Solve GNE and Gradalis Sign Agreement to Develop a Novel Gene Therapy Targeting HIBM

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 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 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 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 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