Hypophosphatemic Rickets With Hypercalciuria, Hereditary

- Data from the largest retrospective analysis of ENPP1 Deficiency provides insights into the evolution of the disease’s serious cardiovascular and musculoskeletal complications - - Findings highlight the urgent need for early and improved diagnosis, care and treatments that address the long-term systemic effects of ENPP1 Deficiency - BOSTON, April 10, 2025 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage biopharmaceutical company developing innovative therapeutics for rare diseases that affect bone health and blood vessel function, today announced the publication of a paper titled, “Phenotypic characterization of ENPP1 deficiency: generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2” in JBMR Plus that characterizes the severity and progression of ENPP1 Deficiency. Inozyme collaborated with leading disease experts Carlos Ferreira, M.D., of the National Institutes of Health (NIH), Frank Rutsch, M.D., of Münster University Children’s Hospital and other global contributors to collect natural history data in the largest retrospective analysis of ENPP1 Deficiency published to date. “This comprehensive study illustrates the devastating, systemic nature of ENPP1 Deficiency, highlighting its severe cardiovascular implications starting as early as infancy and evolving to significant musculoskeletal complications over a lifetime as individuals go through childhood, adolescence, and then adulthood,” said Matt Winton, Ph.D., Senior Vice President and Chief Operating Officer of Inozyme Pharma. “The findings underscore a critical need for earlier diagnosis and effective treatments. Our lead investigational therapy, INZ-701, is uniquely positioned as a potential transformative therapy to address the underlying causes and systemic impacts of this severe condition.” Detailed Analysis Reveals Severity and Disease Progression ENPP1 Deficiency frequently manifests as Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2), representing age-dependent phenotypes that evolve on a continuum over a lifetime. Of the 84 individuals with ENPP1 Deficiency in the analysis, 51 had a recorded diagnosis of GACI, only 19 of whom survived beyond infancy; 22 were diagnosed with GACI and progressed to ARHR2; and 11 presented initially with ARHR2. Importantly, a majority of patients (60%) with a history of GACI had prenatal findings, and a GACI diagnosis (median age of 0.8 months at diagnosis) was usually associated with early-onset arterial calcification, respiratory distress, heart failure, and hypertension, necessitating acute inpatient care. Additional findings from the publication included: By age 55, over 95% of patients with ENPP1 Deficiency will have had cardiovascular, musculoskeletal, and other organ complications.Vascular calcification and cardiovascular complications onset predominately in infancy – 60% of patients had arterial or aortic calcification within the first 3 months of life. Notably, cardiovascular complications were evident in patients without a diagnosis of GACI – 64% of the group diagnosed with ARHR2-only had cardiovascular manifestations.By age 10, approximately 70% of patients developed serious musculoskeletal complications, primarily rickets significantly impairing quality of life. Additional complications associated with ARHR2 include hearing impairment and ongoing risk of cardiovascular problems. These findings highlight that ENPP1 Deficiency is a progressive, lifelong condition requiring coordinated, multidisciplinary care. Even for those who survive infancy, the majority will face ongoing cardiovascular, skeletal, and systemic complications, underscoring the need for early diagnosis and long-term management to improve outcomes. About ENPP1 Deficiency ENPP1 Deficiency is a serious and progressive rare disease that affects blood vessels, soft tissues, and bones. