ASC-518

Transformational in-vivo AAV gene therapy for hemophilia A Efficiently biosynthesized and secreted bioengineered factor VIII Potentially leads to lower therapeutic dose, reduced cost, and extended durability MILPITAS, Calif.--(BUSINESS WIRE)-- ASC Therapeutics, a privately-held biopharmaceutical company pioneering the development of transformative in-vivo gene replacement, gene editing and allogeneic cell therapies for hematologic and other rare disorders, today announced that the first patient has been dosed in the company’s Phase I/IIa clinical trial of the lead candidate, ASC618, at the Arkansas Children’s Hospital. ASC618 is an investigational second-generation gene therapy for patients with severe and moderately severe hemophilia A. The transformational Adeno-Associated Virus (AAV) construct of ASC618, which contains a proprietary B-domain deleted codon-optimized bioengineered chimeric Factor VIII (FVIII) gene and a minimal-length liver-specific promoter, has been shown in pre-clinical studies to produce therapeutic levels of FVIII protein at doses that are significantly lower than other constructs in expressing the native human FVIII, which have been extensively tested in clinical trials. Oscar Segurado, MD, PhD, ASC Therapeutics’ Chief Medical Officer said, “This is a special day for ASC Therapeutics and for patients with hemophilia A hoping to access a more durable and affordable second-generation gene therapy. I am grateful to our team members and the clinical research team at Arkansas Children’s Hospital involved in the successful dosing of our first patient.” Ruhong Jiang, PhD, ASC Therapeutics’ CEO added, “The successful dosing of the first patient is a testament of both our commitment to the hemophilia A community and our team's capability in advancing novel genetic therapies into the clinic.” Shelley Crary, MD, Pediatric Hematologist/Oncologist at the Arkansas Children’s Hospital, principal investigator of the ASC618 phase I/IIa clinical trial, stated, “Treating our first patient with ASC618 reinforces our focus on providing cutting edge therapeutic modalities to our patients with hemophilia A. We are now assessing in a clinical setting the relevance of a novel one-and-done gene therapy that may replace lifelong, burdensome, and expensive treatments to manage hemophilia A.” About Hemophilia A Hemophilia A accounts for most cases of hemophilia (~80%), affecting approximately 1 of every 5000 live-born males. Over a million people around the world are estimated to have hemophilia, including more than 30,000 in the United States (US). Currently, patients with hemophilia A are managed with prophylactic or on-demand therapies that either replace FVIII or bypass FVIII function. The major challenges of current treatment regimens, such the short half-life of hemophilia therapeutics with need for frequent and lifelong treatments, justify ongoing focus on gene replacement therapies. About ASC618 ASC618 is an AAV8-based gene therapy product incorporating a novel liver-specific promoter and a bioengineered, codon-optimized B domain-deleted FVIII variant (ET3). In preclinical studies, ASC618 exhibits at least a 10-fold increase in the biosynthesis and secretion of FVIII compared with a B domain-deleted human FVIII construct. ASC618 has the potential to increase durability of clotting factor biosynthesis and secretion by minimizing cellular stress and induction of the unfolded protein response, which may lead to diminished FVIII production from liver cells over time1. ASC618 was developed based on extensive work on a second-generation gene therapy for hemophilia A from an academic team at Emory University2. ASC Therapeutics has obtained exclusive global rights from Expression Therapeutics to develop ASC618 and has conducted IND-enabling studies in multiple animal models that further demonstrated enhanced FVIII secretion from ASC618 and lower therapeutic doses. ASC Therapeutics is conducting a phase I/IIa clinical trial to evaluate the safety, tolerability, and preliminary efficacy of ASC618. The program has received IND clearance and was granted Fast Track and Orphan Drug Designations by the FDA and Orphan Medicinal Product Designation by the European Commission. The study design is available at 3. About ASC Therapeutics ASC Therapeutics is a biopharmaceutical company pioneering the development of gene replacement therapies, in-vivo gene editing and allogeneic cell therapies for hematological and other rare diseases. Led by a management team of industry veterans with significant global experience in gene and cell therapy, ASC Therapeutics is developing multiple therapeutic programs based on three technology platforms : 1) In-vivo gene therapies that use hepatocytes as a protein biofactory, initially focusing on ASC618 for hemophilia A; 2) In-vivo gene editing, initially focusing on ASC518 for hemophilia A; and 3) Allogeneic cell therapy, initially focusing on Decidua Stromal Cell-based therapy for steroid-refractory acute Graft-versus-Host Disease in patients receiving bone marrow transplantation, mostly to treat hematological malignancies. To learn more please visit . References 1 Steven W. Pipe, Gil Gonen-Yaacovi, Oscar G. Segurado. Hemophilia A gene therapy: current and next-generation approaches, Expert Opinion on Biological Therapy. 2022;22:1099-1115 2 Brown HC, Wright JF, Zhou S, et al. Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery. Mol Ther Methods Clin Dev. 2014;1:14036 3 ASC618 Gene Therapy in Hemophilia A Patients.