LYON - POXEL SA (Euronext - POXEL - FR0012432516), a biopharmaceutical company focused on the development of innovative treatments for metabolic disorders, including type 2 diabetes and non-alcoholic steatohepatitis (NASH), today announced that it presented Imeglimin Phase 3 results for TIMES 2 and TIMES 3 and new preclinical results for PXL770 in a cardio-renal disease model at the 56th European Association for the Study of Diabetes (EASD) Annual Meeting, which is being held virtually.
The poster presentations can be accessed on Poxel's website using the following link: https://www.poxelpharma.com/en_us/product-pipeline/posters.
In two presentations, Phase 3 results from the Imeglimin TIMES 2 and TIMES 3 (Trials of IMeglimin for Efficacy and Safety) trials were presented. The TIMES program in Japan was a joint development effort between Poxel and Sumitomo Dainippon Pharma Co., Ltd. and it included three pivotal trials in over 1,100 patients. In all three trials, Imeglimin met its primary endpoints and objectives and was observed to exhibit a favorable safety and tolerability profile. In July 2020, a New Drug Application (NDA) was submitted by Sumitomo Dainippon Pharma in Japan and is currently under review by the Pharmaceuticals and Medical Devices Agency (PMDA) to request approval for the manufacturing and marketing of Imeglimin for the treatment of type 2 diabetes.
'Across all three TIMES trials, Imeglimin was observed to demonstrate the ability to safely and significantly reduce HbA1c as a monotherapy and in combination with insulin and other existing therapies,' said Pascale Fouqueray, MD, PhD, EVP, Clinical Development and Regulatory Affairs at Poxel. 'In the TIMES 2 trial, we observed clinically meaningful HbA1c reductions when Imeglimin was added to other oral approaches. The greatest efficacy observed was an HbA1c reduction of 0.92% as an add-on to DPP4 inhibitors, suggesting that this combination of mechanisms could be a particularly important treatment option. In the TIMES 3 trial, Imeglimin also demonstrated meaningful efficacy as an add-on to insulin in patients who were not well controlled. In addition to placebo-like overall tolerability, no signal of severe hypoglycemia was observed in either trial. Based on these results, we believe that Imeglimin has the potential to treat type 2 diabetes at multiple disease stages.'
In a poster session focusing on PXL770, a direct AMPK activator, results from a cardio-renal syndrome preclinical model demonstrated observed improvements in diabetic nephropathy and in diastolic cardiac dysfunction that are consistent with the prevention of disease progression in both the kidney and heart. These results demonstrate that PXL770 and direct AMPK activation may lead to broader utility for organ diseases mediated by metabolic pathway dysfunction.
'This study adds to the growing body of data that supports the continued development of our AMPK platform in both chronic and rare metabolic diseases,' said David E. Moller, MD, EVP and Chief Scientific Officer at Poxel. 'These results highlight PXL770's potential to treat co-morbidities related to NASH, such as cardiac diastolic dysfunction, and importantly, the potential to also target significant residual unmet medical need in patients with diabetic kidney disease. These data further validate our hypothesis for the use of AMPK activation more broadly in additional chronic metabolic diseases.'
About Imeglimin TIMES 2 and TIMES 3 Results
The TIMES 2 trial evaluated Imeglimin in combination with several approved anti-hyperglycemic therapies, and as a monotherapy, for the treatment of type 2 diabetes in Japan. The 52-week, open-label, parallel-group trial, evaluated the long-term safety and efficacy of Imeglimin in 714 Japanese patients. During the trial, 1,000 mg of Imeglimin was orally administered twice-daily as an add-on to stable doses of existing approved drug classes that were both oral and injectable. Details of the combination study arms with several other oral agents are featured in the EASD presentation. These included the following (with respective changes in mean HbA1c values): DPP-4 inhibitors (-0.92%), thiazolidinediones (-0.88%), alpha-glucosidase inhibitors (-0.85%), glinides (-0.70%), metformin (a biguanide; -0.67%), SGLT-2 inhibitors (-0.57%), sulphonylureas (-0.56%). The observed robust efficacy benefits in combination with DPP-4 inhibitors are notable given that this drug class is the market leader in Japan and is prescribed to approximately 80% of treated type 2 diabetes patients.1
The TIMES 2 trial further strengthens Imeglimin's differentiated profile by showcasing that its dual mechanism of action of increasing insulin secretion in response to glucose and improving insulin sensitivity can result in added efficacy benefits when combined with a broad range of agents that have complementary mechanisms of action. Imeglimin was also observed to exhibit a favorable safety and tolerability profile across all treatment arms, consistent with prior trials.
The TIMES 3 trial evaluated Imeglimin in combination with insulin. In TIMES 3, Imeglimin was studied in a 16-week, double-blind placebo-controlled randomized period. In this portion of the trial, a mean HbA1c placebo-corrected change from baseline of -0.60% (p
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