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Xencor to Present Initial Data from Phase 1 Study of XmAb®14045 Bispecific Antibody in Acute Myeloid Leukemia at the 2018 ASH Annual Meeting

On November 1, 2018 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported that initial data from its ongoing Phase 1 dose-escalation study of XmAb14045, a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) will be presented in an oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Monday, December 3, 2018 (Press release, Xencor, NOV 1, 2018, View Source [SID1234530578]).

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Key Highlights from the Abstract

At data cut off on June 27, 2018, 63 patients with relapsed/refractory AML and one patient with B cell acute lymphoblastic leukemia had received XmAb14045. Patients had a median age of 61 years and were heavily pretreated, having a median of three prior therapies, and 30% (n=19/64) had undergone prior allogeneic stem cell transplantation.
No MTD was identified, and cytokine release syndrome (CRS) was the most common toxicity occurring in 49 of 64 patients (77%). Seven patients (11%) experienced Grade 3 or 4 CRS. CRS was generally manageable with premedication.
23% of evaluable patients with AML achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest dose levels studied to date (1.3 and 2.3 mcg/kg weekly; n=3/13).
Two patients with responses were bridged to stem cell transplantation, and the third was ineligible but remained in remission at 14+ weeks after initiating therapy.
"Initial results from the ongoing study of our lead bispecific antibody XmAb14045 in heavily pretreated patients with acute myeloid leukemia demonstrate that several patients achieved complete remissions," said Paul Foster, M.D., senior vice president and chief medical offer at Xencor. "XmAb14045 is a full-length immunoglobulin designed to be dosed intermittently. We continue to optimize dosing regimen as we advance the Phase 1 study."

Presentation Details

Abstract:

763

Title:

Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of XmAb14045, a CD123 x CD3 T Cell-Engaging Bispecific Antibody: Initial Results of a Phase 1 Study

Presenter:

Farhad Ravandi, M.D., Professor of Medicine and Chief of Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – M.D. Anderson Cancer Center

Session:

616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: New Treatment Strategies

Date & Time:

Monday, December 3, 2018, 2:45 p.m. PST

Location:

Manchester Grand Hyatt San Diego, Seaport Ballroom F

The accepted abstract is now available on the ASH (Free ASH Whitepaper) conference website.

Analyst & Investor Event and Webcast Information
Xencor will host an analyst and investor event on Monday, December 3, 2018 from 8:00 to 10:00 p.m. PST with formal remarks at 8:30 p.m. PST. The event will feature a discussion of the data presented at ASH (Free ASH Whitepaper) and Xencor’s bispecific oncology pipeline. The event will be webcast live and can be accessed under Events & Presentations in the Investors section of www.xencor.com, where it will be archived for 30 days.

About XmAb14045
XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

bluebird bio Reports Third Quarter 2018 Financial Results and Highlights Operational Progress

On November 1, 2018 bluebird bio, Inc. (NASDAQ: BLUE) reported financial results and business highlights for the third quarter ended September 30, 2018 (Press release, bluebird bio, NOV 1, 2018, View Source [SID1234530577]).

"2018 has been a year of tremendous growth and transition at bluebird, notably exemplified by the filing of our first regulatory application for LentiGlobin in transfusion dependent β-thalassemia (TDT) with the European Medicines Agency (EMA)," said Nick Leschly, chief bluebird. "As we prepare to serve patients with LentiGlobin first in Europe, and later in the U.S., we are advancing the development of our programs in SCD and multiple myeloma, the latter in collaboration with Celgene. We have outlined an accelerated development plan utilizing a surrogate endpoint that we believe allows us to continue to evolve our understanding of the potential of LentiGlobin in patients with SCD. In cerebral adrenoleukodystrophy (CALD), we have regulatory alignment on the path forward and are on track. In multiple myeloma, we and Celgene have begun to lay the plans to bring bb2121 into earlier lines of therapy, while building for the future with bb21217. We look forward to sharing clinical and pre-clinical data across our portfolio – a breadth of progress that is a testament to the tireless work of the bluebird flock."

