GEN Biotechnology

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Defining the Rules of Biology in the Age of Genome Writing


- Second product company using Replay’s next-generation high payload capacity HSV delivery vector developed at the University of Pittsburgh by Professor Joe Glorioso

- Telaria founded by leading HSV scientist and serial entrepreneur, Professor Joe Glorioso, Professor John McGrath, a leading expert in genetic skin diseases, and Alexander Silver, Co-Founder & Chairman Emeritus of the Epidermolysis Bullosa Research Partnership 

__San Diego, California and London, UK, November 21, 2022__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced the launch of Telaria, a HSV gene therapy company targeting rare skin diseases. It is the second of Replay’s product companies to leverage its high payload capacity herpes simplex virus (HSV) delivery vector, synHSV™. Telaria’s co-founders are leading HSV scientists, entrepreneurs, and specialists in genetic skin diseases. 

In addition to Professor Joe Glorioso, Telaria’s co-founders include John McGrath, a leading expert in genetic skin diseases, and Alexander Silver, Co-Founder & Chairman Emeritus of the Epidermolysis Bullosa Research Partnership. Jakub Tolar, distinguished McKnight Professor in the Department of Pediatrics, Blood and Bone Marrow Transplantation & Cellular Therapy at the University of Minnesota Medical School, is the Senior Advisor to the Company. 

Telaria is the second of Replay’s four synHSV™ gene therapy product companies and its launch follows that of Eudora, a company targeting genetic diseases of the retina. Replay’s distinctive corporate structure separates technology development from product development within disease therapeutic area-focused product companies. 

The lead indication in Telaria’s pipeline is recessive dystrophic epidermolysis bullosa (RDEB), a genetic skin disease that causes the skin to be fragile and blister easily. RDEB is generally more severe than its dominant counterpart and involves widespread blistering that may lead to scarring, severe pain, and disfigurement. It can affect multiple internal organs and causes serious medical issues that may include chronic inflammation and squamous cell carcinoma. 

There is currently no cure for the approximately 50,000 RDEB patients world-wide, and palliative wound care is the current standard of care. A disease-modifying gene therapy with the ability to heal wounds more rapidly or prevent their formation would represent a significant benefit to patients. 

Replay’s synHSV™ technology is a high payload capacity gene-deleted HSV-1 vector capable of delivering up to eight times the payload of adeno-associated virus (AAV) vectors. This enables the delivery of genes that are too big to fit into AAV and facilitates polygenic gene therapy. Replay is, additionally, developing an HSV vector capable of delivering up to 30 times the AAV payload.

__Adrian Woolfson, Executive Chairman, President and Co-Founder of Replay__, said: “The skin is an attractive target for gene therapies and is the largest and most accessible organ. Telaria, focused exclusively on the development of transformative treatments for rare genetic skin diseases, and the second of our four synHSV™ product companies to launch, represents another significant step towards building an enduring company with the potential to shape the future of genomic medicine through addressing some of the most substantive challenges that currently limit the progress of clinical medicine.”

__Lachlan MacKinnon, CEO and Co-Founder of Replay__, said: “The launch of Telaria with its accomplished co-founders, further validates Replay’s distinctive hub-and-spoke corporate structure. Through our model, we have been able to build and incentivize a team of leading experts in genetic skin disease and leverage our next-generation high payload capacity synHSV™ technology to progress the development of a much-needed therapeutic treatment for individuals with RDEB and a selection of other rare and debilitating skin diseases.”

__Professor John McGrath, Co-Founder of Telaria__, said: “Leveraging Replay’s synHSV™ technology that enables the delivery of large genes, Telaria is developing a potentially best-in-class polygenic gene therapy to heal existing skin lesions more swiftly and effectively, and to prevent the formation of new ones. I look forward to working with my distinguished colleagues to progress this important therapy into the clinic.”

__Alexander Silver, Co-Founder of Telaria__, said: “There is currently no approved cure for individuals suffering from RDEB and I am aware, from my own personal experience, that the current standard of care is limited and does not provide long-term and sustainable benefit to patients. Replay’s synHSV™ technology, which enables the delivery of big DNA to the skin through its differentiated payload capacity, has the potential to disrupt the genetic skin disease gene therapy field, and to bring much needed treatments to patients as rapidly and safely as possible.”

