Tetra, Shionogi ink $40M pact on PDE4 drug for Alzheimer’s, fragile X

purple brain
Animal models have shown Tetra's PDE4D inhibitor may protect the connections between neurons. (Raman Oza/Pixabay)

Tetra Discovery Partners is teaming up with Shionogi to advance its PDE4-targeting drug in Alzheimer’s disease and fragile X syndrome. In return for the rights to the drug in three Asian countries, Shionogi will hand over a $5 million upfront payment and $35 million in equity. If all goes well, Tetra could also earn up to $120 million in development and commercial milestones. 

The $40 million will allow Grand Rapids, Michigan-based Tetra to complete an ongoing phase 2 trial in fragile X and to kick off another phase 2 trial in early Alzheimer’s disease early next year. The candidate, BPN14770, nicknamed ‘770, is a selective allosteric inhibitor of the enzyme phosphodiesterase-4D, or PDE4D. Tetra is also developing it for brain disorders characterized by cognitive and memory deficits including dementias, schizophrenia, major depression and learning disabilities. 

“’770 modulates a pathway that’s needed both for the maturation of connections between neurons and the stabilization and preservation of connections between neurons,” said Tetra CEO Mark Gurney, Ph.D. This is useful in fragile X, a condition in which a part of the neuron called dendritic spines fail to mature. As for Alzheimer’s, Gurney said, animal models have shown that ‘770 protects dendritic spines that otherwise would be destroyed by the disease process. 

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PDE4D is just one of four PDE4 enzymes in the human genome, three of which are expressed in the brain. Several marketed drugs inhibit PDE4 with most of them targeting skin diseases—these include Otezla for psoriasis and Eucrisa for eczema. But the problem with compounds that inhibit all four types of PDE4 is tolerability—drugs that broadly target PDE4 cause nausea and vomiting. 

“What we’ve done is develop the first subtype-selective PDE4D inhibitor that’s entered human clinical trials, which distinguishes our program from other PDE4 programs,” Gurney said.  

What’s more, ‘770 does not rely on amyloid plaques, the target the majority of Alzheimer’s research has relied on but that hasn’t turned up a new treatment in more than 15 years. 

“Unfortunately, we have not seen great success targeting the amyloid pathway, so there’s a need for us to explore other mechanisms of action. This is a mechanism of action where we expect to see symptomatic improvement, but also, it may be disease-modifying,” Gurney said. 

“This collaboration, if successful, will enable us to move one step closer in realizing a more vigorous society in which patients can be relieved from debilitating central nervous system (CNS) conditions,” said Shionogi CEO Dr. Isao Teshirogi in the statement. Under the deal, Shionogi picked up the rights to ‘770 in Japan, Taiwan and Korea.

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