"The emerging data from our LentiGlobin program in SCD demonstrate the potential to rapidly produce high levels of anti-sickling HbAT87Q that we hope will fundamentally reduce sickling and hemolysis, thereby providing a meaningful increase in total hemoglobin and leading to a reduction in clinical events," said David Davidson, M.D., chief medical officer, bluebird bio. "We continue to have ongoing dialogue with the U.S. Food and Drug Administration (FDA), in the context of our Regenerative Medicine Advanced Therapy (RMAT) designation, and now plan to pursue an accelerated development path that may allow us to initially validate, and then leverage these clinically meaningful biomarkers to form the primary endpoint of a registration-enabling study for patients with a history of vaso-occlusive events (VOEs). We also plan to conduct future clinical investigation of LentiGlobin in patients with other SCD phenotypes, including those at risk of stroke."

Recent Highlights

TDT

LENTIGLOBIN MAA ACCEPTANCE – In October 2018, the EMA accepted for review the company’s marketing authorization application (MAA) for its investigational LentiGlobin gene therapy for the treatment of adolescents and adults with TDT and a non-β0/β0 genotype. LentiGlobin was previously granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA in July 2018, potentially reducing the EMA’s active review time of the MAA from 210 days to 150 days.
SCD

LENTIGLOBIN DEVELOPMENT STRATEGY – Based on ongoing discussions with the FDA, bluebird bio is modifying and expanding its clinical development plans to explore efficacy endpoints that may allow the company to pursue a more accelerated development path in the United States for the treatment of patients with SCD who have a history of VOEs. Enrollment of the HGB-206 study has been expanded to enroll up to 50 adult and adolescent patients. The expanded HGB-206 study has a new primary efficacy endpoint based on HbAT87Q and total hemoglobin, and a key secondary endpoint of frequency of VOEs. As modified, the HGB-206 study will increase the overall set of clinical data regarding the relationship between anti-sickling hemoglobin and clinical outcomes and has the potential to validate the new primary efficacy endpoint as a surrogate endpoint for other SCD clinical outcomes such as VOEs. In 2019, bluebird bio intends to initiate a multi-site, international Phase 3 study of LentiGlobin for the treatment of patients with SCD and a history of VOEs with the same primary and secondary endpoints, and comparable design, as the HGB-206 study. bluebird bio is also engaged in ongoing discussions with the EMA regarding proposed development plans for LentiGlobin in SCD in Europe.
CALD

UPDATED DATA AT THE SOCIETY FOR THE STUDY OF INBORN ERRORS OF METABOLISM SYMPOSIUM – In September 2018, bluebird bio announced updated results from the Phase 2/3 Starbeam study (ALD-102) of its investigational Lenti-D gene therapy in boys 17 years of age and under with CALD, and initial data from ALD-103, the ongoing observational study of outcomes from allogeneic hematopoietic stem cell transplant (allo-HSCT) in boys 17 years of age and under with CALD. bluebird bio has also reached general agreement with the FDA and the EMA to use data from ALD-102 and ALD-103 to support future marketing applications for Lenti-D in CALD.
ALD-104 STUDY – In early 2019, bluebird bio intends to initiate a multi-site Phase 3 study of the Lenti-D product candidate for the treatment of patients with CALD to enable access following completion of enrollment in the Starbeam study, and to evaluate the suitability of additional conditioning regimens for use with the Lenti-D product candidate.
COMPANY

REGENERON COLLABORATION – In August 2018, bluebird bio and Regeneron Pharmaceuticals, Inc. (Regeneron) announced a collaboration to apply their respective technology platforms to the discovery, development and commercialization of novel immune cell therapies for cancer. The collaborators will specifically leverage Regeneron’s VelociSuite technology platforms for the discovery and characterization of fully human antibodies, as well as T cell receptors (TCRs) directed against tumor-specific proteins and peptides, and bluebird bio will contribute its field-leading expertise in gene transfer and cell therapy.
GRITSTONE COLLABORATION – In August 2018, bluebird bio and Gritstone Oncology, Inc. (Gritstone) announced a collaboration to utilize Gritstone’s proprietary technology platform to identify and validate tumor-specific targets and provide TCRs directed to selected targets for use in bluebird’s gene therapy products. bluebird bio will conduct all development, manufacturing and commercial activities.
STRENGTHENED BALANCE SHEET – In July 2018, bluebird bio raised approximately $600.6 million in net proceeds through a public equity offering. bluebird bio anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund operations into 2022 based on the company’s current business plan.
Upcoming Anticipated Milestones