__Professor Joe Glorioso, Co-Founder of Telaria__, said: “Replay is pioneering a next-generation series of skin gene therapies, utilizing a highly differentiated HSV vector technology that provides the opportunity for safe, long-lasting, and physiological transgene expression targeted to specific cell population subtypes in complex tissue environments. This new generation of HSV vectors will be especially important when large or multiple transgene payloads or complex synthetic regulatory circuits are required.”

__Jakub Tolar, Senior Advisor to Telaria__, said: “Replay’s new HSV-based gene therapy for RDEB comprises a compelling opportunity to meaningfully modify some of the most pronounced clinical features of the disease. I look forward to this program’s advancement, and to seeing HSV-based gene therapy helping patients with RDEB as well as those with other rare skin diseases.”

__About the Telaria team__

__Professor John McGrath, MD, FRCP, FMedSci__, is Professor of Cutaneous Medicine and Head of the Genetic Skin Disease Group at St John’s Institute of Dermatology, King’s College London. He is also an honorary Consultant Dermatologist for Guy’s and St Thomas’ NHS Foundation Trust. He qualified from Guy’s Hospital in 1985 and trained in dermatology and dermatopathology at St John’s Institute of Dermatology in London. His research background is in electron microscopy and molecular biology. He is a recent President of the European Society for Dermatological Research and currently serves on the editorial board of nine international journals, including being the section editor for genetics for the Journal of Investigative Dermatology. Since August 2018, he has been the Head of St John's Institute of Dermatology.

__Alexander Silver, BA, MBA__, is Co-Founder and Chairman Emeritus of Epidermolysis Bullosa Research Partnership, the largest foundation dedicated to supporting medical research to heal and cure Epidermolysis Bullosa. He is also a founder and Chairman of Phoenicis Therapeutics, a company focused on developing rare dermatological therapies. Alex is a founding partner at P2 Capital Partners, a private investment firm based in New York City. Prior to starting P2 Capital, Alex held positions at Soros Fund Management, Karsch Capital Management and Lazard Freres. He currently serves on the Children’s Board at Columbia University Medical Center and as a Director at Blackhawk Network, Inc. and Achievers, Inc. He previously served on the NAIMS Advisory Council of the National Institutes of Health. He has a 15-year-old son, Jackson, with RDEB. He received a Master’s in Business Administration from Harvard University where he was a Little Family Fellow and a Bachelor of Arts in Political Science from Brown University where he graduated magna cum laude and was elected to Phi Beta Kappa.

__Professor Joe Glorioso, PhD__, is the synHSV™ Senior Advisor at Replay. 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 established 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 he is an elected fellow of the American Society for Microbiology and of the American Association for the Advancement of Science. 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.

__Jakub Tolar, MD, PhD__, is the Dean of the University of Minnesota Medical School and a Distinguished McKnight Professor in the Department of Pediatrics, Blood and Marrow Transplant & Cellular Therapy. He is also the Vice President for Clinical Affairs at the University of Minnesota, Board Chair for University of Minnesota Physicians and co-leader of M Health Fairview, the Joint Clinical Enterprise between the University of Minnesota Medical School, University of Minnesota Physicians and Fairview Health Services. An internationally recognized physician and researcher, Dr Tolar is known for his care of patients with recessive dystrophic epidermolysis bullosa. His research is focused on using hematopoietic stem cell transplant as a treatment for rare genetic disorders. Originally from the Czech Republic, Dr Tolar received his medical education (MD) in Prague at Charles University. He completed his PhD at the University of Minnesota.
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__About Telaria__

Telaria is Replay’s second gene therapy product company and is focused on rare genetic diseases of the skin. 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. Telaria’s co-founders include Professor John McGrath and Alexander Silver, leading experts in the field of genetic skin diseases. 

