CXCR2

Pivotal Phase 3 4WARD clinical trial is evaluating use of oral mavorixafor as monotherapy and in combination with injectable G-CSFBOSTON, Dec. 04, 2024 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced its upcoming presentations at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, including a trial-in-progress poster on the ongoing pivotal Phase 3 clinical trial exploring the use of mavorixafor, an oral CXCR4 antagonist, for the treatment of people with chronic neutropenia (CN). The meeting will take place December 7-10, 2024, in San Diego, CA. “We’re pleased to be sharing details of our ongoing Phase 3 clinical trial at ASH as we continue to recruit patients and activate study sites across the globe. The initiation of this trial was a significant milestone for the chronic neutropenia community that – unfortunately – hasn’t seen any treatment innovation in nearly 30 years,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “We look forward to connecting with clinicians at the ASH meeting and sharing more about our vision for mavorixafor as an oral option for the treatment of CN that could potentially reduce or replace the use of injectable G-CSF.” The Phase 3 4WARD trial is evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without stable doses of injectable G-CSF) in people with congenital, acquired primary autoimmune or acquired primary idiopathic CN who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants across 90 to 110 sites in 20 to 25 countries. X4 will also be hosting a booth (#2106) at the conference to share information about the ongoing 4WARD clinical trial. Additionally, in an oral presentation at the meeting, the company will present preclinical data on the potential for CXCR4 antagonism to correct peripheral blood neutropenia and bone marrow neutrophil accumulation caused by a loss-of-function in the CXCR2 pathway. Poster Presentation Details: Title: “Trials in Progress: A Phase 3 Study to Investigate Efficacy, Safety, and Tolerability of Mavorixafor in Participants with Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders” Number: 3924.1 Date and Time: Monday, December 9, 2024: 6:00-8:00 p.m. PST Location: Manchester Grand Hyatt San Diego, Halls G-H Oral Presentation Details: Title: “CXCR4 Antagonism Corrects Peripheral Neutropenia and Mature Neutrophil Accumulation in Bone Marrow in a Pharmacological Mouse Model of CXCR2 Loss-of-Function” Number: 418 Date and Time: Sunday, December 8, 2024: 10:15 a.m. PST Location: Manchester Grand Hyatt San Diego, Grand Hall D About the 4WARD Global, Pivotal, Phase 3 Clinical TrialThe 4WARD trial is a global, pivotal Phase 3 clinical trial (NCT06056297) evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without G-CSF) in people with congenital, acquired primary autoimmune or acquired primary idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants with confirmed trough ANC levels less than 1,500 cells per microliter at baseline screening and histories of two or more serious and/or recurrent infections in the prior year. The primary endpoint of the trial is based on two outcome measures: annualized infection rate and positive ANC response. About X4 PharmaceuticalsX4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging our expertise in CXCR4 and immune system biology, we have successfully developed mavorixafor, which has received U.S. approval as XOLREMDI® (mavorixafor) capsules in its first indication. We are also evaluating the use of mavorixafor in additional potential indications. X4 corporate headquarters are in Boston, Massachusetts and our research center of excellence is in Vienna, Austria. For more information, please visit our website at www.x4pharma.com. Company Contact:José JuvesHead of Corporate & Patient Affairsjose.juves@x4pharma.com Investor Contact:Daniel FerryManaging Director, LifeSci Advisorsdaniel@lifesciadvisors.com(617) 430-7576

CAMBRIDGE, Mass.--( BUSINESS WIRE )--Be Biopharma, Inc. (“Be Bio”), a company pioneering the development of engineered B Cell Medicines (BCMs), today announced that an abstract relating to its BCM platform has been accepted for oral presentation at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition to be held in San Diego, California from December 7 to 10, 2024. In addition, a Trials in Progress abstract related to the BeCoMe-9 Phase 1/2 clinical trial for BE-101 in hemophilia B has been accepted for online publication. Both abstracts were published today and are now available on the ASH website at www.hematology.org . Details regarding the Be Biopharma oral presentation are as follows: Abstract Title: A Versatile B Cell Engineering Platform Enables Development of B Cell Medicines for Sustained Delivery of Therapeutic Biologics (Abstract #88) Session Name: 703. Cellular Immunotherapies other than CAR-T Cells: Basic and Translational: Novel Cell Platforms and Delivery Strategies Date: Saturday, December 7, 2024 Presentation Time: 10:15 a.m. PT Session Room: San Diego Convention Center, Ballroom 20AB Details regarding the Be Biopharma online abstract are as follows: Abstract Title: BeCoMe–9: A Phase 1/2 Dose Escalation and Expansion Study of BE-101 for the Treatment of Adults with Moderately Severe or Severe Hemophilia B (Abstract #5479) About Engineered B Cell Medicines – A New Class of Cellular Medicines The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable, titratable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas. About BE-101 BE-101 is a first-in-class BCM that is engineered to insert the human Factor IX (FIX) gene into primary human B cells, allowing for continuous expression of active FIX for the treatment of hemophilia B. BE-101 has the potential to express sustained therapeutic FIX activity levels with a single infusion while having the flexibility to be titrated and/or re-dosed, and without the need for preconditioning. The potential to maintain therapeutic FIX activity levels while the reducing dosing frequency associated with current FIX replacement regimens could address the considerable infusion burden associated with current therapies and potentially drive reductions in the annualized bleeding rates and FIX usage. The US FDA cleared the BE-101 IND in May of 2024, and granted Fast Track designation in September of 2024. The Phase 1/2 BeCoMe-9 Trial is open for enrollment and further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06611436. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020, and is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others to re-imagine medicine based on the power of Engineered B cells. For more information, please visit us at Be.Bio and our LinkedIn page.

