SURF1

Feb. 15, 2024 -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (“Taysha” or “the Company”), a clinical-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS), today provided an update on its deprioritized pipeline programs as part of an ongoing effort to help support their further potential development. Taysha has been working to find ways to advance its deprioritized programs. On November 13, 2023, Taysha terminated its existing loan and security agreement and entered into a new loan and security agreement that provides consent to allow the Company to transfer intellectual property (IP) for several deprioritized programs to third parties in a more efficient manner. The Company’s new loan and security agreement also extended its cash runway into 2026. TSHA-120: The Company initiated the transfer of the United States Food and Drug Administration Investigational New Drug (IND) application and investigational clinical trial material for TSHA-120 in giant axonal neuropathy (GAN) to clinical trial collaborator National Institute of Neurological Disorders and Stroke (NINDS), creating an opportunity for continued clinical evaluation of TSHA-120 in GAN. Additionally, the Company entered discussions with the originating advocacy organization regarding TSHA-120 in an effort to transfer rights back to the advocacy organization to move the program forward. TSHA-101: The Company transferred rights back to Queen’s University (Queen’s) for TSHA-101 in GM2 gangliosidosis, resulting in Queen’s regaining exclusive IP to the program. TSHA-104 and TSHA-112: The Company transferred rights back to the originating institution for select programs, including TSHA-104 in SURF1-associated Leigh syndrome and TSHA-112 in APBD. TSHA-118: The Company provided investigational clinical trial material for TSHA-118 in CLN1 to support an individual-patient investigator-initiated IND request from RUSH University Medical Center for the treatment of a patient with CLN1 disease. “Today’s announcement demonstrates meaningful progress to advance important development work for several deprioritized programs. Creating options for these programs has been a focus since the Company completed a management change in December 2022, and the new loan and security agreement afforded the flexibility to implement certain opportunities,” said Sean P. Nolan, Chairman and Chief Executive Officer of Taysha. “As we continue to focus on advancing our lead TSHA-102 program for the treatment of Rett syndrome, we are pleased that we can ensure these programs are provided to the right advocates, clinicians and scientific experts who can potentially move these programs forward for the benefit of patients.” The Company continues to explore potential partnerships and opportunities for its other deprioritized programs to help support their further potential development. Taysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company’s management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit www.tayshagtx.com. The content above comes from the network. if any infringement, please contact us to modify.

--This initial study found evidence linking changes in organ development with symptoms seen in certain human mitochondrial diseases -- PHILADELPHIA, Sept. 20, 2023 /PRNewswire/ -- Zebrafish have revolutionized research into a wide variety of rare and complex genetic diseases. In early development stages, their transparent bodies allow researchers to more easily study tissues and organs. However, studying organ-level defects in adult zebrafish presents a variety of challenges that prevent researchers from studying them at a microscopic level. In a new study, researchers from Children's Hospital of Philadelphia (CHOP) have developed a noninvasive method for conducting magnetic resonance imaging (MRI) in adult zebrafish. Using this technique, the study team examined the effects of certain genetic mutations associated with mitochondrial disease. The findings were recently published online by the journal Zebrafish. Zebrafish transition from a single cell to fully formed animal in just one day, with continued larval development over the first week of life. This rapid development and ability to remove their body wall pigment during this early period enables scientists to microscopically image whole organs and perform accurate time-lapse analyses of disease progression. They can also screen drug candidates that may be used to treat various illnesses, since the zebrafish can absorb the drug through their gut, skin, or thin gills. In addition, zebrafish are often used to create models to study diseases because zebrafish share about 70% of genes found in humans. However, as zebrafish get older, their tissue becomes denser and their organs become more difficult to study through usual microscopic imaging techniques. While MRI has been used to study zebrafish, prior studies have been very limited and did not provide systematic organ-level analyses. This is particularly important for diseases like mitochondrial disease, which often impacts multiple organs by disrupting energy levels in cells throughout the body. No prior study studied adult zebrafish across different times in their adulthood, which prevented researchers from looking into the progression of disease. "MRI technology is widely used for a variety of clinical and research applications, and as zebrafish become a more preferred model for translational research, we wanted to explore how this technology could improve the research we are doing in these animal models," said first study author Sonal Sharma, MD, a pediatric neurologist within the Division of Neurology and the Mitochondrial Medicine Frontier Program in the Division of Human Genetics at CHOP. "This work demonstrated that MRI allows us to rapidly and comprehensively study organ-level growth defects in mutant adult zebrafish in a low-cost, minimally invasive, and unbiased manner." The researchers developed a new protocol for utilizing MRI in zebrafish research. As a result, they were able to successfully capture high-resolution MRI of eight different organs in adult zebrafish. This allowed the researchers to establish a reference MRI atlas based on images of zebrafish from five to 31 months after fertilization. Using three different mitochondrial disease mutant models of zebrafish, the researchers were able to discover that significantly increased brain growth occurs in zebrafish with deficiency in the SURF1 gene, which encode mitochondrial complex IV activity and is one of the genes associated with Leigh syndrome. They also noticed heart and spinal cord volumes were smaller in these mutant zebrafish as compared to healthy wild-type controls. These findings reflect some of the clinical observations seen in human patients with SURF1 deficiency, since they may suffer from serious neurological issues as well as cardiomyopathy. "We plan on exploring the organ-level discoveries we made by using this novel MRI method to screen organ growth in adult zebrafish," said senior study author Marni Falk, MD, senior author on this study and executive director of the Mitochondrial Medicine Frontier Program at CHOP. "We are also working to develop additional biochemical imaging methods to further refine our understanding of the biochemical changes that occur in specific organs of living animals with primary mitochondrial disease." This study was supported by the Children's Hospital of Philadelphia Mitochondrial Medicine Fellowship Program and the National Institutes of Health grant R35-GM134863. Sharma et al, "Novel Development of Magnetic Resonance Imaging to Quantify the Structural Anatomic Growth of Diverse Organs in Adult and Mutant Zebrafish." Zebrafish. Online August 21, 2023. DOI: 10.1089/zeb.2023.0018. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as an inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Ben Leach Children's Hospital of Philadelphia (609)634-7906 [email protected] SOURCE Children's Hospital of Philadelphia