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1), with about 50% of these infants not surviving beyond six months. Children with this condition typically develop autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia, or softened bones. ARHR2 and osteomalacia cause pain and difficulty with movement. Additionally, patients may experience hearing loss, calcification in arteries and joints, and heart problems. ENPP1 Deficiency is an autosomal recessive disease and biallelic mutations are estimated to occur in approximately 1 in 64,000 pregnancies worldwide. Many individuals with just one copy of the mutated gene (monoallelic ENPP1 Deficiency) exhibit severe symptoms, suggesting that the worldwide prevalence of ENPP1 Deficiency may be much higher than current estimates. Currently, there are no approved therapies for ENPP1 Deficiency. About Inozyme Pharma Inozyme Pharma is a clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics that target the PPi-Adenosine Pathway, a key regulator of bone health and blood vessel function. Disruptions in this pathway underlie a range of severe diseases, including ENPP1 Deficiency. Our lead investigational therapy, INZ-701, is an ENPP1 Fc fusion protein enzyme replacement therapy (ERT) designed to restore PPi and adenosine levels. INZ-701 is currently in late-stage clinical development in ENPP1 Deficiency, with the potential to expand into additional indications where deficiencies in the PPi-Adenosine Pathway contribute to disease pathology. Through our pioneering work, we aim to transform treatment options for patients affected by these devastating conditions. For more information, please visit https://www.inozyme.com/ or follow Inozyme on LinkedIn, X, and Facebook. Contacts Investors:Inozyme PharmaStefan Riley, Senior Director of IR and Corporate Communications(617) 461-2442stefan.riley@inozyme.com Media:Biongage CommunicationsTodd Cooper(617) 840-1637todd@biongage.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/eb5daae6-15b5-4d55-9f50-d2e8d88a974d

– The study aims to evaluate the safety, tolerability, and preliminary efficacy of JR-446 for the treatment of individuals with MPS IIIB, for which there is no approved treatment – TOKYO & HYOGO, Japan I December 05, 2024 I MEDIPAL HOLDINGS CORPORATION (TSE 7459, MEDIPAL) and JCR Pharmaceuticals Co., Ltd. (TSE 4552, JCR) today announced the initiation of the Phase I/II clinical trial of JR-446 in Japan following the dosing of the first individual from the trial. JR-446 is a proprietary blood-brain barrier (BBB)-penetrating α-N-acetylglucosaminidase in development for the treatment of mucopolysaccharidosis type IIIB (Sanfilippo syndrome type B or MPS IIIB). MPS IIIB affects an estimated 500 to 1,000 individuals worldwide, 1 causing severe central nervous system (CNS) symptoms. Despite the dire need, there are currently no approved treatments available for this condition. JR-446, developed using JCR’s proprietary J-Brain Cargo ® technology, has shown promising non-clinical results in addressing the symptoms of this challenging disorder. This Phase I/II clinical trial is an open-label, single-arm, multi-center study that includes individuals under 18 years of age who are diagnosed with MPS IIIB. The study aims to evaluate the safety, tolerability, and exploratory efficacy of JR-446, while also assessing the optimal dosage through the administration of multiple doses. For more details on the trial, visit the Clinical Research Submission and Disclosure System (JR-446-101, jRCT2071240043 ). “We are pleased to be advancing a long-awaited treatment option for MPS IIIB, a condition for which there are no approved therapies,” said Dr. Motomichi Kosuga, Medical Director of the Division of Medical Genetics, National Center for Child Health and Development, and the Medical Expert of the study. “In Japan, MPS IIIB is one of the more frequently observed forms of MPS III, and it primarily affects the CNS, leading to severe symptoms. This trial represents a hopeful step forward in addressing these neurological challenges, and we sincerely hope it will bring meaningful improvements in both the medical outlook and quality of life for patients and their families.” In September 2023, MEDIPAL and JCR entered into a licensing agreement in which MEDIPAL will commercialize JR-446 outside of Japan. In addition, MEDIPAL will support JCR in the clinical development of JR-446 in Japan, including the distribution of investigational drugs, disease awareness, and clinical trial advancement. 