A novel monoclonal antibody-based anti-NK cell anti-inflammatory strategy for treating autoimmune and checkpoint inhibitor induced myocarditis
Ended Project Grant Awarded Last action
- Award ID
- R43HL158344
- Recipient
-
Inflamma Therapeutics, LLC UEI Q4RNJ7NJAAE3
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $801,051
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date
- Funding
-
- $492,400.85 Federal
- $308,650.00 Non-federal
- Place of performance
- Encinitas, CA 92024, USA
Award details come from USAspending.gov.
Description
- Abstract
- The problem: despite current therapies, the prognosis of various forms of acute and chronic inflammation of the heart (myocarditis) remains poor. Immune reactions that attack a patient's own tissues (autoimmune disease) is one major cause of myocarditis. Additionally, one of the complications of immune checkpoint inhibitors (ICI), which attack cancer cells though activation of inflammation, is myocarditis. Innovation: inflammation involves multiple molecules and multiple redundant pathways. The anti-inflammatory monoclonal antibodies (mabs) forming the basis of treatment of inflammation-related diseases target a single molecule and a single inflammatory pathway. Therapeutic efficacy is thereby limited. NK cells are major orchestrators of multiple inflammatory pathways. Inflamma therapeutics (IFT) therefore developed a novel MAB-IFT100-that depletes NK cells. By inhibiting NK cells IFT100 inhibits multiple inflammatory pathways. As proof-of-concept of the efficacy of an NK cell depleting strategy, we demonstrated that an anti-NK cell MAB that depletes mouse NK cells improves myocardial function in mice with acute heart attacks or with chronic heart failure. IFT therefore decided to develop an anti-human NK cell MAB-IFT100-to serve as an immunosuppressive therapeutic agent to treat inflammation-exacerbated human disease. IFT found that IFT 101 binds to and depletes human NK cells. IFT100 was sequenced and patents submitted. The aims of the current proposal, using IFT100: aim 1: determine the dose response for in-vivo NK cell depletion in mice. Aim 2: determine the impact of NK cell depletion on the prevention of experimental autoimmune myocarditis. Aim 3: determine the impact of NK cell depletion on the prevention of experimental autoimmune myocarditis with or without the burden of ICI treatment. Aim 4: humanize our MAB. In this project we will be validating the ability of our specific MAB (IFT100) to improve autoimmune-induced and ICI-induced myocarditis. Importantly, however, we believe IFT100 will also be effective for improving outcomes in many other diseases that are worsened by excessive inflammation. These include myocardial dysfunction in patients with chronic heart failure, with cardiogenic shock, and with acute MI. Another important additional therapeutic target for IFT100 is the massive inflammatory response responsible for most of the deaths seen in covid-19. Each of these conditions has no current effective therapy and, as such, constitute conditions for which there are major unmet therapeutic needs.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | -$124,899 | $0 | |
| Amendment | $308,650 | $0 | |
| Original award | $308,650 | $308,650 |
Quick answers
Who received award R43HL158344?
R43HL158344 was awarded to Inflamma Therapeutics, LLC by National Heart Lung and Blood Institute (National Institutes of Health) on April 15, 2021.
How much is award R43HL158344 worth?
$801,051 has been obligated on R43HL158344: $492,401 in federal funding and $308,650 in non-federal funding.
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