# Development of Ultra Long-Acting Oral HIV Therapies

> **NIH NIH R01** · LYNDRA THERAPEUTICS, INC. · 2021 · $1,272,821

## Abstract

ABSTRACT
A common problem with any chronic drug therapy is non-adherence. Non-adherence to therapy, 
including HIV anti-retroviral therapy, can be due to a combination of factors including pill 
fatigue, intolerable side-affects, and the complexity of therapeutic regimens. Non-adherence is 
associated with a rebound in viral loads which can be  accompanied by the emergence of 
drug-resistant HIV strains. This poses a major public health threat not only because of ensuing 
disease progression, but also because drug-resistant strains are spread in the population through 
de novo infections. Even as the HIV drug pipeline continues to generate novel and potent 
anti-retroviral compounds, much attention is now being directed towards developing long-lasting 
drug delivery options. In order for combination therapy with HAART to continue to be effective in 
improving AIDS-related morbidity and mortality, therapies need to be formulated so as to require 
infrequent and convenient dosing while achieving sustained and effective tissue concentrations. To 
date, the most successful strategy for prolonged and controlled delivery of small molecule    
treatments relies on slow-releasing nano-suspensions or polymeric microspheres that are injected 
either subcutaneously or intramuscularly. There are, however, many drawbacks to the injectable 
approach. Injectables are limited to highly potent, very hydrophobic molecules, and can produce 
long, sub-therapeutic tails with uncertain risk.
Long-acting oral therapies are potentially the most convenient route for patients, and may offer 
significant advantages over injectable solutions. But no existing oral delivery system can provide 
more than 12-24 hours of sustained release of small molecule therapies. Lyndra has developed an 
orally-available, gastric-resident dosage form engineered to deliver therapeutic doses of drug(s) 
over a period of a week, before disintegrating and safely passing out of the body. The basic 
modules of the device are an elastomeric center fused to six arms made of a polymer-drug blend; 
break points called linkers are strategically placed in the arms to ensure timed disintegration of 
the dosage form, leading to quick and safe passage out of the body. We have demonstrated in large 
animal models that this platform is capable of once weekly administration with near steady-state 
pharmacokinetics for a variety of small molecule therapies. The objective of this proposal is to 
integrate a highly potent anti-HIV molecule into this platform for a once weekly oral regimen. In 
Aim 1, we will optimize a formulation of Dolutegravir, a potent integrase inhibitor, for sustained 
delivery from a polymeric matrix blended with various excipients that control the rate of release. 
In Aim 2, we will develop novel, enteric linkers that quickly dissolve in the intestinal 
environment. A tracer system to monitor residence of drug-loaded doses will be based on release of 
sub-therapeutic doses of short half-...

## Key facts

- **NIH application ID:** 10102173
- **Project number:** 5R01AI131416-05
- **Recipient organization:** LYNDRA THERAPEUTICS, INC.
- **Principal Investigator:** Stephen ZALE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,272,821
- **Award type:** 5
- **Project period:** 2017-03-22 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102173

## Citation

> US National Institutes of Health, RePORTER application 10102173, Development of Ultra Long-Acting Oral HIV Therapies (5R01AI131416-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102173. Licensed CC0.

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