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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 .

Focus on in vivo CRISPR-edited medicines based on Editas researchers’ recent scientific progress in multiple tissues: Achieved pre-clinical in vivo proof of concept of high level HBG1/2 promoter editing and HbF induction in a humanized mouse model for treatment of sickle cell disease and beta thalassemia with a single dose of an HSC-targeted lipid nanoparticle (tLNP) formulationAchieved in vivo proof of concept of high efficiency editing in the liver in non-human primates Ending development of reni-cel after extensive search did not yield a commercial partner The Company will work closely with the clinical trial sites, regulators, and other parties to determine the path forward for patients enrolled in the RUBY and EdiTHAL trials Initiating cost savings measures and reduction in headcount to align workforce and resources to in vivo pipeline, extending cash runway into Q2 2027Conference call and webcast today at 5:00 p.m. ET CAMBRIDGE, Mass., Dec. 12, 2024 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (Nasdaq: EDIT), a leading gene editing company, today announced a critical pivot to optimize its cost structure, extend its cash runway into Q2 2027, and position the Company to accelerate its intent to achieve in vivo human proof of concept in approximately two years. “Recent scientific breakthroughs by the Editas team have convinced us that the timelines around the near-term viability of in vivo CRISPR-edited medicines have accelerated meaningfully. Two years ago, we laid out our strategy and objective to become a leader in in vivo programmable gene editing. Based on these advances, we are transitioning to a fully in vivo company. We believe the ability to provide in vivo gene editing that functions via gene upregulation across tissues holds the potential to significantly expand the addressable therapeutic possibilities for CRISPR-based gene editing and uniquely position Editas to be a leader in the field moving forward,” said Gilmore O’Neill, M.B., M.M.Sc., President and Chief Executive Officer, Editas Medicine. The Company transition follows the recent in vivo pre-clinical proof of concept in multiple tissues: Hematopoietic Stem Cells (HSCs): Editas achieved ~40% editing of the HBG1/2 promoter site after using a novel, Editas-proprietary targeted lipid nanoparticle (tLNP) for extrahepatic tissue delivery to deliver a single dose of its clinically validated Cas12a editing machinery directly to human hematopoietic stem cells (HSCs) in mice engrafted with human HSCs.1HBG1/2 biology has been validated and derisked in patients with reni-cel in the RUBY trial.The editing in HSCs with the Company’s proprietary tLNP formulation resulted in the meaningful functional outcome of HbF induction, indicated by the presence of HbF expressing human red blood cells (on average 20%) that populate in the host by one month. Liver: The Company achieved in vivo proof of concept of high efficiency editing in the liver in non-human primates under its collaboration with Genevant. The Company intends to share pre-clinical data and further development timelines from these programs in the first quarter of 2025. In vivo HSC editing success is expected to enable extrahepatic tissues/cell types targeting beyond HSCs and demonstrates the potential of “plug ‘n play” in an in vivo extrahepatic LNP platform. The Company’s upregulation capability additionally enables a differentiated strategy for liver targets for diseases with high unmet need and first-in-class opportunities. In connection with Editas Medicine’s transition to an in vivo company, the Company initiated a reduction in headcount that will eliminate approximately 65% of its workforce over the next six months. As part of this reduction in force, several members of the Editas management team will depart the company over the next six months, including Baisong Mei, M.D., Ph.D., the Company’s Chief Medical Officer. Additionally, Emma Reeve and Meeta Chatterjee, Ph.D. are resigning from the Board of Directors, effective December 31, 2024. Jessica Hopfield, Ph.D., has been named Chair of the Board, effective December 31, 2024. Dr. O’Neill added, “We want to extend our deepest appreciation to patients, investigators, clinical sites staff, and our employees who have shown tremendous dedication and commitment to developing a potentially transformational medicine like reni-cel. We also want to express specific gratitude to the patients in our clinical trials and their caregivers whose dedication to disease research for their community makes us even more committed to accelerating our efforts towards an in vivo program for sickle cell disease and beta thalassemia.” Conference Call The Editas Medicine management team will host a conference call and webcast today at 5:00 p.m. ET. To access the call, please dial 1-877-407-0989 (domestic) or +1 201-389-0921 (international) and ask for the Editas Medicine conference