TDT
Presentation of LentiGlobin clinical data from the Northstar (HGB-204) clinical study in patients with TDT at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting
Presentation of LentiGlobin clinical data from the Northstar-2 (HGB-207) clinical study in patients with TDT and non-β0/β0 genotypes at the ASH (Free ASH Whitepaper) Annual Meeting
Presentation of LentiGlobin clinical data from the Northstar-3 (HGB-212) clinical study in patients with TDT and the β0/β0 genotype at the ASH (Free ASH Whitepaper) Annual Meeting
SCD
Presentation of LentiGlobin clinical data from the HGB-206 clinical study in patients with SCD at the ASH (Free ASH Whitepaper) Annual Meeting
Presentation early data from the investigator-initiated Phase 1 study of shRNAmiR lentiviral vector targeting BCL11A for autologous gene therapy in SCD at the ASH (Free ASH Whitepaper) Annual Meeting
Multiple Myeloma
Presentation of bb21217 clinical data from the CRB-402 clinical study in patients with relapsed/refractory multiple myeloma at the ASH (Free ASH Whitepaper) Annual Meeting
Initiation by Celgene of a Phase 3 clinical study of bb2121 in third line multiple myeloma
Third Quarter 2018 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2018 and December 31, 2017 were $2.0 billion and $1.6 billion, respectively. The increase in cash, cash equivalents and marketable securities is primarily related to the completion of a public offering of common stock in July 2018, which raised net proceeds of approximately $600.6 million, and the receipt of $100.0 million from Regeneron made in connection with the company’s collaboration with Regeneron which was entered into in August 2018. The overall increase in cash, cash equivalents and marketable securities was offset by $40.0 million paid to Gritstone in connection with the company’s collaboration with Gritstone, which was also entered into in August 2018, and cash used in operating activities.
Revenues: Total revenues were $11.5 million for the three months ended September 30, 2018 compared to $7.7 million for the three months ended September 30, 2017. Total revenues were $35.3 million for the nine months ended September 30, 2018 compared to $31.3 million for the nine months ended September 30, 2017. The increase in both periods was primarily attributable to increased manufacturing services under the company’s collaboration agreement with Celgene, offset by decreased license and royalty revenue.
R&D Expenses: Research and development expenses were $116.7 million for the three months ended September 30, 2018 compared to $61.5 million for the three months ended September 30, 2017. Research and development expenses were $328.9 million for the nine months ended September 30, 2018 compared to $180.5 million for the nine months ended September 30, 2017. The increase in both periods was driven by costs incurred to advance and expand the company’s pipeline and is attributable to increased clinical trial-related costs and manufacturing costs for development programs, increased laboratory expenses, increased employee-related costs due to headcount growth, and increased license milestones and fees under the company’s strategic collaboration and license agreements.
G&A Expenses: General and administrative expenses were $44.5 million for the three months ended September 30, 2018 compared to $23.0 million for the three months ended September 30, 2017. General and administrative expenses were $120.6 million for the nine months ended September 30, 2018 compared to $64.5 million for the nine months ended September 30, 2017. The increase in both periods was attributable to increases in employee-related costs due to increased headcount to support overall growth, commercial-readiness activities, and professional and consulting fees.
Net Loss: Net loss was $145.5 million for the three months ended September 30, 2018 compared to $78.8 million for the three months ended September 30, 2017. Net loss was $406.6 million for the nine months ended September 30, 2018 compared to $218.4 million for the nine months ended September 30, 2017.
Conference Call & Webcast Information
bluebird bio will host a conference call and live webcast at 8:00 a.m. ET on Friday, November 2, 2018. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the company’s website at www.bluebirdbio.com. Alternatively, investors may listen to the call by dialing (844) 825-4408 from locations in the United States or (315) 625-3227 from outside the United States. Please refer to conference ID number 5595967.

bluebird bio to Present New Data from Early- and Late-Stage Pipeline of Investigational Gene and Cell Therapies at the American Society of Hematology Annual Meeting

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]).

"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.

Magenta Therapeutics Announces Acceptance of Nine Abstracts Covering Clinical and Preclinical Data at ASH, Representing Progress across the Portfolio of Conditioning, Stem Cell Mobilization and Expansion Programs

On November 1, 2018 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of bone marrow transplant to more patients, reported that the Company will present clinical data and preclinical research at the 60th annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), taking place December 1st through 4th in San Diego, Calif (Press release, Magenta Therapeutics, NOV 1, 2018, View Source [SID1234530575]). Preliminary data in these abstracts became available on the ASH (Free ASH Whitepaper) conference website at 9:00 a.m. ET today. The Company also provided an update today on its ongoing Phase 2 study of MGTA-456 in inherited metabolic disorders, including recent data from the study.

