who have participated in bluebird bio-sponsored beti-cel clinical studies through 15 years, post treatment with beti-cel.

A biologics license application (BLA) for beti-cel has been submitted to the FDA.

About LentiGlobin for sickle cell disease (bb1111)
LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational one-time treatment being studied for sickle cell disease, that is designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications. bluebird bio’s clinical development program for LentiGlobin for sickle cell disease includes the completed Phase 1/2 HGB-205 and ongoing Phase 1/2 HGB-206 and Phase 3 HGB-210 studies. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio sponsored clinical studies of LentiGlobin for sickle cell disease.

As of February 17, 2021, a total of 49 patients have been treated with LentiGlobin for SCD, with up to 6 years of patient follow-up, in the HGB-205 (n=3), HGB-206 (n=44) and HGB-210 (n=2) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2) and C (n=35), representing progressive adaptations to the treatment and manufacturing processes. In the Group C cohort of the Phase 1/2 HGB-206 study of LentiGlobin for sickle cell disease, no severe vaso-occlusive events (VOEs) were reported with up to 24 months of follow-up in patients with a history of at least four severe VOEs and at least six months of follow-up.

The safety data profile remains generally consistent with the risks of autologous stem cell transplantation and myeloablative single-agent busulfan conditioning, as well as underlying SCD.

In the Group C cohort of the HGB-206 study, one patient with underlying cardiopulmonary disease and SCD-related complications died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD.

In the initial cohort (Group A) of the HGB-206 study, two patients treated with LentiGlobin for SCD developed acute myeloid leukemia (AML). After thorough investigations into the cases, bluebird bio determined that these were unlikely related to the insertion of bluebird’s lentiviral vector (LVV) gene therapy for SCD.

For more information on LentiGlobin for SCD studies, visit: View Source or clinicaltrials.gov.

The FDA has granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for sickle cell disease.

LentiGlobin for sickle cell disease is investigational and has not been approved in any geography.