Akston has developed AKS-107, a designer Fc-insulin fusion protein, to interrupt the process leading to insulin autoimmunity. It utilizes a mutated insulin moiety which does not lower blood glucose and an Fc region to direct the immune system to delete targeted B cells. Akston has partnered with the Helmsley Charitable Trust, which is supporting AKS-107 GMP manufacturing and Sanford Research, Inc., a South Dakota not-for-profit corporation, which will conduct the Phase 1 clinical trial. It has also received significant support from the National Institutes of Health (NIH) to support IND-enabling safety pharmacology and toxicology studies.
- Insulin moeity presented to immune system
- Fully-biologic manufacturing
- Insulin modified to eliminate glucose lowering
- Insulin mutations disrupt T cell presentation
- Fc glycosylation targets B cells for deletion
- Animal model studies show T1D prevention
Disease and therapy
Type 1 Diabetes (T1D) is an autoimmune disease in which the body attacks and destroys its own insulin-producing β-cells, leading to a lifetime of dependence on injectable insulin therapy. T1D affects over 1.25 million people in the United States and accounts for over $20B each year in direct medical and indirect costs. Arresting or reversing the disease before β-cell destruction is the most ideal but most difficult solution to implement. Akston’s therapeutic strategy is to intervene in at-risk, pre-diabetic patients and target the problematic cells that may be responsible for T1D, while also creating immunological tolerance to insulin, thereby lowering the chances of patients converting to diabetes.
Akston has developed a novel fusion protein (AKS-107) comprising insulin and the human antibody Fc region that binds and causes the elimination of insulin-specific B cells while preserving the rest of the B cell repertoire. Insulin-specific B cells were chosen as the first target over other islet-antigenic-specific B cells based on the wealth of data and prior experience pointing to insulin as the primary autoantigen in T1D. Due to specific amino acid mutations, AKS-107 also has the potential to induce immunological tolerance and prevent presentation of antigenic insulin fragments to cytotoxic T cells.
Development status and plans
Akston, as well as an academic partner, have completed pre-clinical studies that show AKS-107’s ability to significantly and reproducibly reduce the incidence of Type 1 Diabetes in Non-Obese Diabetic (NOD) mice. Studies of AKS-107 have confirmed the lack of immunogenicity in non-human primates (NHP). Other studies have demonstrated deletion of insulin-specific B cells in mice and in vitro reduction in insulin-specific T cell activation. Akston has developed a Good Manufacturing Practice (GMP) master cell bank (MCB) for producing AKS-107 with satisfactory titers and purity.
Production has been completed in Akston’s manufacturing facility of the AKS-107 drug substance engineering batch. This material will be used to establish a clinical study-enabling safety profile through a GLP toxicity study in cynomolgus monkeys. Akston has partnered with Sanford Research, Inc. to execute the first-in-man safety and proof-of-biology study of AKS-107. Sanford has several main initiatives, chief among which is the Sanford Project with a stated goal to cure Type 1 Diabetes.