call. A live webcast of the call will also be available on the Investors section of the Editas Medicine website at www.editasmedicine.com, and a replay will be available approximately two hours after its completion. About Editas MedicineAs a leading gene editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas12a and CRISPR/Cas9 genome editing systems into a robust pipeline of in vivo medicines for people living with serious diseases around the world. Editas Medicine aims to discover, develop, manufacture, and commercialize transformative, durable, precision in vivo gene editing medicines for a broad class of diseases. Editas Medicine is the exclusive licensee of Broad Institute’s Cas12a patent estate and Broad Institute and Harvard University’s Cas9 patent estates for human medicines. For the latest information and scientific presentations, please visit www.editasmedicine.com. Forward-Looking Statements This press release contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements regarding the Company’s transition to a fully in vivo company, the intention to achieve human proof of concept in approximately two years, and the potential success of its in vivo gene editing programs, the timing for releasing additional pre-clinical data, the anticipated effects, including potential cost savings, of the Company’s decision to discontinue development of reni-cel and initiate the related reduction in headcount, the scope and timing of the reduction in headcount, and the expected extension of the Company’s cash runway. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the initiation and completion of preclinical studies; availability and timing of results from preclinical studies; expectations for regulatory approvals to conduct trials; availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; and that the decision to discontinue clinical development of reni-cel and the related reduction in headcount may have unexpected consequences or not result in the expected cost savings. These and other risks are described in greater detail under the caption “Risk Factors” included in the Company’s most recent Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission, as updated by the Company’s subsequent filings with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise. 1 Previously disclosed editing of 29% in hematopoietic stem and progenitor cell (HSPCs) at one week after a single dose in a Strategic Update webinar in October 2024.

MP0533 phase 1/2a dose escalation study continues with overall acceptable safety profile to date as well as initial antileukemic and pharmacodynamic activity Clinical protocol amendment in process with optimized dosing scheme to overcome target-mediated drug disposition and test the full potential of MP0533 Switch-DARPin MP0621 demonstrates intended mechanism in vivo, achieving killing of cKit+ cells while reducing off-target effects seen with systemic anti-CD47 blockade ZURICH-SCHLIEREN, Switzerland and CONCORD, MA, USA I December 08, 2024 I Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics (“Molecular Partners” or the “Company”), today announced the presentation of additional data pertaining to two programs, including preclinical data on MP0621, a potential next-generation conditioning regimen for patients undergoing hematopoietic stem cell transplantation, and comprehensive data from the first seven cohorts of the ongoing phase 1/2a dose-escalation study of MP0533. The data are presented in two posters at the American Society of Hematology (ASH) annual meeting, being held December 7-10, 2024 in San Diego, CA. “We are at a unique crossroads with the MP0533 program. Data from our Ph1/2a study indicate antitumor and pharmacodynamic activity despite currently sub-optimal exposure levels, mostly driven by target-mediated drug disposition,” said Patrick Amstutz, Ph.D., CEO of Molecular Partners. “The sum of these data, reviewed in close collaboration with our KOLs, allowed us to define a clear hypothesis that introducing a loading-dose-phase will improve MP0533 exposure, thereby testing the full therapeutic potential of MP0533 in AML patients. We are happy to report that these amendments are submitted, while patient treatment is still ongoing. We look forward to providing updates to the program in 2025.” MP0533: Acceptable safety profile, exposure being optimized via protocol amendment MP0533 is a novel tetraspecific T cell engaging DARPin which simultaneously targets the three tumor-associated antigens (TAAs) CD33, CD123 and CD70, as well as CD3 on T cells. The mechanism of action of MP0533 is designed to preferentially kill AML cells that express any combination of these three TAAs while sparing healthy cells, which express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T cell-engagement. The data presented at ASH 2024 are from the ongoing first-in-human dose-escalation phase 1/2a study of MP0533 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)/AML. MP0533 continues to show an acceptable safety profile