New data suggest PBI-4547 offers potential as novel therapy for liver fibrosis, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), diabetes and obesity
New data to be presented at the 2018 American Diabetes Association conference
Overview of New Data on Drug Candidate (PBI-4547)
LAVAL, QUEBEC, CANADA – June 22, 2018 – Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) today announced the presentation of four posters at the American Diabetes Association’s 78th Scientific Sessions taking place in Orlando, Florida, June 22 – 26, 2018. The posters and data to be presented at the conference suggest that PBI-4547 offers the potential to successfully address significant unmet medical needs in liver fibrosis, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), obesity and diabetes.
“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.”
The Key Data
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.
”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.
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.
Prometic (www.prometic.com) is a biopharmaceutical corporation with two drug discovery platforms focusing on unmet medical needs. The first platform (small molecule therapeutics) stems from the discovery of two receptors which we believe are at the core of how the body heals: namely, promoting tissue regeneration and scar resolution as opposed to fibrosis. One of the lead drug candidates emerging from this platform, PBI-4050, is expected to enter pivotal phase 3 clinical trials for the treatment of Idiopathic Pulmonary Fibrosis (IPF). The second drug discovery and development platform (plasma-derived therapeutics) leverages Prometic’s experience in bioseparation technologies used to isolate and purify biopharmaceuticals from human plasma. The Corporation’s primary goal with respect to this second platform is to address unmet medical needs with therapeutic proteins not currently commercially available, such as Ryplazim™ (plasminogen). We are also leveraging this platform’s higher recovery yield potential to advance established plasma-derived therapeutics such as Intravenous Immunoglobulin (IVIG). Furthermore, the Corporation is continuing to secure its plasma supply through the execution of third party contracts and expansion of its own collection activities for its plasma processing needs. The Corporation also provides access to its proprietary bioseparation technologies to enable pharmaceutical companies in their production of non-competing biopharmaceuticals. Recognized as a bioseparations expert, the Corporation derives revenue from this activity through sales of affinity chromatography media which contributes to offset the costs of its own R&D investments.
We are headquartered in Laval, Quebec (Canada) and have R&D facilities in Canada, the United Kingdom (“UK”) and the United States (“USA”), manufacturing facilities in Canada and the Isle of Man and corporate and business development activities in Canada, the USA, and Europe.
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
For further information please contact:
President and CEO
Prometic Life Sciences Inc.
Senior Director, Communications & Investor Relations
Prometic Life Sciences Inc.
Matt Middleman, M.D.
LifeSci Public Relations