Tetra Discovery Partners Research Supports Ability of Novel Selective PDE4D Inhibitor, BPN14770, to Improve Memory and Cognition

Preclinical, PET imaging, and Phase 1 human clinical evidence supporting the ability of Tetra Discovery Partners’ drug candidate, BPN14770, to improve memory formation and provide cognitive benefit was the subject of an oral presentation on Saturday at the 10th Clinical Trials in Alzheimer’s Disease Meeting held November 1‐4, 2017 in Boston, MA. BPN14770 is a highly selective inhibitor of phosphodiesterase‐4D (PDE4D), which regulates brain signaling pathways involved in the early and late stages of memory formation.

“Alzheimer’s disease and other conditions marked by problems of cognition and memory represent a serious and growing problem for U.S. and other aging populations worldwide, and to date, there has been no effective treatment that can stem or help improve such cognitive decline,” said Mark E. Gurney, Ph.D., Chairman and Chief Executive Officer of Tetra Discovery Partners. “Based on the results of our Phase 1 trial of BPN14770, and these supporting preclinical studies, we are cautiously optimistic about the potential of this drug candidate and look forward to conducting its further evaluation in a Phase 2 study in early Alzheimer’s disease patients in the first half of 2018.”

Tetra Discovery and the company’s collaborators at the University of Buffalo and the National Institute of Mental Health demonstrated that single oral doses of BPN14770 at 0.01 or 0.03 mg/kg improved the working and long‐term memory in mice with a humanized PDE4D gene, compared to wild‐type mice. Moreover, after 14 days dosing at the 0.03 mg/kg level, the researchers found elevated levels of biomarkers associated with the cAMP‐PKA‐CREB pathway in the humanized mice. This included elevation of brain‐derived neurotrophic factor (BDNF) in the hippocampus. They also demonstrated by PET imaging that PDE4D distribution was highest in specific regions of the brain in primates that were related to cognition, the hippocampus and prefrontal cortex, which are also targets of Alzheimer’s pathology. The PDE4D PET tracer was displaced from the hippocampus and prefrontal cortex by pretreatment with BPN14770, indicating that the drug enters the brain and engages the desired target.

The researchers also presented data from an initial clinical assessment of BPN14770 cognitive benefit in healthy elderly volunteers that was also consistent with the mechanism of action for the drug. In a Phase 1 dose‐ranging study of BPN14770 in 45 healthy elderly volunteers (age 60 or older), preliminary cognitive assessment suggested that BPN14770 oral doses of 10 and 20 mg bid improved complex attention/ working memory and 24‐hour delayed recall of verbal or sight and space‐related tasks. A pooled, post hoc analysis of the elderly volunteers in the low and mid‐dose groups demonstrated a significant improvement in measures of working memory. There were no adverse events related to gastrointestinal disturbance (nausea, vomiting, or diarrhea).

Working memory is a cognitive system for temporarily storing and managing the information required to carry out complex mental tasks such as learning, reasoning, and comprehension.hippocampus are the parts of the brain responsible for working memory. The prefrontal cortex and hippocampus are the parts of the brain responsible for working memory. These same parts of the brain are impacted by Alzheimer’s disease, and working memory is among the cognitive functions most sensitive to decline.

About BPN14770

BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase‐4D (PDE4D) to enhance early and late stages of memory formation. This unique mechanism of action has the potential

to improve cognitive and memory function in devastating CNS disorders including Alzheimer’s disease and other dementias, Fragile X Syndrome, learning/developmental disabilities, and schizophrenia.

Preclinical animal models show that BPN14770 has the potential to promote the maturation of connections between neurons, which is impaired in patients with Fragile X Syndrome, and to protect connections between neurons which otherwise are lost in patients with Alzheimer’s disease. Tetra currently is conducting an investigational Phase 2 study of BPN14770 in adults with early Alzheimer’s disease and a second investigational Phase 2 study in adults with Fragile X Syndrome, an indication for which BPN14770 has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). BPN14770 currently is approved for investigational use only by the U.S. Food and

Drug Administration and is not currently approved for marketing in any territory.

