Replay targets genetic brain disorders with new gene therapy company, Kaleibe, utilising big DNA HSV technology

  • Third product company from Replay expands use of next-generation high payload capacity HSV delivery vector developed at the University of Pittsburgh by Kaleibe co-founder Professor Joe Glorioso into brain indications
  • Experts in neuroscience and neurology, Professors Richard Wade-Martins and Howard J Federoff, also co-founders of Kaleibe
  • Initial programs to target genetic Parkinson’s disease and Friedreich’s ataxia

San Diego, California and London, UK, December 13, 2022 – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced the launch of Kaleibe, an HSV gene therapy company targeting genetic brain disorders. It is the third of Replay’s product companies to launch since the Company’s formation in July and will leverage Replay’s high payload capacity herpes simplex virus (HSV) delivery vector, synHSV™, to target genetic brain disorders.

Kaleibe’s co-founders include distinguished Professors Richard Wade-Martins, whose research at the University of Oxford focuses on the molecular mechanisms underlying neurodegenerative diseases, and Howard J Federoff, former distinguished Professor of Neurology at University of California, Irvine, and formerly CEO at regenerative medicine company, Aspen Neuroscience, Inc. Professor Joe Glorioso, the inventor of synHSV™, is also a co-founder of Kaleibe.

The initial development programs will focus on genetic Parkinson’s disease (PD) and Friedreich’s ataxia (FRDA). These diseases have a high unmet medical need and known genetic causes. The target genes, 33kb and 135kb, respectively, far exceed the payload capacity of adeno-associated virus (AAV) vectors (5kb). Affecting more than 6 million people worldwide, PD is the most prevalent movement disorder and second most common neurodegenerative disorder globally, after Alzheimer’s disease. It is estimated that approximately 15 per cent of cases are inherited, with a loss of functional genes that can be targeted by genomic medicines. FRDA is a genetic, progressive, neurodegenerative movement disorder affecting around 1 in every 50,000 individuals, with a typical age of onset between 10 and 15 years. It leads to impaired muscle coordination (ataxia) that progresses over time. Treatment options are limited and involve managing the symptoms and complications of the disorder.

The launch of Kaleibe follows the launches of product companies Eudora and Telaria focused, respectively, on diseases of the eye and skin. Replay’s distinctive corporate structure separates technology development from product development within disease therapeutic area-focused product companies.

Adrian Woolfson, Executive Chairman, President and Co-Founder of Replay, said: “HSV’s natural neurotropism allows the virus to establish a latent infection in neurones and enables robust transgene expression across multiple brain regions. It was therefore rational for us to apply our proprietary delivery platform, synHSV™, to target genetic disorders of the brain, where we believe HSV offers the promise of gene delivery that is safer and more durable than AAV-based approaches. The high payload capacity of HSV, furthermore, allows for the expression of genomic genes, thereby deploying natural regulatory sequences and capturing alterative splice forms.”

Lachlan MacKinnon, CEO and Co-Founder of Replay, said: “The launch of Replay’s third product company highlights the strength and broad applicability of our synHSV™ technology, as well as our ability to leverage its payload capacity by delivering cassettes of up to 150kb in length. With Kaleibe, we are fortunate in having leading neuroscience and clinical neuroscience and neurology experts as co-founders, leveraging synHSV™ to bring novel treatments to patients with debilitating brain disorders.”

Professor Richard Wade-Martins, Co-Founder of Kaleibe, said: “Replay’s mission to write and deliver big DNA resonates with my own research interest in this area. Genetic Parkinson’s disease and Friedreich’s ataxia are diseases characterized by mutations in particularly sizeable genes, making them especially difficult targets for AAV-based gene therapies. With the potential to deliver up to 30x the payload of AAV, Replay’s synHSV™ platform facilitates the delivery of large genes – so called ‘big DNA’ – with the promise of a differentiated and compelling therapeutic option for these, to date, intractable disorders.”

Professor Howard J Federoff, Co-Founder of Kaleibe, said: “Kaleibe aims to illuminate genetic brain disorders that have a high unmet medical need and that are associated with a significant detrimental impact on the quality of life of patients. Replay’s differentiated approach brings together the necessary elements to position the Company for success. I look forward to working with the team to leverage Replay’s synHSV™ technology platform to develop novel treatments addressing genetic mechanisms beyond the reach of other technologies that have the potential to have a significant and durable clinical impact.”

Professor Joe Glorioso, Co-Founder of Kaleibe, said: “Our next-generation HSV delivery platform has several distinct advantages over, and has the potential to be disruptive to existing gene delivery platforms. The defined genetic causes of the neurological disorders under investigation at Kaleibe provide us with the opportunity to introduce profound and long overdue technological innovation into the treatment landscape.”

