In support of this year’s Rare Disease Day, the global movement on rare diseases which works towards equity in social opportunity, healthcare, and the provision of diagnostics and therapies for individuals living with rare diseases, we talk to Alex Silver, co-founder of Telaria, Replay’s HSV gene therapy product company targeting rare skin diseases. 

After their son Jackson was born and diagnosed with recessive dystrophic epidermolysis bullosa (RDEB), Alex and his wife started a foundation which grew into the EB Research Partnership; the largest global organization dedicated to funding research to treat and cure epidermolysis bullosa (EB). 

EB comprises a group of devastating and life-threatening skin disorders affecting children from birth and that makes the skin as delicate as a butterfly's wings. There's currently no cure, so treatments aim to relieve symptoms, reduce pain, and prevent complications, such as infection. The genetic skin disease gene therapy field is advancing research intent on bringing a substantive change to how EB is treated. 

__You’ve been actively involved in funding and driving research into epidermolysis bullosa (EB) for more than a decade. How has the field changed in that time?__

When my fifteen-year-old son was born with recessive dystrophic epidermolysis bullosa (RDEB), there were very few active clinical trials. The disease-modifying trials were highly risky and uncertain in the benefit that could be delivered. Furthermore, gene therapies were much more of a fantasy than a reality. While there is still no disease-modifying therapy approved for EB, the progress over the last 15 years has been tremendous. The number of potential therapies and modalities gives me great hope that a life-changing treatment or potential cure is on the horizon. As the parent of a child living with EB, this can't come fast enough. I am encouraged by the amount of people, companies, and investors working together to create this outcome. 

__You established the Epidermolysis Bullosa Research Partnership, which went on to be the largest global organization dedicated to funding research to treat and cure EB. What drove you?__

My son has been my motivation since the day he was born. My wife and I were fortunate to have great medical care, but nothing could have prepared us for his diagnosis. After a routine heel prick to test blood sugar because my wife had gestational diabetes, the nurses placed a Band-Aid on his foot that took off all the skin when it was removed. That was the moment that I decided to do whatever I could to help him. We started a non-profit at our kitchen table that I chaired until mid-2022. We grew that from nothing to raising over $55 million, funding over 85 projects and supporting more than 30 clinical trials, mostly via a venture philanthropy model that I created. As my son's condition has advanced – along with my knowledge of how to get commercially sustainable treatments to the finish line – I have reallocated my time towards the most life-changing and commercially viable possibilities out there.  I am not alone in saying that as an EB parent, I live in awe of my child's strength, and I am inspired every day by him.

__How has the advent of gene therapy changed the EB research field?__

Approximately 12 years ago, I was at a leading academic institution that was pioneering a gene therapy for EB. The timeline being discussed was 20+ years out.  Yet here we are with gene therapies in or near clinical trial stages! That's amazing. The benefit of gene therapy is that it treats the root cause of the problem. What many people don't realize is that skin is your largest organ, and first line of defense. Everything you do in life impacts your skin – sleeping, waking, and even sitting. In addition, EB really is a connective tissue disorder. The same protein that impacts skin integrity is in your eyes, throat, and GI tract. The people living with EB have a systemic condition. By fixing the gene that causes EB, the therapy should help all the downstream effects of EB such as inflammation, infection, etc. Let's also keep in perspective that there are an estimated 7,000 rare diseases that impact 10% of our population. That is 32-33 million people! Gene therapy is a platform technology. If you can show that it works in EB then you can likely have it work in other rare conditions. In other words, gene therapy success in EB bodes well for the thousands of other rare genetic conditions that exist without treatments.

