Developing teixobactin for respiratory infections

Active Project Grant Awarded Last action

Award ID
R01AI159444
Recipient
Awarding agency
Obligated
$16,026,069

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 95% complete
Originally
Funding
  • $14,556,575.00 Federal
  • $1,469,494.00 Non-federal
Place of performance
Cambridge, MA 02138, USA

Award details come from USAspending.gov.

Description

Abstract
The major goal of this proposal is to investigate the potential for teixobactin, our newly discovered antibiotic, to treat respiratory infections. As reported in 2019 by the CDC, pneumonia caused by drug resistant streptococcus pneumoniae, as well as methicillin-resistant staphylococcus aureus (MRSA), are considered serious threats. In addition, respiratory bacterial CO-infections with covid-19 have recently been recognized as a significant problem. Haemophilus influenzae and moraxella catarrhalis are two other respiratory pathogens particularly problematic in patients with chronic obstructive pulmonary disease and are common causes of community-acquired bacterial pneumonia (CABP). The most remarkable, and unexpected property of teixobactin is the lack of any detectable resistance to this compound. Teixobactin hits two related targets-lipid II, precursor of peptidoglycan and lipid III, precursor of wall teichoic acid. These highly conserved targets are not mutable-they are not proteins and are not directly coded by DNA. Since our discovery of teixobactin, we and others have failed to generate resistant mutants in any species including S. Aureus, mycobacterium tuberculosis or bacillus anthracis. Teixobactin is highly efficacious in animal models of thigh, lung and blood infections. Animal infection models predict that the human dose of teixobactin for acute skin and skin structure infections (ABSSSI) will be very low (=1 MG/KG/day), which is advantageous, as a low dose may minimize side effects and reduce manufacturing costs. Teixobactin is in preclinical development as an intravenous (IV) drug for treating skin infections caused by pathogens such as MRSA. A pre-investigational new drug (IND) meeting with FDA was held in december 2018 whereby the FDA generally agreed with our development plan. An IND submission for ABSSSI is planned for 2022. In this project, aim 1 will produce enough teixobactin for all the proposed studies. Aim 2 will conduct efficacy and PK/PD studies in animal models of pneumonia. Aim 3 will test in vitro susceptibility, bactericidal activity, post antibiotic effect (PAE) and resistance in recent clinical isolates from respiratory infections. Aim 4 will prepare and submit an IND application for intravenous treatment of a respiratory infection. Aim 5 will explore alternative routes of TXB administration (inhalation and intramuscular delivery), which would be particularly useful for outpatient treatment of respiratory and other infections. With successful completion of these projects, we will have demonstrated the promise of teixobactin for treating drug resistant respiratory infections and explored more convenient routes of TXB administration.

Transactions

Action Federal Non-federal Date
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Amendment $1,120,776 $0
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Amendment $1,099,219 $0
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Amendment $1,147,950 $0
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Amendment $1,195,129 $0
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Amendment $1,469,494 $0
Original award $1,469,494 $1,469,494
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Quick answers

Who received award R01AI159444?

R01AI159444 was awarded to Novobiotic Pharmaceuticals, LLC by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on March 22, 2021.

How much is award R01AI159444 worth?

$16,026,069 has been obligated on R01AI159444: $14,556,575 in federal funding and $1,469,494 in non-federal funding.

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