# Long Acting Injectable Depots for TB Therapy

> **NIH NIH R61** · UNIVERSITY OF WASHINGTON · 2022 · $692,507

## Abstract

PROJECT SUMMARY/ABSTRACT
Patient dosing adherence is often compromised by the complex pill regimes and long duration of current TB drug
therapies. These challenges are exacerbated in settings for patients in many social and global settings where
TB co-therapy with HIV positive patients is stigmatized. Long-acting drug delivery products should therefore play
an important role to increase patient adherence and increase drug efficacy. This project will develop a new
injectable depot technology that address a general target product profile that includes multiple-month delivery
from a single injection, low volume and low viscosity formulations to reduce patient pain, combination drug
formulation where required, sustained drug release with designable PK profiles, minimal initial and run-out burst
release to increase safety and prevent drug resistance, and for global settings has low cost of goods and lowered
cold-chain requirements. This depot technology also has the important translational product attributes of
streamlined CMC and cGMP manufacturing that could lead to more rapid clinical development achievement. A
new injectable depot product for TB therapy will be developed that is differentiated from current dispersal based
formulation approaches by being a fully synthetic depot. The proposal is structured around 2 specific aims in the
R61 phase and two further aims in the R33 phase: (1) Prodrug monomers made by synthetic chemistry are
directly polymerized in a second synthetic step to create “drugamer” depot therapeutics that have the drugs built
into the depot itself. Compared to current dispersion formulation approaches, the drugamers exhibit higher drug
loading efficiencies, the ability to co-formulate drugs of different lipophilicities, and linear, individually tailorable
PK profiles that minimize first- and last-week burst release. These PK profiles are kinetically controlled by the
linker properties that are tied to the individual drugs, along with polymer architectural design. This aim will exploit
a unique high throughput polymer library and screening platform at CSIRO Melbourne to identify lead injectable
depot designs using bedaquiline and moxifloxicin as initial drug examples. Sophisticated LC-MS/MS PK
characterization will assess the sustained PK profile together with PK/PK modeling. (2) Evolve and optimize
depot lead candidates through efficacy in an initial TB model that allows higher throughput imaging
characterization of activity. This will be followed by an Mtb model assessment and selection to a lead depot
candidate; (3) Test and optimize the two lead drug depot candidates in an A/BSL3 Mtb model, by the criteria of
PK/PD, efficacy and dose dependence, and dosing duration. The lead depot will also be characterized in
accelerated stability studies to test whether they can avoid cold-chain storage. (4) Evaluate iterated up-selected
depots in combination depots from mixing optimized bedaquiline and moxifloxacin depots, including dual ...

## Key facts

- **NIH application ID:** 10436302
- **Project number:** 5R61AI161820-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Patrick S. Stayton
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $692,507
- **Award type:** 5
- **Project period:** 2021-06-22 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436302

## Citation

> US National Institutes of Health, RePORTER application 10436302, Long Acting Injectable Depots for TB Therapy (5R61AI161820-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436302. Licensed CC0.

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