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New NHP data indicate robust silencing at clinically relevant dose levels and highlight potential best-in-class potency achievable with Chroma's epigenetic editors Chroma's epigenetic editor achieved efficient and durable reductions in blood PCSK9 (84%) and LDL-cholesterol (68%) following a single 1.0 mg/kg dose Potential for life-long durability supported by mechanistic data confirming robust and stable CpG methylation at the PCSK9 locus in NHPs BOSTON, Sept. 3, 2024 /PRNewswire/ -- Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-course epigenetic editing therapeutics, presented new preclinical data demonstrating the potency, durability, and specificity of its PCSK9-targeted epigenetic editor in an oral presentation at the 2024 European Society of Cardiology Congress, held August 30-September 2 in London. The data showcase the potential best-in-class potency achievable in NHPs with Chroma's optimized epigenetic editors. They also indicate the company's epigenetic editing platform can effectively silence expression of PCSK9 in the liver, inducing durable reductions in low-density lipoprotein-cholesterol (LDL-C) levels without cutting or nicking the DNA. The PCSK9 gene actively promotes the degradation of LDL receptors, thereby reducing the ability of the liver to clear cholesterol from the blood. This can result in chronically elevated blood levels of LDL-C and lead to increased risk for early onset atherosclerotic cardiovascular disease (ASCVD). Genetic and pharmacologic reductions in PCSK9 levels have been shown to correlate with decreased cardiovascular events, making it an established and compelling target for prevention of ASCVD. "These results underscore the successful optimization and development of a highly potent, durable, and specific PCSK9-targeted therapeutic," said Catherine Stehman-Breen, M.D., Chroma's Chief Executive Officer. "By demonstrating potency at clinically relevant doses, we have achieved a key requirement for successful translation of a lipid nanoparticle-delivered genomic medicine into an efficacious and well-tolerated therapeutic, supporting continued advancement toward clinical studies." Data from the presentation demonstrate best-in-class potency, with Chroma's human PCSK9-targeting epigenetic editor reaching saturating pharmacology at 1.0 mg/kg in NHPs. A significant reduction in circulating PCSK9 (84%) levels was achieved, resulting in a 68% reduction in LDL-C levels, maintained out to three months. Additional data show that the company's epigenetic editor efficiently and durably reduced PCSK9 levels in vivo for one year after a single administration in human transgenic mice. The silencing was maintained in mice pre- and post-partial hepatectomy, the standard surgical model for induction of liver regeneration. "We believe single-course therapies are crucial in the creation of genomic medicines that can disrupt the current treatment paradigm for lowering LDL-cholesterol and reduce the risk of serious cardiovascular disease," said Jenny Marlowe, Ph.D., Chroma's Chief Development Officer. "These data presented at ESC confirm the potential of our epigenetic editing platform to produce a highly potent therapeutic that can bring the promise of better treatment options within reach." Find the presentation on the Chroma website here. About ASCVD Chronically elevated blood levels of low-density lipoprotein-cholesterol (LDL-C) can lead to increased risk for early onset atherosclerotic cardiovascular disease (ASCVD), heart attack, and stroke. ASCVD is the leading cause of death in the United States and globally. Current therapeutic interventions often fail to lower LDL-C below designated therapeutic thresholds and require frequent dosing, leading to treatment adherence challenges. The PCSK9 gene actively promotes the degradation of LDL receptors, which are responsible for clearing LDL-C from the blood, thereby reducing the ability of the liver to clear cholesterol from the blood. Genetic and pharmacologic reductions in PCSK9 have been associated with decreased LDL-C levels and reduced risk for cardiovascular events. Chroma is advancing an in vivo epigenetic editing therapeutic designed to effectively and durably silence the PCSK9 gene without cutting or nicking the DNA, resulting in decreased PCSK9 protein levels and leading to lower LDL-C levels and reduced risk of ASCVD. About Chroma Medicine Chroma Medicine is a biotechnology company pioneering a new class of genomic medicines that harness epigenetics, nature's innate mechanism for gene regulation, to deliver precise, programmable single-course therapeutics while preserving genomic integrity. The company's modular platform enables development of medicines that can address a wide range of complex diseases, whether they require silencing, activation, or targeting multiple genes at once. Chroma was founded by the world's foremost experts in genomic research and is led by a veteran team of industry leaders and scientists with deep experience in genomic medicine, drug discovery, and development. For more information, please visit chromamedicine.com or follow us on LinkedIn and X. SOURCE Chroma Medicine

