Distal Myopathies

LOS ANGELES, Aug. 14, 2023 (GLOBE NEWSWIRE) -- Solve GNE announced today that it has entered into a sponsored research agreement with Genosera to provide funding for a novel Adeno-Associated Virus (AAV) gene therapy aimed at curing GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM). GNE Myopathy is a genetic disorder characterized by muscle weakness that starts in early adulthood. The progression of the disease varies among patients but generally starts in the leg muscles and eventually leads to complete loss of mobility. Although this is a rare disorder, its incidence is remarkably high among Iranians of Jewish decent, where it’s estimated that 10-15% of the population carry at least a single copy of the M743T point mutation. Gidon Akler, MD, and Paul T. Martin, PhD, co-founded Genosera in 2019 with the goal of developing new gene therapy treatments for patients with rare genetic disorders. The company has a particular focus on genetic diseases that are common in members of the Iranian Jewish community, including GNE myopathy and Lysosomal Acid Lipase Deficiency. Genosera is developing novel bicistronic, or two gene, AAV treatments for muscle diseases. Such therapies will, for the first time, provide the possibility of stopping disease progression and also reversing pre-existing muscle disease. Together with Solve GNE, Genosera will work to develop the first bicistronic gene therapy treatment for GNE myopathy patients. Genosera’s product pipeline comes from research done in Dr. Martin’s laboratory in the Center for Gene Therapy at the Abigail Wexner Research Institute at Nationwide Children’s Hospital in Columbus Ohio. Alexander Monsef of Solve GNE commented, “The Center for Gene Therapy at Nationwide Children’s Hospital (NCH) has a distinguished record of research in gene therapy and its scientists have played a major role in the development of landmark therapies like Zolgensma for Spinal Muscular Atrophy, and Elevidys for Duchenne Muscular Dystrophy. Solve GNE is proud to be collaborating with Genosera and NCH towards finding a cure for GNEM.” About Solve GNE Solve GNE is a Los Angeles based non-profit organization focused on developing a cure for GNE Myopathy (or HIBM). Solve GNE has been actively raising funds to support research and development of various gene therapies that are poised to enter human clinical trials in the next 12-18 months. For more information, visit About Genosera Founded in 2019, Genosera is a privately held, gene therapy biotechnology company that focuses on various rare genetic diseases such as GNEM, Lysosomal Acid Lipase Deficiency (LAL-D) and Limb-girdle muscular dystrophy type 2I (LGMD2I). For more information, visit Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements regarding the success, cost, and timing of our product development activities and clinical trials, our plans to research, develop, and commercialize our product candidates, and our plans to submit regulatory filings and obtain regulatory approval of our product candidates. These forward-looking statements are based on Genosera’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include but are not limited to: (a) the timing, costs, and outcomes of our clinical trials and preclinical studies, (b) the timing and likelihood of regulatory filings and approvals for our product candidates, and (c) the potential market size for our product candidates. These forward-looking statements speak only as of the date made and, other than as required by law, we undertake no obligation to publicly update or revise any forward-looking statements. This press release does not constitute an offer to sell, or a solicitation of an offer to buy, any securities. Contact: Alexander Monsef – 310-913-3418 – AlexM@solvegne.org

LOS ANGELES, July 31, 2023 (GLOBE NEWSWIRE) -- Solve GNE, a Los Angeles based non-profit organization, has raised over $2.5 million and negotiated sponsored research agreements with multiple leading medical researchers to help develop a cure for Hereditary Inclusion Body Myopathy (HIBM). Also known as GNE Myopathy (GNEM), HIBM is a muscular disorder that causes progressive muscle weakness which manifests in early adulthood – generally starting with the legs – until reaching eventual complete loss of mobility. While rare, this disease has a remarkably high incidence among Iranians of Jewish descent – with an estimated 10 to 15% of the population carrying at least a single copy of the mutated gene. Solve GNE has been actively raising funds to support a consortium of academic and private sector researchers tasked with the development of various gene therapies. Solve GNE has committed to funding experts in HIBM in four leading organizations: Genosera, Gradalis, Johns Hopkins University School of Medicine and Stanford University. These agreements include detailed development budgets and a commitment from Genosera and Gradalis to start human clinical trials within 12 to 18 months. The Solve GNE consortium is focusing on a common goal but implementing a parallel track strategy that should allow them to approach the FDA with multiple options to get patients enrolled in Phase 1 trials as rapidly as possible. Each consortium participant brings a unique perspective to the collaboration, and Solve GNE funding will be allocated accordingly to the following projects: Genosera, an Ohio-based biotechnology startup, is an offshoot of Nationwide Children’s Hospital, the leading gene therapy research and development center. Co-founders, Dr. Gidon Akler (Aghlar) – a geneticist from the Iranian Jewish community in Great Neck, NY – and Dr. Paul Martin – a pioneer in gene therapy – are leading experts in HIBM. Dr. Martin developed Genosera’s “bicistronic technology” –a proprietary gene therapy that combines a correct copy of the GNE gene with an additional muscle growth factor gene to help build back muscle. This process incorporates a novel AAV delivery system, which has been successfully applied in patients with other muscular diseases. The company’s platform includes cutting-edge HIBM cellular and animal models that are critical for the approval of an Investigational New Drug (IND) application, the gateway to human clinical trials. Genosera’s bicistronic technology is the only gene therapy that is designed to stop the progression of the disease and allow patients to regain their physical capabilities. The approach was designed to be broadly applicable to patients at any stage of disease progression.Gradalis, Inc., an established Texas-based biotechnology company, specializes in novel genetic therapies for cancer. In 2010, Gradalis co-founder and chief scientific officer, Dr. John Nemunaitis, carried out the first and (currently) only gene therapy clinical trial for HIBM in a single patient. Published data showed activity in this early form of HIBM gene therapy that was well tolerated. In addition, there were measurable improvements in certain muscle groups. Financial commitment from Solve GNE will allow dosing of additional patients using an improved liposomal formulation of the original therapy. A successful outcome will stop the progression of the disease and offer an alternative to patients who may not qualify for AAV based gene therapies. Johns Hopkins University School of Medicine researchers spearheaded by Dr. Greg Newby are the recipients of a multi-year grant from Solve GNE. Using a novel precise CRISPR therapy known as prime editing – a pioneering technology developed over the past five years by Harvard Professor David Liu – the team will attempt to directly correct the genetic point mutation in laboratory models. If successful in future clinical trials of patients, the approach could potentially be most useful for younger patients who are not yet showing any disease symptoms. Stanford University researchers led by gene therapy experts Dr. Natalia Gomez-Ospina, Dr. John Day and Dr. Fraser Wright, have developed a sophisticated MRI technique for analyzing the skeletal musculature of HIBM patients with stunning detail, allowing the researchers to follow the progression of the disease more accurately during clinical trials. Additionally, the team is developing a novel Adeno-Associated Virus (AAV) delivery system, which is safer and more efficient than current gene therapy viral delivery systems, potentially allowing a larger percentage of patients to qualify for an HIBM viral gene therapy. Additionally, Solve GNE has already identified Nationwide Children’s Hospital in Ohio as their primary clinical site. Stanford has agreed to serve as the secondary clinical site on the West Coast. Solve GNE is still researching alternative clinical sites in Los Angeles and New York in order to facilitate enrollment of patients who live in those cities. Additional details will be provided by Solve GNE and researchers from Stanford, Johns Hopkins, Gradalis and Genosera during a global webcast presentation followed by a Q&A session on Sunday September 10th, 2023 at 11A New York time (8A Los Angeles time, 6P Tel Aviv time). For those who are unable to attend the live presentation, a recording of the webcast will be made available. For more information and a link to the webcast, please visit www.solvegne.org or follow them on Facebook. Forward-Looking StatementsThis press release contains forward-looking statements, including, without limitation, statements regarding the success, cost, and timing of our product development activities and clinical trials, our plans to research, develop, and commercialize our product candidates, and our plans to submit regulatory filings and obtain regulatory approval of our product candidates. These forward-looking statements are based on Solve GNE’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include but are not limited to: (a) the timing, costs, and outcomes of our clinical trials and preclinical studies, (b) the timing and likelihood of regulatory filings and approvals for our product candidates, and (c) the potential market size for our product candidates. These forward-looking statements speak only as of the date made and, other than as required by law, we undertake no obligation to publicly update or revise any forward-looking statements. Contact Information: Alexander Monsef – 310-913-3418 – Alexm@solvegne.org

LOS ANGELES, July 31, 2023 (GLOBE NEWSWIRE) -- Solve GNE announced today that it has entered into a sponsored research agreement with Gradalis, Inc. to provide funding for a novel lipid nanoparticle gene therapy aimed at curing GNE Myopathy or Hereditary Inclusion Body Myopathy (HIBM). GNE Myopathy is a muscular disorder caused by an inherited mutation of a muscle support gene called GNE. It is characterized by muscle weakness that starts in early adulthood. The progression of the disease varies among patients but generally starts in the leg muscles and eventually leads to complete loss of mobility. Although this is a rare disorder, its incidence is remarkably high among Iranians of Jewish descent, where it’s estimated that 10-15% of the population carry at least a single copy of the GNE M743T point mutation. Gradalis’ earlier human phase 1 data1 indicate that multiple systemic infusions of a GNE- Lipoplex2 into a patient with advanced GNE Myopathy were