__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  www.replay.bio and follow us on LinkedIn and Twitter.  

__Contacts:__

__Replay__

Dr Adrian Woolfson/Lachlan MacKinnon
info@replay.bio

__Consilium Strategic Communications – Media relations__

Amber Fennell/Tracy Cheung/Melissa Gardiner
replay@consilium-comms.com


Replay launches big DNA HSV gene therapy company, Telaria, focused on rare skin diseases

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Replay Bio Construct Illustration

Under hub-and-spoke biotech, serial founders launch new startup hoping to make gene therapies for the eye


- First product company using Replay’s high payload capacity HSV vector
- Utilizes a next-generation HSV delivery vector developed at the University of Pittsburgh by leading HSV scientist and entrepreneur Professor Joe Glorioso
- Eudora founded by Joe Glorioso and distinguished entrepreneurs and retinal gene therapy experts Mark Blumenkranz, David Schaffer, and Vinit Mahajan

__San Diego, California and London, UK, October 31, 2022__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced the launch of Eudora, an HSV gene therapy company targeting genetic retinal diseases. It is the first of Replay’s product companies to leverage its high payload capacity herpes simplex virus (HSV) delivery vector, synHSV™. Eudora’s co-founders, Professors Joe Glorioso, Mark Blumenkranz, David Schaffer, and Vinit Mahajan, are seasoned entrepreneurs, and global leaders in the fields of HSV and retinal disease gene therapy.

Replay’s distinctive corporate structure separates technology development from therapeutic product development within disease area-specific product companies. Eudora is the first of Replay’s four synHSV™ gene therapy product companies, with the other three applying big DNA gene therapy to monogenic diseases of the brain, skin, and muscle.

Eudora’s pipeline includes retinitis pigmentosa, Stargardt disease, and Usher syndrome type 1B. Replay’s synHSV™ technology is a high payload capacity gene-deleted HSV-1 vector capable of delivering up to eight times the payload of adeno-associated virus (AAV) vectors. This facilitates the delivery of genes that are too big to fit into AAV and enables polygenic gene therapy. Replay is, additionally, developing an HSV vector that can deliver up to 30 times the AAV payload.

__Adrian Woolfson, Executive Chairman, President and Co-Founder of Replay__, commented: “Replay’s differentiated corporate structure allows its platform technologies to be applied to indications in areas of high unmet medical need across a portfolio of focused product companies. Eudora, the first of these, is led by some of the world’s most authoritative experts in HSV and retinal gene therapy who are also seasoned entrepreneurs, and three of which have co-founded publicly listed companies. Eudora provides Replay with the first opportunity to showcase the differentiated payload capacity of its synHSV™ technology, which we believe has transformative potential within the field of eye gene therapy and beyond.”

__Lachlan MacKinnon, CEO and Co-Founder of Replay__, said: “We are thrilled to be working with such a distinguished group of scientists, entrepreneurs, and physicians. Eudora is the first of a series of Replay product companies, each of which showcases unique aspects of our suite of proprietary genomic medicine platform technologies. We believe that our distinctive paradigm of separating platform development from product development represents the most optimal structure for efficiently leveraging the potential of our genomic medicine technology platforms and for bringing forward a new generation of genomic medicines to patients with high unmet medical needs.”

__Professor Joe Glorioso, PhD, Co-Founder of Eudora__, commented: “The incorporation of Eudora presents a unique opportunity to leverage Replay’s next-generation HSV-1 delivery platform, developed by my team at the University of Pittsburgh over several decades and licensed to Replay. I believe that our next-generation HSV delivery platform has several distinct advantages, and the potential to be disruptive to existing viral delivery platforms. It will enable the delivery of large genes, as well as genomic genes that cannot readily be accommodated by AAV vectors. I am delighted to be able to further advance this technology with this distinguished team, who have a compelling track record of developing eye gene therapies and progressing them into the clinic.”

__Professor Mark Blumenkranz, MD, Co-Founder of Eudora__, added: “This is an exciting moment for retinal gene therapy, and I look forward to working with this experienced group of entrepreneurs and drug developers to advance our promising new HSV-based gene therapies into the clinic. Replay’s broad biomedical expertise and resources provide a solid foundation for Eudora’s future success.”

__Professor David Schaffer, PhD, Co-Founder of Eudora__, remarked: “The opportunity to increase the genetic payload that can be selectively delivered to target tissues using this next-generation HSV-1 delivery platform is intriguing. I look forward to working with the team to progress this new gene therapy modality into the clinic.”

__Professor Vinit Mahajan, MD, PhD, Co-Founder of Eudora__, said: "With its current ability to deliver up to eight times the payload of AAV, the University of Pittsburgh synHSV™ technology licensed to Replay offers the possibility of addressing genetic eye diseases caused by large genes and genomic genes. This will result in an increased variety of gene therapy options for patients with genetic eye diseases.”

