ASC Therapeutics and Professor Steven W. Pipe Publish Expert Review on Novel Gene Therapies of Hemophilia A

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 hematological, metabolic, and other rare diseases , announces peer-reviewed, open access publication of “Hemophilia A Gene Therapy: Current and Next-Generation Approaches” in Expert Opinion in Biological Therapy1. This publication provides an update on scientific and clinical advances in gene replacement therapies for hemophilia A, with an emphasis on:

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Professor Steven W. Pipe, University of Michigan. (Photo: Business Wire)

  • Current and future approaches to achieving safe, sustained and stable transgene expression while avoiding the challenges of factor VIII replacement therapies;
  • A thorough review of current and past clinical trials of gene therapies conducted in patients with haemophilia A;
  • Examination of the critical role of the viral construct in reducing the therapeutic dose and minimizing cellular stress, inducing the unfolded protein response and the resulting loss of protein production in liver cells;
  • Second generation gene therapies, which include chimeric DNA sequences in the transgene, can increase the synthesis and secretion of clotting factors and improve the effectiveness, safety, and durability of gene replacement therapy for hemophilia A and other bleeding disorders.

Steven W. Pipe, MD, Professor of Pediatrics and Pathology and Pediatric Medical Director of the Hemophilia and Coagulation Disorders Program at the University of Michigan and Principal Investigator of the Phase 1/2 Clinical Trial ASC618, said, “This comprehensive overview summarizes several Decades of work by my team and others, which show the critical role of cellular stress and the unfolded protein response in the disturbed production of coagulation factors in the liver. The development of a novel biotechnological construct that has been shown in preclinical studies to improve factor VIII biosynthesis, protein folding and secretion leads me to predict that in a clinical setting it will reduce therapeutic dosage and increase shelf life. “

Oscar G. Segurado, Dr A. This overview describes step by step the critical elements that are necessary for the permanent, safe and effective biosynthesis and production of a coagulation factor in liver cells. We firmly believe that learning the underlying molecular, cell and protein biology of coagulation factor production will improve our competitive advantage in the field of liver-directed gene therapies. “

About hemophilia A.

Hemophilia A is responsible for the majority of cases of hemophilia (~ 80%), affecting approximately 1 in 5,000 live born men. It is estimated that over a million people have haemophilia worldwide, including more than 30,000 in the United States (US) 1.

Currently, patients with haemophilia A are treated with prophylactic or need-based replacement therapy with recombinant FVIII or bypass agents. The major challenges of current treatment regimens, such as the short half-life of hemophilia therapeutics with the need for frequent intravenous injections, justify the continued focus on gene replacement therapies.

About ASC618

ASC618 is an AAV8-based gene therapy used to treat hemophilia A, which affects approximately 1 in 5,000 live born men. ASC618 contains a new liver-specific promoter and a biotechnologically produced, codon-optimized B-domain-deleted FVIII variant2; In preclinical studies, ASC618 shows at least a 10-fold increase in the biosynthesis and secretion of FVIII compared to native human biotechnologically produced FVIII gene constructs3. ASC618 has the potential to increase the duration of coagulation factor biosynthesis and secretion by minimizing cellular stress and the induction of the unfolded protein response, which can lead to decreased FVIII production from liver cells.

ASC Therapeutics will conduct a phase 1/2 clinical trial to evaluate the safety, tolerability, and preliminary efficacy of ASC618. The program received IND approval from the U.S. Food and Drug Administration in 2021 and received orphan drug status in 2020. The study design is available at

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, metabolic, and other rare diseases. Led by a management team of industry veterans with significant global gene and cell therapy experience, ASC Therapeutics is developing multiple therapeutic programs based on four technology platforms: 1) In vivo gene therapy for hereditary bleeding disorders, initially with a focus on ASC618 for Hemophilia A, for that recently received IND approval from the US FDA; 2) In vivo gene therapy for metabolic disorders, initially focusing on maple syrup urine disease, in collaboration with the Universities of Massachusetts and Pennsylvania; 3) In vivo gene editing, initially with a focus on ASC518 for hemophilia A; and 4) allogeneic cell therapy, with the first indication of Decidua stromal cell-based therapy for steroid-refractory acute graft-versus-host disease. To learn more, please visit


1 Steven W. Pipe, Gil Gonen-Yaacovi & Oscar G. Segurado (2022) Hemophilia A gene therapy: current and next generation approaches, Expert Opinion on Biological Therapy, DOI: 10.1080 / 14712598.2022.2002842
2 Brown HC, Wright JF, Zhou S, et al. The biotechnologically produced coagulation factor VIII enables a long-term correction of hemophilia A in mice after liver-directed adeno-associated viral vector delivery. Mol Ther Methods Clin Dev. 2014; 1: 14036
3 M. Veselinovic, A. Gilam, A. Ross 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

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