Brain Diseases, Metabolic, Inborn

- BLA submitted to FDA for Upstaza™ for the treatment of AADC deficiency - - NDA to be submitted mid-year for Translarna™ based on FDA feedback - SOUTH PLAINFIELD, N.J., March 19, 2024 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced the submission of a BLA to the U.S. FDA for Upstaza™ (eladocagene exuparvovec), a gene therapy for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. In addition, based on recent feedback from the FDA, PTC plans to re-submit an NDA for Translarna™ (ataluren) for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD). PTC expects to make the NDA resubmission by mid-year. "We are excited to bring Upstaza one step closer to children in the United States with the highly mortal and fatal disease of AADC deficiency. The data collected to date continue to demonstrate the transformative clinical benefits the gene therapy provides to patients," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "In addition, we look forward to the Translarna NDA resubmission this summer. We know U.S. patients and families have been waiting for an approved therapy that specially targets nmDMD." In addition, the sepiapterin MAA for PKU remains on schedule for submission to the EMA by the end of this month. About Upstaza™ (eladocagene exuparvovec) Upstaza is a one-time gene replacement therapy indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L–amino acid decarboxylase (AADC) deficiency with a severe phenotype. It is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy, containing the human DDC gene.1 It is designed to correct the underlying genetic defect, by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production.2,3 The efficacy and safety profile of Upstaza has been demonstrated across clinical trials and compassionate use programs.1 The first patient was dosed in 2010. In clinical trials, Upstaza demonstrated transformational neurological improvements. The most common side effects were initial insomnia, irritability and dyskinesia. Administration of Upstaza occurs through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure used for the treatment of a number of pediatric and adult neurological disorders. The Upstaza administration procedure is performed by a qualified neurosurgeon in centers specialized in stereotactic neurosurgery. Upstaza has received marketing authorization in Europe, Great Britain and Israel. About aromatic L-amino acid decarboxylase (AADC) deficiency AADC deficiency is a fatal, rare genetic disorder that typically causes severe disability and suffering from the first months of life, affecting every aspect of life – physical, mental and behavioral. The suffering of children with AADC deficiency may be exacerbated by: episodes of distressing seizure-like oculogyric crises causing the eyes to roll up in the head, frequent vomiting, behavioral problems, and difficulty sleeping. The lives of affected children are severely impacted and shortened. Ongoing physical, occupational and speech therapy, and interventions, including surgery, also are often required to manage potentially life-threatening complications such as infections, severe feeding and breathing problems. About Translarna™ (ataluren) Translarna (ataluren), discovered and developed by PTC Therapeutics, is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in Duchenne. Translarna, the tradename of ataluren, is licensed in multiple countries for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) in ambulatory patients aged 2 years and older. Ataluren is an investigational new drug in the United States. About Duchenne Muscular Dystrophy (Duchenne) Primarily affecting males, Duchenne is a rare and fatal genetic disorder that results in progressive muscle weakness from early childhood and leads to premature death in the mid-20's due to heart and respiratory failure. It is a progressive muscle disorder caused by the lack of functional dystrophin protein. Dystrophin is critical to the structural stability of all muscles, including skeletal, diaphragm, and heart muscles. Patients with Duchenne can lose the ability to walk (loss of ambulation) as early as 10 years old, followed by loss of the use of their arms. Duchenne patients subsequently experience life-threatening lung complications, requiring the need for ventilation support, and heart complications in their late teens and 20s. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC's mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC's strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, Instagram, LinkedIn and Twitter at @PTCBio. For More Information: Investors: Kylie O'Keefe +1 (908) 300-0691 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statement This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; the extent, timing and financial aspects of our strategic pipeline prioritization and reductions in workforce; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; PTC's ability to use the results of Study 041, a randomized, 18-month, placebo-controlled clinical trial of Translarna for the treatment of nmDMD followed by an 18-month open-label extension, and from its international drug registry study to support a marketing approval for Translarna for the treatment of nmDMD in the United States; whether investigators agree with PTC's interpretation of the results of clinical trials and the totality of clinical data from our trials in Translarna; expectations with respect to Upstaza, including any regulatory submissions and potential approvals, commercialization, manufacturing capabilities, the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Translarna and Upstaza. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. Acronyms: BLA: Biologics License Application DMD: Duchenne Muscular Dystrophy EMA: European Medicines Agency FDA: U.S. Food and Drug Administration MAA: Marketing Authorization Application NDA: New Drug Application PKU: Phenylketonuria References: Tai CH, et al. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022;30(2):509-518. Chien et al. AGIL-AADC gene therapy results in sustained improvements in motor and developmental milestones through 5 years in children with AADC deficiency. Poster presented at the 48th Annual Meeting of the Child Neurology Society, Charlotte, NC, USA, Oct 23-26, 2019. Chien YH, et al. Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial. Lancet Child Adolesc Health. 2017;1(4):265-273. SOURCE PTC Therapeutics, Inc.

