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April 2, 2025 Manuscript in the Journal of Inherited Metabolic Disease indicates increased survival in patients treated with fosdenopterin Solana Beach, CA – April 2, 2025 – Sentynl Therapeutics, Inc. (“Sentynl”), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences, Ltd. (“Zydus Group”), is pleased to announce the publication of NULIBRY’s three clinical studies comparing the treatment effect of NULIBRY versus a natural history study in the Journal of Inherited Metabolic Disease. Fosdenopterin gained its approval by the United States Food and Drug Administration (FDA) in February 2021, the Israeli Ministry of Health (MoH) in July 2022, the European Medicines Agency (EMA) in September 2022, and the Medicines and Healthcare products Regulatory Agency (MHRA) in April 2024 for the treatment of MoCD Type A. These data represent the first comprehensive body of clinical research in the only approved treatment for MoCD Type A patients, as well as the most abundant findings on the natural progression of the disease. The results showed statistically significant prolonged survival in treated versus untreated patients, as well as genotype-match controls with the risk of death at 5.1 times higher in the untreated patients (Cox proportional hazards 5.1; 95% CI 1.32-19.36; p=0.01). Additionally, significant improvements were seen in cognitive and motor functioning in the treated versus the untreated patients. Fosdenopterin-treated patients experienced mild to moderate treatment emergent adverse events with the most common adverse events being catheter-related complications and infections. There were no discontinuations or dose modifications due to adverse events. MoCD Type A is an ultra-rare, autosomal recessive disease caused by variants in the MOCS1 gene. It typically presents at birth or shortly thereafter and if left untreated causes rapid, irreversible neurogeneration due to a build up of toxic sulfite levels in the brain, and ultimately a premature death. Fosdenopterin, a synthetic form of cPMP, restores normal sulfite levels thereby reducing the toxic sulfite concentration. “This publication marks the end of a truly collaborative and enthusiastic path from basic research to the bedside that started 21 years ago, when we reported the successful treatment of a mouse model of MoCD type A with cPMP (cyclic pyranopterin monophosphate, fodenopterin),” said Guenter Schwarz, Professor, Institute of Biochemistry, Department of Chemistry and Biochemistry & Center for Molecular Medicine, Cologne University, Germany. “Increased awareness and expeditious testing upon suspicion of MoCD are critical to improve neurological outcomes and overall survival in patients with MoCD Type A who can be treated early with fosdenopterin.” “It is important that clinicians consider the diagnosis of MoCD type A in neonates with intractable seizures, encephalopathy, feeding difficulties or increased startle response as earlier treatment appeared to improve achievement of developmental milestones,” said Liza Squires, MD, Sentynl Medical Consultant. Sentynl Therapeutics is committed to treating rare genetic diseases, which often present in infancy and early childhood. “The publication of these data in JIMD is a huge milestone for MoCD Type A patients, caregivers, and the medical community,” said Matt Heck, CEO, Sentynl. “It is the culmination of four companies’ commitment in NULIBRY’s clinical development program spanning over two decades.” About Molybdenum Cofactor Deficiency (MoCD) Type A MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity.1,2 The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites (such as S-sulfocysteine) in the brain, which causes irreversible neurological damage.2 MoCD Type A is an ultra-rare disease. The incidence and prevalence of MoCD Type A in the United States are not known, but the estimated incidence is 1 per 342,000 to 411,000 live births (0.24 and 0.29 per 100,000).3 Based on these estimates, MoCD Type A is likely to be underdiagnosed. The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment. Mechler K et al. Genet Med. 2015;17(12):965-970. Veldman A et al. Pediatrics. 