Molybdenum Cofactor Deficiency

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

OXFORD, England, March 07, 2023 (GLOBE NEWSWIRE) -- MitoRx Therapeutics (MitoRx), a biotechnology company developing revolutionary therapeutics that reverse mitochondrial dysfunction to arrest the progression of degenerative diseases, announces Christine Charman as Chief Development Officer, David Richardson as Finance Director, and four appointments to its Scientific Advisory Board (SAB): Prof Chas Bountra, Prof Dame Kay Davies, Prof Laurent Servais, and Dr Bernd C Schwahn. Prof Chas Bountra OBE is now Chair of the Scientific Advisory Board. He commented on his appointment: “It’s an honour and a pleasure to come together with top international scientific and clinical experts to build the MitoRx Scientific Advisory Board. Together we are working to become a global leader in treating diseases caused by impaired mitochondrial function.” Chas is Pro-Vice Chancellor for Innovation at the University of Oxford, Professor of Translational Medicine in the Nuffield Department of Clinical Medicine, Director of the Centre for Medicines Discovery, and Professorial Fellow at Keble College, Oxford. Prior to coming back to Oxford in 2008, Chas was Vice President and Head of Biology at GlaxoSmithKline. Chas is an invited expert on several government and charitable research funding bodies, and an advisor for many academic, biotech and pharma drug discovery programmes. In 2012 he was voted one of the “top innovators in the industry”, in 2014 received the “Rita and John Cornforth Award” from the Royal Society of Chemistry, in 2017 and 2018 was voted “Master of the Bench” from the Medicine Maker Power List, and in 2018 was awarded the “Order of the British Empire” in the New Years Honours List. Also joining the board is Prof Dame Kay Davies CBE DBE FRS FMedSci, Dr Lee’s Professor of Anatomy Emeritus at the University of Oxford with an international reputation for work on Duchenne muscular dystrophy paving the way for several nucleic acid related therapies. Prof Davies is a co-founder and co-Director of the MDUK Oxford Neuromuscular Centre, and co-founded Summit Therapeutics plc to translate her work into the clinic. Prof Laurent Servais MD PhD directs the Specialised Translational Research Oxford Neuromuscular Group as Professor of Paediatric Neuromuscular Disease at the University of Oxford, and he is Professor of Child Neurology at the University of Liège. He brings a wealth of experience to the Scientific Advisory Board having led many clinical trials as principal investigator for Duchenne muscular dystrophy and spinal muscular atrophy treatments. Dr Bernd C Schwahn MD PhD FRCPCH, Consultant in Paediatric Metabolic Medicine at the Manchester University NHS Foundation Trust and Honorary Clinical Senior Lecturer in Genomic Medicine, also joins the board. Dr Schwahn’s scientific interest focuses on disorders of sulfur amino acid metabolism and has been involved as principal and chief investigator in clinical trials for the treatment of molybdenum cofactor deficiency, lysosomal storage disorders and disorders of intermediary metabolism. Chief Development Officer Christine Charman PhD comes with close to 26 years’ experience in accelerating transformational therapies as Senior Global Program Lead for Takeda’s Rare Diseases, Respiratory and Immunology and Neuroscience therapy areas. She also worked as consultant CDO at Izana Bioscience and development consultant for a range of Biotechs and NewCos and Program Lead supporting UK Vaccine and Antiviral Task Forces, with further development experience at Novartis from preclinical research leadership to Senior Global Programme Director, including the planning, clinical execution and launch of two products. David Richardson BSc ACMA AMCT brings over 30 years finance experience to his new role as Finance Director. He has held board positions at a number of venture-backed technology companies and his experience in the industry includes senior finance roles within both AstraZeneca and Evotec. Jonathan Rees PhD, CEO of MitoRx, said, “We are thrilled to welcome our new SAB members, as well as Christine Charman as Chief Development Officer and David Richardson as Finance Director, who together bring a wealth of renowned experience across financial, scientific and clinical backgrounds. The wide ranging expertise gained from our growing team and advisory board will accelerate progress of our first-in-class, first-in-target small molecules which are now being pre-clinically tested in a mammalian model of muscular dystrophy. We look forward to working with them all.” Notes to Editors Media Contact (Scius Communications) Katja StoutEmail: katja@sciuscommunications.comPhone: +44(0)7789 435990 Daniel Gooch Email: Daniel@sciuscommunications.comPhone: : +44(0)7747 875 479 Company Contact (MitoRx) Jonathan Rees, CEOEmail: jon.rees@mitorxtherapeutics.comPhone: +44(0)7826 556622 About MitoRx At MitoRx our mission is to become the leading global developer of medicines arresting the progression of degenerative diseases driven by mitochondrial dysfunction. We are a preclinical research stage biotechnology company developing our first-in-class, orally delivered, mitochondrial protective therapeutics targeting rare neuromuscular disorders, rare metabolic diseases, and neurodegenerative diseases. Located in Harwell Oxford, we have raised seed financing from a broad range of investors including the UK Innovation & Science Seed Fund, The Fink Family Office, Science Angel Syndicate, Oxford Technology Management, Wren Capital, Longevitytech.fund, as well as angel investors. For more information visit our website at www.mitorxtherapeutics.com and follow us on LinkedIn.