__What are some of the biggest challenges you’ve had to overcome in your EB journey so far?__ 

The greatest challenge for me has been the timeline to an approved life-changing treatment. By that I mean, we established a foundation and drove clinical trials, created a biotech, and advocated for funding in front of the US Senate. I have no doubt that our efforts have helped advance EB therapies and changed the landscape in a positive way. Developing approved, life-changing treatments takes time, and time is something that someone living with a rare disease values the most. I am optimistic though that we are closer to therapies that will really change the lives of those living with EB. When we started our foundation, there were some wonderful supporters, and also some with the view that we couldn't impact the lives of those living with EB because it was too hard to drive change. Looking back now, I can draw a line to almost every single late-stage therapy in clinical trial and our funding of it. That gives me solace, as even if we aren't there yet, we are well on the way.

__Given what you know today, compared to when Jackson was born, what advice would you give to a new parent of a child living with EB?__ 

This is a hard question to answer as every child with EB has a unique journey. I think the best advice that I can offer is to try as hard as possible to live in the present and not fantasize about the life that you imagined you would have had as a parent. Nobody believes that his or her child will be born with a rare disease, and there are some very, very hard days. We each have one trip on this earth and, as hard as it has been for my son quite often, I consider myself among the luckiest of people to have him in my life. 


Portraits Alex Silver Green Background

Rare Disease Day 2023: In conversation with Alex Silver 


- Cord blood-derived T-Cell Receptor Natural Killer (TCR-NK) platform offers potential for scalable off-the-shelf cell therapy 
- Syena co-founded by Professor Katy Rezvani, M.D., Ph.D., an oncologist and pioneer of engineered NK cell therapy
- Phase 1 study in solid tumors and hematological malignancies anticipated to commence in Q2 2023 

__San Diego, California, London, UK, and HOUSTON, February 14, 2023__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, and The University of Texas MD Anderson Cancer Center, today announced the launch of Syena, a new oncology-focused product company pioneering T-cell receptor (TCR) natural killer (NK) cell therapies (TCR-NKs). 

Building on the intellectual property and technology from MD Anderson and Replay, Syena has the potential to create the next generation of cell therapy, combining the safety, potency, and scalability of NK cells with the ability of TCRs to target intracellular tumor antigens. The new company’s TCR-NK cell platform is based upon the scientific discoveries of Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. 

“This first-in-class TCR-NK technology provides an opportunity for Replay to disrupt the existing cell therapy paradigm and positions Syena to become a leader in this space,” said __Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay__. “While clinical successes in hematological malignancies have demonstrated the transformative potential of engineered cell therapies, these successes have not yet been realized in solid tumors. NK cells offer distinct advantages over T-cells and building on Dr. Rezvani’s research to arm them with TCRs has the potential to significantly impact oncology cell therapy.” 

Based on the contributions of Replay and MD Anderson, Syena will build a pipeline of engineered cell therapies using its novel TCR-NK cell platform, licensed exclusively from MD Anderson. It is targeting a selection of validated cancer neoantigens, including NY-ESO-1, and additional undisclosed TCRs. The NY-ESO-1 program in hematological malignancies and solid tumors is anticipated to enter the clinic in Q2 2023.

Syena’s TCR-NK cell therapy platform will combine the advantages of engineered TCR cancer therapy with those of NK cells, offering the possibility of improved safety and efficacy through a multi-armored approach incorporating natural and artificial mechanisms. Unlike chimeric antigen receptor (CAR)-based therapies, which recognize specific surface proteins, TCR therapies are engineered to recognize proteins normally found inside the cell. The use of a TCR allows the NK cell to recognize externalized protein fragments presented by the cell’s surface immune proteins. 

“NK cells play a pivotal role in anticancer immunity and, following the successes of CAR T-cell therapy, and the potential for CAR-NK therapies, TCR-NK cells are positioned to be a next-generation agent for cancer therapy,” said __Dr. Katy Rezvani__. “We believe that the TCR-NK cell approach will allow targeting of a broad range of tumor antigens, including cancer-specific neoantigens, and could pave the way for potentially safe and efficacious ‘off-the-shelf’ cell therapies for hematological malignancies and solid tumors.”

