# PDE4D PET Ligand

> **NIH NIH R44** · TETRA DISCOVERY PARTNERS, INC. · 2020 · $625,084

## Abstract

Tetra Discovery Partners was the recipient of an NIH Blueprint Neurotherapeutics Network award to develop a
phosphodiesterase-4D (PDE4D) allosteric inhibitor for treating cognitive impairment in patients affected by psychiatric
and neurologic diseases. The Tetra-NIH Blueprint drug, BPN14770, currently is in human Phase 2 clinical trials for the
treatment of Fragile X Syndrome and Alzheimer’s disease and has received US FDA Orphan Drug Designation in Fragile
X Syndrome. The Phase II SBIR project will develop a phosphodiesterase-4D (PDE4D) PET tracer for imaging the
distribution of the enzyme in human brain. Human studies with the PDE4D PET tracer may benefit patients by improving
understanding of how changes in cAMP signaling and altered regulation of PDE4 subtypes contribute to the
pathophysiology of disease. The PET tracer also will be useful for determining the dose of BPN14770 to be used in
pivotal human clinical trials by assessing PDE4D target occupancy in brain. The target occupancy study adds value to the
BPN14770 neurotherapeutic and is a critical gate keeper for partnering the drug program with a larger pharmaceutical
company. Human studies with the first PDE4D PET tracer developed by the company revealed an intriguing pattern of
specific PDE4D binding in regions of the brain known to be important for cognition, namely prefrontal cortex, temporal
cortex and hippocampus. However, accumulation of radiolabeled metabolites precluded further advancement of the
compound. The Phase II SBIR proposes a straightforward chemical optimization strategy to address this issue. The goal
of the Phase II SBIR is to optimize a PDE4D PET ligand for advancement into human clinical trials.

## Key facts

- **NIH application ID:** 9985445
- **Project number:** 3R44MH107077-02A1S1
- **Recipient organization:** TETRA DISCOVERY PARTNERS, INC.
- **Principal Investigator:** Mark E Gurney
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $625,084
- **Award type:** 3
- **Project period:** 2019-12-08 → 2020-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985445

## Citation

> US National Institutes of Health, RePORTER application 9985445, PDE4D PET Ligand (3R44MH107077-02A1S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9985445. Licensed CC0.

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