CYBB

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 announced the U.S. Food and Drug Administration (FDA) has granted both rare pediatric disease and orphan drug designations to the company’s lead program, EN-374, for the treatment of X-linked chronic granulomatous disease (X-CGD). Ensoma anticipates it will submit an investigational new drug application (IND) for EN-374 in the first half of 2025. Chronic granulomatous disease (CGD) is a rare and severe genetic disorder, which significantly impairs the immune system. It leaves patients vulnerable to recurrent and severe bacterial and fungal infections, often leading to chronic and life-threatening dysregulated inflammation and serious complications. CGD affects approximately 1 in 100,000-200,000 live births, and the median life expectancy for individuals with the condition is around 45 years. X-CGD is the most common form of the condition, affecting 60-70% of CGD patients, and is caused by mutations in the CYBB gene that prevent white blood cells called neutrophils from fighting infection. EN-374 is designed to treat X-CGD through the delivery of a functional CYBB gene directly to hematopoietic stem cell (HSCs) in vivo . It uses a promoter for selective expression in neutrophils, the primary cell type affected by X-CGD. Successful expression will restore patients’ ability to fight infection. “These designations from the FDA highlight the significant medical need in chronic granulomatous disease,” said Drew Dietz, M.D., MSCR, vice president of clinical development at Ensoma. “Current treatments, including antibiotics, antifungals, interferon gamma and allogeneic stem cell transplantation, offer limited benefit and/or come with significant burdens. EN-374 represents the first in vivo HSC-directed therapy for X-CGD, building on a mechanism that has been validated ex vivo . Designed to function for any CYBB mutation, this approach offers the potential to improve upon transformative benefits of ex vivo gene therapies in a way that’s simpler, potentially safer and more accessible for patients. Our team is incredibly proud to be at the forefront of advancing this groundbreaking therapy. We remain on track to submit an IND in the first half of this year.” Rare pediatric disease designation is granted by the FDA to incentivize development of treatments for serious or life-threatening rare diseases that primarily affect children aged 18 years or younger and impact fewer than 200,000 people in the U.S. If a Biologics License Application for EN-374 is approved in the U.S., Ensoma may be eligible to receive a Priority Review Voucher from the FDA. Orphan drug designation is granted by the FDA to products that prevent, diagnose or treat a rare disease or condition affecting fewer than 200,000 people in the U.S. The designation affords Ensoma the potential for certain benefits, including up to seven years market exclusivity after approval, tax credits for qualified clinical trials and exemption from certain FDA fees. 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 an 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 .

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 .

-- Prioritizing Set of High Value Programs in Core Areas of Focus; Modularity of Prime Editing Platform Expected to Allow Prime Medicine to Generate Follow-on Candidates Rapidly and Efficiently -- -- Initial Clinical Data from Phase 1/2 Trial in CGD Expected in 2025 While Advancing Wilson’s Disease Program Toward Expected IND Application and/or CTA in 1H 2026 -- -- Today Announced Strategic Research Collaboration and License Agreement with Bristol Myers Squibb to Develop and Commercialize Multiple Prime Edited Ex Vivo T-cell Therapies -- -- Together with $110 Million Upfront Consideration Received Under Agreement with Bristol Myers Squibb, Anticipated Cost Savings are Expected to Extend Cash Runway into the First Half of 2026 -- CAMBRIDGE, Mass., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology company committed to delivering a new class of differentiated one-time curative genetic therapies, today announced that it is focusing its pipeline on a set of high value programs, each targeting a disease with well-understood biology and a clearly defined clinical development and regulatory path, and each expected to provide the foundation for expansion into additional opportunities. “We founded Prime Medicine with a singular vision: to apply our groundbreaking Prime Editing platform to address the genetic causes of debilitating diseases and provide patients with long-lasting cures,” said Keith Gottesdiener, M.D., President and Chief Executive Officer of Prime Medicine. “Over the past four years, we have started to translate this vision into reality, advancing PM359 into the clinic and generating preclinical data that show we can reproducibly and durably correct disease causative mutations in multiple cell types and successfully deliver Prime Editors across target tissues. In addition, we are encouraged by recent commentary from the U.S. Food and Drug Administration, which is increasingly supportive of modular approaches to developing genetic therapies, for which we believe Prime Editing is uniquely suited. We believe that Prime Medicine has the potential to change the treatment paradigm for a wide range of diseases, which collectively impact millions of people.” Dr. Gottesdiener continued, “In order to maximize Prime Editing’s reach, we believe now is the time to strategically focus our efforts on a set of high value programs. Importantly, each prioritized program is intended to serve as a beachhead, allowing us to advance our technological leadership across a number