ASH Abstracts
"Magenta is developing potentially transformative drugs to broaden the reach of one-time, curative cell therapies – including bone marrow transplant, haploidentical transplant, cell and gene therapy and genome editing – to more patients with devastating diseases, including blood cancers, genetic diseases and autoimmune diseases," said Jason Gardner, D.Phil., president, chief executive officer and co-founder, Magenta Therapeutics. "This year’s nine data presentations at ASH (Free ASH Whitepaper) highlight our patient conditioning, mobilization and stem cell expansion programs, giving further insight into our progress in addressing the major unmet needs of the transplant process, including toxic conditioning regimens, inadequate stem cell mobilization and low cell doses. We anticipate building on this progress over the coming year as we move our mobilization program into the clinic and advance our clinical development plan for stem cell expansion in multiple diseases."

Conditioning Programs

CD117-Amanitin Antibody Drug Conjugates Effectively Deplete Human and Non-Human Primate HSCs: Proof of Concept as a Targeted Strategy for Conditioning Patients for Bone Marrow Transplant, Abstract #3314

Presenter: Brad Pearse, Ph.D., Magenta Therapeutics
Session Name: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster II
Session Date: Sunday, December 2, 2018
Session Time: 6:00 PM – 8:00 PM
Room: San Diego Convention Center, Hall GH

Targeting CD45 with an Amanitin Antibody-Drug Conjugate Effectively Depletes Human HSCs and Immune Cells for Transplant Conditioning, Abstract #4526

Presenter: Rahul Palchaudhuri, Ph.D., Magenta Therapeutics
Session Name: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster III
Session Date: Monday, December 3, 2018
Session Time: 6:00 PM – 8:00 PM
Room: San Diego Convention Center, Hall GH

Single Doses of Antibody Drug Conjugates (ADCs) Targeted to CD117 or CD45 Have Potent In Vivo Anti-Leukemia Activity and Survival Benefit in Patient Derived AML Models, Abstract #3316

Presenter: Jennifer Proctor, Magenta Therapeutics
Session Name: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster II
Session Date: Sunday, December 2, 2018
Session Time: 6:00 PM – 8:00 PM
Room: San Diego Convention Center, Hall GH

Antibody Drug Conjugates Targeted to CD45 or CD117 Enable Allogeneic Hematopoietic Stem Cell Transplantation in Animal Models, Abstract #3324

Presenter: Rahul Palchaudhuri, Ph.D., Magenta Therapeutics
Session Name: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster II
Date: Sunday, December 2, 2018
Presentation Time: 6:00 PM – 8:00 PM
Location: San Diego Convention Center, Hall GH

Non-genotoxic conditioning facilitates robust HSPC engraftment and multi-lineage development in a dose dependent manner in Fanconi anemia

Presenter: Meera Srikanthan, Ph.D., Fred Hutchinson Cancer Research Center
Session Name: TBA
Date: TBA
Presentation Time: TBA
Location: TBA

Preclinical Data, Stem Cell Mobilization Program

MGTA-145 in Combination with Plerixafor Rapidly Mobilizes High Numbers of Hematopoietic Stem Cells and Graft-Versus-Host Disease Inhibiting Myeloid-Derived Suppressor Cells in Non-Human Primates, Abstract #116

Presenter: Kevin Goncalves, Ph.D., Magenta Therapeutics
Session Name: 711. Cell Collection and Processing I
Session Date: Saturday, December 1, 2018
Session Time: 9:30 AM – 11:00 AM
Presentation Time: 9:45 AM
Room: Manchester Grand Hyatt San Diego, Grand Hall A

Clinical Data, MGTA-456 Stem Cell Expansion Program

Preliminary Phase 2 Results Demonstrate Engraftment with Minimal Neutropenia with MGTA-456, a CD34+ Expanded Cord Blood Product in Patients Transplanted for Inherited Metabolic Disorders, Abstract #3467

Presenter: John Wagner, M.D., Director, Blood and Marrow Transplantation Division, University of Minnesota
Session Name: 732. Clinical Allogeneic Transplantation: Results: Poster II
Session Date: Sunday, December 2, 2018
Session Time: 6:00-8:00 p.m. PT
Room: San Diego Convention Center, Hall GH

