HHS Recovery Act Recipient Reporting Readiness Tool
Step 4. Review and Copy the Grant Awards Data
TAGGS provides some – but not all – of the data needed for the Recipient Report. Recipients are responsible for directly collecting and reporting all required data to FederalReporting.gov. Data that HHS does not currently collect are highlighted in yellow. Do not copy this highlighted information. Please enter the appropriate data for your organization in these required fields. For assistance with entering these data please contact FederalReporting.gov.
You may capture the data HHS does provide by copying data from this screen and pasting it into the reporting format of your choice, such as the Excel spreadsheet template, the XML template, or by logging into the online form. For assistance with copying and pasting these data please e-mail our help desk at Readiness Help.
| Recipient Report: Grant or Loan | ||
| Prime Recipient |
| Reporting Information | ||
| Award Type | Award Number | Final Report |
| Grant | 3R21AI070982-02S1 | Recipient responsible for this data |
| Award Recipient Information | ||
| Recipient DUNS Number | Recipient Account Number | Recipient Congressional District |
| 125129606 | Recipient responsible for this data | 8 |
| Award Information | ||
| Funding Agency Code | Awarding Agency Code | Award Date |
| 7529 | 7529 | 09-15-2009 |
| Amount of Award | Sub Account Number for Program Source (TAS) | |
| $ 693,529 | Recipient responsible for this data | |
| Program Source (TAS)* | CFDA Number | |
| 750900 | 93.701 | |
| Total Number of Sub Awards to Individuals | Total Amount of Sub Awards to Individuals | |
| Recipient responsible for this data | Recipient responsible for this data | |
| Total Number of Payments to Vendors less than $25,000/award | Total Amount of Payments to Vendors less than $25,000/award | |
| Recipient responsible for this data | Recipient responsible for this data | |
| Total Number of Sub Awards less than $25,000/award | Total Amount of Sub Awards less than $25,000/award | |
| Recipient responsible for this data | Recipient responsible for this data | |
| Award Description | ||
| DESCRIPTION (provided by applicant): SQ109 is a new anti-TB drug candidate that is currently undergoing Phase Ia Clinical Trials in humans. SQ109 was selected out of the library of 63,238 compounds, because it is highly efficacious in killing M. tuberculosis within infected macrophages and in experimental animals, has relatively low cytotoxicity in cultured mammalian cells, has activity against both drug-susceptible and drug-resistant M. tuberculosis, and has drug-like pharmacokinetic and pharmacodynamic profiles. Any new anti-TB drug will be used in combination with other drugs in order to prevent the emergence of drug resistant M. tuberculosis. How SQ109, a new drug compound with unique attributes, interacts with existing first line anti-TB drugs is crucial for us to understand, as this knowledge enables us to design the most efficacious therapeutic combination and to avoid any antagonistic side effects of a new combination therapy. We investigated the drug interaction in various combinations of SQ109 with the first line anti-TB drugs in both in vitro assays and in vivo murine models of TB. We found that SQ109 preferentially synergized with RIF in in vitro growth inhibition assays and demonstrated enhanced bactericidal activity in mice when used in combination with INH and RIF. These findings are significant for optimizing the drug combination therapies to be tested in future clinical trials. In this exploratory R21 grant Application we will: 1. Assess whether SQ109 is metabolized within M. tuberculosis and how co-administration of RIF influences SQ109 metabolism. If SQ109 metabolites exist, we will study their structures by mass spectrometry and will compare them to the SQ109 metabolites generated by human CYP. If the metabolites are the same, we will prepare and purify them in sufficient quantities and test them against M. tuberculosis for potency in vitro. 2. Determine the expression of individual CYP in RIF-treated M. tuberculosis in order to identify candidate SQ109 activators that are induced by RIF. 3. Generate M. tuberculosis knock out mutants of the candidate CYP(s) and re-examine the synergy of interaction between SQ109 and RIF in the CYP knockout mutants. Public Health Relevance: One of the most vexing problems with standard tuberculosis (TB) therapy is the lengthy treatment course (6-9 months) and toxicity of the drugs in the regiment. This prolonged therapeutic regimen results in a high level of noncompliance, and ineffective concentrations of drugs lead to the emergence of multidrug resistant (MDR) M. tuberculosis. There are an estimated 400,000 new cases of MDR TB each year, and the World Health Organization (WHO) estimates there are 50 million individuals worldwide infected with a resistant strain of TB. MDR strains of M. tuberculosis cause increased mortality, and the fatality rate of untreated cases of MDR TB can be as high as 70%. The likelihood of cure for MDR M. tuberculosis-infected individuals becomes even less in the setting of secondary immunosuppression caused by HIV and malnutrition, conditions that are rampant in developing countries. Because of