Longstanding global partnership provides an efficient and timely diagnosis to patients with Lysosomal Storage Disorders (LSDs) CAMBRIDGE, Mass. and ROSTOCK, Germany and BERLIN, March 19, 2024 (GLOBE NEWSWIRE) -- Centogene N.V. (Nasdaq: CNTG), the essential life science partner for data-driven answers in rare and neurodegenerative diseases, today announced the extension of an ongoing partnership with Takeda (TSE: 4502/NYSE: TAK) to diagnose patients with Lysosomal Storage Disorders (LSDs). Under the renewed agreement, CENTOGENE will continue to provide Takeda with access to diagnostic testing for patients around the world. The agreement was established to enhance patient access to rapid and reliable diagnostics for LSDs, including Fabry disease, Gaucher disease, and Hunter syndrome. “Extending our longstanding partnership with Takeda highlights the continuing need to accelerate diagnoses for LSD patients globally and the ability of CENTOGENE to fulfill this vital service,” said Ian Rentsch, CENTOGENE Chief Commercial Officer and General Manager - Pharma. “Leveraging our targeted genomic and multiomic testing portfolio, we are uniquely positioned to deliver improved health outcomes for underserved patient communities, particularly in the rare disease sector.” “We believe that great solutions require great collaboration,” said Kim Stratton, Chief Executive Officer at CENTOGENE. “From long standing partners like Takeda to new partners like Lifera, a biopharmaceutical company wholly-owned by the Public Investment Fund (PIF) in Saudi Arabia, we are committed to teaming up with global players to deliver life-changing answers to rare and neurodegenerative disease patients around the world.” In January 2015, CENTOGENE originally entered into an agreement with Shire Pharmaceuticals, which was acquired in 2019 by Takeda, to provide diagnostic testing capability to enhance early diagnosis of patients suffering from rare genetic diseases. About CENTOGENE CENTOGENE’s mission is to provide data-driven, life-changing answers to patients, physicians, and pharma companies for rare and neurodegenerative diseases. We integrate multiomic technologies with the CENTOGENE Biodatabank – providing dimensional analysis to guide the next generation of precision medicine. Our unique approach enables rapid and reliable diagnosis for patients, supports a more precise physician understanding of disease states, and accelerates and de-risks targeted pharma drug discovery, development, and commercialization. Since our founding in 2006, CENTOGENE has been offering rapid and reliable diagnosis – building a network of approximately 30,000 active physicians. Our ISO, CAP, and CLIA certified multiomic reference laboratories in Germany utilize Phenomic, Genomic, Transcriptomic, Epigenomic, Proteomic, and Metabolomic datasets. This data is captured in our CENTOGENE Biodatabank, with over 800,000 patients represented from over 120 highly diverse countries, over 70% of whom are of non-European descent. To date, the CENTOGENE Biodatabank has contributed to generating novel insights for more than 285 peer-reviewed publications. By translating our data and expertise into tangible insights, we have supported over 50 collaborations with pharma partners. Together, we accelerate and de-risk drug discovery, development, and commercialization in target and drug screening, clinical development, market access and expansion, as well as offering CENTOGENE Biodata Licenses and Insight Reports to enable a world healed of all rare and neurodegenerative diseases. To discover more about our products, pipeline, and patient-driven purpose, visit www.centogene.com and follow us on LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the U.S. federal securities laws. Statements contained herein that are not clearly historical in nature are forward-looking, and the words “anticipate,” “believe,” “continues,” “expect,” “estimate,” “intend,” “project,” “plan,” “is designed to,” “potential,” “predict,” “objective” and similar expressions and future or conditional verbs such as “will,” “would,” “should,” “could,” “might,” “can,” and “may,” or the negative of these are generally intended to identify forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties, and other important factors that may cause CENTOGENE’s actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the possibility that no strategic alternatives