Laminopathies

New Trial to Study Progerinin Treatment for Ultra-Rare Condition BUSAN, KOREA; PEABODY, MA; and GERMANTOWN, MD / ACCESSWIRE / October 2, 2024 / The United States Food and Drug Administration (FDA) has authorized the start of patient enrollment for a Phase 2a clinical trial of Progerinin, an investigational drug being developed for the treatment of Progeria. Advancing the development of Progerinin could potentially provide an additional treatment for this fatal disease. PRG Science & Technology logo Hutchinson-Gilford Progeria Syndrome (“Progeria”) is an ultra-rare, genetic, “rapid-aging” condition affecting approximately 1 in 18 million people. Without treatment, children with Progeria die of heart disease at an average age of 14.5 years old. Progeria is caused by a random genetic mutation that produces an overabundance of the toxic protein, progerin. The accumulation of progerin occurs with aging in the general population, in the cardiovascular system and elsewhere in the body, such as the skin. In children and young adults with Progeria, the rate of progerin accumulation is highly accelerated, resulting in progressive cellular damage and atherosclerotic heart disease. Progerinin was developed by Korean-based biotech company PRG Science & Technology Co., Ltd. (PRG S&T) with research funding from The Progeria Research Foundation (PRF). The trial is a collaborative effort between PRG S&T, PRF, and trial site Boston Children’s Hospital, and will be managed by contract research organization Amarex. In the Phase 2a randomized open label trial, Progerinin will be administered in combination with the current standard-of-care, Zokinvy, to 10 patients with Progeria and Progeroid Laminopathies (PL) who are one year of age and older. Zokinvy has been shown to increase lifespan in a Progeria mouse model by 25%, and data published in the journal Cells in April 2023 indicated that Progerinin showed a potential increase in Progeria mouse lifespan by 50%. Zokinvy works by blocking the toxic, disease-causing protein, progerin, from developing and attacking normal cells, while Progerinin appears to reduce the level of progerin that accumulates in the body. Currently, Zokinvy is the only treatment for Progeria and PL approved by the FDA (in 2020), the European Medicines Agency (EMA, in 2022) and the Japanese Ministry of Health, Labor and Welfare (MHLW, in 2024). “Since its establishment, PRG S&T has focused on developing rare genetic disease treatments. This clinical trial demonstrates PRG S&T’s R&D capabilities to improve access to new drugs and expand treatment opportunities for children with progeria worldwide,” said Bumjoon Park, president of PRG S&T. “PRG S&T will focus on R&D and technological innovation to accelerate the development of treatments, including preparation for follow-up clinical trials, and lead to the development of new drugs.” “This new trial represents another step forward in our mission to treat and cure these amazing children and young adults with Progeria,” said PRF Executive Director Audrey Gordon, Esq. “Each Progeria clinical trial builds on learnings from our previous trials, so that we are continually making progress toward even better treatments and the cure. Most importantly, we are grateful for the courage and resilience of these children and young adults with Progeria and their families for participating in research programs and contributing to this important mission.” “Patients with Progeria and their families deserve more options,” said Dr. Kush Dhody, President, Amarex Clinical Research. “This is an especially devastating diagnosis given the shortened lifespan it causes. We’re honored to support a study that brings more hope to these patients.” About Progeria Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), and PL are ultra-rare, multisystemic, premature aging diseases that accelerate mortality in young patients. Progeria is caused by a genetic mutation in the LMNA (“lamin A”) gene, and results in a disease-causing abnormal protein called progerin. There are approximately 400-450 children and young adults worldwide with Progeria. Thanks to PRF-funded research, we now know that progerin is produced in all of us as we age, but at a much lower rate than in children with Progeria. Due to this discovery of the biological connection between Progeria, heart disease and aging, finding the cure for one of the rarest diseases on earth could provide keys for treating millions of adults with heart disease and stroke associated with the natural aging process, as well as help the entire aging population. About PRG Science & Technology Co., Ltd. PRG S&T is a research & development company specializing in the treatment of rare genetic diseases. PRG S&T has been developing therapeutics for rare genetic diseases (laminopathies, neurodegenerative diseases, neuro-oncology etc.) with small molecules, which are derived from target sites on aberrant Protein-Protein Interactions (PPI). All four pipelines currently in PRG S&T’s possession have been designated as orphan drugs by the US FDA. Progerinin, the investigational treatment for Progeria has been approved by the FDA to enter phase 2 clinical trials, and is about to enter Phase2 at Boston Children’s Hospital. The non-clinical study of PRG-N-01, the treatment for neurofibromatosis type2, has been completed. IND for Phase I/II of PRG-N-01 has been approved by the Korea FDA and has been administered to patients at Asan Medical Center (South Korea) in June 2024. If these two drugs, Progerinin and PRG-N-01, are developed successfully, they are expected to become first-in-class innovative