On November 1, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported data presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting that highlight the Company’s robust off-the-shelf, allogeneic T-cell immunotherapy pipeline and next-generation CAR T technologies (Press release, Atara Biotherapeutics, NOV 1, 2018, View Source [SID1234530500]). The event will be held December 1-4, 2018, at the San Diego Convention Center in San Diego, CA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to rapidly advance our T-cell and CAR T immunotherapy pipeline across multiple therapeutic areas leveraging cutting edge discoveries by our external collaborators," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Eight highlighted ASH (Free ASH Whitepaper) abstracts include an oral presentation on December 3 that describes a next-generation CAR T technology that may have wide applications including as a component of our pipeline programs in acute myeloid leukemia (AML) and B-cell malignancies. In addition, promising clinical results from our Phase 2 studies of tab-cel for patients with EBV+ PTLD involving the CNS as well as health outcome and treatment pattern assessments for transplant and PTLD patients will be featured. We are pleased with these strong results and continued demonstration of the broad potential of our off-the-shelf, allogeneic T cell platform."

Atara is also scheduled to present tab-cel efficacy and safety results in patients with EBV-associated leiomyosarcoma (EBV+ LMS) solid tumors at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress held December 13-16, 2018, in Geneva, Switzerland.

60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting

Abstract 966: Mutation of the CD28 Costimulatory Domain Confers Increased CAR T Cell Persistence and Decreased Exhaustion
Session: 703. Adoptive Immunotherapy: Preclinical Studies to Improve Safety and Efficacy of CAR-T Cells
Oral Presentation Date and Time: Monday, December 3, 2018 at 5:45 pm PST
Location: Marriott Marquis San Diego Marina, San Diego Ballroom B
Authors: Justin C Boucher, Gongbo Li, Bishwas Shrestha, Maria L Cabral, Dylan Morrissey, Lawrence Guan, Marco L Davila
Affiliations:Moffitt Cancer Center
Summary: The investigators created mutated CAR T cells with mutations in intracellular co-stimulatory domains (PYAP-only CAR T-cell) resulting in reduced cytokine secretion, but maintained cytotoxic activity compared to non-mutated (CD28 CAR T cells). PYAP-only CAR T treated immunocompetent mice showed a significant survival advantage compared to treatment with non-mutated CAR T cells. PYAP-only CAR T cells exhibited increased persistence in spleen and bone marrow. The work enables the development of next-generation CAR T cell therapies with potential improved persistence and reduced toxicities.

Abstract 4590: Adoptive Therapy with EBV-Specific T Cells for Treatment of CNS EBV Post-Transplant Lymphoproliferative Disease Arising after Hematopoietic Stem Cell Transplant or Solid Organ Transplant
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location: Hall GH
Authors: Susan Prockop, MD, Stephanie Suser, Ekaterina Doubrovina, MD, PhD, Hugo R. Castro-Malaspina, MD, Esperanza B. Papadopoulos, MD, James W. Young, MD, Victoria Szenes, PNP, Alison Slocum, MA, Karim Baroudy, MS and Richard J. O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center
Summary: Off-the-shelf, allogeneic EBV-specific T cells (tab-cel) have demonstrated efficacy in the treatment of EBV+ PTLD. However, PTLD involving the central nervous system is particularly challenging due to poor CNS bioavailability of the current available treatment (rituximab). This study evaluated the activity of tab-cel in treating CNS EBV+ PTLD in patients who have failed prior rituximab therapy. The overall response rate was 63% of the 19 patients treated in the study. The one-year overall survival (OS) was 60% with responding and non-responding patients demonstrating a one-year OS of 92% and 14%, respectively. The authors concluded that tab-cel can treat an otherwise often lethal CNS complication of transplantation and that the availability of tab-cel enables early treatment of the disease.