Rezvani’s work at MD Anderson has explored the role of NK cells in mediating innate immunological activity against human malignancies, as well as strategies to enhance their killing function. She was the first investigator to conduct a clinical trial with cord blood derived CAR-NK cells (Liu et al, NEJM 2020), and has successfully advanced 11 cell therapies into the clinic through MD Anderson’s institutional support and commitment to advance innovative science. 

“We are delighted to have Dr. Rezvani, a world-leading expert in NK-based cell therapy and pioneer of CAR-NK cell therapy, as the scientific founder of Syena,” said __Lachlan MacKinnon, CEO and Co-Founder of Replay__. “Dr. Rezvani has generated compelling clinical data with CAR-NK cell therapies, and her expertise with engineered NK cells will prove invaluable in guiding our scientific efforts. We believe Syena has the potential to redefine this emerging area of medicine and to provide compelling new cell therapy options for patients in need.”

Syena will receive licenses to various Replay cell and genome engineering platform technologies.

“MD Anderson and Dr. Rezvani have advanced outstanding science in this space, and we look forward to working with them to accelerate the development of these novel cell therapies,” said __Kugan Sathiyanandarajah, Managing Director at KKR and a Board Director at Replay__. “Coupled with Replay’s platform technologies and oncology drug development experience, Syena has the potential to have a significant impact on this important life science sector and to make a meaningful contribution to human health.”

__Ends__

__Disclosure__

MD Anderson has an institutional conflict of interest with Replay and Syena, and these relationships will be managed according to an MD Anderson Institutional Conflict of Interest Management and Monitoring Plan.

__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 https://replay.bio/ www.replay.bio and follow us on LinkedIn and Twitter.  

__About The University of Texas MD Anderson Cancer Center__

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 53 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672). 

__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

__MD Anderson__

Clayton Boldt, Ph.D.
CRBoldt@MDAnderson.org


KKR-backed Replay and MD Anderson form new product company Syena to pioneer first-in-class TCR-NK cell therapy 

endpts.com

31 Katy Rezvani light green

Replay Bio partners with MD Anderson’s Katy Rezvani, heads to clinic with new TCR NK cell company


- 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.

__Ends__

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

- Replay developing uCell™, its universal, off-the-shelf, genomically rewritten, renewable cell source hypoimmunogenic technology, with support from the Bill & Melinda Gates Foundation
- uCell™ has the potential to democratize cell therapy by reducing cost-of-goods, facilitating access to high-impact cell therapy products for underserved communities around the world
- uCell™ forms part of Replay’s genomic medicine toolkit that encompasses a portfolio of potentially disruptive platform technologies, including a high payload capacity HSV delivery platform, synHSV™, and a proprietary genome writing platform
- uCell™ applicable to cell therapy across a broad range of therapeutic areas including cancer, infectious diseases, neurodegenerative diseases, and regenerative medicine

__San Diego, California and London, UK, November 28, 2022__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced that it has received a $1.56 million grant from the Bill & Melinda Gates Foundation to accelerate the development of uCell™, a proprietary hypoimmunogenic technology platform.

Replay’s uCell™ platform is an off-the-shelf, genomically rewritten, hypoimmunogenic technology that allows allogeneic donor-derived primary cells and iPSCs (Induced Pluripotent Stem Cells) to be made immune silent. The technology is expected to substantially decrease the cost-of-goods of cell therapies, improve product volume and consistency, enable extensive genome engineering, and in the case of cancer cell therapy, enable deeper clinical responses and reduced relapse rates. uCell™ is anticipated to form the basis of several off-the-shelf iPSC-derived immune cell therapies applicable to a multiple therapeutic areas, including cancer and infectious diseases. The technology is relevant to both the developed and developing worlds, with the anticipated reduced cost-of-goods improving equity of access.

__Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay__, commented: “Hypoimmunogenic technology is the ‘holy grail’ of cell therapy and the non-dilutive funding received from the Bill & Melinda Gates Foundation will help accelerate the development of our uCell™ technology. It is expected to address many of the key challenges of cell therapy, including scalability, the ability to introduce extensive genomic modifications, and need to reduce cost-of-goods. We are immensely grateful to the foundation and our investors for supporting Replay’s vision for the future of genomic medicine, which includes a focus on the development of high-impact and affordable cell therapies that are accessible to both industrialized and rural communities.”

__Lachlan MacKinnon, Chief Executive Officer, and Co-Founder of Replay__, added: “Replay’s hypoimmunogenic technology is the result of a convergence of synthetic biology, computational design, and protein engineering with iPS cell technology. It will enable the Company to develop a universal off-the-shelf platform in a reliable, scalable, and cost-effective manner, and broaden the utility and accessibility of cell therapy, including regenerative medicine applications. The ability to reprogram hypoimmunogenic iPSCs with our high payload synHSV™ platform will unlock a differentiated set of opportunities. As is the case with synHSV™, and given the substantive opportunity in the space, we plan to progress our uCell™ technology through distinct therapeutic area-focused product companies.”

__Professor Herman Waldmann, Co-inventor of uCELL™ and Emeritus Professor of Pathology at the Sir William Dunn School of Pathology at the University of Oxford__, said: “As a physician scientist, it is encouraging to see Replay advance the uCell™ platform, which has the potential to overcome many of the current limitations of cell therapies. By making iPSCs immune silent to generate a universal cell with utility as a renewable source for cell therapies, uCell™ has the potential to bring the benefits of this important therapeutic modality to patients across the world.”

__Ends__

__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

synHLA 1/2

Replay receives $1.5 million grant for its hypoimmunogenic technology platform

Replay Bio Construct Illustration

Maker of new gene therapy vector launches its second company, looking to zero in on rare skin conditions


- 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.
Ends

__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

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

Graph showing 6 squares, connected by the Replay logo

Replay Product Company Founders

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

__San Diego, California and London, UK, October 17, 2022__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced that it has established a scientific advisory board (SAB) comprising ten experts across a broad range of areas of scientific importance in genomic medicine and cell therapy. 

The newly formed SAB will provide input into Replay’s strategy, portfolio of next-generation genomic and cell therapy medicines, and associated technology platforms. The SAB complements Replay’s industry seasoned management team and board. 

__Adrian Woolfson, Executive Chairman, President and Co-founder of Replay__, commented: “The multi-disciplinary nature of our scientific advisory board reflects Replay’s commitment to invoking innovation from a broad range of scientific specialties and leveraging this across our research and development programs. Our new advisors represent some of the best scientific minds of their generation and bring a unique and differentiated portfolio of expertise into the Company. Their contribution to Replay will be invaluable as we continue to address some of the most significant challenges in genomic medicine and cell therapy.”

__Lachlan MacKinnon, Chief Executive Officer and Co-founder of Replay__, added: “Following on from our recent launch, the formation of our uniquely distinguished scientific advisory board further demonstrates Replay’s commitment to developing a cutting-edge portfolio of medicines guided by world-class science. The combined inter-disciplinary expertise of our scientific advisory board brings tremendous knowledge and experience into the Company as we continue to expand our operations, with a view to developing transformative genomic medicines.”

Replay’s SAB will be chaired by Professor Roger Kornberg, PhD, a biochemist whose laboratory work has focused on the molecular basis of eukaryotic transcription and in particular the structure of RNA polymerase and the nucleosome.

__Professor Roger Kornberg, PhD, Chairman of Replay’s Scientific Advisory Board__, said: “Replay’s scientific advisory board incorporates expertise across several areas relevant to Replay’s genomic medicine and cell therapy technology platforms. I am excited to be working with this exceptional group of scientists and believe we can make a compelling contribution and help Replay realize its vision for genomic medicine.” 

Replay’s SAB members are as follows:

__Professor Roger D. Kornberg PhD (Chairman)__, is the Winzer Professor of Medicine in the Department of Structural Biology at Stanford University School of Medicine. He was awarded the Nobel Prize in Chemistry (2006).

