Phoenicis Therapeutics, Inc.

Replay’s "hub-and-spoke" business model is structured so tech development is separate from product development within different product companies. Less than a month after unveiling its first gene therapy company, Replay is now launching rare skin-disease-focused Telaria. While other biotechs are culling pipeline programs and staff, newly launched gene writing biotech Replay is using its $55 million seed financing to send out a series of companies armed with next-generation genomic products. At the end of October, the company revealed its first offshoot—Eudora, an HSV gene therapy company targeting inherited retinal diseases. Replay plans to form a total of four gene therapy product companies that use its high payload capacity HSV delivery platform, dubbed synHSV. The platform was developed by Joe Glorioso, Ph.D., a co-founder of Eudora and Telaria as well as a synHSV senior adviser at Replay. Telaria's other co-founders are John McGrath, M.D., head of the genetic skin disease group at St. John’s Institute of Dermatology at King’s College London, and Alexander Silver, co-founder of the Epidermolysis Bullosa Research Partnership, founder of Phoenicis Therapeutics and founding partner at P2 Capital Partners.   Telaria will initially focus on recessive dystrophic epidermolysis bullosa (RDEB), an inherited disease that can cause fragile skin that blisters easily. There’s currently no cure for the disease, which can affect multiple internal organs and causes serious medical issues for the 50,000 patients impacted globally. “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,” McGrath said in a Nov. 21 release.   The synHSV technology can deliver up to eight times the payload of adeno-associated virus (AAV) vectors, allowing for polygenic gene therapy and the delivery of genes too big for AAV. The Replay team has even bigger ambitions, however, including working on an HSV vector that can deliver up to 30 times more than an AAV payload. “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,” Silver said in the release, adding that Replay’s tech allows for the delivery of big DNA to the skin through its differentiated payload capacity. Replay’s "hub-and-spoke" business model is structured so that tech development is separate from product development within different product companies. Its other two companies, which have yet to debut, will apply the same big DNA gene therapy principles to genetic diseases of the brain and muscle.

Replay launches big DNA HSV gene therapy company, Telaria, focused on rare skin diseases Second product company using Replay’s next-generation high payload capacity HSV delivery vector developed at the University of Pittsburgh by Professor Joe GloriosoTelaria 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

DermBiont axed trials of its original lead dermatology gel, the biotech confirmed to Endpoints News , and with little investor appetite for microbiome-based therapies, the company is raising a Series B to bankroll studies of other topicals it acquired in recent years. The Boston biotech — led by Karl Beutner, a former CMO of atopic dermatitis drugmaker and Pfizer-acquired Anacor Pharmaceuticals — is ending work in eczema and halting plans in athlete’s foot and onychomycosis, a fungal infection in toenails and fingernails, chief business officer Nick Eliovits told Endpoints. Karl Beutner For now, the private upstart is focused on bringing forward small molecule topicals for seborrheic keratosis, sunspots and melasma. The AKT inhibitor gel, known as SM-020 and brought into the DermBiont fold via a 2020 acquisition of SeylanMED, passed a Phase II in seborrheic keratoses, the company said in June . After disclosing a $28 million “Series A2” last December, DermBiont has raised at least $3.3 million more, according to SEC filings from January and last month. Eliovits said he anticipates DermBiont will announce “a significant financing in the coming” weeks or months, noting the round will be billed as a Series B. Boston startup lands $28M, closes small biotech buyout; New longevity fund takes shape That will get the biotech into Phase III studies for its revamped pipeline, which includes SM-020 and PKC-beta inhibitor SM-030. Multiple mid-stage studies are on tap for next year ahead of late-stage clinical trials in 2024, he said. SM-030 is currently in a 75-patient Phase II study for photodamage hyperpigmentation. SM-020 will go through another 105-patient Phase II in SK next year, and SM-030 will go through a 150-patient study in melasma, a spotty skin condition, pending the photodamage trial results, Eliovits said. “People want to be able to be monochromatic and solve their hyperpigmentation issues, and we have a topical there that hits the root cause and it blocks PKC beta, which is required for the phosphorylation of tyrosinase which regulates melanin production,” he said of SM-030. DermBiont acquired SM-030, or ruboxistaurin, via its purchase of Chromaderm, announced at the same time as the Series A2 last winter. Chromaderm was founded by the same executive as five other biotechs, all of which merged with Phoenicis Therapeutics, Endpoints reported last week. Six biotechs merge to take on BridgeBio, Abeona in 'butterfly skin' disease, with eyes also set on Duchenne The goal with SM-030 is to provide a topical in the face of a federal decision to take OTC hydroquinone off the market as part of the CARES Act. “I think that if somebody had a safe product that they could use,” Eliovits said, “it would really add a lot of value and improve a lot of patients’ lives and make sure people aren’t using junk on their face, so that’s why we took the decision there.” The clinical development pruning came in late August or early September, Eliovits said, pointing to a variety of factors. DermBiont went through the Illumina accelerator program and emerged in 2017 with IP out of James Madison University. The goal was to develop microbiome-based therapeutics that were the result of research that identified bacteria that produces anti-fungal metabolites, Eliovits said. But the biotech ran into hurdles during the pandemic, when Covid-19 hampered trial sites and the company was forced to halt studies in athlete’s foot and AD. By the time DermBiont regrouped to try a turnaround, during which those two acquisitions were being made, the upstart ran faced an uphill battle. Competition in atopic dermatitis drug R&D heated up , athlete’s foot was viewed by funders as a “retail OTC indication” and microbiome companies flopped, Eliovits said, with the latter reasoning exemplified by the shuttering of Kaleido Biosciences earlier this year. Eliovits is also a managing partner at Olive Tree Capital, a fund that helped bankroll Kaleido. UPDATED: Flagship-backed microbiome company Kaleido Biosciences shuts down “[I]nvestors are depleted and have zero interest in microbiome therapeutics,” he said. If the microbiome whets investor appetite again, the company could consider returning to DBI-001 and DBI-002, its original therapies, he said. Of course, if DermBiont had infinite dollars, the programs would’ve still been in the clinic, Eliovits said. The trial stoppages were disclosed on the federal clinical trials database in recent weeks and the two DBI assets were removed from the company’s public pipeline webpage in recent months, according to internet archives. In addition to Olive Tree, DermBiont’s backers include Pivotal Life Sciences, Viking Global Investors, Toba Capital and Civilization Ventures, among other undisclosed funders.