Abstract 4777: Treatment Patterns for Patients with Post-Transplant Lymphoproliferative Disorder Who Fail Rituximab after Allogeneic Hematopoietic Stem Cell Transplantation: Findings from a Systematic Literature Review
Session: 902. Health Services Research—Malignant Diseases: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location: Hall GH
Authors: Hairong Xu, MD, PhD, Crystal Watson, MS, Shan Ashton Garib, MA, Anna Forsythe, PharmD, MSc, MBA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 3556: Estimating Long-Term Survival in a Cohort of Allogeneic Hematopoietic Stem Cell Transplant Patients
Session: 902. Health Services Research—Malignant Diseases: Poster II
Poster Presentation Date & Time: Sunday, December 2, 2018 from 6:00 pm – 8:00 pm PST
Location: Hall GH
Authors: Stephen Palmer, MSc, Casey Quinn, PhD, MPhil, Crystal Watson, MS and Arie Barlev, PharmD
Affiliations:Centre for Health Economics, University of York, PRMA Consulting Ltd., Atara Biotherapeutics

Abstract 4596: Dual-Sensitized T-Cells Responding to EBV Blcl and Either CMVpp65 or WT-1 Peptide Pools Have Distinct or Shared HLA Restrictions That May Depend on the Presenting HLA Alleles
Session: 723. Clinical Allogeneic and Autologous Transplantation
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location: Hall GH
Authors: Ekaterina Doubrovina, MD, PhD, Aisha N. Hasan, MD, Susan Prockop, MD, Karim Baroudy, MS, and Richard O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center

Abstract 5839: A Systematic Literature Review of Real-World Evidence in Post-Transplant Lymphoproliferative Disorder
Authors: Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Arie Barlev, PharmD, Nazia Rashid, PharmD and Crystal Watson, MS
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5841: Younger Patients Are Impacted By Post-Transplant Lymphoproliferative Disorder: Findings from a Systematic Literature Review of Real-World Evidence
Authors: Crystal Watson, MS, Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Shan Ashton Garib, MA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5840: Risk of Patients Developing Post-Transplant Lymphoproliferative Disorder within the First Year after an Allogeneic Hemopoietic Stem Cell Transplant, 2011 to 2016: A US Claims Database Analysis
Authors: Arie Barlev, PharmD, Hairong Xu, MD, PhD, Nicole Fulcher, MA, Crystal Watson, MS, Ila Sruti, MPH and Akshay Sudhindra, MD
Affiliations:Atara Biotherapeutics, IBM Watson Health

European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2018

Abstract 222 (Session 37): Efficacy and safety of tabelecleucel in patients with Epstein‑Barr Virus-associated leiomyosarcomas (EBV+ LMS)
Oral Presentation Date and Time: Saturday, December 15, 2018 at 8:05 a.m.
Location: Room A, Palexpo Exhibition Centre, Geneva, Switzerland
Authors:L.S. Kurlander, A. Srinivasan, A. Ghobadi, S. Suser, E. Doubrovina, F. Boulad, L. Mascarenhas, M. Laquaglia, A. Price, G. Behr, B. Shulkin, A. Sudhindra, Y. Wei, M. Hiremath, W. Navarro, R. O’Reilly, S. Prockop
Affiliations: Weill Cornell New York Presbyterian Hospital, St. Jude Children’s Research Hospital, Washington University School of Medicine, Children’s Hospital of Los Angeles, Atara Biotherapeutics, Memorial Sloan Kettering Cancer Center

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) represents a life-threatening condition. Median overall survival in patients with EBV+ PTLD following HCT who have failed rituximab-based first line therapy is 16-56 days. In EBV+ PTLD following SOT, patients failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is 36% and 0%, respectively.

About tab-cel (tabelecleucel)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. Atara also received positive regulatory feedback from Health Canada in September 2017 supporting the submission of tab-cel for an expedited approval pathway. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara is planning a Phase 1/2 study in NPC.

On November 1, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that ten abstracts have been selected for presentation, including three oral presentations, at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting being held December 1-4, 2018 in San Diego (Press release, Karyopharm, NOV 1, 2018, View Source [SID1234530516]). Four key abstracts to be presented at the meeting will feature clinical data for selinexor, the Company’s first in class, oral SINE compound, from Karyopharm-sponsored trials. The presentations will include: top-line results from the Phase 2b SADAL study in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), additional data from the pivotal Phase 2b STORM study in patients with penta-refractory multiple myeloma, and updated data from the Darzalex (daratumumab) and Pomalyst (pomalidomide) arms of the Phase 1b/2 STOMP study of selinexor in combination with backbone therapies for the treatment of patients with relapsed or refractory multiple myeloma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With ten abstracts to be presented at this year’s ASH (Free ASH Whitepaper) meeting, we believe the depth and breadth of the selinexor clinical data is highly compelling," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "We look forward to the presentation of top-line results from the fully enrolled SADAL study in DLBCL. These data, if positive, could support our second planned New Drug Application in the first half of 2019, with a request for accelerated approval for selinexor as a new treatment for patients with relapsed or refractory DLBCL. In the previously reported interim analysis for the Phase 2b SADAL study, single-agent oral selinexor demonstrated activity and independently-confirmed durable responses in patients with heavily pretreated DLBCL, and these responses correlated to improved overall survival. We are delighted that data from the selected research abstracts will be shared with the medical community at ASH (Free ASH Whitepaper) this year."

