AKS-321d and AKS-425c
Akston is partnered with Dechra Pharmaceuticals PLC to commercialize AKS-321d, a one-a-week insulin therapy for dogs that is a drop-in replacement to the current twice-a-day insulin treatment. It utilizes a specially-designed insulin to increase glucose-lowering bioactivity and a modified dog Fc, which enables a long half-life through FcRn recycling, with no immune system activation. Multiple field studies have demonstrated successful multi-month treatment of dozens of client-owned diabetic dogs. AKS-425c, the variant for cats, which is designed to provide substantially the same performance, is currently in field testing in client-owned, diabetic cats.
- Design balances FcRn recycling and bioactivity
- Drop-in replacement for current therapies
- Fc selected for species-specificity (dog and cat)
- Fc modified to eliminate immune system activation
- Once-a-week dosing with negligible hypoglycemia
- Fully-biologic maufacturing
Disease and therapy
Approximately 80,000 dogs per year in the United States are diagnosed with diabetes, with a similar number in the European Union and an increasing number elsewhere. Current therapy is indicated for twice-a-day subcutaneous injection and owners generally find the treatment regimen to be onerous and error-prone. A significant number of animals are euthanized within one year of diagnosis. Cats are diagnosed with diabetes in generally similar numbers and require similar treatment. Clearly, a treatment option offering satisfactory glucose control with once-a-week dosing could provide a significant improvement that owners would welcome.
Over 100 ultra-long acting canine insulin candidates were synthesized and tested to find leads that would provide proper glucose control with weekly dosing, would not activate the dog’s immune system to produce neutralizing antibodies and could be produced efficiently at commercial scale. Akston, working with several leading academic veterinary centers including the University of California – Davis, Tufts University, and the University of Georgia, mounted studies of client-owned animals to test the final candidates. In August, 2019 Akston signed a license and supply agreement for its canine insulin with Dechra Pharmaceuticals PLC.
Akston has also developed AKS-425c after the synthesis and testing of a large number of candidates in a manner similar to AKS-321d. It uses a feline Fc in place of the dog Fc and has also been successfully tested in academic veterinary centers with client-owned animals. Dechra holds an option to take Akston’s feline insulin into commercial development.
Development status and plans
Akston’s primary responsibilities in the commercialization program are manufacturing development, the preparation of CMC regulatory documentation and submissions, and the provision of AKS-321d materials for pivotal safety and efficacy studies. Dechra is responsible for conducting an initial Proof-of-Concept (PoC) study, overseeing the pivotal safety and efficacy studies and managing the regulatory process. Dechra has successfully completed the POC study in privately-owned veterinary practices with client-owned diabetic dogs.
Akston will be the sole provider of finished drug product for sale by Dechra world-wide. It will use its biologics manufacturing facility to produce finished AKS-321d drug substance for subsequent filling and finishing. A key impediment to the commercialization of veterinary biologics has been the high cost of candidate development and production. Akston has addressed this by employing a focused, efficient candidate selection and testing program with a production process and facility tailored to the task.