SHANGHAI, July 11, 2024 /PRNewswire/ -- YolTech Therapeutics, a biotech company developing in vivo gene editing therapies to treat rare genetic diseases, announced today the successful enrollment of the first patient in the Phase I clinical trial of YOLT-201, its independently developed in vivo gene editing therapy. This marks a significant milestone in the clinical development of this therapeutic candidate. ATTR is a debilitating genetic disease, caused by misfolded transthyretin protein (TTR) forming amyloid fibrils and depositing in various organs and tissues in the body such as myocardium in the heart and peripheral nerves in the limbs. Depending on the mutation involved, hATTR can occur in people in their teens and 20s, though other forms are typically diagnosed in people over 50 years of age. YOLT-201 is a world leader in the development of in vivo gene editing therapies and lipid nanoparticle (LNP) delivery systems. A single dose infusion of YOLT-201 has been shown to safely and durably knock down TTR protein level in the serum in preclinical NHP models, potentially providing effective and lifelong clinical benefits to patients. Eligible ATTR patients will be recruited nationwide for this clinical trial. The first enrolled patient received their first dose on June 28, 2024. Two weeks post-dosing, the patient was in good health with no significant drug-related adverse events observed. "The completion of the first patient dosing and safety assessment is a critical milestone in the clinical development of YOLT-201." Dr. Yuxuan Wu, Founder and CEO of YolTech, expressed that, "The early clinical trials have demonstrated excellent safety and efficacy for YOLT-201, and we believe it has the potential to transform the global clinical treatment landscape for ATTR diseases.". On March 1, 2024, YolTech Biotech announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) had approved the clinical trial application (IND) for YOLT-201. This is the first in vivo gene editing drug mediated by lipid nanoparticles (LNP) to receive clinical trial approval in China. About YOLT-201-101 Study YT-YOLT-201-101 trial is a multicenter, open-label, single-dose phase I/IIa clinical study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic parameters of YOLT-201 in patients with transthyretin amyloidosis polyneuropathy (ATTR-PN) and transthyretin amyloidosis cardiomyopathy (ATTR-CM). The trial consists of two stages: the first stage is an open-label, single-dose, dose-escalation study to determine the optimal biological dose (OBD) of YOLT-201; the second stage is an open-label, single-dose, dose-expansion study to preliminarily assess the safety and preliminary efficacy of YOLT-201 at the OBD. About YOLT-201 YOLT-201 Injection utilizes several lipid components including ionizable lipids as primary excipients to encapsulate mRNA and sgRNA raw materials, forming lipid nanoparticles (LNP). Upon intravenous injection into the body, plasma ApoE protein binds to the surface of LNP particles. Liver cells expressing the LDLR receptor recognize ApoE protein and engulf the LNP through endocytosis, forming endosomes. The decrease in pH within endosomes promotes electrostatic interactions between ionizable lipids and endosomal membranes, leading to membrane disruption and the release of mRNA and sgRNA. mRNA, in the cytoplasm, binds to ribosomes, translating the editor protein. The editor protein, in combination with sgRNA, enters the cell nucleus. sgRNA specifically locates the editor to the TTR gene sequence, and the editor protein modifies the target TTR gene, preventing its normal transcription into mRNA. This process stops the production of the TTR protein, achieving the goal of a one-time administration for a comprehensive cure of ATTR diseases. About YolTech YolTech Therapeutics is a pioneering gene editing company dedicated to develop a robust gene editing medicines to treat patients with serious diseases, which has built leading high-throughput evolution platform and innovative LNP deliver system. It possesses strong capability of novel Cas and base editor discovery and exceptional in-house LNP production capacity for GMP manufactory, with independent intellectual property rights and core patent protection globally. It has created a pipeline with 10+ genetic medicines focusing on cardiovascular diseases, metabolic diseases, infectious diseases as well as more common and rare diseases. Clinical trial clearance has been received for its leading asset. For more information, please visit:

- Across robust slate of presentations, company highlights compelling new data and strong differentiation -SOUTH SAN FRANCISCO, Calif., April 23, 2024 (GLOBE NEWSWIRE) -- Epic Bio, a leading epigenetic editing company that plans to have its FSHD program enter the clinic this year, today shared details of data being presented at the Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), taking place May 7-11, 2024, in Baltimore, Maryland. Across three oral presentations and three poster presentations, Epic Bio will present new data demonstrating the differentiation of the company’s epigenetic editing platform and the promise of lead candidate EPI-321 for the treatment of facioscapulohumeral muscular dystrophy (FSHD). “We’re proud of the robust presence Epic Bio will have at this year’s ASGCT, reflecting the high degree of excitement and interest in epigenetic editing we’re seeing across the biopharma industry as well as Epic Bio’s leading position within this space,” said Amber Salzman, Ph.D., chief executive officer of Epic