__Professor Carl H. June, MD__, is the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania. He is Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Director of the Center for Cellular Immunotherapies at the Perelman School of Medicine, and Director of Translational Research at the Abramson Cancer Center. He was the co-founder of TMunity.

__Professor Robert S. Langer, ScD, FREng__, is one of 12 Institute Professors at the Massachusetts Institute of Technology (MIT), co-founder of Moderna, and was formerly Chair of the FDA’s Science Board. He has been awarded 40 honorary doctorates, written over 1,500 articles, and received over 220 awards.

__Professor Lynne E. Maquat, PhD__, is the J. Lowell Orbinson Endowed Chair and Professor of Biochemistry and Biophysics, University of Rochester Medical Center, and founding Director of the Center for RNA Biology, University of Rochester, Rochester NY. She was awarded the Wolf Prize in Medicine from Israel (2021) and the Warren Alpert Foundation Prize from Harvard Medical School (2021).

__Professor Dame Carol Robinson, DBE FRS FMedSci FRSC__, is the Dr Lee’s Professor of Physical and Theoretical Chemistry, the Founding Director of the Kavli Institute for Nanoscience Discovery at Oxford, and a Founder of OMass Therapeutics. She is a Professorial Fellow at Exeter College, Oxford, and was formerly President of the Royal Society of Chemistry.

__Professor David V. Schaffer, PhD__, is the Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Neuroscience at the University of California, Berkeley, where he is Director of the Bakar BioEnginuity Hub and Director of the California Institute for Quantitative Biosciences (QB3). He was the co-founder of 4D Molecular Therapeutics, Ignite Immunotherapies, Rewrite, and 5 additional companies.

__Professor Stuart L. Schreiber, PhD__, is the Morris Loeb Professor of Chemistry and Chemical Biology at Harvard University. He is a co-founder of the Broad Institute at Harvard University and MIT and co-founder of Harvard’s Institute of Chemistry and Cell Biology. He was awarded the Wolf Prize in Chemistry (2016).

__Professor Pamela Silver, PhD__, is the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology in the Department of Systems Biology at Harvard Medical School, and a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School. 

__Professor Sir John E. Walker, FRS FMedSci__, is Emeritus Director and Professor at the MRC Mitochondrial Biology Unit at the University of Cambridge, England, and a fellow of Sidney Sussex College, Cambridge. He was awarded the Nobel Prize in Chemistry (1997).

__Professor John Fraser Wright, PhD__, is Professor of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, and Director of Technology Innovation at the Center for Definitive and Curative Medicine at Stanford University. He is co-founder and was Chief Technology Officer at Spark Therapeutics and is co-founder and Chief Scientific Advisor at Kriya Therapeutics.

__Ends__

__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 cell therapy platform, and a genome writing platform – to address the scientific challenges currently limiting clinical progress and preventing genomic medicine from realising its full potential. The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in product companies that leverage its 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 that leverages its evolutionary inference machine learning and genome writing technology to optimize enzyme 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 including: 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/Andrew Stern
replay@consilium-comms.com 


Kornberg

Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts

- KKR and OMX Ventures lead $55 million seed funding round
- Replay’s genomic medicine toolkit encompasses a portfolio of disruptive platform technologies to write and deliver big DNA, including a high payload capacity HSV delivery platform, a hypoimmunogenic cell therapy platform, and a proprietary genome writing platform
- Company is led and supported by a world-class team of academics, entrepreneurs, and industry experts 
- Innovative hub-and-spoke business model separates technology development from product development, leveraging Replay’s technologies within discrete product companies 
- Five product companies have been incorporated to date

__San Diego, California and London, UK, 25 July 2022__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced its launch with $55 million in seed financing. The round was led by KKR and OMX Ventures, with additional participation from ARTIS Ventures and Lansdowne Partners, SALT, DeciBio Ventures, and Axial.