BOSTON--( BUSINESS WIRE )--Ensoma, a genomic medicines company advancing the future of medicine through one-time, in vivo treatments capable of precisely and durably engineering the hematopoietic system, today unveiled its three lead programs targeting genetic, immune and oncological diseases. These innovative programs leverage Ensoma’s in vivo hematopoietic stem cell (HSC) engineering platform and aim to address critical unmet needs in chronic granulomatous disease (CGD), sickle cell disease (SCD) and solid tumors. Ensoma’s in vivo HSC engineering approach has the potential to offer greatly improved patient access to therapy and a vastly reduced treatment burden. Ensoma’s in vivo HSC engineering platform combines an off-the-shelf delivery system with an advanced gene engineering toolkit that, together, offer durable and transformative therapies across a range of diseases. The delivery system is based on virus-like particles (VLPs) that preferentially bind to HSCs, efficiently deliver DNA to the nucleus and de-target the liver. With a 35-kilobase cargo capacity, these VLPs carry a diverse range of sophisticated genomic engineering tools capable of precise changes, from single base edits up to large multi-gene insertions. Importantly, the platform leverages HSCs as a self-renewing reservoir of engineered cells, providing durable therapies with improved patient access and outcomes across genetic and immune disorders, as well as oncology. Ensoma’s lead program is for individuals living with X-linked CGD (X-CGD), a condition that severely compromises immune function and leaves patients vulnerable to life-threatening infections. X-CGD is the most common form of the condition, affecting 60-70% of CGD patients. “Science and medicine have shown the curative impact of HSC-based therapies through bone marrow transplantation and ex vivo HSC-targeted gene therapy, but access to these treatments is limited and comes with significant burden for the patient and the healthcare system,” said Jim Burns, CEO of Ensoma. “At Ensoma, we believe the time for in vivo HSC engineering has come. Our proof-of-concept data in X-CGD demonstrate our in vivo approach for CGD and position us for an IND filing in the first half of 2025, which would make it the first in vivo HSC-directed therapy to be tested in humans. We are following CGD with preclinical programs in sickle cell disease and solid tumors, underscoring our dedication to advancing the future of medicine through precision in vivo treatment.” Ensoma will present key preclinical data at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting and the 66 th American Society of Hematology (ASH) Annual Meeting, highlighting the potential of its in vivo HSC engineering platform in advancing treatments for CGD, SCD and solid tumors. Below is a summary of the findings and presentation details. Chronic Granulomatous Disease: Key Findings from ASH: Preclinical data to be presented at the ASH Annual Meeting will highlight proof-of-concept for Ensoma's innovative in vivo gene therapy, EN-374, designed to treat X-CGD. X-CGD is caused by a mutant CYBB gene that prevents white blood cells called neutrophils from producing functional NADPH oxidase, a protein important for fighting bacterial and fungal infections. Ensoma’s novel approach employs VLPs to efficiently engineer HSCs for sustained expression of a CYBB transgene in neutrophils, restoring function of the NADPH oxidase enzyme complex critical for immune defense. The study demonstrated therapeutic restoration of CYBB protein expression and NADPH oxidase activity in murine circulating neutrophils, achieving levels shown to confer meaningful clinical benefits for X-CGD patients. This research positions EN-374 as a pioneering therapy that addresses an unmet medical need and offers the potential to expand access to HSC-directed gene therapies for genetic, immune and oncological disorders. Presentation Details: Title : In Vivo Hematopoietic Stem Cell Engineering Restores the Function of NADPH Enzyme Complex in X-Linked Chronic Granulomatous Disease Model in Mice Abstract: 801 Poster Presentation Time/Date: 5:30-7:30 p.m. PT, Saturday, Dec. 7 Location: San Diego Convention Center, Halls G-H Presenter: Sravya Kattula, Ph.D., Ensoma Sickle Cell Disease: Key Findings from ASH: At the ASH Annual Meeting, Ensoma will also showcase compelling preclinical data demonstrating the safety and efficacy of its wholly owned single-dose truncated Gro-Beta (tGROβ), EN-145 (formerly MGTA-145), combined with plerixafor for mobilizing primitive HSCs in mouse models of SCD. This innovative approach addresses the limitations of current mobilization regimens, particularly the use of granulocyte colony-stimulating factor (G-CSF), which is contraindicated in SCD patients. In a SCD mouse model, the combination of EN-145 and plerixafor mobilized six-fold more long-term HSCs than plerixafor alone, significantly enhancing HSC yield for gene therapies. Studies in humanized NBSGW mice further demonstrated rapid and effective mobilization of human CD34+ cells, along with superior transduction efficiency—meaning that Ensoma’s VLPs were more effective at delivering the genetic material into the target cells, ensuring a higher percentage of modified cells with therapeutic potential. These findings highlight EN-145's potential use in a robust alternative HSC mobilization regimen in SCD, paving the way for improved outcomes in both ex vivo and in vivo gene therapies. Presentation Details: Title: Single Dose of tGROβ (EN-145)/Plerixafor Safely and Effectively Mobilizes Primitive HSCs in Mouse Models for In Vivo Gene Therapy of Sickle Cell Disease Abstract: 4770 Poster Presentation Time/Date: 6-8 p.m. PT, Monday, Dec. 9 Location: San Diego Convention Center, Halls G-H Presenter: Courtney Mercadante, Ph.D., Ensoma Solid Tumors: Key Findings from SITC: Preclinical data to be presented at SITC 2024 will highlight the transformative potential of Ensoma’s novel platform for in vivo engineering of multi-lineage CAR-immune cells, offering a new approach to overcoming the significant challenges in solid tumor therapies. Solid tumors, unlike hematological malignancies, present a complex microenvironment that limits access for current therapies and complicates immune cell infiltration and efficacy. Ensoma’s VLPs target CD46-positive cells, including both HSCs and mature immune cells, to enable efficient transduction and generate durable anti-tumor responses. In immune-competent mice, administration of VLPs encoding an anti-HER2 CAR generated CAR+ myeloid (M), NK and T cells within just a few days, followed by long-term HSC renewal of multi-lineage effectors. Upon challenge with HER2+ tumors, these engineered immune cells effectively controlled tumor growth, indicating robust and durable anti-tumor activity. Presentation Details: Title: In vivo VLP-based engineering generates multi-lineage CAR-immune cells that mediate potent and durable anti-tumor activity Abstract: 1098 Poster Presentation Time/Date: 3:30-5 p.m. CT, Thursday, Nov. 7 & 9 a.m. – 8:30 p.m. CT, Saturday, Nov. 9 Location: Grand Ballroom AB - George R. Brown Convention Center Presenter: Corinne Decker, Ph.D., Ensoma "At Ensoma, our commitment to addressing critical unmet needs in genetically driven diseases is reflected in the promising preclinical data from our lead programs, including for chronic granulomatous disease, where we are pioneering innovative solutions to restore immune function,” said Robert Peters, Ph.D., chief scientific officer of Ensoma. “Our VLPs enable the delivery of large, complex cargo, creating the unprecedented ability to engineer multi-lineage immune responses in vivo . Beyond initiating our first clinical program in X-CGD and demonstrating the safety and efficacy of our platform, our focus for 2025 is to progress two development candidates while continuing to innovate our technology. We are also actively exploring partnerships that can further expand the potential of our groundbreaking platform. Together, we aim to transform the landscape of genomic medicine and improve outcomes for patients suffering from these challenging conditions." About Ensoma Ensoma is developing curative medicines through precision in vivo cellular engineering. Our platform combines class-leading proprietary base editing and high-efficiency gene integration systems with high-capacity virus-like particles (VLPs) to provide one-time and durable genetic medicines in a simple outpatient procedure. We are focused on in vivo engineering of hematopoietic stem cells (HSCs) to address genetic diseases, immune disorders and cancer. Ensoma is supported by top-tier investors and a passionate team committed to a bold, global vision for genomic medicines. Ensoma is based in Boston. For more information, visit ensoma.com .