In addition to top-line data from the SADAL study, this year’s ASH (Free ASH Whitepaper) meeting will also feature updated data from the STORM study in an oral presentation. As part of this presentation, data from an independent database of patients with heavily pretreated myeloma will also be presented, further underscoring how poor the prognosis is for patients with penta-refractory multiple myeloma. In October 2018, the U.S. FDA accepted Karyopharm’s New Drug Application for selinexor seeking accelerated approval as a new treatment for patients with penta-refractory multiple myeloma. The FDA has assigned a Priority Review and given an action date of April 6, 2019 under the Prescription Drug User-Fee Act (PDUFA).

Other key abstracts at the meeting include data from two arms of the Phase 1b/2 STOMP study. There will be an oral presentation with updated data from the arm evaluating selinexor in combination with Darzalex and low-dose dexamethasone (SDd). In previously reported data, the once weekly SDd combination without a proteasome inhibitor or immunomodulatory drug demonstrated high response rates in the patient population as a doublet regimen. Finally, a poster presentation will highlight updated data from the arm evaluating selinexor in combination with Pomalyst and low-dose dexamethasone (SPd). In data reported previously from these arms, selinexor demonstrated evidence of synergistic anti-myeloma activity when combined with these standard approved therapies.

Details for the ASH (Free ASH Whitepaper) 2018 presentations are as follows:

Oral Presentations – Company-Sponsored Trials

Title:Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta-Refractory MM
Presenter:Ajai Chari, Icahn School of Medicine at Mount Sinai, New York, New York
Abstract Number/Publication ID: 598
Session: 653. Myeloma: Therapy, excluding Transplantation: Antibodies and Targeted Therapies
Date and Time:Monday, December 3, 2018; 7:45 AM PT
Location:San Diego Convention Center, Room 6F

Title:Deep and Durable Responses with Selinexor, Daratumumab, and Dexamethasone (SDd) in Patients with Multiple Myeloma (MM) Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs: Results of Phase 1b Study of SDd
Presenter:Cristina Gasparetto, Duke University Cancer Center, Durham, North Carolina
Abstract Number/Publication ID: 599
Session: 653. Myeloma: Therapy, excluding Transplantation: Antibodies and Targeted Therapies
Date and Time:Monday, December 3, 2018; 8:00 AM PT
Location:San Diego Convention Center, Room 6F

Oral Presentations – Investigator-Sponsored Trials

Title:Selinexor, a First-in-Class XPO1 Inhibitor, Is Efficacious and Tolerable in Patients with Myelodysplastic Syndromes Refractory to Hypomethylating Agents
Presenter:Virginia M. Klimek, Memorial Sloan Kettering Cancer Center, New York, New York
Abstract Number/Publication ID: 233
Session: 637. Myelodysplastic Syndromes—Clinical Studies: Novel Therapeutics I
Date and Time:Saturday, December 1, 2018; 5:00 PM PT
Location: Manchester Grand Hyatt San Diego, Grand Hall A

Poster Presentations – Company-Sponsored Trials

Title: Single Agent Oral Selinexor Demonstrates Deep and Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study
Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium
Abstract Number/Publication ID: 1677
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster I
Date and Time:Saturday, December 1, 2018; 6:15-8:15 PM PT
Location:San Diego Convention Center, Hall GH

Title:Selinexor Plus Pomalidomide and Low Dose Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma
Presenter:Christine Chen, Princess Margaret Cancer Center, Toronto, Ontario
Abstract Number/Publication ID: 1993
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Date and Time:Saturday, December 1, 2018; 6:15-8:15 PM PT
Location:San Diego Convention Center, Hall GH