in 37 patients up to dose cohort 7, with the majority of adverse events reported being infusion-related reactions and cytokine release syndrome. Initial pharmacodynamic data provide evidence of MP0533 target engagement and resulting immune activation. Despite lower than anticipated drug exposure, four responders in total were reported in cohorts 1-7 and encouraging blast reductions were observed in patients bone marrow, particularly in patients with lower disease burden. Based on these observations Molecular Partners is amending the protocol of this study to further optimize the dosing schedule and improve the exposure profile of MP0533 in subsequent dosing cohorts. The goal is to achieve higher response rates, as well as an improved quality and duration of response in this heterogeneous patient population. MP0621: Intended mechanism of HSC depletion confirmed preclinically MP0621 is a Switch-DARPin candidate designed to induce killing of hematopoietic stem cells (HSCs) as a next-generation conditioning regimen for HSC transplantation (HSCT). The Switch-DARPin platform provides a logic-gated “on/off” function (the “Switch”) to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. In MP0621, the Switch-DARPin binds to either cellular cKit or to the anti-CD47 DARPin binder. Upon MP0621 binding to cKit on HSCs, the Switch-DARPin will unmask the anti-CD47 DARPin, which in turn will bind CD47 and block the “don’t-eat-me” signal, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells The preclinical results presented support the intended MP0621 mechanism of action and provide further evidence for its potential as a viable approach for HSC depletion in patients. The blockade of CD47 exclusively on target cells allows MP0621 to enhance efficacy of cKit-targeting, while reducing off-target effects seen with systemic anti-CD47 blockade. The currently available non-human primate data however do not allow Molecular Partners to conclude that MP0621 would serve as a treatment for AML patients, as previously hypothesized.As Molecular Partners’ portfolio strategy prioritizes therapeutic candidates for oncology, MP0621 is being evaluated for partnering. Details of the poster presentations at ASH 2024: Session Name: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster II Publication Number: 2881 Title: MP0533 (CD33 x CD123 x CD70 x CD3), a Tetra-Specific CD3-Engaging DARPin for the Treatment of Patients with Relapsed/Refractory AML or MDS/AML: Results of an Ongoing Phase 1/2a Study Session Location: San Diego Convention Center, Halls G-H Presentation Date & Time: Sunday, December 8, 2024, 6:00–8:00 pm PT Session Name: 701. Experimental Transplantation: Basic and Translational: Poster III Publication Number: 4775 Title: MP0621 (cKit x CD16a x CD47), a Multi-Specific Switch-DARPin with Conditional Blockade of CD47 Targeting Hematopoietic Stem Cells: Preclinical Evaluation of a Next-Generation Conditioning Agent for Stem Cell Transplantation Session Location: San Diego Convention Center, Halls G-H Presentation Date & Time: Monday, December 9, 2024, 6:00–8:00 pm PT Both posters will be made available on Molecular Partner’s website in the Scientific Documents section . About DARPin Therapeutics DARPin (Designed Ankyrin Repeat Protein) therapeutics are a new class of custom-built protein drugs based on natural binding proteins that open new dimensions of multi-functionality and multi-target specificity in drug design. The flexible architecture, intrinsic potential for high affinity and specificity, small size and high stability of DARPins offer benefits to drug design over other currently available protein-based therapeutics. DARPin candidates can be radically simple, with a single DARPin unit acting as the delivery vector to a specific target; or multispecific, with the possibility of engaging more than five targets, and combining multiple and conditional functionalities in a unique DARPin drug candidate. The DARPin platform is designed to be a rapid and cost-effective drug discovery engine, producing drug candidates with optimized properties and high production yields. DARPin therapeutics have been clinically validated across several therapeutic areas and developed through to the registrational stage. About Molecular Partners AG Molecular Partners AG is a clinical-stage biotech company pioneering the design and development of DARPin therapeutics for medical challenges other drug modalities cannot readily address. The Company has programs in various stages of pre-clinical and clinical development, with oncology as its main focus. Molecular Partners leverages the advantages of DARPins to provide unique solutions to patients through its proprietary programs as well as through partnerships with leading pharmaceutical companies. Molecular Partners was founded in 2004 and has offices in both Zurich, Switzerland and Concord, MA, USA. For more information, visit www.molecularpartners.com and find us on LinkedIn and Twitter/X @MolecularPrtnrs SOURCE: Molecular Partners