Replay’s portfolio of next-generation genomic medicine technologies aims to solve the key challenges currently limiting clinical progress, including the need for increased payload capacity and off-the-shelf cell therapies that substantially reduce cost of goods, improve production speed, volume and consistency, and expand the potential for genome engineering. 

Replay’s genomic medicine toolkit comprises several synergistic technology platforms, including:

- __synHSV™__ - a high payload capacity HSV vector able to deliver up to 30x the payload of AAV. synHSV™ facilitates the delivery of large genes, genomic genes, multiple genes, and multiple transcriptional activators and repressors, thereby extending the reach of genomic medicine and opening up the possibility of polygenic therapy
- __uCell™__ - a universal, renewable, off-the-shelf, genomically rewritten, hypoimmunogenic iPSC-derived cell source for regenerative medicine and cell therapy
- __DropSynth™__ - a genome writing platform enabling rapid, efficient, and low-cost synthesis of libraries of synthetic genes and big DNA 
- __LASR™__ - an evolutionary inference algorithm platform for rewriting proteins to optimize functionality

Replay’s innovative corporate structure separates technology development from therapeutic product development within disease area-specific product companies. Each product company is co-founded by seasoned entrepreneurs in conjunction with global thought leaders in each therapeutic area. To date, Replay has established four synHSV™ gene therapy product companies, aimed at bringing big DNA therapies to monogenic diseases affecting the skin, eye, brain and muscle, and an enzyme writing product company using LASR™ and DropSynth™ to optimize enzyme functionality.

Replay was co-founded by Dr. Adrian Woolfson BM BCh PhD, formerly Executive Vice President and Head of Research and Development at Sangamo Therapeutics, Chief Medical Officer at Nouscom, Global Clinical Leader of Early and Late Stage Immuno-Oncology/Hematology at Pfizer and Global Medical Lead in Oncology at Bristol Myers Squibb; Lachlan MacKinnon, a member of the founding team at Oxford Science Enterprises (formerly OSI) and founding investor in Base Genomics, ONI and OMass Therapeutics; Professor David Knipe PhD, a world-renowned virologist and pioneer of HSV research; and Professor Ron Weiss PhD, one of the pioneers of synthetic biology and Professor of Biological Engineering at Massachusetts Institute of Technology (MIT).

__Adrian Woolfson, Executive Chairman, President, and Co-founder of Replay__, commented: “Genomic medicine has the potential to transform the future of clinical therapeutics. Over my three decades of experience working in clinical medicine, academia, and the biopharmaceutical industry, it has become clear that we require a more robust and comprehensive toolkit of molecular genetic platform technologies to solve biology’s most complex problems and realize its full therapeutic potential. In Replay we have assembled a world-class team of entrepreneurs, subject matter experts, and cutting-edge genomic medicine and synthetic biology technologies into a coherent structure that will enable us to address medicine’s greatest challenges, including solid tumors and polygenic diseases.”

__Lachlan MacKinnon, Chief Executive Officer, and Co-founder of Replay__, added: “Technology and product development have different talent requirements, timelines, costs and cultures. By separating technology development from product development, we have generated a model to accommodate these differences. Our ability to write and deliver big DNA has the potential to disrupt many areas of genomic medicine. We have the right team, corporate structure, portfolio of technology platforms, and financial backing to build an enduring company that shapes the future of the industry.”

__Kugan Sathiyanandarajah, Managing Director at KKR and Board Member at Replay__, said: “Replay’s mission is to create a world-leading company that develops and owns the tools to reprogram biology by writing and delivering big DNA; we believe these capabilities will unlock the largest untapped opportunity in medicine. Replay has tremendous entrepreneurial experience within the Company, as well as a team of seasoned industry players to guide the development of the platform technologies and product companies to bring new treatments to patients.”

