TB latitude (long-acting treatment innovation for tuberculosis drug effectiveness) - R220 - OPI section 7

The National Institute of Allergy and Infectious Diseases awarded The Global Alliance For TB Drug Development Inc. $802,418 on May 7, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop long-acting injectable formulation technologies for tuberculosis treatment.

The recipient will develop optimized formulation technologies for four drugs from TB Alliance's pipeline—TBAJ-876, TBAJ-587, telacebec, and pretomanid—designed to reduce active TB treatment duration to two months or less for both drug-sensitive and drug-resistant tuberculosis. The project comprises two phases. The R61 phase focuses on formulation developability, stability, and in vitro release combined with in vivo pharmacokinetics and pharmacokinetic modeling. This work includes in vivo mouse infection studies to evaluate the pharmacokinetic/pharmacodynamic correlation of long-acting injectable drug exposure and efficacy. Up to four drug and formulation technology configurations will advance to the R33 phase for continued assessment. The R33 phase emphasizes nonclinical development activities supporting transition to clinical evaluation.

Work is performed in New York, New York. The period of performance runs through April 30, 2028.

Abstract

Tuberculosis (TB) is the most common cause of premature death among people living with HIV (PLWH), and effective TB prevention and treatment strategies are critical for preventing TB-related deaths in PLWH. Currently a minimum of six months oral therapy with a multidrug regimen is required for active drug-sensitive (DS-) or drug-resistant (DR-) TB, including for patients with TB/HIV coinfections. Recent approvals in HIV treatment have paved the way for long-acting injectable (LAI) drug development in infectious diseases, including TB where there is high potential to improve on current treatment options. The ultimate goal of this project is to develop an optimized LAI-based regimen for use in the continuation phase of active TB treatment to minimize the total "active treatment" duration to two months or less for both DS- and DR-TB. This will represent a significant advancement in the treatment of TB by reducing the burden on patients who currently must take daily oral medicines for up to six months or longer. The project's four key research aims will focus on the development of formulation technologies for four drugs from TB alliance's pipeline (tbaj-876, tbaj-587, telacebec, and pretomanid) that have appropriate anti-TB activity and physicochemical properties and show promise for an LAI-based clinical application. The first phase of the project (R61 phase) will focus on formulation developability, stability and in vitro release combined with in vivo pharmacokinetics (PK) and PK modeling (aim 1). This will be combined with in vivo mouse infection studies to evaluate the PK/PD correlation of LAI-drug exposure and efficacy (aim 2). We will select up to four drug and formulation technology configurations for continued assessment and support transition to the R33 phase. The second phase of the project (R33 phase) will focus on the nonclinical studies of injection site safety and tolerability, LAI stability, and GMP-compliant LAI formulations for regimens to enable investigational new drug (IND) application(S) (aim 3). LAI drug regimens will be selected based on a strong potential to achieve cures when administered following a short oral lead-in therapy (aim 4). The key goal of aim 4 will be to show that a single coadministration of only two LAI-formulated drugs following an oral lead-in of two months or less is feasible based on the comparative activity of an all-oral regimen versus an oral lead-in and LAI continuation regimen in the relapsing mouse model (RMM) studies.