Technology Overview

Dynamis has discovered a unique enzymatic pathway that causes chronic inflammation:

The fructosamine-3-kinase (F3K) enzyme initiates the inflammatory process associated with sugar toxicity by triggering the formation of a highly reactive sugar-breakdown product called 3-deoxyglucosone (3DG), which causes inflammation and oxidative stress. Prolonged accumulation of 3DG inevitably leads to aging and a number of inflammatory diseases, most importantly diabetic complications.

Data from Dynamis and independent scientific investigation demonstrate that the 3DG enzymatic pathway directly contributes to inflammation. Dynamis' scientists have also confirmed that the Company's lead compound (DYN15) reduces both 3DG formation and advanced glycation end-products (AGEs) in normal rats. Independent studies have shown that AGEs affect the physiological aging process in humans because AGEs accumulate in various tissues such as the skin, kidney and eyes in the course of aging. Studies on the negative consequences of AGEs to diseases have primarily focused on its relationship to diabetes and diabetes-related complications including retinopathy, optic neuropathy and cataract. However, it has become clear that AGEs-associated damage is not limited to patients with diabetes. Mostly because of their association with oxidative stress, AGEs have also been implicated in many neurodegenerative diseases, such as Alzheimer disease, amyotrophic lateral sclerosis and Huntington disease. This confirmation presents a great opportunity for Dynamis to utilize its technology platform to pursue realistic goals of producing pharmaceuticals to treat patients with chronic inflammatory diseases.

3DG triggers a burst of cytokines from macrophages and mesothelial cells which starts the inflammatory cascade. The reaction to 3DG can be considered to be equivalent to the reaction of cells to a bacterial infection. This cascade causes inflammation, oxidative stress, and the production of free radicals and advanced glycation end products (AGEs). These processes are related to the development of cancer, autoimmune diseases, and diabetic complications (i.e. blindness, kidney disease and neuropathy). 3DG also contributes to the loss of collagen and other structural proteins.

Independent breakthrough study confirms that 3DG inhibition prevents nephropathy:

A recently published study by Nakamura showed that use of a 3DG inhibitor prevented the progression of diabetic nephropathy in diabetic rats, providing confirmation that inhibition of 3DG may be a valuable approach for drug intervention.

Key: C= normal rats; DM= diabetic rats; PLP= 3DG inactivator, PM= 3DG non-reactive comparator. Imidazolone is a surrogate marker for 3DG (3DG adduct); ****P<0.0001 vs. C, +++P<0.001, ++++P<0.0001 vs. DM.

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