or trading market will be available to CENTOGENE, negative economic and geopolitical conditions and instability and volatility in the worldwide financial markets, possible changes in current and proposed legislation, regulations and governmental policies, pressures from increasing competition and consolidation in our industry, the expense and uncertainty of regulatory approval, including from the U.S. Food and Drug Administration, our reliance on third parties and collaboration partners, including our ability to manage growth, execute our business strategy and enter into new client relationships, our dependency on the rare disease industry, our ability to manage international expansion, our reliance on key personnel, our reliance on intellectual property protection, fluctuations of our operating results due to the effect of exchange rates, our ability to streamline cash usage, our continued ongoing compliance with covenants linked to financial instruments, our requirement for additional financing, and our ability to continue as a going concern, or other factors. For further information on the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to CENTOGENE’s business in general, see CENTOGENE’s risk factors set forth in CENTOGENE’s Form 20-F filed on May 16, 2023, with the Securities and Exchange Commission (the “SEC”) and subsequent filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and CENTOGENE specifically disclaims any obligation to update any CONTACT CENTOGENE Melissa HallCorporate Communications Press@centogene.com Lennart StreibelInvestor Relations IR@centogene.com

Pictured: FDA signage at its headquarters in Maryland/iStock, hapabapa The FDA on Monday approved Orchard Therapeutics’ autologous gene therapy atidarsagene autotemcel, which will now be marketed as Lenmeldy, for the treatment of metachromatic leukodystrophy in pediatric patients. Lenmeldy is the first authorized gene therapy for children with pre-symptomatic late infantile or early juvenile metachromatic leukodystrophy (MLD), according to the FDA’s press release on the approval. Lenmeldy is also the first approved therapy for early juvenile or early symptomatic forms of the disease. Orchard CEO Bobby Gaspar in a statement said that Lenmeldy’s approval “opens up tremendous new possibilities” for children suffering from these early-onset forms of MLD, “who previously had no treatment options beyond supportive and end-of-life care.” The company on Monday did not provide specific launch details for Lenmeldy but promises to do so within the week. MLD is a rare and heritable metabolic disease that affects one in every 100,000 live births. It is characterized by a pathological build-up of sulfatides in the brain, liver, kidneys, spleen and other body parts, which over time can cause organ damage and neurological issues. Those with MLD often suffer from motor, behavioral and cognitive problems, as well as seizures. Patients also slowly lose the ability to move, talk, swallow and eat. Children with MLD often degenerate to a vegetative state and require round-the-clock care. Most patients die within five years of disease onset. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene, which under healthy circumstances produces an enzyme that breaks down sulfatides. Orchard’s Lenmeldy is an autologous gene therapy that uses a patient’s own stem cells to deliver a functioning copy of the ARSA gene. This mechanism of action won Lenmeldy the FDA’s Rare Pediatric Disease and Regenerative Medicine Advanced Therapy designations. Lenmeldy was also approved by the European Union in December 2020, where it is marketed as Libmeldy. The FDA’s approval of Lenmeldy is backed by data from two single-arm, open-label trials enrolling a total of 37 pediatric MLD patients. Over a median follow-up of 6.76 years, Lenmeldy led to significantly better overall survival compared with natural history data. The gene therapy also preserved motor and cognitive function in late-infantile MLD patients, whereas untreated counterparts had severe impairments. In terms of safety, Lenmeldy’s most common adverse events were febrile neutropenia, stomatitis, respiratory tract infections and rashes. These are reflected in the therapy’s label, which also bears warnings for thrombosis and thromboembolic events, encephalitis and the risk of hypersensitivity reactions. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.