new drugs. For more information, please visit . About The Progeria Research Foundation The Progeria Research Foundation (PRF) was established in 1999 by the family of Sam Berns, a child with Progeria. Within four years of its founding, the PRF Genetics Consortium discovered the Progeria gene, a collaboration led by Dr. Francis Collins, former Director of the National Institutes of Health (NIH). PRF has funded and co-coordinated all lonafarnib-associated clinical trials for Progeria and Progeroid Laminopathies, conducted at Boston Children’s Hospital, and supports scientists who conduct Progeria research worldwide. PRF’s International Patient Registry includes over 370 children with Progeria in 70 countries. PRF is the only non-profit organization solely dedicated to finding treatments and the cure for Progeria and its aging-related conditions, including heart disease. The organization fills a void, putting these children and Progeria at the forefront of scientific efforts. For more information and to support PRF’s mission, please visit . About Amarex Clinical Research, LLC, an NSF company Amarex Clinical Research, LLC, is a global, full-service Contract Research Organization (CRO) with significant expertise conducting biomedical research. The leadership team’s combined experience includes the design and conduct of several hundred clinical research projects in many therapeutic indications. Amarex provides services in Project Management: Phase I-IV, BE/BA, PK/PD; Regulatory Affairs: FDA Applications and meetings, applications to International Health Authorities, GxP Compliance Audits; Clinical Operations; Adaptive Study Designs; Statistical Analysis; Data Management; Medical Monitoring; Safety and Pharmacovigilance; and General Consulting. Amarex can take your product through the entire approval process, from creating the regulatory approval strategy, to conducting trials, to writing the marketing approval application. Join our growing list of clients with approved products assisted by quality, cost-efficient services. For more information visit . Contact Information Eleanor Maillie PRF emaillie@progeriaresearch.org 978.879.9244 Sunghee Kim PRG S&T shkim@prgst.com Kalli DeWeese Amarex kdeweese@nsf.org Related Images PRG Science & Technology logo Amarex Clinical Research logo PRF logo SOURCE: The Progeria Research Foundation View the original press release on newswire.com.

New cell lines will advance study of common genetic heart conditions. SEATTLE, June 4, 2024 /PRNewswire/ -- The Allen Institute for Cell Science unveiled a set of tools to accelerate research into hypertrophic cardiomyopathy (HCM), the most common genetic heart condition in the world: six new cell line collections, each carrying a different mutation associated with HCM. HCM is primarily caused by mutations that thicken heart muscle and, in rare cases, lead to heart failure and cardiac arrest. The new cell line collections will help scientists investigate the impact of specific mutations in myosin, a protein that powers heart contractions, on heart function. Continue Reading Six new cell lines, each carrying a different mutation aim to help researchers find new treatments and therapies Post this The Institute also released cell line collections targeting skeletal muscle disorders, specifically those related to a myosin mutation, and laminopathies, rare diseases caused by mutations in proteins that maintain a cell's nucleus. "Providing researchers with these robust tools paves the way for the discovery of new treatments and insights into disease progression," said Ru Gunawardane, Ph.D., Executive Director of the Allen Institute for Cell Science. "These cell lines are a perfect bridge between our expertise and the efforts of leading scientists to tackle disease." Gene-edited tools The Allen Cell Catalog's latest offerings are known as human induced pluripotent stem cells. These are skin cells that have been reprogrammed back into their stem cell form. Using CRISPR/Cas9 technology, Allen Institute scientists introduced disease-associated mutations into these cells along with fluorescent tags that illuminate the structures that drive heart contractions. Researchers can use these cells to generate cardiac muscle cells, providing a dynamic model to investigate the intricate biomechanics of heart disease. Developing the HCM tools offered an opportunity to try a new technique: altering single base pairs of DNA. The combination of these gene editing methods enabled Allen Institute scientists to rapidly create a series of disease-specific cell lines, said Brock Roberts, Ph.D., a scientist at the Allen Institute. "This is the beginning of a different era in human health, where the scalpels and implements of surgery have become molecular," he said. "We're still quite a ways from regularly doing that in patients, but this was an exciting opportunity to get into the early stages of research in a human cell." Partnering in the lab to make progress in the clinic Today's release of the HCM cell lines stems from a collaboration among scientists at the University of Washington; Stanford; and the University of California, Santa Barbara. Their goal was to explore why mutations linked to HCM cause varying symptoms in patients: some display few or no symptoms, while others, even within the same family, suffer from severe illness. The team turned to the Allen Institute for Cell Science, which leveraged their decade of experience making gene-edited stem cell lines to generate a robust suite of cells that could be used for this sensitive research. "Working with the Allen Institute for Cell Science, we knew