Novel cyclic boronate penicillin binding protein inhibitors to eliminate the threat posed by ?-lactamases and enable a future treatment option for carbapenem-resistant enterobacterales infections
Active Project Grant Awarded Last action
- Award ID
- R01AI160269
- Recipient
-
Spring Mill Pharma Incorporated UEI UWZNAK5HJLN7
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $11,816,231
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 91% complete
- Originally
- Funding
-
- $10,277,504.00 Federal
- $1,538,727.00 Non-federal
- Place of performance
- Malvern, PA 19355, USA
Award details come from USAspending.gov.
Description
- Abstract
- Carbapenem-resistance in enterobacterales has steadily increased over the past decade, leading to multidrug and pan-drug resistance (MDR/PDR), further emphasizing the need for new innovative therapies. Carbapenem- resistant enterobacterales (CRE) is a serious global health problem classified by the US centers for disease control and prevention as an "urgent threat" and by the world health organization as a "priority 1 critical threat". The SS-lactams have long been the front line therapeutic option for such infections, but efficacy of these agents, including last resort carbapenems, is threatened by recent expansion of SS-lactamases, particularly subtypes (e.g., NDM) spreading rapidly among enterobacterales that are unaffected by clinically-available SS-lactam/SS- lactamase inhibitor combinations. To address the medical need, venatorx has identified a novel series of highly selective cyclic boronates that bind to and disrupt penicillin-binding protein (PBP) transpeptidase (tpase) function while avoiding the action of all current and future SS-lactamases. This approach creates the first prospect and "rare" new class gram negative agent to treat infections caused by any SS-lactamase-producing CRE pathogen. Significant strides in microbiological activity have already been achieved within the series by the lead compound vnrx-6736, with an MIC90 of 32 ΜG/ML relative to 128 ΜG/ML for meropenem-vaborbactam and =1,024 ΜG/ML for ceftazidime-avibactam in a recent challenge set of 100 CRE isolates. Not only does vnrx- 6736 outperform these clinical comparators from an MIC90 perspective, but does so with a narrow range of MIC owing to SS-lactamase avoidance, a feature that will ultimately benefit setting of breakpoints. The series is rapidly bactericidal, exhibits a low spontaneous mutational frequency (frequency of resistance at 4X MIC of
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $1,103,779 | $0 | |
| Amendment | -$1,103,779 | $0 | |
| Amendment | -$1,103,779 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $1,220,775 | $0 | |
| Amendment | $1,220,775 | $0 | |
| Amendment | $1,220,775 | $0 | |
| Amendment | $1,220,775 | $0 | |
| Amendment | $1,220,775 | $0 | |
| Amendment | $1,183,227 | $0 | |
| Amendment | $1,183,227 | $0 | |
| Amendment | -$55,500 | $0 | |
| Amendment | -$55,500 | $0 | |
| Amendment | -$55,500 | $0 | |
| Amendment | $1,538,727 | $0 | |
| Original award | $1,538,727 | $1,538,727 |
Show all 18
Quick answers
Who received award R01AI160269?
R01AI160269 was awarded to Spring Mill Pharma Incorporated by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on May 4, 2021.
How much is award R01AI160269 worth?
$11,816,231 has been obligated on R01AI160269: $10,277,504 in federal funding and $1,538,727 in non-federal funding.
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