2010;125(5):e1249-e1254 Mayr SJ, et al. Forecasting the incidence of rare diseases: an iterative computational and biochemical approach in molybdenum cofactor deficiency type A. Presented at the 2019 SSIEM meeting; September 3-6, 2019; Rotterdam, The Netherlands. About NULIBRY® (fosdenopterin) for Injection NULIBRY (fosdenopterin) for Injection is a substrate replacement therapy that provides a synthetic source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites. NULIBRY was approved by the U.S. FDA in February 2021, and by the Israel Ministry of Health in July 2022 and is indicated to reduce the risk of mortality in patients with MoCD Type A. NULIBRY was also approved by the EMA in September 2022, with an indication for treatment of patients with MoCD Type A. Important Safety Information Warnings and Precautions Potential for Photosensitivity NULIBRY can make the patient oversensitive to sunlight. NULIBRY-treated patients or their caregivers are advised to avoid or minimize patient exposure to sunlight and artificial UV light and adopt precautionary measures when exposed to the sun, including wearing protective clothing and sunglasses, and use broad-spectrum sunscreen with high SPF in patients 6 months of age and older. If photosensitivity occurs, caregivers/patients are advised to seek medical attention immediately and consider a dermatological evaluation. Adverse Reactions The most common adverse reactions in NULIBRY-treated patients were infusion catheter–related complications (89%), pyrexia (fever) (78%), viral infection (56%), pneumonia (44%), otitis media (ear infection) (44%), vomiting (44%), cough/sneezing (44%), viral upper respiratory infection (33%), gastroenteritis (33%), diarrhea (33%) , and bacteremia (33%). Adverse reactions for rcPMP-treated patients were similar to the NULIBRY-treated patients. Patient Counseling Information Please read the FDA-approved NULIBRY Prescribing Information and Instructions for Use and follow the instructions on how to prepare and administer NULIBRY. NULIBRY has a potential for photosensitivity; see Warnings and Precautions. Seek medical attention immediately if the patient develops a rash or if they notice symptoms of photosensitivity reactions (redness, burning sensation of the skin, blisters). You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. About Sentynl Therapeutics Sentynl Therapeutics, Inc. (“Sentynl”) is a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl’s experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well-differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is dedicated to ensuring no patient is overlooked, and is committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines. For more information, visit https://sentynl.com. About Zydus Group Zydus Lifesciences Ltd. with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global life sciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 27,000 people worldwide, including 1,400 scientists engaged in R & D, and is driven by its mission to unlock new possibilities in life sciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. For more information, visit https://www.zyduslife.com/zyduslife. Contacts: Media: Maureen Roberts, maureen.roberts@fleishman.com Sentynl: Michael Hercz, ir@sentynl.com For U.S. Audiences Only < Back This website uses cookies for data analytics. This website may also use cookies to enhance your experience with the website. We do not use cookies to sell or share your personal information. By selecting “Accept all,” you agree to our use of cookies. By selecting “Reject all,” you agree to a single strictly necessary cookie to prevent the use of data analytics cookies. For more information, please read our privacy statement.

NULIBRY is the first and only treatment in Great Britain for patients with molybdenum cofactor deficiency (MoCD) Type A, an ultra-rare, life-threatening genetic disorder that often progresses rapidly in infants with a median overall survival age of about four years The Medicines and Healthcare products Regulatory Agency's (MHRA) decision is based on efficacy and safety data collected to date SOLANA BEACH, Calif., April 16, 2024 /PRNewswire/ -- Sentynl Therapeutics, Inc. (Sentynl), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences, Ltd. (Zydus Group), today announced The Medicines and Healthcare products Regulatory Agency (MHRA) authorization of NULIBRY® (fosdenopterin) for Injection as the first therapy for the treatment of patients in Great Britain (GB) with molybdenum cofactor deficiency (MoCD) Type A, an ultra-rare, life-threatening genetic disorder that often progresses rapidly in infants. MoCD Type A is known to impact fewer than 150 patients globally with a median survival age of four years. NULIBRY is a first-in-class synthetic cPMP substrate replacement therapy that was approved by the U.S. Food and Drug Administration (FDA) in 2021 to reduce the risk of mortality in patients with MoCD Type A. Following this decision by the MHRA, NULIBRY is the first and only approved therapy in GB for MoCD Type A. "The MHRA approval of NULIBRY opens the door for healthcare providers in Great Britain to