- CHMP recommendation for approval of NULIBRY in the European Union (EU) for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A is based on the efficacy and safety data collected to date compared to data from a natural history study - Under an accelerated assessment pathway, a decision by the European Commission (EC), which authorizes marketing approval in the European Union (EU), is expected on the NULIBRY application later this year - If approved by the EC, NULIBRY would be the first and only approved therapy in the EU to treat patients with 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 - NULIBRY was BridgeBio's first FDA-approved therapeutic; Sentynl acquired global rights to NULIBRY in March 2022 PALO ALTO, Calif. and SOLANA BEACH, Calif., July 25, 2022 /PRNewswire/ -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, and Sentynl Therapeutics, Inc. (Sentynl), a U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases owned by Zydus Lifesciences Ltd. (formerly known as Cadila Healthcare Ltd.), today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended that the European Commission authorize marketing under exceptional circumstances for NULIBRY ® (fosdenopterin) for Injection as the first therapy for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A. MoCD Type A is an ultra-rare and progressive condition, known to impact less than 150 patients globally with a median survival of four years. Understanding MoCD Type A BridgeBio Pharma and Sentynl Therapeutics Receive Positive CHMP Opinion for NULIBRY® (fosdenopterin) Tweet this NULIBRY is a first-in-class 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. If approved by the European Commission, NULIBRY would be the first and only approved therapy in the EU for MoCD Type A. In March 2022, Sentynl acquired the global rights to NULIBRY and is responsible for the ongoing development and commercialization of NULIBRY in the United States and developing, manufacturing, and commercializing fosdenopterin globally. Sentynl and BridgeBio share development responsibilities through the approval of the marketing authorization application under accelerated assessment with the EMA and through approval of NULIBRY's regulatory submission with the Israeli Ministry of Health. "Our work on NULIBRY and MoCD Type A epitomizes BridgeBio's belief that no disease is too rare to address. With this positive CHMP opinion, we are closer to delivering a treatment option to all children across the globe who suffer with MoCD Type A," said BridgeBio founder and CEO Neil Kumar, Ph.D. The positive CHMP opinion is supported by data from three clinical trials that demonstrated 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 reduced the risk of death by 86% and increased the probability of survival to 86% at three years compared to 52% in the untreated, genotype-matched, historical control group in the natural history study. "We are thrilled by the CHMP's recommendation in favor of NULIBRY and hope that patients living with MoCD Type A in Europe and around the world can access this therapy," said Matt Heck, CEO of Sentynl. "The CHMP positive opinion marks important progress not only for the program but also for the MoCD Type A patients outside of the U.S. who are seeking ways to treat their life-threatening and progressive disease." Based on the CHMP recommendation, a decision by the EC, which authorizes marketing applications in the EU, is expected on the NULIBRY application later this year. The recommendation for marketing authorization under exceptional circumstances is granted to medicines where the applicant is unable to provide comprehensive data under normal conditions of use because the disease being treated is so rare. In April 2022, BridgeBio received New Drug Application (NDA) Approval in Principle from the Israeli Ministry of Health and the application is currently undergoing the final review processes. 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 European Union are not known, but the estimated prevalence is 0.005 per 10,000 persons. 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. It is the first and only FDA-approved therapy indicated to reduce the risk of mortality in patients with MoCD Type A, and 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 BridgeBio Pharma, Inc. BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio's pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter. 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 highly 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 The Zydus Group, with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global pharmaceutical company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 23000 people worldwide and is driven by its mission to unlock new possibilities in life-sciences through quality healthcare solutions that impact lives. The group aspires to become a global life-sciences company transforming lives through pathbreaking discoveries. For more information, visit . BridgeBio Pharma, Inc. Forward-Looking Statements This press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the "Securities Act"), and Section 21E of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements relating to, the timing and outcome of the EC's decision on NULIBRY, the potential ability for NULIBRY to be the first and only approved therapy in the EU to treat patients with MoCD type A, and the potential ability to provide treatment options to MoCD Type A patients in Europe and around the world, reflect our current views about our plans, intentions, expectations, strategies and prospects, and are based on the information currently available to us and on assumptions we have made and are not forecasts, promises nor guarantees. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by these forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, the success of our ongoing collaboration with Sentynl, including our co-development responsibilities through approval of the marketing authorization application under accelerated assessment with the EMA and through approval of NULIBRY's regulatory submission with the Israeli Ministry of Health, Sentynl's ability to successfully develop and commercialize NULIBRY in the United States and to develop, manufacture, and commercialize fosdenopterin globally, , as well as those risks set forth in the Risk Factors section of our most recent Annual Report on Form 10-K and BridgeBio Pharma's other SEC filings. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Contact: Grace Rauh [email protected] (917) 232-5478 Sentynl Therapeutics Contact: Michael Hercz [email protected] (888) 507-5296 SOURCE Sentynl Therapeutics