MGTA-456 Contains Large Numbers of Expanded Cord Blood (CB) CD34+CD90+ Hematopoietic Stem Cells (HSC) Which Confer All Engraftment Activity and Correlate with Accelerated Neutrophil Recovery after Myeloablative Conditioning in Patients with Hematologic Malignancy, Abstract #2083

Presenter: Tony Boitano, Ph.D., Magenta Therapeutics
Session Name: 721 Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities
Session Date: Saturday, December 1, 2018
Session Time: 6:15-8:15 p.m. PTRoom: San Diego Convention Center, Hall GH

Preclinical Data, MGTA-456 Stem Cell Expansion Program

MGTA-456, A First-in-Class Cell Therapy Produced from a Single Cord Blood Unit, Enables A Reduced Intensity Conditioning Regimen and Enhances Speed and Level of Human Microglia Engraftment in the Brains of NSG Mice, Abstract #115

Presenter: Kevin Goncalves, Ph.D., Magenta Therapeutics
Session Name: 711. Cell Collection and Processing
Session Date: Saturday, December 1, 2018
Presentation Time: 9:30 a.m. PT
Room: San Diego Convention Center, Grand Hall A

MGTA-456 Clinical Development Update

MGTA-456 is a cell therapy providing a high dose of hematopoietic stem cells that are well-matched to the patient, administered through a transplant procedure. The ongoing Phase 2 study in inherited metabolic disorders aims to enroll 12 patients with Hurler’s syndrome, cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy or globoid cell leukodystrophy. The primary endpoint is engraftment after transplantation and the secondary endpoint is transplant-related safety and tolerability.

The data as of October 22, 2018 show:

Five patients treated and evaluable: three with Hurler’s syndrome, two with cALD
Five of five patients treated with MGTA-456 met the primary endpoint of successful engraftment by day 42 following the transplant procedure.
In recent historical cohorts of patients undergoing regular cord blood transplantation with identical pre-transplant conditioning, up to 32% did not engraft at comparable time points.
The patients treated with MGTA-456 had minimal neutropenia, lasting for a median of 1 day.
In the historical cohort, neutropenia lasted for a median of 8 days.
Two patients less than 2 years of age with Hurler’s syndrome treated with MGTA-456 in the Magenta study developed autoimmune cytopenia, a known and frequent complication of transplant in these younger patients and patients with Hurler’s syndrome.
The first patient subsequently died from this complication. This was determined to be not related to the MGTA-456 product.
The second patient is currently undergoing treatment for the autoimmune cytopenia.
"Blood stem cell transplantation remains the standard of care for inherited metabolic disorders, which if untreated are generally progressive and lethal. Unfortunately, transplantation remains a difficult and complex procedure," said Paul Orchard, M.D., Medical Director of the Inherited Metabolic & Storage Disease Bone Marrow Transplantation Program, University of Minnesota and principal investigator in the MGTA-456 study. "Many patients experience significant and life-threatening complications, such as dysregulation of the immune system following transplantation, including the emergence of antibodies to components of the blood system. Patients with inherited metabolic disorders, particularly patients with Hurler’s syndrome, are at higher risk for these antibody-associated cytopenias. In a prior transplant protocol using the identical combination of chemotherapy agents for pre-transplant conditioning, evidence of cytopenias was present in 9 of 15 patients under 2 years of age (53%). This has proven less common in older patients."

In light of the elevated incidence of autoimmune cytopenias in very young patients and patients with Hurler’s syndrome, the Company announced today that it has voluntarily focused future enrollment towards pediatric patients older than 2 years of age diagnosed with leukodystrophies. The Company plans to continue enrolling patients with leukodystrophies in the study.

"MGTA-456 is a first-in-class cell therapy with high doses of stem cells, and larger doses of stem cells are correlated with more successful transplant outcomes and faster time to engraftment and immune recovery. It has demonstrated engraftment and robust immune recovery in all 41 evaluable patients that have been treated to date in our Phase 2 study in inherited metabolic disorders and our Phase 1/2 study in blood cancers," said John Davis, M.D., M.P.H., chief medical officer, Magenta Therapeutics. "We are developing MGTA-456 for patients with a broad range of diseases, including leukodystrophies, sickle cell disease and blood cancers, where we believe it has the potential to deliver transformative benefit."

