# Next generation drugs for bipolar depression and maintenance

> **NIH NIH R44** · BLUE OAK PHARMACEUTICALS, INC. · 2021 · $1,425,888

## Abstract

Blue Oak Pharmaceuticals is developing the next generation of drugs for the treatment of acute bipolar
depression and long-term maintenance (BPD), a mental disorder that affects ~6 million adult Americans. Existing
drug classes are relatively ineffective and very few new modes-of-action have been developed in the past 40+
years. This is due, in part, to the biopharma industry’s focus on drugging single molecular targets, and the lack
of predictive animal models for bipolar disorder. To overcome these significant hurdles, Blue Oak’s drug
discovery paradigm combines custom-designed privileged chemotypes with a proven deep behavioral profiling
method. Successful Phase I studies using this novel, but previously validated, approach resulted in the discovery
and optimization of a novel lead compound for the treatment of BPD. The therapeutic utility of drug candidates
was confirmed using molecular target profiling, ex vivo imaging of the forebrain circuits implicated in BPD and
predictive translational medicine biomarkers. Phase II studies are focused on advancing the lead compound
through Investigational New Drug (IND)-enabling studies, the necessary next step for FDA review and approval
of human studies. Aims include: (1) quantification of the preclinical therapeutic (safety) margin for the lead, or
superior back-up molecule, including analyses of antidepressant activity; (2) confirmation of an enhanced EEG
gamma band as a reliable translational biomarker of BPD drug activity and efficacy in non-human primates; (3)
manufacture and qualification of cGLP drug product suitable for IND-enabling studies; and (4) completion of
preclinical studies necessary for an IND filing with the FDA, including standard absorption, distribution,
metabolism, excretion, and toxicity (ADME/TOX) preclinical studies and preclinical dose escalation studies
necessary prior to first-in-human clinical studies. The successful completion of these aims will result in a Type B
meeting to obtain guidance from the FDA and the filing of an IND package. The Blue Oak Pharmaceuticals team
includes experienced “drug hunters” with expertise in systems neurobiology, medicinal chemistry and
informatics, and advisors with proven track records in drug development and commercialization. The internal
team is supported by trusted partners in preclinical research, development and validation of translational
medicine biomarkers, clinical site management, and clinical development. If successful, this program will deliver
a new drug candidate for bipolar depression that will improve the quality of life of patients and their families.

## Key facts

- **NIH application ID:** 10080262
- **Project number:** 2R44MH116746-03
- **Recipient organization:** BLUE OAK PHARMACEUTICALS, INC.
- **Principal Investigator:** Thomas H Large
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,425,888
- **Award type:** 2
- **Project period:** 2018-09-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080262

## Citation

> US National Institutes of Health, RePORTER application 10080262, Next generation drugs for bipolar depression and maintenance (2R44MH116746-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10080262. Licensed CC0.

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