generally tolerable and safe. The results provide evidence that such a therapy may act to delay or prevent the progression of HIBM. Gradalis will look to improve the efficacy and safety of a next generation GNE-Lipoplex therapy by applying their proprietary bi-shRNAi gene silencing platform to reduce adverse anti-muscle effects related to the GNE mutation and to correct the mutant GNE activity by providing normal GNE gene replacement activity. Funding from Solve GNE will support the filing of an IND and a multi-centered Phase 1 trial that is projected to start recruiting in 2024. John Nemunaitis, M.D., Chief Scientific Officer of Gradalis, commented, “Gradalis previously treated a young woman with this debilitating disease under a compassionate IND with FDA, using our DNA based technology. We were able to show a benefit of muscle activity and clinical safety. We have continued to develop our technology and will apply what we have learned as we move forward to establish a Phase 1 trial treatment IND in coordination with Solve GNE.” 1 Nemunaitis, G., et al., Hereditary inclusion body myopathy: single patient response to GNE gene Lipoplex therapy. J Gene Med, 2010. 12(5): p. 403-12. doi: 10.1002/jgm.1450. 2 Nemunaitis, G., et al., Hereditary inclusion body myopathy: single patient response to intravenous dosing of GNE gene lipoplex. Hum Gene Ther, 2011. 22(11): p. 1331-41. doi: 10.1089/hum.2010.192 About Solve GNESolve GNE is a Los Angeles based non-profit organization focused on developing a cure for GNE Myopathy (or HIBM). Solve GNE has been actively raising funds to support research and development of various gene therapies that are poised to enter human clinical trials in the next 12-18 months. For more information, visit www.solvegne.org About Gradalis, Inc.Gradalis is a privately held, late-stage clinical biotechnology company that has developed a proprietary bi-shRNA technology that can be used to “silence” the expression of specific genes. Gradalis’ lead product is a personalized immunotherapy called Vigil, that has been tested in multiple studies in ovarian and other cancer tumor types. Vigil is the first cellular immunotherapy to demonstrate survival benefits in a randomized controlled trial of ovarian patients with solid tumors. Vigil is a novel, triple function immunotherapy platform that modifies a patient’s tumor by using bi-shRNA to reduce furin, an enzyme which facilitates immunosuppressive TGF beta protein production, and to maximize DNA expression of GM-CSF, which stimulates the immune system and attracts key immune system effector cells, including T cells. By utilizing the patient's own tumor as the antigen source, Vigil is designed to elicit an immune response that is specifically targeted and broadly relevant to each patient's unique “clonal” tumor neoantigens. Gradalis is preparing to initiate a Phase 2 clinical study of Vigil in platinum sensitive recurrent ovarian cancer patients with the HRP molecular profile. For more information, visit www.gradalisinc.com About Vigil®Vigil® is a novel personalized triple function immunotherapy. Vigil is composed of autologous tumor cells that are harvested from the patient and transfected with a plasmid encoding for GMCSF DNA, and a bifunctional short-hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of 2 TGFβ isoforms (TGFβ1 and TGFβ2), which act to suppress the immune system. Vigil takes advantage of the immune stimulation and anti-tumor immunity resulting from increased GMCSF levels while simultaneously decreasing immune suppression that results from TGFβ1, 2 expression. Through transfection of autologous tumor cells, Vigil also presents the clonal neoantigens of the patient’s own tumor to systematically prime and educate circulating T cells to dominant anticancer targets while generating a systemic immune-permissive “training” environment against the cancer. In VITAL, a Phase 2b trial in Stage III/IV newly diagnosed, frontline ovarian cancer patients, Vigil showed a positive trend in the primary endpoint of recurrence free survival (RFS) in the overall population and a statistically significant improvement in the secondary endpoint of recurrence free survival and overall survival (OS) in patients with the BRCAwt molecular profile, with a median survival time of three years to date. Importantly in patients with tumors of the HRP type, where there is a high unmet medical need, an even greater statistically significant improvement was seen in RFS and OS. Additionally, Phase 1 results in an “all-comer” clinical trial showed positive signals of activity in 19 tumor types. Forward-Looking StatementsThis press release contains forward-looking statements, including, without limitation, statements regarding the success, cost, and timing of our product development activities and clinical trials, our plans to research, develop, and commercialize our product candidates, and our plans to submit regulatory filings and obtain regulatory approval of our product candidates. These forward-looking statements are based on Solve GNE’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include but are not limited to: (a) the timing, costs, and outcomes of our clinical trials and preclinical studies, (b) the timing and likelihood of regulatory filings and approvals for our product candidates, and (c) the potential market size for our product candidates. These forward-looking statements speak only as of the date made and, other than as required by law, we undertake no obligation to publicly update or revise any forward-looking statements. Contact Information: Alexander Monsef - 310-913-3418 - alexm@solvegne.org