Spotlight: Shionogi’s Big Bet on Tetra Therapeutics

By Ruchi Jhonsa, Ph.D.

With more than 50 million affected worldwide, dementia can make day-to-day functioning challenging for a person. Caused by neuronal death, memory loss is one of the most prominent symptoms of Alzheimer’s and Fragile X syndrome. Some big names such as Biogen and Sangamo are already in line to develop new therapies using the latest technologies to fight Alzheimer’s albeit with much less success. However, one drug that is making the headlines is Biogen’s aducanumab, which got all eyes on it when it’s topline results were presented in the Clinical Trials on Alzheimer’s disease meeting late last year.

Towards this effort, two more companies had joined the league. In 2018, Tetra Therapeutics teamed up with Shionogi to advance its PDE4-targeting drug in Alzheimer’s disease, fragile X syndrome, and other indications marked by cognitive and memory deficits. In return, Shionogi handed over $5 million upfront with $35 million in equity and an additional $120 million in development and commercial milestones. The $40 million was used in advancing ongoing phase 2 trials for fragile X and to kick off phase 2 trials for early Alzheimer’s disease in 2019.

Now that Tetra is ready to reveal its topline results from Phase II PICASSO study in early Alzheimer’s disease in a month’s time, the bet has gone up from Shionogi’s end. Earlier today, the company announced an increase in its equity investment in the Tetra therapeutics to 50% along with an option to complete a structured buyout of the remaining equity if certain closing conditions are met based on the topline results of the company’s clinical Phase 2 PICASSO AD trial in patients with early Alzheimer’s disease.

Mark Gurney, Ph.D., Chairman and Chief Executive Officer of Tetra Therapeutics expressed his views and said, “We are delighted to be expanding our collaboration with Shionogi and thank them for their continued conviction in our mission. We look forward to announcing topline results from our Phase 2 PICASSO AD trial in Alzheimer’s disease later this month.”

Dr. Isao Teshirogi, President and Chief Executive Officer, Shionogi & Co., Ltd. in support of the collaboration said, “We are pleased to strengthen our strategic alliance with Tetra. With the aging of our society, cognitive disorders are becoming a serious social issue. We believe BPN14770 has the potential to become an innovative new treatment to help solve for this issue. This new collaboration with Tetra reinforces our steadfast commitment to advancing cutting-edge science in central nervous system (CNS) disorders including Alzheimer’s disease”.

BPN14770, A Drug that Protects the Brain Connections

BPN14770 is a selective allosteric inhibitor of the enzyme phosphodiesterase-4D. The drug has a unique mechanism of action that can improve nerve health, protect the brain from memory deficits and biochemical impairments and prevent dementia even with the progression of Alzheimer’s. It was first tested in preclinical studies where it was found to promote the maturation of connections between neurons, which are otherwise impaired in patients with Fragile X syndrome, as well as protect these connections, which are lost in patients with Alzheimer’s. It was further validated in Phase 1 double-blind, placebo-controlled, dose-ranging studies in healthy volunteers where it significantly improved cognition in elderly patients.

Currently, the drug is being evaluated in PICASSO AD Phase 2 trial in 255 patients with early Alzheimer’s as well in an investigational Phase 2 study in adults with Fragile X syndrome.

Is It Too Early to Celebrate?

Given that nearly every effort to develop an Alzheimer’s medication has failed over the past 15 years, this deal looks like a big risk. But several experts are hoping that perhaps the drug will work. The reason being that the drug doesn’t target amyloid plaques, which has been the target for most of the drugs in the past. Instead, BPN14770 relies on phosphodiesterase inhibition to bump up the level of cyclicAMP, which is known to improve neuronal health and functioning. With Phase 1 completed and Phase 2 results in the offing, we just have to wait and watch if the drug can become the first-ever drug to treat Alzheimer’s.

References

1. https://tetratherapeutics.com/tetra-therapeutics-and-shionogi-announce-expanded-alliance/
2. https://investors.biogen.com/news-releases/news-release-details/biogen-plans-regulatory-filing-aducanumab-alzheimers-disease

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Author

Ruchi Jhonsa