utilize this innovative treatment to meet the previously unmet needs of patients and their caregivers," said Matt Heck, President & Chief Executive Officer of Sentynl. "This approval advances our mission to make a positive impact in the lives of patients suffering from rare diseases, especially one as devastating as MoCD Type A." NULIBRY's MHRA approval was supported by data from three clinical trials that demonstrated the safety and efficacy of NULIBRY for the treatment of patients with MoCD Type A compared to data from a natural history study. These studies showed that NULIBRY-treated patients had a 5.5 times lower risk of death than that of the untreated patients. Moreover, the survival probability at 3 years of age was 85.5% for NULIBRY-treated patients and 55.1% for untreated control patients. In March 2022, Sentynl acquired the global rights to NULIBRY from BridgeBio Pharma, Inc. and is responsible for the ongoing development, manufacturing and commercialization of fosdenopterin globally. For questions on continued access to NULIBRY, please contact the Sentynl Cares support team at 1-888-251-2800. About Molybdenum Cofactor Deficiency (MoCD) Type A MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity.1,2 The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites (such as S-sulfocysteine) in the brain, which causes irreversible neurological damage.2 MoCD Type A is an ultra-rare disease. The incidence and prevalence of MoCD Type A in Great Britain are not known, but the estimated prevalence is 0.005 per 10,000. Based on these estimates, MoCD Type A is likely to be underdiagnosed. The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment. About NULIBRY® (fosdenopterin) for Injection NULIBRY (fosdenopterin) for Injection is a substrate replacement therapy that provides a synthetic source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites. NULIBRY was approved by the U.S. FDA in February 2021, and by the Israel Ministry of Health in July 2022 and is indicated to reduce the risk of mortality in patients with MoCD Type A. NULIBRY was also approved by the EMA in September 2022, with an indication for treatment of patients with MoCD Type A. References 1 Mechler K et al. Genet Med. 2015;17(12):965-970. 2 Schwarz G. Cur Op in Che Bio. 2016;31:179-187. Important Safety Information Warnings and Precautions Potential for Photosensitivity NULIBRY can make the patient oversensitive to sunlight. NULIBRY-treated patients or their caregivers are advised to avoid or minimize patient exposure to sunlight and artificial UV light and adopt precautionary measures when exposed to the sun, including wearing protective clothing and sunglasses, and use broad-spectrum sunscreen with high SPF in patients 6 months of age and older. If photosensitivity occurs, caregivers/patients are advised to seek medical attention immediately and consider a dermatological evaluation. Adverse Reactions The most common adverse reactions in NULIBRY-treated patients were infusion catheter–related complications (89%), pyrexia (fever) (78%), viral infection (56%), pneumonia (44%), otitis media (ear infection) (44%), vomiting (44%), cough/sneezing (44%), viral upper respiratory infection (33%), gastroenteritis (33%), diarrhea (33%) , and bacteremia (33%). Adverse reactions for rcPMP-treated patients were similar to the NULIBRY-treated patients. Patient Counseling Information Please read the FDA-approved NULIBRY Prescribing Information and Instructions for Use and follow the instructions on how to prepare and administer NULIBRY. NULIBRY has a potential for photosensitivity; see Warnings and Precautions. Seek medical attention immediately if the patient develops a rash or if they notice symptoms of photosensitivity reactions (redness, burning sensation of the skin, blisters). You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. About Sentynl Therapeutics Sentynl Therapeutics is a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl's experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well-differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines. For more information, visit . About Zydus Group Zydus Lifesciences Ltd. with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global lifesciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group has a significant presence in cancer related therapies and offers a wide range of solutions with cytotoxic, supportive & targeted drugs. The group employs nearly 25,000 people worldwide, including 1,400 scientists engaged in R & D, and is driven by its mission to unlock new possibilities in lifesciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. For more information, visit .

