Prometic Presents New Data on NASH Drug Candidate PBI-4547

"We have seen that our late stage candidate PBI-4050's reduction of fibrosis in the heart and liver in preclinical models has translated to clinical activity in patients with Alström Syndrome ("AS")," commented Dr. John Moran, Chief Medical Officer of Prometic.  "PBI-4547's performance on the liver in preclinical models is more impressive, especially in the context of concomitant diabetes, elevated cholesterol and triglycerides. As we progress PBI-4547 into the clinic in the second half of 2018, we anticipate demonstrating the same translation to clinical activity not only in NASH but also in other selected orphan diseases."

Pierre Laurin, CEO of Prometic, commented: "With PBI-4050's demonstrated clinical activity in humans in three phase 2 clinical trials, including the AS patients with established severe liver fibrosis and cirrhosis, advancing PBI-4547 into the clinic provides us with even more optionality in the positioning of our drug candidates and partnering discussions."

Key data presented at the conference in four poster presentations entitled:

"PBI-4547 Improves Glucose Metabolism and Insulin Resistance, and Reduces Liver Damage in a High-Fat Diet Mouse Model of Obesity and Metabolic Syndrome"

"PBI-4547 Prevents Progression of Prediabetic Condition to Type 1 Diabetes in NOD Mice"

"PBI-4547 Reverses Diabetes and Metabolic Syndrome through Regulation of Lipid/Glucose Metabolism, β-Oxidation and Fibrosis in Liver and White Adipose Tissue in ob/ob Mice"

 "PBI-4050 Improves Metabolic Regulation and Diabetic Nephropathy through Reduction of ER Stress, Pro-Inflammatory/Fibrotic Markers, Galectin-3 Expression and Inflammatory Cell Infiltration in ob/ob Mouse Model"

Key observations from these presentations included:

• In a mouse model of high-fat-diet induced obesity and metabolic syndrome, PBI-4547: 1) improved glucose metabolism by reducing insulin resistance and preserving β-cell function. 2) reduced hepatic steatosis and ballooning., 3) reduced serum triglycerides and increased adiponectin level and 4) regulated pro-inflammatory / fibrotic gene expression in liver and adipose tissues.
• In an ob/ob mouse model, PBI-4547 reduced blood glucose, cholesterol and triglyceride levels, as well as pro-inflammatory/pro-fibrotic markers in liver and adipocyte size and fibrosis in white adipose tissue. PBI-4547 increased serum adiponectin and modulated biomarkers associated with glucose and lipid metabolism, fibrosis, mitochondrial metabolism and browning of adipose tissue.
• In a prediabetic type 1 NOD mouse model, PBI-4547 significantly prevented the evolution to severe diabetes, resulting in increased survival.
• In an ob/ob mouse model, PBI-4050 improved triglycerides and glucose metabolism, reduced collagen and galectin-3 deposition in white adipose tissue and kidney and reduced ER stress and pro-inflammatory/fibrotic markers in kidney.

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About NASH

"NASH", or nonalcoholic steatohepatitis, is a liver disease characterized by an accumulation of fat (lipid droplets), along with inflammation and degeneration of hepatocytes. Once installed, the disease is accompanied with a high risk of cirrhosis, a state where the liver functions are altered and can progress to liver insufficiency. Thereafter, the NASH often progresses to liver cancer.

About PBI-4547 

PBI-4547 is an orally active drug candidate and analogue to PBI-4050. Prometic has observed that the "up-regulation" of receptor GPR40 concomitant to the "down-regulation" of receptor GPR84 promotes the normal healing process as opposed to promoting the fibrotic process. PBI-4547 like PBI-4050 are agonists ("stimulators") of GPR40 and antagonists ("inhibitors") of GPR84. GPR40 and GPR84 are known to be involved in diverse physiological processes related to metabolic regulation and to inflammation, but the fundamental importance of these receptors in the fibrosis pathways had not been recognized until now. Prometic uncovered a novel antifibrotic pathway involving these receptors, showing that GPR40 is protective and GPR84 is deleterious in fibrotic diseases. Through its binding to these receptors, PBI-4050 and PBI-4547 can attenuate fibrosis in many injury contexts, as evidenced by the global antifibrotic activity observed in the kidney, liver, heart, lung, pancreas, or skin.

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Forward Looking Statements
This press release contains forward-looking statements about Prometic's objectives, strategies and businesses that involve risks and uncertainties. These statements are "forward-looking" because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, Prometic's ability to develop, manufacture, and successfully commercialize value-added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Prometic to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Prometic's Annual Information Form for the year ended December 31, 2017, under the heading "Risk and Uncertainties related to Prometic's business". As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.