Bio. “We are laser-focused on translating these capabilities into medicines that can make a meaningful difference for patients, starting with our lead candidate EPI-321 for FSHD, which will enter the clinic later this year.” Best-in-class epigenetic activators In an oral presentation at the conference, the company will present new data demonstrating the best-in-class profile of its proprietary epigenetic activators. While epigenetic gene silencing has been widely successful, robust and persistent activation of genes remains a significant challenge, and an area where epigenetic editing may offer the greatest therapeutic potential compared to other genetic medicines. New data on Epic Bio’s epigenetic activators show that they can produce long-term activation of IL-21 — an interleukin crucial for enhancing CAR-T function — at levels far exceeding those produced by one of today’s gold-standard activators, VPR. A second study evaluated the use of proprietary epigenetic activators to boost transcription of the LDL Receptor (LDLR) gene. Mutations in one copy of LDLR are the most common cause of familial hypercholesterolemia, and thus epigenetic activation of LDLR is a highly promising potential treatment approach. In liver cells, Epic Bio’s epigenetic activators produced sustained LDLR expression. Critically, this activation was shown to persist for 70 days though the activator itself was only transiently expressed. Furthermore, in a humanized mouse model the proprietary activators boosted LDLR expression by twofold, sustained for up to 5 weeks, even though the activator was transiently delivered — far exceeding all previously reported outcomes of in vivo testing of a CRISPR-based epigenetic activator. These insights will inform Epic Bio’s ongoing preclinical efforts to develop an epigenetic editing therapy for heterozygous familial hypercholesterolemia (HeFH) utilizing one or more mechanisms of action. Establishing the standard for off-target characterization in epigenetic editing In a second oral presentation, Epic Bio is presenting the design and results of its whole-genome off-target assessment for the company’s lead candidate, EPI-321. As a leader in the field of epigenetic editing, Epic Bio has done pioneering work to craft a comprehensive off-target assessment platform to ensure the safety of epigenetic editing therapies for human testing. This analysis, designed with inputs from regulators in the U.S. and elsewhere, leverages genome-wide methylation profiling, genome-wide transcriptomic profiling, in silico prediction, and targeted validation assays across various model systems in order to robustly identify putative off-target effects. In the application of this off-target assessment to EPI-321, the company found that there are no direct off-target events caused by EPI-321 treatment, supporting the clinical initiation for EPI-321 later this year. A tool to expand access to hypercompact Cas proteins A third oral presentation at ASGCT spotlights a novel, freely available tool recently developed by Epic Bio to assist researchers who wish to use the hypercompact dCasMINI protein for epigenetic editing. The small size of dCasMINI — less than half the size of dCas9 — makes it ideally suited for single-vector delivery, regardless of cargo capacity. However, unlike Cas9 or Cas12a, there are no available computational tools for designing CasMINI guides, which presents a significant barrier to its ease-of-use by academic and industry researchers as well as drug developers. Epic Bio developed a web-based application to support design, selection, and comprehensive off-target prediction of guide RNAs for epigenetic activation and suppression (CRISPRa/i) using the catalytically inactivated dCasMINI CRISPR-Cas system against any gene in the human genome. The tool should enable researchers to easily employ dCasMINI in their investigations, and thereby foster continued scientific and medical innovation. Poster presentations In addition to the above oral presentations, the company will present posters on: The complete nonclinical data package for lead candidate EPI-321, including supplemented efficacy and safety data since the company’s oral presentation at ASGCT last year, along with new data on functional measures using 3-D engineered human muscle tissue.Details of a generative AI approach to design de novo transcriptional activators, andResults of work to characterize and optimize Epic Bio’s proprietary Cas proteins. About Epic BioEpic Bio is a leading epigenetic editing company, leveraging the power of CRISPR without cutting DNA. The company’s proprietary Gene Expression Modulation System (GEMS) includes the smallest Cas protein known to work in human cells, enabling in vivo or ex vivo delivery via a single viral vector. Epic plans to begin dosing patients in a clinical trial of its lead program — EPI-321 for the treatment of facioscapulohumeral muscular dystrophy (FSHD) — in 2024; additional programs seek to address alpha-1 antitrypsin deficiency (A1AD), heterozygous familial hypercholesterolemia (HeFH), and retinitis pigmentosa (RP). Visit www.epic-bio.com for more information or follow us on X and LinkedIn. Investor ContactShawn M. CoxEpic BioManager, Investor Relations, and Corporate Communicationsshawn.cox@epic-bio.com Media ContactLisa RaffenspergerTen Bridge Communicationslisa@tenbridgecommunications.com(617) 903-8783