MILPITAS, Calif. – 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 U.S. Food & Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for ASC618, an investigational second-generation gene therapy for patients with severe and moderately severe hemophilia A. The transformational Adeno-Associated Virus (AAV) construct contains a proprietary B-domain deleted codon-optimized bioengineered chimeric Factor VIII (FVIII) gene and a minimal-length liver-specific promoter, shown in pre-clinical studies to produce therapeutic levels of FVIII protein at doses that are significantly lower than other constructs expressing the native human FVIII currently in clinical trials.
Ruhong Jiang, PhD, ASC Therapeutics’ CEO said, “FDA’s IND clearance of ASC618 is a significant endorsement of the discovery, pre-clinical, analytical, clinical, regulatory, quality, manufacturing, and overall capabilities of our organization. This milestone culminates our transformation into a clinical-stage gene and cell therapy biopharmaceutical company.”
Steven Pipe, MD, PhD, professor of pediatrics and pathology and pediatric medical director of the hemophilia and coagulation disorders program at the University of Michigan, and the principal investigator of the ASC618 phase 1/2 clinical trial, stated, “ASC618 design provides a novel perspective to the field of hemophilia gene therapy. For the first time we will be able to investigate in a clinical setting the relevance of a novel bioengineered construct that has been proven in pre-clinical studies to significantly improve the biosynthesis, protein folding and secretion of factor VIII.”
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 replacement therapy with recombinant FVIII or bypassing agents. The major challenges of current treatment regimens, such the short half-life of hemophilia therapeutics with need for frequent intravenous injections, justify ongoing focus on gene replacement therapies.
ASC618 is an AAV8-based gene therapy product incorporating a novel liver-specific promoter and a bioengineered, codon-optimized B domain-deleted FVIII variant; in preclinical studies, ASC618 exhibits at least a 10-fold increase in the biosynthesis and secretion of FVIII compared with native human FVIII bioengineered constructs. 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. ASC618 was developed based on extensive work on a second-generation gene therapy for hemophilia A from an academic team at Emory University . ASC Therapeutics has obtained exclusive global rights to ASC618 from Expression Therapeutics and has conducted IND-enabling studies in multiple animal models .
ASC Therapeutics will conduct a phase 1/2 clinical trial to evaluate the safety, tolerability, and preliminary efficacy of ASC618. The program was granted Orphan Drug Designation by the FDA in 2020. The study design is available at www.clinicaltrials.gov.
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 www.asctherapeutics.com.
 Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016 Jul 9;388(10040):187-97
 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
 Veselinovic M, Gilam A, Ross A, et al. Preclinical Development of ASC618, an Advanced Human Factor VIII Gene Therapy Vector for the Treatment of Hemophilia A: Results from FRG KO Humanized Liver Mice, C57Bl/6 Mice and Cynomolgus Monkeys. Molecular Therapy 2020;28/4:167-8
 ASC618 Gene Therapy in Hemophilia A Patients. https://www.clinicaltrials.gov/ct2/show/NCT04676048
Oscar Segurado, MD, PhD
Chief Medical Officer