Congenital Disorders of Glycosylation

STURGIS, Mich., March 18, 2024 /PRNewswire/ -- Maggie's Pearl, a collaboration between Perlara, Maggie's Cure, and the Mayo Clinic, announced that the Phase III trial of oral epalrestat therapy in pediatric subjects with PMM2-CDG (formerly, Congenital Disorder of Glycosylation Type 1a) has been green-lighted to transition to open label. All study subjects on placebo may transition to open label epalrestat at their 15-month study visit. The principal investigator, study team, participants, and their families remain blinded to original treatment assignments until all subjects reach their 15-month visit. The crossover recommendation was unanimous among an independent three-member data monitoring committee, comprising two physician scientists with PMM2 expertise and a biostatistician. The DMC concluded the planned interim analysis and determined that the trial can proceed safely. They recommended that each study participant continue with their randomly assigned treatment until the 15-month visit, when they can transition to open label epalrestat. Administered by the Mayo Clinic, the clinical trial is a prospective, single-center, randomized, double-blind, placebo-controlled study. In December 2021, the Food and Drug Administration notified Maggie's Pearl that the Phase III clinical trial in 40 patients with PMM2-CDG could proceed. The trial recruited 38 study subjects and closed enrollment in November 2023. The first 29 participants will complete their 15-month visits over the next 2-3 months. PMM2-CDG (phosphomannomutase-2-congenital disorder of glycosylation) is caused by mutations in a gene that supplies the instructions for making the PMM2 enzyme. The enzyme is involved in a process called glycosylation, in which sugar chains are created, altered, and chemically attached to specific proteins to form glycoproteins. Those proteins are key to normal growth and function of tissues and organs. No approved treatment options exist for patients with PMM2-CDG. "The DMC recommendation to allow study participants to receive epalrestat upon completing 15 months of randomized treatment is very encouraging," said Ethan Perlstein, CEO of Maggie's Pearl. "We can't thank participating families enough. They are medical pioneers and an example for all rare disease communities of what is possible despite the hardships of a placebo-controlled study. We look forward to opening discussions with FDA in the coming months to make epalrestat widely available for all PMM2-CDG families." The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. More at: clinicaltrials.gov/ct2/show/NCT04925960. About Maggie's Pearl : Established in August 2020, Maggie's Pearl LLC is a joint venture between Perlara, Maggie's Cure, and the Mayo Clinic to identify potential drug therapies to treat and improve the lives of PMM2-CDG patients. Maggie's Pearl was inspired by Maggie Carmichael, a 10-year-old girl from Sturgis, Michigan, who was diagnosed with PMM2-CDG at eight months of age. At that time, Maggie's parents were told there was no treatment for the rare, and potentially fatal, genetic disease. Globally, roughly 1,000 people are known to have PMM2-CDG. More at . CONTACT: Pete Johnson, [email protected] SOURCE Maggie's Pearl

MENLO PARK, Calif.--(BUSINESS WIRE)-- Grace Science, LLC announced today that the first patient was dosed in an open-label Phase 1/2/3 clinical trial of GS-100, an AAV9 gene replacement therapy for the treatment of NGLY1 Deficiency. Part 1/2 of the study will investigate dose-escalation and the safety and efficacy of a single intracerebroventricular (ICV) infusion of GS-100 in NGLY1 Deficiency patients aged 2-18 years. Part 3 of the study will assess the co-primary outcomes at 52 weeks following treatment at the selected dose: 1) change from baseline of the NGLY1 Deficiency Primary Disease Activity Biomarker, GlcNAc-Asn (GNA, or N-acetylglucosamine) in cerebrospinal fluid, and 2) change from baseline in the motor subdomain of the Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-4). Further details regarding the Phase 1/2/3 study can be found at . Matt Wilsey, CEO & Co-Founder of Grace Science, LLC, stated that "Treating the first patient is a tremendous milestone for our company and the NGLY1 Deficiency patients we strive to cure. We believe this drug will improve the lives of individuals living with this devastating disease. Time is precious as our community has lost sixteen individuals since January of 2020.” “This study is a true partnership between the scientific community and the NGLY1 patient community,” said Carolyn Bertozzi, Co-Founder of Grace Science, LLC. Dr. Bertozzi went on to say “The team has worked incredibly hard to reach the goal of treating the first NGLY1 Deficiency patient with this potentially life-changing therapy. We are so thankful to the patients and their families for helping Grace Science turn this treatment into a reality.” About GS-100 GS-100 is a recombinant, single-stranded AAV9 vector that encodes a full-length version of the human NGLY1 gene. GS-100 was previously granted Orphan Drug Designation (ODD) by both the FDA and the European Medicine Agency (EMA) in 2021, Rare Pediatric Disease Designation by the FDA in 2021, and Fast Track Designation by the FDA in 2023. About NGLY1 Deficiency NGLY1 Deficiency is a serious, life-threatening disease with no approved therapy. Patients with this disease suffer from debilitating symptoms that present early in life, including global developmental delay, cognitive impairment, (hypo)alacrima, movement disorders, and other neurological symptoms. About Grace Science Grace Science, LLC is a biotechnology company founded in 2017 by Matt Wilsey and Dr. Carolyn Bertozzi to develop novel therapies based on the function of NGLY1, a key enzyme involved in proteostasis. The company’s deep knowledge of the NGLY1 pathway is key to its ability to identify new ways of treating NGLY1 Deficiency as well as more common diseases. For more information about Grace Science, LLC and NGLY1 Deficiency, please visit gracescience.com.

