Abstract: FR-PO0806
Design of a Single-Center, Phase 1b Trial Evaluating the Efficacy and Safety of First-in-Class Myeloid-Directed ONT01 as a Treatment for Lupus Nephritis
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Gupta, Vineet, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Wadhwani, Shikha, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Balza Pineda, Santiago, Allosite Therapeutics, Miami, Florida, United States
- Lopez-Rodriguez, Darlah M., Allosite Therapeutics, Miami, Florida, United States
- Niewold, Timothy B., Hospital for Special Surgery Department of Medicine, New York, New York, United States
Background
Lupus nephritis (LN) is an autoimmune disease caused by underlying systemic inflammation. Complete remission rates remain low despite new approved agents in recent years. Myeloid cell activation and kidney infiltration are key disease drivers. However, current treatments do not directly target these cells. CD11b is a key receptor on myeloid cells and a validated therapeutic target. Our pre-clinical studies showed that a novel CD11b small molecule agonist, ONT01, therapeutically treats LN. Recent Phase 1 studies with ONT01 in oncology also show that it has a good safety profile, no dose limiting toxicity, and desirable dose-dependent systemic exposure in patients.
Methods
We provide a design for phase 1b clinical trial to evaluate the efficacy and safety of ONT01 for the treatment of LN. Study IND has been approved by the regulatory agencies. We plan to enroll a total of 25 LN patients with active nephritis and no or partial responses to standard of care treatments in this phase of the study. ONT01 will be administered orally BID.
Results
Our phase 1b trial will provide insights into potential efficacy and safety of this novel therapeutic in LN patients. In pre-clinical models, ONT01 treatment resulted in reduction of splenomegaly, splenic expansion of CD11b+ leukocytes, alopecia, decreased levels of LN biomarkers (anti-dsDNA antibodies, IL-6 and suPAR, proteinuria) and kidney pathology. The planned study will add ONT01 on top of the standard of care, will help establish the highest safe dose of ONT01 and will provide, for the first time, mechanistic proof of concept for targeting systemic myeloid cell activation and their kidney infiltration via integrin CD11b. In a recently completed clinical trial in oncology, ONT01 was well tolerated with no drug-related serious or Grade ≥3 adverse events.
Conclusion
The evaluation of the first- and best-in-class novel CD11b allosteric agonist, ONT01, in LN patients will provide important data for future phase 2 studies. Given the central role of innate immune cells and the toll like receptor pathways, our studies will also establish additional criteria for targeting overactive myeloid cells with novel CD11b agonist ONT01 as a novel, personalized approach.
Funding
- NIDDK Support