of target tissues and cell types, while providing insights into research and development, regulatory strategy, CMC and delivery that will potentially allow us to progress our follow-on programs more rapidly and efficiently. In parallel, we plan to continue to leverage strategic business development, such as the collaboration with Bristol Myers Squibb that we announced this morning, to further extend Prime Editing’s reach. We expect to share first-in-human clinical data from our Phase 1/2 trial in CGD in 2025 and new preclinical data for our Wilson’s Disease program in the fourth quarter of 2024, as we work to bring this paradigm-shifting technology to patients.” Prime Medicine’s Focused Pipeline Hematology, Immunology & Oncology Prime Medicine will focus on the development of two programs for the treatment of chronic granulomatous disease (CGD), which together have the potential to address the vast majority of people living with CGD: PM359, an ex vivo autologous hematopoietic stem cell (HSC) product for the treatment of p47phox CGD. Approximately one quarter of patients with CGD present with a mutation in p47phox. In April 2024, the U.S. Food and Drug Administration (FDA) cleared Prime Medicine’s investigational new drug (IND) application for PM359, less than one month after the IND filing. The Company has initiated a Phase 1/2 clinical trial to assess the safety, biological activity and preliminary efficacy of PM359 in adult and pediatric patients and continues to expect initial clinical data from the study in 2025. Once proof-of-concept is established, Prime Medicine expects to advance PM359 rapidly into a pivotal study. PM359 has received rare pediatric drug designation and orphan drug designation from the FDA. Ex vivo HSC product for the treatment of X-linked CGD. Prime Medicine today announced its first follow-on program in hematology and immunology. Building on its efforts in p47phox CGD, Prime Medicine is advancing a program for X-linked CGD, which utilizes its Prime Assisted Site-Specific Integrate Gene Editing (PASSIGE™) technology, and is expected to address over 90 percent of known mutations in the CYBB gene with a single approach. Mutations in the CYBB gene occur in approximately two thirds of patients with CGD. Prime Medicine intends to leverage modular elements from across the PM359 program, including the IND filing, chemistry, manufacturing and controls (CMC) work and clinical trial, with the aim to accelerate advancement of its X-CGD program. BMS Collaboration: Ex vivo T-Cell Therapies. As announced this morning, Prime Medicine entered into a strategic research collaboration and license agreement with Bristol Myers Squibb, a global leader in cell therapy for hematology, immunology, and oncology, to develop and commercialize multiple Prime Edited ex vivo T-cell therapies. Under the terms of the agreement, Prime Medicine will design optimized Prime Editor and PASSIGE reagents for a select number of targets in immunological diseases and cancer; Bristol Myers Squibb will be responsible for development, manufacturing and commercialization of the next generation cell therapies, with support from Prime Medicine in gene editing strategy and reagent development. Under the terms of the agreement, Prime Medicine will receive a $55 million upfront payment and a $55 million equity investment from Bristol Myers Squibb. Prime Medicine is also eligible to receive more than $3.5 billion in milestones, including up to $1.4 billion in development milestones and more than $2.1 billion in commercialization milestones, along with royalties on net sales. Liver Lipid nanoparticle (LNP) Prime Editor for the treatment of Wilson’s Disease. Prime Medicine is focused on advancing its Wilson’s Disease program, which targets prevalent mutations in the ATP7B gene. Prime Medicine expects to present new preclinical data and initiate IND-enabling activities for this program in the fourth quarter of 2024, and intends to file an IND and/or clinical trial application (CTA) in the first half of 2026. The program will use Prime Medicine’s universal LNP, a multi-component and modular delivery system that the Company expects will be used across all liver disease programs, allowing more rapid and cost-efficient expansion into follow-on rare and non-rare liver indications. Lung LNP / adeno-associated virus (AAV) Prime Editors for the treatment of Cystic Fibrosis (CF). With funding from the Cystic Fibrosis Foundation, Prime Medicine is continuing to advance two strategies to potentially cure CF: hotspot editing and PASSIGE. Using hotspot editing, the Company aims to address multiple mutations at mutational hotspots with a small number of Prime Editors; using PASSIGE, the Company aims to address nearly all people with CF with a single superexon insertion strategy. Through the Cystic Fibrosis Foundation, Prime Medicine has access to infrastructural support and foundational guidance, including established assays, animal models reagents and patient samples, which may accelerate advancement of the Company’s Prime Editors for CF. Additional ProgramsIn order to pursue its prioritized high value programs as rapidly as possible, the Company is identifying partnership opportunities to advance its other programs, including those for neurological diseases, cell therapy, ocular diseases and hearing loss. Prime Medicine expects that business development will continue to play a critical role in accelerating and funding its pipeline, allowing the Company to maximize the potential and reach of Prime Editing, including in areas outside its core focus. Prime Medicine may also choose to advance these programs through internal efforts