First-in-class, covalent, oral small molecule inhibitor targeting IRF5
IRF5 is a genetically validated driver of autoimmune diseases, including systemic lupus erythematosus, Sjögren’s disease, and rheumatoid arthritis
Proprietary AI-powered OmniDEL™ platform shows high-speed discovery, from target identification to in vivo PoC in 9 months
EMERYVILLE, Calif., April 16, 2026 (GLOBE NEWSWIRE) -- Totus Medicines, a clinical stage, precision medicine company leveraging a novel covalent DNA-encoded library + AI-powered small molecule drug discovery platform to advance therapeutics against high-value difficult to drug targets in multiple therapeutic areas, today announced the presentation of new preclinical data highlighting the discovery and proof of concept of a first-in-class covalent small molecule inhibitor of Interferon Regulatory Factor 5 (IRF5) at the American Association of Immunologists (AAI) Annual Meeting, taking place April 16, 2026, in Boston, Massachusetts.
“IRF5 represents a highly compelling but previously undruggable target at the center of autoimmune pathology. Here we demonstrate that our first-in-class covalent small molecule can selectively and effectively inhibit IRF5, opening a new therapeutic avenue for patients with autoimmune and inflammatory diseases. Selective covalent targeting of IRF5 has the potential to address multiple clinically validated drivers of autoimmune disease – including TNFα, IL-6, IL-12, and Type I interferons – with a single oral therapy,” said Dr. Zelanna Goldberg, Chief Medical Officer of Totus Medicines. “Collectively, these findings provide strong support for continued development of a potentially best-in-class oral therapy targeting IRF5.”
The poster, titled “Targeting IRF5 with a selective covalent oral small molecule attenuates Type I interferon and pro-inflammatory cytokine responses in human PBMCs and mice,” showcases comprehensive in vivo proof of concept, demonstrating strong inhibition of pro-inflammatory cytokines in normal and CD34+ humanized mice, while showing clear covalent target engagement with selectivity for IRF5 over related family members.
Poster Presentation Details:
Event: American Association of Immunologists (AAI) Annual Meeting – IMMUNOLOGY2026
Date: April 16, 2026
Abstract #: 581
Location: Thomas M. Menino Convention & Exhibition Center (MCEC), Boston, MA
Key Highlights:
- First-in-class covalent, oral IRF5 inhibitor identified using the proprietary Totus OmniDEL™ platform in cell lysates
- High selectivity for IRF5 over related family members
- Covalent target engagement confirmed by mass spectrometry
- Inhibition of cytokine secretion in TLR-stimulated primary human immune cells
- Selective inhibition of IRF5, but not IRF3, nuclear translocation
- In vivo inhibition of pro-inflammatory cytokines in R848-treated normal and humanized mouse models
- Improved chemical matter demonstrates enhanced potency both in vitro and in vivo, to be presented at an upcoming scientific meeting.
About Totus Medicines
Totus Medicines is a clinical-stage, precision medicines company, discovering novel covalent small molecules against previously undrugged or difficult to drug targets, based on its proprietary AI-powered OmniDEL platform (DNA-encoded covalent library technology). The company's lead program, TOS-358, the first and only covalent PI3Kα inhibitor in clinical development, has shown efficacy, response and long-term disease control with class-leading tolerability in breast, endometrial and head & neck cancers. The company's lead pre-clinical program is targeting IRF5, a key genetically validated but previously undrugged target across multiple I&I indications.
For more information, please visit www.totusmedicines.com
Contact:
ir@totusmedicines.com
External Contact:
Brian Mullen
LifeSci Advisors, LLC
Managing Director
bmullen@lifesciadvisors.com
+1.203.461.1175