__Nick Haft, Managing Director at OMX Ventures and Board Observer at Replay__, added: “Replay has assembled an impressive portfolio of step-change technologies to propel the field of genomic medicine forward. We are excited to support these technologies, Replay’s creative business model and the excellent team of entrepreneurs and investors that brings it all together.”

__Errik Anderson, CEO of Alloy Therapeutics and Independent Board Member at Replay__, stated: “Substantial technological advances in biotechnology often create opportunities for new business models. I am very excited to partner with Replay’s ambitious founders and investors who have devised a new structure around the significant opportunity space afforded by synHSV™, uCell™, and Replay’s related genomic medicine and synthetic biology technologies.” 

Alongside a highly experienced management team and board, which includes serial entrepreneur Errik Anderson, Replay is supported by a distinguished team of entrepreneurs and international experts including product company co-founders: Professor Joe Glorioso PhD, inventor of Replay’s synHSV™ technology and Senior Advisor for Gene Therapy Programs at Replay, Co-founder of Oncorus, and Professor of Microbiology and Molecular Genetics at the University of Pittsburgh; Mark Blumenkranz, MD, MMS, the HJ Smead Professor of Ophthalmology, Emeritus, at the Stanford School of Medcine, Co-Director of the Stanford Opthalmology Innovation Program, and former Chairman of the Board and Co-founder of Adverum Biotechnologies; Professor Howard Federoff MD PhD, Co-Founder of Brain Neurotherapy Bio, and former CEO of Aspen Neuroscience and Brooklyn Immunotherapeutics; and Professor David Schaffer PhD, Professor of Chemical and Biomolecular Engineering, Bioengineering and Neuroscience at University of California, Berkeley, and Co-founder of 4D Molecular Therapeutics. 

KKR is investing in Replay through KKR Health Care Strategic Growth Fund II, a $4.0 billion fund focused on investing in high-growth health care companies.

__Ends__

__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 realising 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 has raised $55 million in seed financing 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, CA and London, UK. For further information please visit www.replay.bio and follow us on [LinkedIn](https://www.linkedin.com/company/replay-bio/) and [Twitter](https://twitter.com/Replaybio).  

__About KKR__

KKR is a leading global investment firm that offers alternative asset management as well as capital markets and insurance solutions. KKR aims to generate attractive investment returns by following a patient and disciplined investment approach, employing world-class people, and supporting growth in its portfolio companies and communities. KKR sponsors investment funds that invest in private equity, credit and real assets and has strategic partners that manage hedge funds. KKR’s insurance subsidiaries offer retirement, life and reinsurance products under the management of Global Atlantic Financial Group. References to KKR’s investments may include the activities of its sponsored funds and insurance subsidiaries. For additional information about KKR & Co. Inc. (NYSE: KKR), please visit KKR’s website at www.kkr.com and on [Twitter](https://twitter.com/kkr_co?lang=en).

__About OMX Ventures__

OMX Ventures is an early stage, tech-bio focused venture capital fund – a force multiplier for scientists and innovators pushing the boundaries of what’s possible in biology and beyond. Visit OMX Venture’s website at OMX.VC and follow us on [LinkedIn](https://www.linkedin.com/company/omx-ventures/) and [Twitter](https://twitter.com/omxventures).

__Contacts:__

__Replay__

Dr. Adrian Woolfson or Lachlan MacKinnon  
[info@replay.bio](mailto:info@replay.bio)

__Consilium Strategic Communications – Media relations__

Amber Fennell/Tracy Cheung/Jessica Hodgson  
[replay@consilium-comms.com](mailto:replay@consilium-comms.com)

__KKR__

Alastair Elwen / Sophia Johnston  
Finsbury Glover Hering  
[KKR-LON@fgh.com](mailto:KKR-LON@fgh.com)  
+44 20 7251 3801


Replay’s genomic medicine toolkit encompasses a portfolio of disruptive platform technologies to write and deliver big DNA, including a high payload capacity HSV delivery platform, a hypoimmunogenic cell therapy platform, and a genome writing platform

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