The Company is on track to initiate a Phase 2 study of MGTA-456 in patients with sickle cell disease in the first half of 2019, and an investigator-initiated Phase 2 study in blood cancers is on track to start in 2018.

Genocea Reports Third Quarter 2018 Financial and Operating Results

On November 1, 2018 Genocea Biosciences, Inc. (NASDAQ: GNCA), a biopharmaceutical company developing neoantigen cancer immunotherapies, reported its financial and operating results for the third quarter ended September 30, 2018 (Press release, Genocea Biosciences, NOV 1, 2018, View Source [SID1234530574]).

"In the year since our strategic pivot, we have made significant progress by advancing our lead cancer vaccine candidate, GEN-009, into the clinic and using our ATLAS platform to identify and characterize the T cell responses cancer patients make to both tumor-associated antigens and neoantigens," said Chip Clark, president & CEO of Genocea. "We continue to believe that ATLAS, which lets patients’ own T cells identify the optimal antigens for their cancer immunotherapies, stands apart from peer approaches that instead rely on software to predict antigens. We believe that the next evidence for this will emerge from our upcoming presentations at SITC (Free SITC Whitepaper) and then from the first patient cohort in our Phase 1/2a clinical trial for GEN-009, from which we expect to report immunogenicity data in the first half of 2019."

Recent Milestones & Events
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October 2018: Announced multiple presentations at the upcoming meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2018) taking place November 7-11, 2018 at the Walter E. Washington Convention Center in Washington, D.C. These posters further highlight the advantages of Genocea’s ATLAS platform over in silico methods in identifying both neoantigens for vaccine inclusion and "inhibitory" neoantigens for exclusion. Genocea believes that the "inhibitory" antigen findings may point to novel biological insights only available through ATLAS. The following posters will be presented simultaneously on Saturday, November 10 from 12:20 – 1:50 p.m. and 7:00 – 8:30 p.m. ET in Poster Hall E:
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Poster Number: P154
Title: Empiric profiling of neoantigen-specific T cell responses in NSCLC patients with ATLAS reveals unexpected neoantigen and inhibitory antigen profiles
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Poster Number: P166
Title: Ex vivo ATLAS-identified inhibitory neoantigens promote mouse melanoma tumor progression
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Poster Number: P174
Title: A phase 1/2a study to evaluate the safety, tolerability, immunogenicity, and anti-tumor activity of GEN-009 adjuvanted neoantigen vaccine in adult patients with selected solid tumors
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October 2018: Strengthened its leadership team with the addition of Thomas Davis, M.D. as Chief Medical Officer and Derek Meisner, J.D., as General Counsel. Dr. Davis joins Genocea with 20+ years of academic

and industry experience in immuno-oncology and cancer drug development. Mr. Meisner brings broad legal expertise to Genocea as the company’s first General Counsel.

Third Quarter 2018 Financial Results
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Cash Position: As of September 30, 2018, cash and cash equivalents were $34.5 million compared to $12.3 million, as of December 31, 2017.
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Research and Development (R&D) Expenses: R&D expenses were $6.4 million for the quarter ended September 30, 2018, compared to $10.2 million for the same period in 2017. The decrease was due largely to reduced headcount-related costs, external development, clinical, and consulting costs.
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General and Administrative (G&A) Expenses: G&A expenses were $4.1 million for the quarter ended September 30, 2018, compared to $3.8 million for the same period in 2017. The increase was primarily due to increases in professional services expenses, partially offset by decreases in consulting costs.
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Net Loss: Net loss was $7.8 million for the quarter ended September 30, 2018, compared to a net loss of $16.9 million for quarter ended September 30, 2017.

Financial Guidance
Genocea expects that its existing cash and cash equivalents are sufficient to support its operating expenses and capital expenditure requirements into the fourth quarter of 2019.

Genocea continues to explore strategic alternatives for GEN-003, its Phase 3-ready investigational immunotherapy for the treatment of genital herpes.

Conference Call
Genocea will host a conference call and webcast today at 9:00 a.m. ET. The conference call may be accessed by dialing (844) 826-0619 (domestic) or (315) 625-6883 (international) and referring to conference ID number 9864055. A live webcast of the conference call will be available online from the investor relations section of the Company’s website at View Source A webcast replay of the conference call will be available on the Genocea website beginning approximately two hours after the event and will be archived for 90 days.