Initial data from adult patients with PMM2-CDG showed promising evidence of clinical benefit with GLM101 Notable improvements were seen in ataxia, one of the most frequent disease-associated clinical symptoms Data from this study provides key insights into future planned clinical trials SAN CARLOS, Calif.--(BUSINESS WIRE)-- Glycomine Inc, a biotechnology company focused on developing new therapies for orphan diseases, announced the presentation of summary findings from its ongoing Phase 2 clinical study (GLM101-002) in adult patients with PMM2-CDG at the Rare Disease Day 2024 Symposium, CDG Scientific and Family Conference, that took place March 1-3 in San Diego. The findings highlight the potential for clinically meaningful benefit with a notable improvement in the International Co-operative Ataxia Rating Scale (ICARS) score in four adult patients in the 30 mg/kg cohort, with an average improvement of 12 points after 12 weeks (n=4) of treatment. This compares favorably to prior results reported with acetazolamide which demonstrated an average improvement of 6 points after 25 weeks in adult and pediatric patients (n=25). “We are thrilled to present data for the first time showing the potential for GLM101 to have a meaningful impact on ataxia, one of the most frequent and challenging clinical manifestations of this debilitating disease,” said Rose Marino, M.D., CMO of Glycomine. “These data provide invaluable input for the design of our future planned studies in adult and pediatric PMM2-CDG patients.” “Reducing ataxia has the potential to significantly impact the quality of life for PMM2-CDG patients and their caregivers,” added Mercedes Serrano, M.D., Ph.D., Child Neurologist and Clinical Researcher, U-703 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Sant Joan de Déu Hospital in Barcelona, Spain. “We are very encouraged by the initial results we have seen and delighted to be part of this important study.” The GLM101-002 Phase 2 clinical study has enrolled 10 adult patients in the U.S. and Spain (ClinicalTrials.gov Identifier: NCT05549219). Study participants have received GLM101 at either 10 mg/kg (n=3), 20 mg/kg (n=3), or 30 mg/kg (n=4) for up to 24 weeks. Over 200 doses of GLM101 have been administered to patients with PMM2-CDG. The drug appears to be safe and well tolerated with no serious adverse events and only mild to moderate adverse events reported to date. Four adolescent patients have initiated treatment, and the study is planned to be extended into younger PMM2-CDG patients in the coming months. About GLM101 GLM101 is a mannose-1-phosphate replacement therapy in development to treat phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), previously known as CDG Type Ia. GLM101 has received Orphan Drug Designation in the U.S. and Europe and Rare Pediatric Disease Designation in the U.S. PMM2-CDG is caused by genetic mutations that lead to a deficiency of the enzyme phosphomannomutase 2 (encoded by the PMM2 gene). GLM101 is designed to deliver mannose-1-phosphate directly into cells and thereby bypass the PMM2 enzyme deficiency and address disease-causing PMM2 mutations to restore pathway function. About Glycomine, Inc. Glycomine is a clinical-stage biotechnology company developing novel drugs for serious rare disorders of metabolism and protein misfolding for which no other therapeutic options exist. The company's approach is to use replacement therapies – substrates, enzymes, or proteins – and to target those molecules to clinically relevant cellular compartments. The company is based in San Carlos, California and supported by leading international life sciences investors. For more info visit .