we were getting high-quality stem cells," said Stanford University's Daniel Bernstein, M.D., "If we did this on our own, it would have taken us several years and would have been extraordinarily expensive, and it would have eaten up a large part of the budget of the grant we had gotten from the NIH." The cell lines serve as a platform to study myosin mutations across molecular, cellular, and tissue levels, offering a comprehensive understanding of their impact on heart function. The researchers' first study confirmed that a specific rare mutation causes abnormal heart function at all biological levels, countering prior skepticism about its clinical significance. "Being able to study this in the dish was really important because some cardiologists were beginning to doubt whether this mutation really caused the disease," said Bernstein, the senior author on the study. The cells lines also provide opportunities to observe how the disease develops over time, potentially revealing critical phases where targeted interventions might alter or halt its progression. "Most of the studies we do in human tissue are at the end stage of disease," said Michael Regnier, Ph.D., a professor of bioengineering at the University of Washington involved with the study. "But what we really want to know is: how is the disease initiated, and how does it progress over time? These cell lines let us do that." 'An invaluable resource' Today's releases introduces the first disease-specific cell lines in the Allen Cell Catalog, with hopefully more to come, said Jacqueline Smith, M.S., a senior research associate. "As an institute, we've been really focused on how normal cells function," Smith said. "Now we're exploring them in a diseased state to deepen our understanding of these genetic conditions and hopefully lead to new treatments." "Studies of cardiomyocytes derived from the Allen Institute for Cell Science's cell lines enable us to understand how those molecular changes manifest at the sarcomeric and cellular levels," said Kathleen Ruppel, M.D., Ph.D., a pediatric cardiologist and investigator at Stanford University. "These lines are an invaluable resource to the cardiac muscle community and will lead to important insights into hypertrophic cardiomyopathy." About the Allen Institute The Allen Institute is an independent, 501(c)(3) nonprofit research organization founded by philanthropist and visionary, the late Paul G. Allen. The Allen Institute is dedicated to answering some of the biggest questions in bioscience and accelerating research worldwide. The Institute is a recognized leader in large-scale research with a commitment to an open science model. Its research institutes and programs include the Allen Institute for Brain Science, launched in 2003; the Allen Institute for Cell Science, launched in 2014; the Allen Institute for Immunology, launched in 2018; and the Allen Institute for Neural Dynamics, launched in 2021. In 2016, the Allen Institute expanded its reach with the launch of The Paul G. Allen Frontiers Group, which identifies pioneers with new ideas to expand the boundaries of knowledge and make the world better. For more information, visit alleninstitute.org. Media Contact Peter Kim, Sr. Manager, Media Relations 206-605-9884 | [email protected] SOURCE Allen Institute

The therapy is indicated for treating Hutchinson-Gilford Progeria Syndrome and processing-deficient progeroid laminopathies. Credit: LeviaUA / Shutterstock.com. Zydus Lifesciences subsidiary Sentynl Therapeutics has announced the worldwide acquisition of the Zokinvy (lonafarnib) programme from Eiger BioPharmaceuticals for the treatment of progeria. Zokinvy is the first and only treatment to obtain US FDA approval that targets the cause and symptoms of Hutchinson-Gilford Progeria Syndrome (HGPS) and processing-deficient progeroid laminopathies (PDPL), collectively called progeria. The treatment is indicated for usage in individuals aged 12 months and above. An ultra-rare, fatal genetic condition, progeria causes premature aging in young patients, leading to accelerated mortality. Since its approval in the US in 2020, Zokinvy has also received authorisation in the European Union and Great Britain in 2022, and most recently in Japan in January this year. See Also: Novartis acquires Mariana in $1.75bn deal to strengthen radioligand portfolio Vertex Pharmaceuticals gets grant for treatment of alpha-1 antitrypsin deficiency with compound of formula (i) The latest sale comes after Eiger and its subsidiaries filed for Chapter 11 bankruptcy in the US Bankruptcy Court in April this year. Subsequently, an auction was held as part of Eiger’s court-supervised sale process of Zokinvy. Sentynl emerged as the winning bidder for net base price of $45.2m. The Bankruptcy Court subsequently approved the sale to Sentynl with the transaction finalised on 3 May. Following the acquisition, Sentynl holds the worldwide rights to Zokinvy and will oversee its manufacturing and commercialisation efforts. The new deal will bolster Sentynl’s portfolio of biopharmaceutical products for rare and ultra-rare diseases. Sentynl president and CEO Matt Heck said: “It is an honour to add Zokinvy to our portfolio of products that have a tangible impact on the lives of rare disease patients, whose needs are too often unmet or overlooked. “We are firmly committed to provide best-in-class global access to Zokinvy and are eager to serve the patients and their families affected by progeria. We are grateful to Eiger and The Progeria Research Foundation for their dedicated effort to develop and secure availability of this life-changing product.”