Poster Presentations – Investigator-Sponsored Trials

Title:Phase I Study of the Selinexor in Relapsed/Refractory Childhood Acute Leukemia
Presenter:Andrew E. Place, Dana-Farber Cancer Institute and Boston Children’s Hospital, Boston, Massachusetts
Abstract Number/Publication ID: 1405
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Date and Time:Saturday, December 1, 2018; 6:15 PM PT
Location:San Diego Convention Center, Hall GH

Title:E2F1 Is a Biomarker of Selinexor Resistance in Relapsed/Refractory Multiple Myeloma Patients
Presenter:Alessandro Lagana, Icahn School of Medicine at Mount Sinai, New York, New York
Abstract Number/Publication ID: 3216
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster II
Date and Time:Sunday, December 2, 2018; 6:00-8:00 PM PT
Location:San Diego Convention Center, Hall GH

Title:Final results from a phase I trial combining selinexor with high-dose cytarabine (HiDAC) and mitoxantrone (Mito) for remission induction in acute myeloid leukemia (AML)
Presenter:Hongtao Liu and Amy Wang, University of Chicago Medicine, Chicago, Illinois
Abstract Number/Publication ID: 4073
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Date and Time:Monday, December 3, 2018; 6:00-8:00 PM PT
Location:San Diego Convention Center, Hall GH

Title:NAMPT inhibitor KPT-9274 selectively targets self-renewal capacity in acute myeloid leukemia
Presenter:Shaneice Mitchell, Ohio State University College of Medicine, Columbus, Ohio
Abstract Number/Publication ID: 3931
Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster III
Date and Time:Monday, December 3, 2018; 6:00-8:00 PM PT
Location:San Diego Convention Center, Hall GH

Title:Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT) Activity Selectively Targets Human Acute Myeloid Leukemia Stem Cells
Presenter:Amit Subedi, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario
Abstract Number/Publication ID: 3932
Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases
Date and Time: Monday, December 3, 2018; 6:00-8:00 PM PT
Location: San Diego Convention Center, Hall GH

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,600 patients have been treated with selinexor. In April and September 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On November 1, 2018 bluebird bio, Inc. (Nasdaq: BLUE) reported that new data from its early- and late-stage investigational gene and cell therapy programs will be presented during the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California, December 1 – 4 (Press release, bluebird bio, NOV 1, 2018, View Source [SID1234530576]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The breadth of data we are presenting at ASH (Free ASH Whitepaper) illustrates the potential of our gene and cell therapies to provide meaningful benefits to people living with severe diseases," said David Davidson, M.D., chief medical officer, bluebird bio. "Our presentations will include data from the pivotal trials of LentiGlobin gene therapy in patients with transfusion-dependent β-thalassemia, bluebird bio’s first treatment under review for potential approval by the European Medicines Agency. We will also share updated data from our study of LentiGlobin in patients with sickle cell disease and initial results from our next generation anti-BCMA CAR T therapy, bb21217, in patients with relapsed/refractory multiple myeloma."

bluebird bio will present initial data from patients with transfusion-dependent β-thalassemia (TDT) with a β0/β0 genotype treated with LentiGlobingene therapy in the Phase 3 Northstar-3 (HGB-212) study as well as updated results, including up to 3.5 years of follow-up, from the completed Phase 1/2 Northstar study (HGB-204).

Abstracts outlining bluebird bio’s accepted data at ASH (Free ASH Whitepaper) will be available on the ASH (Free ASH Whitepaper) conference website at 9:00 a.m. EDT today.

First Data from Clinical Programs

Initial Results from a Phase 1 Clinical Study of bb21217, a Next-Generation Anti-BCMA CAR T Therapy
Presenter: Nina Shah, M.D., University of California San Francisco, San Francisco, Calif.
Date & Time:Sunday, December 2, 2018, 4:45 p.m. PST (7:45 p.m. EST)

bluebird bio’s lead oncology programs, bb2121 and bb21217, are anti-BCMA CAR T programs partnered with Celgene. bb21217 is a next-generation anti-BCMA CAR T cell therapy using the bb2121 CAR molecule with a manufacturing process designed to improve T cell persistence. bb21217 has exhibited improved persistence and increased anti-tumor activity in preclinical animal studies.

This presentation will include early data from the Phase 1 CRB-402 study of bb21217 in patients with relapsed/refractory multiple myeloma. CRB-402 is a two-part (dose escalation and dose expansion), open label, multi-site Phase 1 study of bb21217 in adults with relapsed/refractory multiple myeloma with a projected final enrollment of 50 patients.

