Shionogi Acquires Tetra Therapeutics, Rights to Fragile X Treatment Candidate

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by Vanessa Pataia |

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Tetra Therapeutics BPN14770

Shionogi has acquired Tetra Therapeutics, the developer of a treatment candidate known as BPN14770 for fragile X syndrome and Alzheimer’s disease.

With the agreement, Shionogi obtains global rights to Tetra’s entire pipeline. It will continue developing BPN14770 — an investigational therapy for improving cognition — for disorders affecting the central nervous system (CNS), which includes the brain and spinal cord.

“We are excited to combine Tetra’s portfolio with our drug development capabilities to further advance BPN14770 in CNS disorders, including AD [Alzheimer’s disease] and FXS [fragile X syndrome],” Isao Teshirogi, president and CEO of Shionogi, said in a press release

BPN14770 is designed to improve cognition by blocking the enzyme phosphodiesterase 4D (PDE4D), known to affect learning and memory. The enzyme is most active in brain regions affected by fragile X. Specifically, BPN14770 is an allosteric inhibitor of PDE4D, which means that it alters the enzyme’s structure to render it inactive.

The scientists hope the treatment will avoid some of the common side effects, such as nausea, seen in similar compounds.

“With over a decade of research, development and investment, Tetra has demonstrated the unique ability of allosteric inhibitors of phosphodiesterase-4D (PDE4D) to deliver disease-modifying potential in central nervous system (CNS) disorders,” said Mark Gurney, PhD, chairman and CEO of Tetra.

Tetra and Shionogi first teamed up to accelerate the development of BPN14770 in December 2018. The companies expanded their partnership earlier this year, with Shionogi increasing its investment in Tetra to support the development of BPN14770 for the treatment of fragile X, Alzheimer’s, and other diseases.

“Shionogi has been a valued partner for the last two and half years, and with the company’s development and commercialization expertise, we believe Shionogi is ideally positioned to bring the potential of our platform to patients and provide new treatment options within these areas of urgent medical need,” Gurney said.

Studies in animal models suggest that BPN14770 has the potential to promote connections between nerve cells that otherwise fail to develop in people with fragile X, and are lost in individuals with Alzheimer’s disease.

BPN14770 has been found safe and tolerable in two Phase 1 clinical trials (NCT02840279 and NCT02648672). In addition to a favorable safety profile, the results showed cognitive benefits among healthy elderly participants.

These findings led the U.S. Food and Drug Administration to grant orphan drug designation to BPN14770 in 2018 as a treatment for fragile X.

Tetra now is conducting a double-blind Phase 2 trial (NCT03569631) to evaluate the effects of BPN14770 on cognitive function and behavior in up to 30 men with fragile X. 

The trial is divided into two 12-weeks periods. At the start of the first period, the participants are randomly assigned to receive either 25 mg BPN14770 or a placebo, twice daily, in oral capsules. In period two, the men previously on a placebo are given BPN14770, while those who initially received the investigational therapy are switched to a placebo.

Cognitive and behavioral evaluations are performed at weeks six and 12 of each study period. Treatment-related adverse events also are recorded.

In addition to testing the therapy for fragile X, Tetra has completed a Phase 2 study among early Alzheimer’s patients. Topline results from that trial, named PICASSO AD (NCT03817684), are expected soon.

“Tetra’s deep level of drug discovery know-how in the CNS area will help us to solve for the cognitive disorders our ageing population is facing, and we believe we are well-positioned to bring BPN14770 to patients in need,” Teshirogi said.

With the merger, Tetra will become a subsidiary of Shionogi. Based on the achievement of certain predetermined regulatory and commercial milestones, the total transaction value may reach $500 million, the companies said.