__About Eudora’s Co-Founders__

Professor Joe Glorioso, PhD, is the synHSV™ Senior Advisor at Replay. He is 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 established over a 35-year history of research related to the basic biology and genetics of herpes simplex virus (HSV). His contributions to the field include defining antiviral immune responses to infection, the genetics of viral pathogenesis and latency, and mechanisms of viral infection. Furthermore, he has been a pioneer in the design and application of HSV gene vectors for the treatment of nervous system diseases such as peripheral neuropathies, chronic pain, and brain tumors. He continues to be a worldwide leader in the HSV gene vector field through the creation of innovative gene vectors and the development of manufacturing methods for Phase I and Phase II human clinical trials for pain gene therapy. In addition to being a Founding Member of the American Society of Gene Therapy and the International Society for NeuroVirology, Dr. Glorioso is a member of the American Society for Microbiology, the American Society for Virology, Society of Neurooncology, the International Pain Society, and American Society of Cancer Research.

Professor Mark Blumenkranz, MD, is the HJ Smead Professor Emeritus in the Department of Ophthalmology at the Stanford School of Medicine. He serves as a Director of Kala Pharmaceuticals, BVI Visitec, One Medical, Iveric Bio and as the Managing Director of Lagunita Biosciences LLC. Mark co-founded, Optimedica Corporation, Peak Surgical, Adverum Biotechnologies, Verana Health and Oculeve. He was Chairman and CEO of Kedalion Therapeutics prior to its acquisition by Novartis. He founded the Retinal Fellowship Training Program at the William Beaumont Eye Institute in Royal Oak, Michigan prior to returning to Stanford where he served as Department Chair for eighteen years and the inaugural Director of the Byers Eye Institute.

Professor David Schaffer, PhD, is the Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology at the University of California, Berkeley. He serves as the Director of QB3, as well as the Director of the Bakar BioEnginuity Hub at the University of California, Berkeley. Among some of his awards are the NSF CAREER Award, AIChE Andreas Acrivos Award, and ACS Marvin Johnson Award. David was named a Technology Review Top 100 Innovator and a member of the National Academy of Inventors.

Professor Vinit Mahajan, MD, PhD, is a Professor of Ophthalmology at the Stanford School of Medicine. He is the Vice Chair for Research and directs the Molecular Surgery Program and the NIH-funded Omics Laboratory. Vinit’s team has discovered new genes for eye disease and performed the first CRISPR gene editing therapy for eye disease in human stem cells. Vinit has performed human gene therapy surgery and has developed enhanced surgeries for complex cases of retinal disease. He holds patents and has co-founded eye therapy companies that apply gene, small molecule and cell therapies to retinal disease.

__Ends__

__About Eudora__

Eudora is Replay’s first gene therapy product company. It will, in the first instance, be focused on genetic diseases of the retina. 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. Three of Eudora’s co-founders, Joe Glorioso, Mark Blumenkranz and David Schaffer, have previously founded publicly traded biotech companies, Oncorus, Adverum and 4D Molecular Therapeutics, respectively.

__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 www.replay.bio and follow us on LinkedIn and Twitter.

__Contacts:__

__Replay__

Dr Adrian Woolfson/Lachlan MacKinnon

info@replay.bio

__Consilium Strategic Communications – Media relations__

Amber Fennell/Tracy Cheung/Melissa Gardiner

replay@consilium-comms.com

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Replay Product Company Founders

Replay launches its first HSV gene therapy company, Eudora, focused on retinal eye disease

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- Write and deliver big genes, genomic genes, or multiple genes 
- Complex regulatory elements 
- Address polygenic medicine

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- Deliver DNA to autologous, allogeneic, and iPSC-derived cell therapies
- Write and install large constructs to replace multiplex editing 
- Potential to multiplex CARs and TCRs

Building the next generation of genomic medicines

Latest news

Defining the Rules of Biology in the Age of Genome Writing

Replay launches big DNA HSV gene therapy company, Telaria, focused on rare skin diseases

Under hub-and-spoke biotech, serial founders launch new startup hoping to make gene therapies for the eye

Replay launches its first HSV gene therapy company, Eudora, focused on retinal eye disease