LONDON – Poxel SA has landed an all-embracing deal in Asia for Imeglimin with new partner Sumitomo Dainippon Pharma Co. Ltd. taking on the costs of conducting phase III development and commercializing the first-in-class, oral, type II diabetes treatment in Japan, China and 11 other countries. Under the terms of the agreement Poxel receives an upfront payment of $42 million, plus future development and sales-based milestones of $257 million. In addition, the Lyon, France-based company will be eligible for double-digit royalties on net sales.

"We are really excited about this partnership, which is transformative for the company," Poxel CEO Thomas Kuhn told BioWorld Asia. "This will bring a lot of visibility to Imeglimin."

Most immediately Sumitomo will finance phase III development in Japan, with the first of three studies due to get underway before the end of the year.

Poxel is to produce trial supplies of the drug, but Sumitomo will subsequently take on manufacturing for Asian markets.

The two partners will collaborate on the phase III development in Japan, where Poxel has been laying the ground work over the past year. Elsewhere in Asia, Sumitomo will have sole responsibility for clinical trials.

While Poxel was contemplating funding the Japanese phase III program itself, Kuhn said that phase IIb results in Japan showing good efficacy opened the way to close a commercialization deal in advance of pivotal trials.

Peter Welford, analyst at Jefferies in London, said this was a key de-risking step. "The Sumitomo partnership significantly reduces the near-term funding risk and provides an important third-party endorsement of Imeglimin's profile," he said.

Poxel met the Japanese regulator PMDA in the summer to discuss the phase III program and the data required for approval. Poxel and Sumitomo will now work together on completing the three trials, which will involve a total of 1,100 patients.

"We will be very active in the joint steering committee that will supervise and track progress," Kuhn said.

The results of the first trial, comparing Imeglimin to placebo, are expected in mid-2019. With the whole program taking two years to complete, Kuhn said Imeglimin could be filed for approval in Japan in 2020 and launched in 2021.

Japan became the lead market for Poxel after the phase IIb trial there turned in better results than a previous phase IIb in U.S./European patients. In the Japanese study Imeglimin showed a statistically significant (p<0.0001) dose-dependent effect on blood glucose at each of three dose levels. The mean reduction in glycated hemoglobin (HbA1c) was 0.52 percent, 0.94 percent and 1 percent vs. placebo, in 500-mg, 1,000-mg and 1,500-mg dose cohorts, respectively.

It cannot be compared directly, but in the phase IIb in U.S./European patients there was a mean reduction of HbA1c of 0.63 percent at the optimum dose (p<0.001). (See BioWorld Today, May 10, 2017.)

Kuhn said this is likely to reflect the different pathology of type II diabetes in Asia, where insulin deficiency is the driver, compared to U.S./Europe, where insulin resistance is the main cause.

The Japanese data are in line with the mechanism of action of Imeglimin, which works by boosting the performance of mitochondria in cells in the liver, muscles and pancreas. This leads to increased secretion of insulin in the pancreas, whilst decreasing production of excess insulin in the liver and promoting insulin sensitivity in the muscles.

Poxel said this mechanism offers the prospect of slowing down progression of type II diabetes and reducing complications. There is evidence Imeglimin blocks cytochrome C release, cutting off an apoptotic cascade and protecting cells from oxidative stress caused by high glucose levels.

At the same time, the drug prevents the endothelial dysfunction that is at the heart of cardiovascular complications of diabetes, and also preserves beta cell mass and beta cell function.

While in Japan and other Asian countries lack of insulin secretion is currently the main cause of type II diabetes, there is evidence that insulin resistance linked to diet and lifestyle is on the rise.

"[Type II] diabetes is an environmental disease, related to food and exercise. We think obesity will happen in Asia, too. [Imeglimin] acts on insulin resistance as well," Kuhn said.

Japan already is the second largest market for type II diabetes after the U.S., with sales of $4 billion forecast to reach $6 billion by 2020. Meanwhile in China, there is an increasing incidence of the disease and the market is growing strongly as more patients are diagnosed and get access to type II diabetes drugs.

As likely first of the novel tetrahydrotriazine-containing class of glimins to market, Imeglimin will be slotted into Sumitomo's strong diabetes franchise. That currently consists of four products, each with a different mechanism of action, which Sumitomo markets in each of the countries covered by the agreement.

The Asia deal will advance Imeglimin's prospects elsewhere, said Kuhn. "We intend to partner in the U.S./Europe and are having a lot of discussions. We believe the data [from Japan] will give further visibility," he said.

Imeglimin was discovered by Merck Serono SA, which spun out Poxel in 2009 with a portfolio of six programs targeting metabolic disease.

Poxel's stock (Paris:POXEL) rose 45 percent on Monday morning after the deal was announced to €7.84 (US$9.10).