Data in the abstract include results as of the data cutoff date of June 15, 2018 for eight patients who have received bb21217. These patients had a median of nine prior lines of therapy (4 – 17 lines) and all received a dose of 150 x 106 CAR+ T cells. The median follow-up after bb21217 infusion was 16 weeks (2 – 27 weeks).

The adverse events observed as of the data cut-off were consistent with known toxicities of CAR T therapies. Five of eight patients developed cytokine release syndrome (CRS); one Grade 1, three Grade 2 and one Grade 3 case. All responded to supportive care with or without tocilizumab. This included one patient with high tumor burden who experienced dose-limiting toxicity (DLT) consisting of Grade 3 CRS and Grade 4 encephalopathy with signs of posterior reversible encephalopathy syndrome on MRI. This patient received tocilizumab, corticosteroids and cyclophosphamide, improved neurologically and achieved a stringent complete response (sCR). Following this event, the dose escalation cohort was divided into two groups based on tumor burden and dosing continued at 150 x 106 CAR+ T cells.

Seven patients were evaluable for initial (one-month) clinical response. Six of seven patients demonstrated clinical response per the International Myeloma Working Group (IMWG) Uniform Response Criteria for multiple myeloma, including one sCR, three very good partial responses (VGPR) and two partial responses (PR). Robust CAR+ T cell expansion during the first 30 days was observed in seven of seven evaluable patients and the two patients evaluable at six months both had CAR vector copies detectable in peripheral blood.

This study is ongoing to evaluate the potential safety and efficacy of treatment with bb21217 and updated results will be shared at the ASH (Free ASH Whitepaper) conference.

Flipping the Switch: Initial Results of Genetic Targeting of the Fetal to Adult Globin Switch in Sickle Cell Patients
Presenter:Erica Esrick, M.D., Pediatric Hematology and Oncology, at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, Mass.
Date & Time:Monday, December 3, 2018, 6:45 p.m. PST (9:45 p.m. EST)

This presentation will include early data from the investigator-initiated Phase 1 study of shRNAmiR lentiviral vector (LVV) targeting BCL11A for autologous gene therapy in SCD. As of July 28, 2018, one patient had received treatment with BCL11a shRNAmiR. In the patient’s immature red blood cells, expression of the BCL11A protein was reduced by approximately 90 percent compared to levels prior to gene therapy. At 76 days following treatment this patient had a sustained overall hemoglobin of >10 g/dL and, compared to what was observed pre-gene therapy, there was a notable absence of irreversibly sickled cells as assessed by peripheral blood smear, a blood test used to identify abnormalities in the number or shape of blood cells.

Adverse events were consistent with myeloablative conditioning, and there have been no product-related adverse events and no SCD-related complications. Updated results will be shared at the ASH (Free ASH Whitepaper) conference.

Oral Presentations

LentiGlobin for Transfusion-Dependent β-Thalassemia

Clinical Outcomes of LentiGlobin Gene Therapy for Transfusion-Dependent β-Thalassemia Following Completion of the Northstar HGB-204 Study (Abstract #167)
Presenter:John Rasko, Ph.D., Central Clinical School Centenary Institute of Cancer Medicine & Cell Biology, University of Sydney, Sydney, Australia
Date & Time: Saturday, December 1, 2018, 3:00 – 3:15 p.m. PST (6:00 – 6:15 p.m. EST), Room 30D
LentiGlobin Gene Therapy for Patients with Transfusion-Dependent β-thalassemia (TDT): Results from the Phase 3 Northstar-2 and Northstar-3 Studies (Abstract #1025)
Presenter:Franco Locatelli, M.D., Ph.D., Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
Date & Time:Monday, December 3, 2018, 7:15 – 7:30 p.m. PST (10:15 – 10:30 p.m. EST), Room 6B
LentiGlobin for Sickle Cell Disease

Current Results of LentiGlobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under Refined Protocol (Abstract #1026)
Presenter:John Tisdale, M.D., National Heart, Lung and Blood Institute, Bethesda, Md.
Date & Time:Monday, December 3, 2018, 7:30 – 7:45 p.m. PST (10:30 – 10:45 p.m. EST), Room 6B
bb21217 for Relapsed/Refractory Multiple Myeloma