About the Kaleibe team

Professor Richard Wade-Martins is a Co-Founder of Kaleibe. He graduated from Cambridge in Natural Sciences taking Part II Genetics in 1995. He then moved to the Wellcome Trust Centre for Human Genetics in Oxford for a DPhil followed by a Wellcome Trust Fellowship. In 2000 Richard moved to Massachusetts General Hospital, Harvard Medical School as a Wellcome Trust Travelling Research Fellow. He returned to Oxford and in 2004 was awarded a Wellcome Trust Research Career Development Fellowship and started his own group. In 2007 he moved to the Department of Physiology, Anatomy and Genetics, University of Oxford, as a University Lecturer. Richard gained tenure in his faculty position in the University of Oxford in 2013, was appointed an Associate Professor in 2014 and Professor in 2015. His research is focused on the molecular mechanisms underlying neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease. It combines studies on human post-mortem brain tissue, the generation and analysis of novel transgenic and knockout mouse models, and the development of improved induced pluripotent stem cell (iPS) derived dopaminergic neuronal culture models. His work focuses on the study of the functional and genetic mechanisms underlying key neurodegeneration disease loci, including alpha-synuclein (SNCA), microtubule associated protein tau (MAPT), and leucine rich repeat kinase 2 (LRRK2).

Professor Howard J Federoff, MD, PhD, is a Co-Founder of Kaleibe. He is former distinguished professor of neurology at the University of California, Irvine. He is the former CEO of UCI Health, vice chancellor for Health Affairs and dean of the UCI School of Medicine. Prior to joining UCI Health, Federoff was Executive Vice President of Health Sciences and executive dean at Georgetown University. Federoff has published more than 275 peer-reviewed and invited articles and serves on editorial boards of five journals. He co-founded MedGenesis Therapeutix and Brain Neurotherapy Bio, both advancing therapeutics for neurologic diseases. He became CEO of the regenerative medicine company, Aspen Neuroscience, Inc, in San Diego. Aspen is developing an autologous iPSC drug product for Parkinson’s disease. Federoff chaired the NIH Recombinant DNA Advisory Committee, the NHLBI Gene Therapy Resource and the Board of the Association of the Academic Health Centers. He has served as an advisor/director for several companies. He is an elected Fellow of the American Association for the Advancement of Science and the National Academy of Inventors. He received his MD, MS and PhD in biochemistry from the Albert Einstein College of Medicine in New York. He completed his residency and clinical and research fellowships at Massachusetts General Hospital and Harvard Medical School.

Professor Joe Glorioso, PhD, is the Senior Advisor on synHSV™ at Replay and Co-Founder of Kaleibe. He is the former Chair and a Professor in the Department of Microbiology and Molecular Genetics at the University of Pittsburgh School of Medicine and holds a secondary appointment in the Department of Human Genetics, University of Pittsburgh Graduate School of Public Health. He has a 40-year history of research related to the basic immunobiology, genetics and pathogenesis of herpes simplex virus (HSV). He has pioneered the design and application of HSV gene vectors for the treatment of nervous system diseases such as peripheral neuropathies, chronic pain, and brain tumors, and has developed manufacturing methods for human clinical trials. Professor Glorioso was a Founding Board Member and former president of the American Society of Gene Therapy, and is an elected fellow of the American Society for Microbiology, the American Association for the Advancement of Science and the National Academy of Inventors. Professor Glorioso is a founding member of the International Society for Neurovirology and an active member of the American Society for Virology, Society of Neurooncology, the International Pain Society, and American Society of Cancer Research.


About Kaleibe

Kaleibe is Replay’s third gene therapy product company and is focused on genetic brain disorders. The company’s next-generation HSV-1 technology was licensed from the University of Pittsburgh, where it was developed by leading HSV specialist and entrepreneur Professor Joe Glorioso. Kaleibe’s co-founders include Professors and experts in neurology, Richard Wade-Martins and Howard J Federoff.

About Replay

Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies – including a high payload capacity HSV platform, a hypoimmunogenic platform, and a genome writing platform – to address the scientific challenges currently limiting clinical progress and preventing genomic medicine from realizing its full potential. The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in product companies, which leverage the technology platforms. For example, Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replay’s four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. The Company has, additionally, established an enzyme writing product company engaging its evolutionary inference machine learning and genome writing technology to optimize functionality. Replay is led by a world-class team of academics, entrepreneurs and industry experts.

The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors that includes KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners.

Replay is headquartered in San Diego, California, and London, UK. For further information please visit and follow us on LinkedIn and Twitter.



Dr Adrian Woolfson/Lachlan MacKinnon

Consilium Strategic Communications – Media relations

Amber Fennell/Tracy Cheung/Melissa Gardiner

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