Pipeline

Praetego is currently developing lead Amadorin candidate PTG-630 as an early intervention to slow or prevent progression of Alzheimer’s Disease (AD). That development is complemented by work in treating Diabetic Peripheral Neuropathy and Diabetic Retinopathy. A second Amadorin, PTG-670, is also being considered for AD.


 

Amadorins

Praetego’s candidates are called ‘Amadorins’. These proprietary small molecules are potent 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. AGE formation and accumulation drive a cascade of damage affecting the vascular system and the central and peripheral nervous systems. Long- term consequences of the AGE pathway lead to neurodegenerative diseases and serious diabetic complications. AGE pathology is implicated in most of the chronic diseases of aging.

The Amadorins have been developed and tested over 4 generations. Novel candidates under development offer the greatest potency and margin of safety in nonclinical testing. Praetego has patent protection pending for the series of candidates from GEN 4.

Lead Candidate

PTG-630 has demonstrated remarkable potency as an AGE inhibitor. In preclinical safety studies, PTG-630 demonstrated a wide therapeutic window and a low risk of drug-drug interactions. In preclinical efficacy studies, PTG-630 is consistently demonstrating protection of both the Central Nervous System (CNS) and the Peripheral Nervous System (PNS) in rodent models of Alzheimer’s Diseases and Diabetic Peripheral Neuropathy. The data reflects functional benefits confirmed by direct biochemical measures of neurodegeneration.

Alzheimer’s Disease (AD)

Alzheimer’s Disease is a tremendous burden on patients, caregivers, and our healthcare system.  A disease limiting agent is critically needed to address this devastating disease. In a preclinical model of AD, the lead Amadorin, PTG-630, preserved memory and demonstrated other neuroprotective features. Intended as an oral candidate, it is highly absorbed and permeates brain tissue. 

This work is funded by the National Institutes of Health (NIH).

Diabetic Retinopathy (DR)

Diabetic Retinopathy is a leading cause of blindness. Starting as a degenerative process, DR becomes a neurovascular insult to the retina. The retina serves as a critical connection of visual data and neural processing. Current treatments for DR include intravitreal injections. While these eye injections are effective in many patients, they are offered after measurable damage has occurred. Praetego’s Amadorin candidates are oral and could be introduced prior to significant retinal compromise, thus preserving visual function to the fullest extent possible. 

Diabetic Peripheral Neuropathy (DPN)

Diabetic Peripheral Neuropathy (DPN)—a degenerative process of the nerves, typically starts 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, all Amadorins tested 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. It is demonstrating neuroprotective and neurorestorative effects in the animal model of DPN.  

This work is funded by the National Institute of Diabetic and Digestive and Kidney Diseases (NIDDK) of the NIH.

Other Indications

AGE inhibition and reducing oxidative stress holds clinical value for serious diabetic complications and age-related diseases.  As the original Amadorin demonstrated clinical efficacy against Diabetic Kidney Disease, Praetego may pursue this indication as resources allow.