Friday, August 22, 2025 8/22/2025

Translating oral CD11b agonist as a novel therapeutic for lupus nephritis

Award Number: R01DK084195
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2011
PERIOD OF PERFORMANCE END DATE: 06/30/2029

Group Awards By:

View Award Description

Translating oral CD11b agonist as a novel therapeutic for lupus nephritis - Project Summary Lupus nephritis (LN) is a highly debilitating disease associated with Systemic Lupus Erythematosus (SLE, lupus). >40% of lupus patients develop LN and many progress to end stage kidney disease (ESKD). Thus, LN remains the strongest predictor of morbidity and mortality in lupus patients. LN is currently managed with aggressive immunosuppressive and cytotoxic agents that have considerable side effects and long-term toxicity. Therefore improved, targeted new treatments are urgently needed. Uncontrolled toll-like receptor (TLR) signaling in myeloid cells results in their overactivity and produces a feed-forward cycle of pro-inflammatory mediators, such as type I interferon (IFN I), IL-6, IL-1b and soluble uPAR (suPAR). IFN I is increased in sera of LN patients, and suPAR is a circulating risk factor for glomerular diseases, including LN. Three single nucleotide polymorphisms (SNPs) in ITGAM gene (coding for integrin CD11b) are found in ~20% of LN patients and produce dysfunctional CD11b. We found that 1) these SNPs not only show strong correlation with the incidence of LN (and SLE), but are also associated with significantly higher levels of IFN I and suPAR in LN patient sera; and that 2) CD11b is a natural regulator of uncontrolled TLR signaling, and the variant CD11b is especially ineffective in controlling the TLR pathways in myeloid cells. To address this deficiency, we developed a novel, highly selective CD11b agonist small molecule, termed ONTEGIMOD, that activates both wildtype and mutant CD11b and reduces uncontrolled TLR-signaling in vitro and in vivo. It also reduces myeloid infiltration in inflamed kidneys. New data in multiple LN murine models also shows that oral ONTEGIMOD therapeutically reduces serum IFN I, anti-dsDNA antibody and suPAR levels, reduces myeloid influx in kidneys, decreases albuminuria and protects against kidney injury in LN. Therefore, we propose that CD11b activation, by rescuing the functional deficit in CD11b and thereby suppressing TLR-dependent inflammatory signaling, will provide us with a new therapeutic for LN. Direct proof of ONTEGIMOD’s potential as a LN therapeutic requires a new clinical trial in LN patients. Here, we propose such a pilot, mechanistic clinical trial and propose three aims. First, we plan to use ex vivo assays to identify LN patients most likely to respond to CD11b activator ONTEGIMOD, especially patients homozygous for ITGAM SNPs, thereby developing a personalized therapeutic approach. We also plan to perform a Phase I/II clinical trial to generate preliminary evidence of safety, tolerability and efficacy of ONTEGIMOD in LN patients. Finally, we plan to define molecular changes in sera and in circulating immune cells from ONTEGIMOD treated LN patients. Successful completion of our pilot trial will generate crucial preliminary evidence for a larger, placebo-controlled efficacy trial in the future to help develop it as a novel, first-in- class, oral LN therapeutic.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $721,611 )
2025	2025	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	14	7/28/2025	NON-COMPETING CONTINUATION	$721,611
2025	2024	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	5/7/2025	COMPETING CONTINUATION	$35,108
2025	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	12	5/7/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$35,108
														Subtotal = $721,611

Issue Date FY: 2024 ( Subtotal = $746,829 )
2024	2024	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	13	7/10/2024	COMPETING CONTINUATION	$746,829
2024	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	12	6/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$27,167
2024	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	11	6/26/2024	NON-COMPETING CONTINUATION	-$27,167
2024	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	12	2/29/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$14,724
2024	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	2/28/2024	NON-COMPETING CONTINUATION	-$14,724
2024	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	12	7/2/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $746,829

Issue Date FY: 2023 ( Subtotal = $476,182 )
2023	2023	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	12/5/2022	NON-COMPETING CONTINUATION	$428,563
2023	2023	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	1/25/2023	NON-COMPETING CONTINUATION	$47,619
														Subtotal = $476,182

Issue Date FY: 2022 ( Subtotal = $477,515 )
2022	2022	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	3/29/2022	NON-COMPETING CONTINUATION	$47,752
2022	2022	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	11/8/2021	NON-COMPETING CONTINUATION	$429,763
														Subtotal = $477,515

Issue Date FY: 2021 ( Subtotal = $478,809 )
2021	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	11/17/2020	NON-COMPETING CONTINUATION	$430,927
2021	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	9	2/2/2021	NON-COMPETING CONTINUATION	$47,882
														Subtotal = $478,809

Issue Date FY: 2020 ( Subtotal = $480,065 )
2020	2020	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	11/27/2019	NON-COMPETING CONTINUATION	$432,058
2020	2020	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	2/28/2020	NON-COMPETING CONTINUATION	$48,007
														Subtotal = $480,065

Issue Date FY: 2019 ( Subtotal = $509,784 )
2019	2019	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	12/14/2018	COMPETING CONTINUATION	$509,784
														Subtotal = $509,784

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2015	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	12/20/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $229,500 )
2015	2015	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	9/2/2015	NON-COMPETING CONTINUATION	$229,500
														Subtotal = $229,500

Issue Date FY: 2014 ( Subtotal = $229,500 )
2014	2014	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	7/30/2014	NON-COMPETING CONTINUATION	$229,500
														Subtotal = $229,500

Issue Date FY: 2013 ( Subtotal = $221,468 )
2013	2013	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	8/2/2013	NON-COMPETING CONTINUATION	$221,468
2013	2012	UNIVERSITY OF MIAMI	P.O. BOX 248106	CORAL GABLES	FL	33124	MIAMI-DADE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/10/2013	NON-COMPETING CONTINUATION	-$210,450
2013	2012	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/10/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$210,450
														Subtotal = $221,468

Issue Date FY: 2012 ( Subtotal = $229,500 )
2012	2012	UNIVERSITY OF MIAMI	P.O. BOX 248106	CORAL GABLES	FL	33124	MIAMI-DADE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/28/2012	NON-COMPETING CONTINUATION	$229,500
														Subtotal = $229,500

Issue Date FY: 2011 ( Subtotal = $227,515 )
2011	2011	UNIVERSITY OF MIAMI	P.O. BOX 248106	CORAL GABLES	FL	33124	MIAMI-DADE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/16/2011	NEW	$227,515
														Subtotal = $227,515

Grand Total All Awards = $5,028,278

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Translating oral CD11b agonist as a novel therapeutic for lupus nephritis

Award Number: R01DK084195

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2011

PERIOD OF PERFORMANCE END DATE: 06/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer