Pipeline

The Amadorins inhibit AGE formation at its earliest stages. By interrupting the pathway at the first step of oxidative breakdown, Amadorins offer the greatest promise of protection against serious diabetic complications

 


 

Pipeline Diagram

Amadorins

Praetego’s candidates are called ‘Amadorins’. These proprietary small molecules are unique inhibitors of the oxidative breakdown of proteins modified by glucose (Amadori products). This non-enzymatic process forms byproducts called Advanced Glycation End-products, or AGEs. In the AGE pathway, AGE formation and accumulation lead to diabetic microvascular disease. In diabetic patients, these glucose-mediated reactions damage blood vessels, nerves, the retina, and kidney. The AGE pathway is a powerful instigator of oxidative stress. This mechanism of damage is also active in cardiovascular disease and neurodegeneration.

The Amadorins have been developed and tested over 3 generations. The latest series of novel candidates offer the greatest potency and margin of safety in nonclinical testing. Praetego has filed for patent protection of this series. The lead candidate, PTG-630 comes from this series.

 

Diabetic Peripheral Neuropathy (DPN)

Our lead indication is Diabetic Peripheral Neuropathy (DPN)—a degenerative process of the nerves, often starting in the extremities. Affecting approximately 50% of diabetics, DPN can be very painful. It can also lead to foot ulcers and amputations. Praetego’s Amadorins mitigate an underlying cause of the damage.

In proof of concept studies using a standard animal model of DPN, each previous generation of Amadorins restored nerve function. They reversed nerve deficits in both large and small nerve fibers. Across the Amadorins tested, we confirmed that stronger AGE inhibition meant greater potency.

PTG-630 has demonstrated optimal potency as an AGE inhibitor. In preclinical safety studies, PTG-630 demonstrated a wide therapeutic window and minimal off-target hits.

Our current drug development work is funded by the National Institute of Diabetic and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH).

 

Other Serious Diabetic Complications

Beyond DPN, we are exploring how the Amadorins could address Diabetic Mild Cognitive Impairment, and Nephropathy (Chronic Kidney Disease).