Texas-based Taysha Gene Therapies announced last week that it had concluded a Series B round of financing worth $95 million. Texas-based Taysha Gene Therapies announced last week that it had concluded a Series B round of financing worth $95 million. The round was led by Fidelity Management & Research Company, with additional investment from BlackRock, GV, Invus, Casdin Capital, Franklin Templeton, Octagon Capital, Perceptive Advisors LLC, Sands Capital, ArrowMark Partners and Venrock Healthcare Capital Partners. Taysha is currently working on developing a pipeline of 17 gene therapy product candidates. TSHA-101 is expected to enter clinical studies later this year for the treatment of GM2 Gangliosidosis. TSHA-102 will follow, with a focus on the treatment of Rett syndrome. TSHA-103 is also being developed for the treatment of SLC6A1 haploinsufficiency disorder, while TSHA-104 is being examined for the treatment of SURF1 deficiency. Taysha will New Drug applications for each of these four product candidates by the end of next year. “We have brought together experts in gene therapy with leading healthcare and institutional investors to create a company that is uniquely positioned to advance the development of potentially curative gene therapies for CNS disease in rare and large patient populations,” said Sean Nolan, Chairman of the Board of Taysha. “We believe this financing provides significant validation of our corporate strategy and will enable us to continue to rapidly translate programs from preclinical development into the clinic.” Taysha Gene Therapies launched with $30 million in seed financing back in April of this year. The goal of the company is to eradicate severe and life-threatening monogenic diseases of the central nervous system through the use of adeno-associated virus (AAV) gene therapy programs. “Gene therapies have proven to deliver transformational benefit to patients who suffer from devastating diseases with significant, unmet medical need,” said RA Session II. “Our mission at Taysha is to build upon these advancements to eradicate monogenic CNS diseases for the thousands affected. In joining forces with UT Southwestern—home to some of the brightest minds in gene therapy—we will advance our deep pipeline of potentially curative medicines with speed and scale. At Taysha, we are ushering in a new era of gene therapy drug development, one in which we can rapidly translate early discoveries into the clinic and beyond.” Taysha has also entered a strategic partnership with UT Southwestern, which has developed a GMP viral vector manufacturing facility with the capacity to support Taysha’s preclinical and clinical development programs. Under the agreement, UT Southwestern will conduct discovery and preclinical research, lead IND-enabling studies, provide clinical GMP manufacturing, and execute natural history studies. Taysha will be responsible for all clinical development, regulatory strategy, commercial manufacturing and commercialization activities. “Together with Taysha, we are merging cutting-edge translational research, hands-on clinical care, and proven regulatory and commercial expertise – ultimately creating an engine for new cures,” said Claire Aldridge, Ph.D., Taysha Board Member and Associate Vice President of Commercialization and Business Development at UT Southwestern Medical Center. “In a short amount of time, I’ve already witnessed how quickly and efficiently we can leverage our collective expertise and resources to advance new gene therapies to the patients who so desperately need them.” Taysha is working on developing an AAV capsid platform that utilizes machine learning, DNA shuffling and directed evolution to improve more targeted delivery of its product candidates. Currently, the company has 15 AAV gene therapy programs in its pipeline with options to an additional four programs.