GNE

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

In 2020, The Neuromuscular Disease Foundation (NDF), a Beverly Hills based non-profit in order to advance research to end the muscle wasting disease, began its International Gene Therapy Development Program (IGTDP). That program is designed to find an effective treatment to halt the progression of GNEM and is the culmination of more than a decade of NDF’s funding of global scientific research into GNEM and treatment options. In 2021, the organization promptly enlisted a world-renowned team of researchers and scientists, having multiple areas of expertise, to collaborate in this initiative and to leverage the accumulated data from their global research efforts. The impressive team of leading scientific experts that NDF assembled for this initiative includes Angela Lek (VP of Research at the Muscular Dystrophy Association), Richard Horgan (founder of Cure Rare Disease) and other prominent scientists in the field, such as Dr. Stella Mitrani Rosenbaum (Hadassah), Dr. Marjan Huizing (NIH), Dr. Kelly Crowe (Xavier University), Dr. Julie Crudele (UW), Dr. Monkol Lek (Yale) and Dr. Noah Weisleder (Ohio State College of Medicine). The objective of the NDF led team’s research is to treat patients who have a confirmed diagnosis of GNEM, by slowing the progression of the disease. If successful, NDF’s effort will be a historic milestone in the gene therapy field, and could serve as a blueprint for other institutions to take similar approaches in developing gene therapy treatments for patients with other diseases. NDF’s board of directors worked with the team of leading scientists during the winter of 2021 to determine how to best reach the goal of developing the proposed pre-IND package and secure future IND approval from the FDA. In late 2021, the team began producing the viral vector containing the GNE gene, looking forward to finalizing the proof-of-concept preclinical studies. They then progressed to the pre-clinical development testing phase, testing the gene therapy and In mouse models identified a lead drug candidate for development and further trials . . Over the past twelve months: ● Cell based studies have continued to show that the NDF gene therapy candidate can restore healthy GNE protein in cell lines from GNE patient donors. ● Using reversal of cryo-preservation, researchers were able to reestablish a previously established mouse model for the testing of gene therapy drug candidates. ● The NDF has spoken with multiple corporate interests, who have launched drug development efforts focused on GNE myopathy. ● The NDF team was able to Provide vital, foundational resources including the novel mouse model to newly founded GNEM therapy drug development efforts at Stanford University. ● The NDF has funded research that laid the foundation for the current ManNAc trial. Having seen auspicious progress thus far, the organization is continuing full steam ahead with its ambitious plan to deliver a viable treatment that will halt the progression of GNEM in affected patients, in a nearly unprecedented timeframe. The NDF’s donor community continues to sustain this NDF sponsored science, to facilitate these measurable steps toward delivering a cure to GNEM patients worldwide. At the time of this writing, the NDF scientific budget for 2023 is $1 million, with leadership seeking to grow that amount through the involvement of interested corporate partners and private donorship. Recently, it was announced that Rich Horgan, NDF’s biotechnology consultant, had obtained FDA approval through the company Cure Rare Disease, (of which he is founder and CEO), to administer the first-in-human CRISPR therapeutic for Duchenne muscular dystrophy. As the global research community watches this trial and the overall future of the therapeutic, NDF anticipates that with Rich Horgan as part of its scientific team it will soon see a similar trial for GNEM therapy. About NDF The Neuromuscular Disease Foundation (NDF) works to enhance the quality of life for those living with GNE Myopathy by funding critical research focused on treatments and a cure through The International Gene Therapy Development Program (IGTDP) and by advocacy, education and outreach. Donations to the NDF benefit research toward a cure as well as an impressive roster of patient programs, including a Holistic Wellness Center that offers counseling services, patient support groups, a multidisciplinary clinic, access to genetic screening, and a learning library of webinars, podcasts and educational resources involving experts from around the globe, to keep the GNEM patient community well apprised of real time developments in the science to treat GNEM, and more. For more information, please visit