Congenital Disorder of Glycosylation Type 1A

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

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 .

PDUFA target action date of August 28, 2024 MAA validated and accepted for review by EMA in December 2023 NEW YORK, Feb. 28, 2024 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, today announced that the U.S. Food and Drug Administration (FDA) has accepted the filing of the New Drug Application (NDA) for govorestat (AT-007) for the treatment of Classic Galactosemia. The NDA was granted Priority Review status, and the FDA assigned a Prescription Drug User Free Act (PDUFA) target action date of August 28, 2024. The FDA also noted that it is planning to hold an advisory committee meeting to discuss the application. Govorestat was previously granted Pediatric Rare Disease designation, and will qualify for a Priority Review Voucher (PRV) upon approval. “The FDA’s acceptance of the NDA for govorestat for the treatment of Galactosemia represents a critical milestone for Applied Therapeutics and more importantly, for patients with Galactosemia and their families. The Agency’s decision to grant Priority Review for this NDA underscores the urgent unmet medical need as there are currently no treatment options for this devastating disease,” said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. “We want to thank the patients, families, collaborators and physicians involved in reaching this achievement. We look forward to continuing to work with the FDA throughout the review process, as we hope to bring govorestat to patients as quickly as possible.” “We are excited to see that the FDA has accepted the govorestat NDA for priority review,” said Nicole Casale, President of the Galactosemia Foundation. “The Galactosemia community is in urgent need of a safe and effective treatment, and the potential approval of govorestat provides hope for many families. Acceptance of the govorestat NDA brings us one step closer to availability of a first-ever treatment.” Govorestat is an investigational, novel Aldose Reductase Inhibitor (ARI) being developed for the treatment of several rare diseases. It is a potent and selective compound, which crosses the blood brain barrier into the Central Nervous System (CNS). The NDA filing of govorestat is supported by rapid and sustained reduction in galactitol, which resulted in a meaningful benefit on clinical outcomes across pediatric patients, alongside a favorable safety profile. The submission package included clinical outcomes data from the Phase 3 registrational ACTION-Galactosemia Kids study in children aged 2-17 with Galactosemia, the Phase 1/2 ACTION-Galactosemia study in adult patients with Galactosemia, and preclinical data. If approved, govorestat would be the first medication indicated for the treatment of Galactosemia and would be Applied Therapeutics’ first commercial product. The FDA grants Priority Review to applications for potential medicines that, if approved, may offer significant improvements in the treatment, prevention or diagnosis of a serious condition. Govorestat for the treatment of Galactosemia has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) and Orphan Drug Designation, Pediatric Rare Disease Designation and Fast Track Designation from the FDA. The Company has also submitted a Marketing Authorization Application (MAA) for govorestat for the treatment of Classic Galactosemia to the EMA, which was validated in December 2023 and is under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The Company expects a decision by the EMA in the fourth quarter of 2024. About Galactosemia Galactosemia is a rare genetic metabolic disease resulting in an inability to metabolize the simple sugar galactose. Galactose is found in foods, but is also produced endogenously by the body. When not metabolized properly, galactose is converted to the toxic metabolite, galactitol, which causes neurological complications, including deficiencies in speech, cognition, behavior, and motor skills, and also results in juvenile cataracts and ovarian insufficiency (in women). There are approximately 3,000 patients with Galactosemia in the US and 80 new births per year, and approximately 4,000 patients with Galactosemia in the EU and 120 new births per year. Newborn screening for Galactosemia is mandatory in the US and most EU countries, leading to rapid identification of affected patients. About Govorestat (AT-007) Govorestat is a central nervous system (CNS) penetrant Aldose Reductase Inhibitor (ARI) in development for the treatment of several rare neurological diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. In a study in children with Galactosemia aged 2-17, treatment with govorestat demonstrated clinical benefit on activities of daily living, behavioral symptoms, cognition, fine motor skills and tremor. Govorestat also significantly reduced plasma galactitol levels in both adults and children with Galactosemia. Galactitol is a toxic metabolite responsible for tissue damage and long-term complications in Galactosemia. Govorestat is also being studied in the ongoing Phase 3 INSPIRE trial, which is evaluating the effect of AT-007 vs. placebo in patients with SORD Deficiency on sorbitol reduction as well as clinical outcomes in approximately 50 patients aged 16-55 in the U.S. and Europe. In an interim analysis at 12 months, govorestat achieved statistical significance on the prespecified primary endpoint of correlation of sorbitol with the clinical outcome composite and demonstrated sustained, statistically significant reduction in sorbitol level vs. placebo. Govorestat also demonstrated highly statistically significant effects on the CMT Health Index (CMT-HI) patient reported outcome measure, with benefit of govorestat on categories of lower limb function, mobility, fatigue, pain, sensory function, and upper limb function. Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) for both Galactosemia and SORD Deficiency. Govorestat has also received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of Galactosemia, PMM2-CDG, and SORD Deficiency; Pediatric Rare Disease designation for Galactosemia and PMM2-CDG; and Fast Track designation for Galactosemia. About Applied Therapeutics Applied Therapeutics is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need. The Company’s lead drug candidate, govorestat, is a novel central nervous system penetrant Aldose Reductase Inhibitor (ARI) for the treatment of CNS rare metabolic diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. The Company is also developing AT-001, a novel potent ARI, for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal fibrosis of the heart. The preclinical pipeline also includes AT-003, an ARI designed to cross through the back of the eye when dosed orally, for the treatment of Diabetic retinopathy. To learn more, please visit www.appliedtherapeutics.com and follow the company on Twitter @Applied_Tx. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding the strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” “predicts” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are forward-looking statements. These include, without limitation, statements regarding the likelihood that the NDA submission will be approved. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, (i) our plans to develop, market and commercialize our product candidates, (ii) the initiation, timing, progress and results of our current and future preclinical studies and clinical trials and our research and development programs, (iii) our ability to take advantage of expedited regulatory pathways for any of our product candidates, (iv) our estimates regarding expenses, future revenue, capital requirements and needs for additional financing, (v) our ability to successfully acquire or license additional product candidates on reasonable terms and advance product candidates into, and successfully complete, clinical studies, (vi) our ability to maintain and establish collaborations or obtain additional funding, (vii) our ability to obtain and timing of regulatory approval of our current and future product candidates, (viii) the anticipated indications for our product candidates, if approved, (ix) our expectations regarding the potential market size and the rate and degree of market acceptance of such product candidates, (x) our ability to fund our working capital requirements and expectations regarding the sufficiency of our capital resources, (xi) the implementation of our business model and strategic plans for our business and product candidates, (xii) our intellectual property position and the duration of our patent rights, (xiii) developments or disputes concerning our intellectual property or other proprietary rights, (xiv) our expectations regarding government and third-party payor coverage and reimbursement, (xv) our ability to compete in the markets we serve, (xvi) the impact of government laws and regulations and liabilities thereunder, (xvii) developments relating to our competitors and our industry, (xviii) our ability to achieve the anticipated benefits from the agreements entered into in connection with our partnership with Advanz Pharma and (xiv) other factors that may impact our financial results. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. Factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Contacts Investors:Maeve Conneighton (212) 600-1902 orappliedtherapeutics@argotpartners.com Media:media@appliedtherapeutics.com