Roivant Sciences will partner with Poxel to codevelop its Phase III-ready lead candidate, the type 2 diabetes treatment imeglimin, in the U.S., Europe, and elsewhere in the world, except 13 Asian nations, through a partnership that could generate up to $650 million-plus for Poxel.

The deal expands Roivant into metabolic drugs, a specialty of Poxel, and bolsters Roivant’s pipeline with a late-stage treatment that showed promising Phase IIb results in December 2014. Back then, Poxel trumpeted topline results showing that imeglimin achieved its primary endpoint of HbA1c reduction versus placebo, and statistically significant decrease in fasting plasma glucose at the 1500-mg dose that Poxel envisions using for its Phase III studies.

That trial was among 18 Phase I and Phase II studies completed by imeglimin in the U.S., Europe, and Japan, in which the drug was assessed in more than 1200 patients with type 2 diabetes. In those studies, the companies said, imeglimin met its primary and secondary endpoints, including a statistically significant decrease of HbA1c and fasting plasma glucose versus placebo, with a favorable side-effect profile.

Poxel said it plans this year to publish preclinical and clinical data on imeglimin and present those findings at multiple unspecified scientific and medical congresses.

Imeglimin is a first-in-class oral agent whose mechanism of action targets mitochondrial bioenergetics and is designed to act on the liver, muscles, and the pancreas. According to Poxel, studies carried out to date suggest potential glucose-reduction benefits through increased insulin secretion in response to glucose, improved insulin sensitivity, and suppression of gluconeogenesis. The company added that imeglimin’s method of action also has the potential to prevent endothelial and diastolic dysfunction and provide protective effects on beta-cell survival and function.

Through a collaboration with Sumitomo Dainippon Pharma announced in October, Poxel has launched the Phase III TIMES type 2 diabetes program in Japan, and has targeted the year 2020 for completing a Japanese New Drug Application submission.

Phase III Studies Planned for U.S., Europe

Poxel and Roivant said imeglimin is slated for Phase III studies in the U.S. and Europe starting in 2019. This year, to support initiation of those studies, the companies said, they will carry out differentiation studies to confirm imeglimin’s potential in sensitive patient populations, such as those with chronic kidney disease, and iron out manufacturing plans for the Phase III program.

“Roivant’s vision complements Poxel’s strategy of bringing novel treatments for type 2 diabetes and other metabolic disorders to patients,” Poxel CEO Thomas Kuhn, PharmD, said in a statement. “2018 will be a transformative year for Poxel as we advance the TIMES program in Japan, collaborate with Roivant on imeglimin, and increase our focus on our earlier-stage pipeline.”

Poxel’s agreement with Roivant covers the U.S., Europe, and elsewhere in the world, except 13 Asian nations where Poxel has licensed imeglimin rights to Sumitomo Dainippon for up to ¥34 billion ($313 million). Those 13 Asian nations are: Japan, China, South Korea, Taiwan, Indonesia, Vietnam, Thailand, Malaysia, The Philippines, Singapore, Myanmar, Cambodia, and Laos.

Sumitomo Dainippon agreed to pay Poxel ¥4.75 billion upfront ($43.7 million) and up to ¥29.25 billion ($269.3 million) in development and sales milestone payments, plus double-digit royalties.

In the latest licensing agreement, Roivant has agreed to pay Poxel $35 million upfront and invest $15 million in Poxel through a subscription to 1,431,399 newly-issued ordinary shares at €8.50 ($10.41) per share, an approximately 6% stake. Roivant has also agreed to pay Poxel up to $600 million in payments tied to achieving development, regulatory, and sales milestones—as well as double-digit royalties on net sales.

Roivant also agreed to oversee development and commercialization costs, with Poxel agreeing to pay $25 million toward the development program. The companies will decide on a potential copromotion before commercialization.

Roivant is the parent for six biotechs focused on specific therapeutic areas that include neurology, dermatology, urology, endocrinology, women’s health, and rare diseases. One of those biotechs, Axovant, disclosed today the resignations of its CEO David Hung, M.D.; its president and COO Marion McCourt; and three directors, Kate Falberg, Tony Vernon, and Patrick Machado.

Those resignations come a month after Axovant’s Alzheimer’s disease candidate intepirdine missed its primary efficacy endpoints in the Phase IIb HEADWAY study in patients with dementia with Lewy bodies (DLB), and pilot Phase II Gait and Balance studies in patients with DLB, Alzheimer’s disease, and Parkinson’s disease dementia.

Poxel is a spinout of Merck KGaA. On October 6, Merck said it sold its entire 4.74% stake of 1,088,531 shares in Poxel, citing a “reassessment of strategic priorities,” but retains an economic interest in the spinout through royalties derived from a license agreement.

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