Poxel in €506m diabetes deal with Roivant Sciences

Under the deal, Poxel will receive €28m upfront and and Roivant will directly invest €12m in Poxel ordinary shares at a 37% premium to the company’s share price before the agreement was announced. Future milestones could sum up to additional €486m plus double-digit royalties on net sales in case of EU and US market approval.

While Roivant will be responsible for commercialisation of imeglimin, a blocker of mitochondrial permeability transition pore (mPTP) opening, in all markets except the 12 Asian markets covered by a previous deal with Sumitomo Dainippon Pharma, Lyon-based Poxel has the option to decide if it will co-promote the programme before the Phase III development programme in Europe and the US kicks of next year. In any case Poxel will contribute €20m to the development programme.

Imeglimin is an oral first-in-class oxidative phosphorylation blocker, which preclinically and clinically inhibited hepatic gluconeogenesis, increased muscle glucose uptake, and restored insulin sensivity. According to Poxel, it might also prevent endothelial and diastolic dysfunction and support beta-cell survival and function. The mitochondrial permeability transition pore (mPTP) facilitates the exchange of molecules between the mitochondrial matrix and cytoplasm, and opening of the mPTP occurs in response to physiological stressors that are associated with insulin resistance.

Under conditions of mitochondrial calcium overload, especially when accompanied by oxidative stress, elevated phosphate concentrations and adenine nucleotide depletion, MPTP opens in the inner mitochondrial membrane. The resulting uncoupling of oxidative phosphorylation leads to ATP depletion and necrotic cell death, a process aseemingly inhibited by imeglimin.