FIGHTING AUTOIMMUNE DIABETES

In-licensed technologies for the development of therapeutics for the treatment and prevention of autoimmune diabetes

 

GAD

The GAD-based diabetes vaccine Diamyd® is considered the world’s furthest developed Antigen Specific Immunotherapy for treating autoimmune diabetes

GABA

GABA combined with Antigen Specific Immunotherapy in preclinical type 1 diabetes studies has shown synergistically improved results and may have applications in many inflammatory disorders

Combining Technologies

Type 1 diabetes is a complex disease. The dominating hypothesis among diabetes researchers today is that the key to curing type 1 diabetes is to simultaneously tackle the disease on several fronts by combining various therapeutics or by providing treatment before onset of the disease. Antigen Based Therapy (ABT) is considered of importance for treating the disease.

The development of the in-licensed technologies for GAD and GABA, individually, in combination or with other substances with various mechanisms of action, is carried out in preclinical studies and clinical trials.

 

DEVELOPMENT PIPELINE

Pre-clinical and clinical development projects with novel dosing strategies and combinations using GAD, GABA and other immunomodulatory agents.

 

GAD, the active ingredient in the diabetes vaccine Diamyd®, is an endogenous human enzyme which catalyzes the synthesis of GABA from glutamic acid. GAD is well known to be expressed in nerve cells, but also in beta cells, where its role is not yet fully understood. It is clear, however, that GAD is one of the most important autoantigens involved in the degenerative autoimmune process directed against the beta cells in type 1 diabetes.

Antigen Based Therapy using Diamyd® is intended to halt the destruction of beta cells by the immune system in type 1 diabetes and LADA by inducing tolerance to autoantigens. The therapy has been studied in clinical trials with over 1,000 patients.

By combining Diamyd® with other anti-inflammatory or immunosuppressive compounds, initiating treatment earlier or by alternative administration routes, the efficacy of the therapy can be enhanced.

Diamyd®, the Antigen Based Therapy, is the Company’s furthest developed project. Six clinical trials are currently ongoing evaluating the diabetes vaccine Diamyd® through alternative approaches with various immunomodulatory compounds, including a combination treatment with GABA.

Diamyd Medical licenses exclusive rights to GAD, the active component of the therapy, from UCLA for the treatment of type 1 diabetes for which the last patent expires in 2032.

GABA, or gamma-aminobutyric acid, is synthesized from the amino acid glutamate in cells by the enzyme GAD. It is a well-known inhibitory neurotransmitter, but it also plays a key role in the regulation of metabolism and the immune system. It is produced in many peripheral tissues including the insulin-producing beta cells of the pancreas, and cellular surface receptors for the molecule are found on cells of the immune system.

Ingestion of GABA has been shown to synergistically enhance the effect of Antigen Based Therapy in type 1 diabetes animal models. It has also been shown to increase the proliferation and decrease apoptosis of transplanted human beta cells in association with increased serum insulin levels and a decrease in serum glucagon. GABA also decreased blood sugar levels and improved glucose homeostasis.

It is anticipated that GABA can be used in the general treatment of autoimmune and inflammatory disorders such as type 2 diabetes, rheumatoid arthritis and metabolic syndrome.

GABA is being administered in an ongoing placebo-controlled clinical study in Birmingham (Alabama, USA) in combination with the diabetes vaccine Diamyd®. Diamyd Medical licenses exclusive rights to use GABA for the treatment of diabetes and other inflammatory disorders.

 

ANTIGEN BASED THERAPY WITH DIAMYD®

Diamyd® is a GAD-based diabetes vaccine aiming to stop or delay the autoimmune process by inducing tolerance to GAD, one of the major autoantigens in autoimmune diabetes

 

DEVELOPMENT PROCESS

A candidate drug passes a number of development stages. Parallel to the discovery, preclinical and clinical phases, a commercially viable manufacturing process must be secured to obtain future market approval.

GMP Production

Diamyd Medical’s diabetes vaccine is produced via an established manufacturing process
and is approved for testing in children in clinical trials

 

GMP Manufacturing Process

Drug manufacturing is controlled by a strict regulatory framework called Good Manufacturing Practice (GMP), which sets high quality standards. Production of biologics requires complex technology and a stable manufacturing process. Diamyd Medical’s GMP production of the recombinant GAD protein has been subject to rigorous development work in collaboration with Ortho-McNeil-Janssen Pharmaceuticals, Inc. (OMJPI), resulting in a biologics manufacturing process prepared for commercial launch.

Recombinant GAD Protein

Diamyd Medical's recombinant protein GAD (rhGAD65), the active ingredient in the diabetes vaccine Diamyd®, is manufactured by the US vaccine development and protein production company Protein Sciences Corporation. Protein Sciences is manufacturing GMP recombinant GAD protein using Protein Sciences’ proprietary Baculovirus Expression Vector System (BEVS) technology for Diamyd Medical’s upcoming late stage clinical trials for autoimmune diabetes.

GABA drug product

GABA forms alongside the diabetes vaccine Diamyd® a key asset of Diamyd Medical. The Company intends to develop a proprietary GABA drug product. With a preferred provider for GMP production and with preclinical studies, the formulation technology and dosage will be determined. At a later stage the production can be scaled up in alignment with the clinical development strategy including formulation, administration and dosage of the drug.

Antigen Based Therapy with Diamyd®

GAD is one of the major autoantigens in autoimmune diabetes and is found in the insulin-producing beta cells of the pancreas. It is an important target when the immune system attacks the beta cells in autoimmune diabetes. The Antigen Based Therapy Diamyd® is a GAD-based diabetes vaccine aiming to induce tolerance to GAD, thereby intervening in the autoimmune attack and preserving the capacity to produce insulin in patients with autoimmune diabetes, e.g. type 1 diabetes and LADA.

Investigator-Initiated Trials

Diamyd Medical’s GMP manufactured clinical study drug Diamyd® has been approved for several clinical trials in children and is available for investigator-initiated trials conducted by academia and industry.