Initial Results from a Phase 1 Clinical Study of bb21217, a Next-Generation Anti-BCMA CAR T Therapy (Abstract #488)
Presenter: Nina Shah, M.D., University of California San Francisco, San Francisco, Calif.
Date & Time: Sunday, December 2, 2018, 4:45 – 5:00 p.m. PST (7:45 – 8:00 p.m. EST), Room 6B
BCL11a shRNAmiR for Sickle Cell Disease

Flipping the Switch: Initial Results of Genetic Targeting of the Fetal to Adult Globin Switch in Sickle Cell Patients (Abstract #801)
Presenter:Erica Esrick, M.D., Pediatric Hematology and Oncology, Boston Children’s Hospital, Boston, Mass.
Date & Time:Monday, December 3, 2018, 6:45 – 7:00 p.m. PST (9:45 – 10:00 p.m. EST), Room 6B
Preclinical Presentations

Knockout of CBLB Greatly Enhances Anti-Tumor Activity of CAR T Cells (Abstract #338)
Presenter:Kathryn Hooper, bluebird bio, Cambridge, Mass.
Date & Time: Sunday, December 2, 2018, 9:45 – 10:00 a.m. PST (12:45 – 1:00 p.m. EST), Room 28D
Persistence of CRISPR/Cas9-edited Hematopoietic Repopulating Cells with Therapeutically Relevant Reactivation of Fetal Hemoglobin in Nonhuman Primates (Abstract #806)
Presenter:Olivier Humbert, Fred Hutchinson Cancer Center, Seattle Children’s Hospital, Seattle, Wash.
Date & Time:Monday, December 3, 2018, 3:00 – 3:15 p.m. PST (6:00 – 6:15 p.m. EST), Grand Hall C
Poster Presentations

LentiGlobin for Sickle Cell Disease

Outcomes for Initial Patient Cohorts with Up To 33 Months of Follow-up in the HGB-206 Phase 1 Trial (Abstract #1080)
Presenter:Julie Kanter, M.D., Medical University of South Carolina, Charleston, S.C.
Date & Time:Saturday, December 1, 2018, 6:15 – 8:15 p.m. PST (9:15 – 11:15 p.m. EST), Hall GH
Analysis of RBC Properties in Patients with SCD Treated with LentiGlobin Gene Therapy (Abstract #2195)
Presenter:Nicolas Hebert, St. Anthony Research Center, Paris, France
Date & Time: Saturday, December 1, 2018, 6:15 – 8:15 p.m. PST (9:15 – 11:15 p.m. EST), Hall GH
Characterizing the U.S. Population with Severe Manifestations of Sickle Cell Disease Using Real-World Evidence (Abstract #4811)
Presenter:Clark Paramore, bluebird bio, Cambridge, Mass.
Date & Time:Monday, December 3, 2018, 6:00 – 8:00 p.m. PST (9:00 – 11:00 p.m. EST), Hall GH
Investor Event & Webcast Information
bluebird bio will host a live webcast of an investor and analyst event at 8:30 p.m. PST (11:30 p.m. EST) on Monday, December 3, 2018, during the ASH (Free ASH Whitepaper) Annual Meeting. To access the webcast, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcast will be available on the bluebird bio website for 90 days following the call.

About LentiGlobin
LentiGlobin is an investigational one-time gene therapy being studied as a potential treatment to address the underlying genetic cause of transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD).

bluebird bio’s clinical development program for LentiGlobin includes ongoing studies around the world with sites in Australia, Germany, Greece, France, Italy, Thailand, the United Kingdom and the United States. In addition, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for TDT and SCD.

The European Medicines Association (EMA) granted Priority Medicines (PRIME) eligibility and Orphan Medicinal Product designation to LentiGlobin for the treatment of TDT and SCD. LentiGlobin is also part of the EMA’s Adaptive Pathways pilot program, which is part of the EMA’s effort to improve timely access for patients to new medicines.

The U.S. Food and Drug Administration granted LentiGlobin Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT and SCD.