Risk of death was 5.1 times higher in untreated patients versus patients treated with NULIBRY Treatment also led to improvements in urinary biomarker levels and development outcomes NULIBRY is the first therapy to reduce the risk of mortality in patients with known or presumed MoCD Type A SOLANA BEACH, Calif., Sept. 7, 2023 /PRNewswire/ -- Sentynl Therapeutics, Inc. (Sentynl), a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases, announced that data evaluating NULIBRY® (fosdenopterin) for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A were presented at the 2023 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Meeting on Aug. 30 in Jerusalem. NULIBRY is indicated to reduce the risk of mortality in patients with MoCD Type A, an ultra-rare, autosomal recessive, inborn error of metabolism causing sulfite-induced neurodegeneration and early death. "Clinicians must consider MoCD in infants with encephalopathy or intractable seizures," said Dr. Guenter Schwarz, Professor for Biochemistry at the Department of Chemistry & Center for Molecular Medicine, Cologne University, Germany. "Early treatment with fosdenopterin (NULIBRY) improves survival and neurodevelopmental outcomes, reducing burden on patients and caregivers." In comparison of three non-randomized retrospective and prospective open-label studies versus a retrospective and prospective natural history study, the authors reported the following survival and clinical outcomes of patients treated with recombinant cPMP/NULIBRY: Risk of death was 5.1 times higher in untreated MoCD Type A patients compared to those treated with rcPMP/NULIBRY (Cox proportional hazards [95% CI]=5.1 [1.32, 19.36], P=0.0144). Treatment with rcPMP/NULIBRY led to a normalization of MoCD Type A-associated urinary biomarker levels. Treated patients were more likely than untreated patients to feed orally and meet growth and developmental milestones. "These results were pooled from a series of carefully designed studies and corroborate previous anecdotal findings. Early treatment of children with typical neonatal disease manifestation has a dramatic effect on their survival and overall development," said Dr. Bernd C. Schwahn, Consultant in Paediatric Metabolic Medicine, Manchester Centre for Genomic Medicine, St. Mary's Hospital, in Manchester, United Kingdom. "Increased disease awareness and the use of new technologies, including improved biochemical testing and rapid whole genome sequencing, will help to shorten the diagnostic gap and allow timely access to effective treatment for a higher proportion of affected children." Based on these data, NULIBRY was approved by the U.S. Food and Drug Administration, the European Medicines Agency and the Israeli Ministry of Health. To further evaluate the safety and efficacy of NULIBRY, a post-approval non-interventional study is being initiated in Europe. "Given Sentynl's focus on meaningful treatments for serious rare diseases, we are grateful to the authors for presenting these data and increasing awareness of MoCD Type A in the medical community," said Matt Heck, CEO of Sentynl. "We thank the patients, their families and caregivers, and all investigators involved in this study. We remain focused on continued evaluation of NULIBRY to reduce the risk of mortality and progression of this devastating disease." Treatment with NULIBRY/rcPMP was generally well-tolerated in patients with MoCD Type A. Most patients experienced a treatment-emergent adverse event (TEAE), the majority of which were catheter-related or infections and were mild to moderate in severity. In the retrospective study, two serious TEAEs of death occurred, one from RSV pneumonia (unrelated to treatment), and one from necrotizing enterocolitis (possibly related to treatment). Please click here for full Prescribing Information of NULIBRY. About Molybdenum Cofactor Deficiency (MoCD) Type A MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity.1,2 The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites (such as S-sulfocysteine) in the brain, which causes irreversible neurological damage.2 MoCD Type A is an ultra-rare disease. The estimated prevalence of MoCD Type A in the European Union is 0.005 per 10,000. Based on these estimates, MoCD Type A is likely to be underdiagnosed. The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment. About NULIBRY® (fosdenopterin) for Injection NULIBRY® (fosdenopterin) for Injection is a substrate replacement therapy that provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites. NULIBRY is approved by the U.S. Food and Drug Administration, the European Medicines Agency and the Israeli Ministry of Health for the treatment of patients with known or presumed MoCD Type A (discontinued if MoCD Type A is not confirmed), and it is the first and only FDA-approved therapy indicated to reduce the risk of mortality in patients with MoCD Type A. Clinical trials have demonstrated that patients treated with NULIBRY or rcPMP had an improvement in overall survival compared to the untreated, genotype-matched, historical control group. References 1 Mechler K et al. Genet Med. 2015;17(12):965-970. 2 Schwarz G. Cur Op in Che Bio. 2016;31:179-187. About Sentynl Therapeutics Sentynl Therapeutics is a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl's experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well-differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is committed to the highest ethical standards and compliance with all applicable laws, regulations and industry guidelines. For more information, visit . SOURCE Sentynl Therapeutics