2 This collaboration highlights the commitment of MEDIPAL and JCR to pioneer treatments for ultra- rare diseases. By advancing therapies like JR-446, we aim to bring hope to patients and their families, while enhancing corporate value and contributing to a society where everyone can live with physical and mental well-being. About Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B) Mucopolysaccharidosis type IIIB, or Sanfilippo syndrome type B, is an autosomal recessive disease caused by pathogenic mutations in the NAGLU gene, encoding a lysosomal enzyme involved in the degradation of heparan sulfate. With the accumulation of heparan sulfate in the central nervous system in the brain, individuals with this condition present rapid neurological decline, including sleep disorders, loss of speech, and behavioral changes, which may significantly affect the quality of life of patients and their families. About the J-Brain Cargo ® Platform Technology JCR Pharmaceuticals has developed a proprietary blood-brain barrier-penetrating technology J- Brain Cargo ® , to bring biotherapeutics into the central nervous system. The first drug developed based on this technology is IZCARGO ® (INN: pabinafusp alfa) and was approved in Japan for the treatment of a lysosomal storage disorder. About MEDIPAL HOLDINGS CORPORATION MEDIPAL is a holding company which controls, administers and supports the operating activities of companies in which it holds shares in the Prescription Pharmaceutical Wholesale Business; the Cosmetics, Daily Necessities and OTC Pharmaceutical Wholesale Business; and the Animal Health Products and Food Processing Raw Materials Wholesale and Related Business, and conducts business development for the MEDIPAL Group. For more information, visit https://www.medipal.co.jp/english/ . About JCR Pharmaceuticals Co., Ltd. JCR is a global specialty pharmaceuticals company dedicated to advancing treatments for rare and genetic diseases. With nearly 50 years of expertise in Japan, we are expanding to the US, Europe, and Latin America. Our innovative therapies address conditions like growth disorder, MPS II, Fabry disease, acute graft-versus-host disease, and renal anemia. We are also developing treatments for rare diseases like MPS I, MPS II, MPS IIIA and B, and more. Our core values of reliability, confidence, and persistence drive our mission to enhance global medical progress. For more information, visit https://www.jcrpharm.co.jp/en/site/en/ . References SOURCE: JCR Pharmaceuticals

HYOGO, Japan I October 31, 2024 I JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”) announced the initiation of the first patient dosing in Japan in the Phase I clinical trial of JR-441, an investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome type A). JR-441 is a proprietary recombinant heparan N-sulfatase capable of crossing the blood-brain barrier (BBB). MPS IIIA is a rare genetic disorder characterized by severe central nervous system (CNS) symptoms, for which there is currently no approved treatment. Preclinical studies have demonstrated the potential of JR-441 to address CNS-related symptoms associated with MPS IIIA. This open-label, multicenter, single-arm study aims to assess the safety profile, biological effect, and pharmacokinetic profile of JR-441 in patients aged 1 to under 18 years with MPS IIIA. “MPS IIIA has been one of the most significant challenges in the treatment of CNS symptoms,” said Dr. Kimitoshi Nakamura, Professor of Pediatrics at the Graduate School of Medical Sciences, Kumamoto University, and the Medical Expert of the study. “This novel therapeutic approach represents a new era for managing the condition. We have been eagerly awaiting the opportunity to offer this treatment, and I am hopeful that its effectiveness will be confirmed in the clinical setting, ultimately improving the daily lives of both patients and their families.” JR-441 received Orphan Drug Designation from both the European Commission (EC) and the U.S. Food and Drug Administration (FDA), with a Phase I/II trial underway in Germany, which began in 2023 (JR-441-101, NCT06095388 ). For more details on the Japanese Phase I trial, visit the Clinical Research Submission and Disclosure System (JR-441-JP11, jRCT2071240053 ). About Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is an autosomal recessive disease caused by pathogenic mutations in the SGSH gene, encoding a lysosomal enzyme involved in the degradation of heparan sulfate. The accumulation of heparan sulfate in several types of cells of the body, especially in the central nervous system in the brain, results in severe neurological deterioration, cognitive impairment, mild somatic involvement, and shortened lifespan. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 49-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. JCR strives to expand the possibilities for patients while accelerating medical advancement at a global level. Our core values – reliability, confidence, and persistence – benefit all our stakeholders, including employees, partners, and patients. For more information, please visit https://www.jcrpharm.co.jp/en/site/en/ . SOURCE: JCR Pharmaceuticals