the failures of the existing therapies, the world desperately needs new drugs that can shorten treatment duration and kill MDR M. tuberculosis. Sequella, Inc., founded in 1997, focuses its R&D on developing new diagnostic tools and new drugs for TB disease. One of our most successful projects is the development of SQ109, a new anti-TB drug candidate that is currently undergoing Phase Ia Clinical Trials. SQ109 was selected as our lead drug candidate out of the library of 63,238 compounds, because it is highly efficacious in killing M. tuberculosis within infected macrophages and in experimental animals, has relatively low cytotoxicity in cultured mammalian cells, has activity against both drug-susceptible and drug-resistant M. tuberculosis, and has drug-like pharmacokinetic and pharmacodynamic profiles. Importantly, when used in combination with rifampin (RIF) + isoniazid (INH) + pyrazinamide (PZA), SQ109 is able to increase bacterial killing and reduce the time by at least 25% to achieve the same level of CFU as the standard drug regimen, RIF + INH + PZA + ethambutol (EMB) in a mouse model of TB. Any new anti-TB drug will be used in combination with other drugs in order to prevent the emergence of drug resistant M. tuberculosis. How SQ109, a new drug compound with unique attributes, interacts with existing first line anti-TB drugs is crucial for us to understand, as this knowledge enables us to design the most efficacious therapeutic combination and to avoid any antagonistic side effects of a new combination therapy. In this R21 exploratory grant application, we propose to investigate one of the several hypotheses that may contribute to the synergistic interaction between SQ109 and RIF in M. tuberculosis: (1) SQ109 is readily metabolized in M. tuberculosis, (2) RIF is able to induce the expression of one or more M. tuberculosis CYP- like proteins, and (3) CYP induced by RIF is involved in SQ109 metabolism. Tasks 1 and 2 are two independent areas of study, which are linked by task 3. In this application, we outline the experiment design for all three tasks in sequence. Further, we provide alternative directions for the study of this interesting synergy if the data obtained do not support our hypothesis. | ||
| Project Information | ||||||||||||||||||||||||||
| Project Name or Project/Program Title |
Project Status | Total Federal Amount ARRA Funds Received/Invoiced |
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| INVESTIGATION OF SYNERGY BETWEEN RIFAMPIN AND SQ109, A NEW ANTI-TB DRUG CANDIDATE | Recipient responsible for this data | Recipient responsible for this data | ||||||||||||||||||||||||
| Number of Jobs | Description of Jobs Created | |||||||||||||||||||||||||
| Recipient responsible for this data | Recipient responsible for this data | |||||||||||||||||||||||||
| Quarterly Activities/Project Description | ||||||||||||||||||||||||||
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| Total Federal Amount of ARRA Expenditure |
Total Federal ARRA Infrastructure Expenditure |
Infrastructure Contact Name | ||||||||||||||||||||||||
| Recipient responsible for this data | Recipient responsible for this data | Recipient responsible for this data | ||||||||||||||||||||||||
| Infrastructure Contact Email | Infrastructure Contact Phone | Infrastructure Contact Phone Ext. | ||||||||||||||||||||||||
| Recipient responsible for this data | Recipient responsible for this data | Recipient responsible for this data | ||||||||||||||||||||||||
| Infrastructure Contact Street Address 1 | Infrastructure Contact Street Address 2 | Infrastructure Contact Street Address 3 | ||||||||||||||||||||||||
| 9610 MEDICAL CENTER DR STE 200 | Not Available | Recipient responsible for this data | ||||||||||||||||||||||||
| Infrastructure City | Infrastructure State | Infrastructure ZIP Code+4 | ||||||||||||||||||||||||
| ROCKVILLE | MD | 20850 | ||||||||||||||||||||||||
| Infrastructure Purpose and Rationale | ||||||||||||||||||||||||||
| Recipient responsible for this data | ||||||||||||||||||||||||||
| Primary Place of Performance | ||
| Street Address 1 | Street Address 2 | City |
| 9610 MEDICAL CENTER DR, STE 200 | Recipient responsible for this data | ROCKVILLE |
| State | Zip Code+4 | Congressional District |
| MD | 208506332 | Not Available |
| Country | ||
| US | ||
| Recipient Highly Compensated Officers | |||
| Prime Recipient Indication of Reporting Applicability | # | Officer Name | Officer Compensation |
| Recipient responsible for this data | 1 | Recipient responsible for this data | Recipient responsible for this data |
| 2 | Recipient responsible for this data | Recipient responsible for this data | |
| 3 | Recipient responsible for this data | Recipient responsible for this data | |
| 4 | Recipient responsible for this data | Recipient responsible for this data | |
| 5 | Recipient responsible for this data | Recipient responsible for this data | |
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USE IN THE RECIPIENT REPORT
The information provided by this tool is baseline data that the Recipient should include in the Recipient Report that must be submitted to FederalReporting.gov beginning October 1, 2009. The data from this tool can be cut and pasted directly into the Recipient Report.