On November 1, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported financial results for the third quarter ended September 30, 2018, and provided a business update (Press release, Corvus Pharmaceuticals, NOV 1, 2018, View Source [SID1234530625]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to make significant progress in the clinic both with CPI-444 and with CPI-006," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We are encouraged by ongoing presentation of data related to both programs at medical meetings and in peer-reviewed journals. This includes biomarker data for CPI-444 that our team presented at the ESMO (Free ESMO Whitepaper) 2018 Congress on October 22, 2018. We also are looking forward to presenting additional new clinical and biomarker data for both programs at the SITC (Free SITC Whitepaper) annual meeting on November 9 and 10, 2018. Our progress continues to demonstrate that we are a leader in designing and developing medicines that modulate the adenosine pathway and that have demonstrated efficacy as monotherapies and in combination with other agents. We are also advancing our ITK inhibitor, CPI-818, toward the clinic and expect to initiate a clinical trial in early 2019."

Recent Achievements
CPI-444: A2A Receptor Antagonist of Adenosine

Continued enrollment of up to 50 patients with renal cell cancer (RCC) in an amended Phase 1/1b clinical trial evaluating CPI-444, the Company’s lead product candidate, administered alone and in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 antibody. Patients in the study have failed no more than two prior treatment regimens, which must have included an anti-PD-(L)1 and a tyrosine kinase inhibitor, compared to having failed up to five (median three) prior treatment regimens in prior CPI-444 studies.
Continued enrollment of up to 60 patients with non-small cell lung cancer (NSCLC) in a Phase 1b/2 trial being conducted by Genentech as part of their MORPHEUS platform. The study is evaluating CPI-444 and Tecentriq in patients who have failed no more than two prior regimens.
CPI-444 preclinical study results were published in and featured on the cover of the October issue of the journal Cancer Immunology Research, which is an official journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The results demonstrated that CPI-444 induces dose dependent anti-tumor responses as a monotherapy and in combination with anti-PD-1, anti-PD-L1 and anti-CTLA-4 therapies.
Presented new data on the "adenosine gene signature," a biomarker associated with patient response to therapy with CPI-444, in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress.
CPI-006: Anti-CD73 Antibody

Continued enrollment of up to 350 patients with advanced cancer in a Phase 1/1b clinical trial evaluating CPI-006 as a single agent and in combination with CPI-444, and in combination with an anti-PD-1. The trial is designed to select the dose and evaluate the safety, pharmacokinetics, immune biomarkers and efficacy in patients with NSCLC, RCC, and other cancers who have failed standard therapies.
CPI-818: A small molecule ITK inhibitor

Plan to submit an Investigational New Drug (IND) filing for CPI-818, the Company’s interleukin-2-inducible kinase (ITK) inhibitor, in early 2019.
Preclinical data on CPI-818 to be presented by Douglas H. Thamm, VMD, DACVIM (Oncology) at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium, November 13 through 16, 2018 in Dublin, Ireland.
Financial Results

As of September 30, 2018, Corvus had cash, cash equivalents and marketable securities totaling $122.6 million. This compared to cash, cash equivalents and marketable securities of $90.1 million at December 31, 2017.

Research and development expenses for the three months ended September 30, 2018 totaled $8.4 million compared to $10.7 million for the same period in 2017. The decrease of $2.3 million was primarily due to a decrease in CPI-444 clinical trial expenses.

General and administrative expenses for the three months ended June 30, 2018 totaled $2.8 million compared to $2.2 million for the same period in 2017. The increase of $0.6 million was primarily due to an increase of $0.3 million in patent and public company expenses, and an increase of $0.2 million in personnel costs.

The net loss for the three months ended September 30, 2018 was $10.5 million compared to $12.7 million for the same period in 2017. Total stock compensation expense for the three months ended September 30, 2018 was $1.8 million compared to $1.5 million for the same period in 2017.

On November 1, 2018 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, reported that members of the management team will participate at the following upcoming investor conferences (Press release, Arcus Biosciences, NOV 1, 2018, View Source [SID1234530658]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Credit Suisse 27th Annual Healthcare Conference in Scottsdale, AZ on Tuesday, November 13, 2018, at 4:35 pm MT.
Piper Jaffray 30th Annual Healthcare Conference in New York City, NY on Tuesday, November 27, 2018, at 3:50 pm ET.
Evercore ISI HealthCONx in Boston, MA on Wednesday, November 28, 2018, at 10:15 am ET.
To access the live audio webcast of the presentations, please visit the "Events & Presentations" section of the Arcus website at View Source A replay of the webcast will be available for 30 days following the live event.