About Tetra Therapeutics

Tetra Therapeutics is a clinical stage biotechnology company developing a portfolio of therapeutic products that will bring clarity of thought to people suffering from Alzheimer’s disease, Fragile X Syndrome, traumatic brain injury, and other brain disorders. Tetra uses structure-guided drug design to discover mechanistically novel, allosteric inhibitors of phosphodiesterase 4 (PDE4), an enzyme family that plays key roles in memory formation, learning, neuroinflammation, and traumatic brain injury.  BPN14770 was developed through a cooperative research agreement with the Blueprint Neurotherapeutics Program of the National Institutes of Health with funding from the National Institute on Aging, National Institute on Neurological Disorders and Stroke, the National Institute of Mental Health, the FRAXA Research Foundation and the Alzheimer’s Drug Discovery Foundation. Tetra Therapeutics is headquartered in Grand Rapids, Michigan. For more information, please visit the company’s website at http://www.tetratherapeutics.com.

Forward looking Statements

Certain other statements made throughout this press release that are not historical facts contain forward‐looking statements regarding the company’s future plans, objectives and expected performance. Any such forward‐looking statements are based on assumptions that the company believes are reasonable, but are subject to a wide range of risks and uncertainties and, therefore, there can be no assurance that actual results may not differ materially from those expressed or implied by such forward‐looking statements.

###

Tetra Therapeutics:
Mark Gurney, Ph.D., Chief Executive Officer
Tetra Therapeutics
info@tetratherapeutics.com

For Media:  
Joan Kureczka
Bioscribe, Inc.
Joan@bioscribe.com
+1 (415) 821-2413

Download PDF

Podcast

The Bio Report
January 2, 2020
Stabilizing Neuronal Connections to Treat Cognitive Impairment in Alzheimer’s

BioTech Nation Radio
April 3, 2019
Treatments for Fragile X, Alzheimer’s disease, and traumatic brain injury.

Awards

Michigan Celebrates
May 3, 2018
Michigan 50 Company to Watch 2018

GRBJ
December 12, 2016
2016 Newsmaker of the Year finalists

PM360
December 21, 2016
Innovators 2016: Startups

In The News

July 12, 2022

Tetra Therapeutics Initiates Phase 2b/3 Clinical Studies of Investigational Drug BPN14770 in Fragile X Syndrome

July 23, 2021

Tetra Therapeutics CEO Mark Gurney retires

July 23, 2021

Tetra Therapeutics Announces Retirement of Mark Gurney and Names Chad Coberly Chief Executive Officer in Planned Succession

July 11, 2021

Decades-long quest to beat Fragile X fueled by persistence, science and relentless optimism

April 30, 2021

Experimental Treatment Boosts Cognitive Function in Fragile X Syndrome

NPR

April 29, 2021

Memory Loss Drug Appears To Help People With The Genetic Disease Fragile X

April 29, 2021

Treatment Found to Improve Cognitive Function in Patients With Fragile X Syndrome

April 29, 2021

Drug boosts cognition in men with fragile X syndrome

April 29, 2021

Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial

April 29, 2021

Fragile X Treatment Shows Promise in Phase II Trial

April 22, 2021

Researchers take a big step in treating a genetic disorder closely linked to autism.

February 9, 2021

People with dementia had significantly greater risk of contracting the coronavirus.

February 9, 2021

Research documents more cases, hospitalizations and deaths.

December 11, 2020

New drug moves closer to becoming first treatment for Fragile X Syndrome

More News

Zatolmilast, an Investigational Treatment for Fragile X Syndrome, Receives Rare Pediatric Disease Designation from the U.S. FDA

OSAKA, Japan, September 27, 2023 – Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter “Shionogi”) announced the U.S. Food and Drug Administration (FDA) has granted Tetra Therapeutics Inc. (hereafter “Tetra”), a Shionogi Group Company, Rare Pediatric Disease Designation for zatolmilast (BPN14770), an investigational

Read More »

Tetra Therapeutics Announces Positive Topline Results from Phase 2 Study of BPN14770 in Patients with Fragile X Syndrome

GRAND RAPIDS, Mich.–(BUSINESS WIRE)–Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co. Ltd., today announced positive topline results from its Phase 2 exploratory study in adult patients with Fragile X Syndrome (FXS). The study evaluated its lead candidate, BPN14770, a first-in-class phosphodiesterase‐4D (PDE4D) allosteric inhibitor. In this single-center, randomized,

Read More »