in the future. Updated Financial GuidanceAs a result of this strategic pipeline prioritization, Prime Medicine will streamline its operating expenses and capital expenditures. Together with the $110 million upfront consideration received from Bristol Myers Squibb under the strategic research collaboration and license agreement announced this morning, Prime Medicine expects its cash runway to fund operations into the first half of 2026. About Prime MedicinePrime Medicine is a leading biotechnology company dedicated to creating and delivering the next generation of gene editing therapies to patients. The Company is deploying its proprietary Prime Editing platform, a versatile, precise and efficient gene editing technology, to develop a new class of differentiated one-time curative genetic therapies. Designed to make only the right edit at the right position within a gene while minimizing unwanted DNA modifications, Prime Editors have the potential to repair almost all types of genetic mutations and work in many different tissues, organs and cell types. Taken together, Prime Editing’s versatile gene editing capabilities could unlock opportunities across thousands of potential indications. Prime Medicine is currently progressing a diversified portfolio of investigational therapeutic programs organized around our core areas of focus: hematology, immunology and oncology, liver and lung. Across each core area, Prime Medicine is focused initially on a set of high value programs, each targeting a disease with well-understood biology and a clearly defined clinical development and regulatory path, and each expected to provide the foundation for expansion into additional opportunities. Over time, the Company intends to maximize Prime Editing’s broad and versatile therapeutic potential, as well as the modularity of the Prime Editing platform, to rapidly and efficiently expand beyond the diseases in its current pipeline, potentially including additional genetic diseases, immunological diseases, cancers, infectious diseases, and targeting genetic risk factors in common diseases, which collectively impact millions of people. For more information, please visit www.primemedicine.com. © 2024 Prime Medicine, Inc. All rights reserved. PRIME MEDICINE, the Prime Medicine logos, and PASSIGE are trademarks of Prime Medicine, Inc. All other trademarks referred to herein are the property of their respective owners. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Prime Medicine’s beliefs and expectations regarding: the potential of PM359 to correct the causative mutation of CGD; the anticipated maturation into a clinical-stage company by bringing PM359 into clinical development in 2024 with initial clinical data from the ongoing Phase 1/2 clinical trial of PM359 expected in 2025; the initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials, and the release of data related thereto; the collaboration with Bristol Myers Squibb and the intended and potential benefits thereof, including the receipt of potential milestone and royalty payments from commercial product sales, if any; certain activities and next steps to support the Company’s maturation into a clinical-stage company, including opening an IND and/or CTA application, clinical data expectations, establishing proof-of-concept, advancing programs into lead optimization, advancing preclinical studies and initiating IND-enabling activities, and establishing AAV delivery platform and route of administration for neuromuscular programs; the potential for Prime Editors to more precisely and effectively achieve genetic modification; the potential for Prime Editors to repair genetic mutations and offer curative genetic therapies for a wide spectrum of diseases; the potential of Prime Editors to reproducibly correct disease-causing genetic mutations across different tissues, organs and cell types, and the capacity of its Prime Editing and PASSIGE technology to edit CAR-T cells for the treatment of certain cancers and immune diseases; its ability to demonstrate superior off-target profiles for Prime Editing programs; exploring business development opportunities that could accelerate existing work and the benefits thereof; the modularity of the Prime Editing platform and the benefits thereof; its expectations regarding the breadth of Prime Editing technology and the implementation of its strategic plans for its business, programs, and technology; the potential of Prime Editing to unlock opportunities across thousands of potential indications; and its expected cash runway.. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the development and optimization of new technologies; the scope of protection Prime Medicine is able to establish and maintain for intellectual property rights covering its Prime Editing technology; Prime Medicine’s ability to identify and enter into future license agreements and collaborations; the effect of unfavorable macroeconomic conditions or market volatility resulting from general economic, industry and market conditions, including rising interest rates, inflation, and adverse developments affecting the financial services industry; and Prime Medicine’s expectations regarding the anticipated timeline of its cash runway and future financial performance. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Prime Medicine’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Prime Medicine’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Prime Medicine explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor ContactHannah DeresiewiczPrecision AQ212-362-1200hannah.deresiewicz@precisionaq.com Media ContactDan Budwick, 1ABdan@1ABmedia.com