Drug Farm today announced positive preclinical findings demonstrating that DF-003, its proprietary, first-in-class oral ALPK1 inhibitor, reduced kidney inflammation and fibrosis in experimental models of chronic kidney disease (CKD). The findings were presented at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado.

The research identifies a previously unrecognized role for primary cilia in linking bacterial pathogen recognition and tissue injury to inflammatory and fibrotic responses that contribute to CKD progression. Importantly, treatment with DF-003 reduced renal fibrosis in a rat model of obstructive kidney injury and suppressed inflammatory responses in primary human kidney epithelial cells, providing new mechanistic and pharmacological evidence supporting ALPK1 inhibition as a potential therapeutic strategy for kidney diseases.

Presentation Details

The poster, titled “Primary cilia couple host-pathogen sensing to chronic kidney disease progression,” was presented by Dr. Amandine Viau during the poster session “CKD: Mechanisms of Injury and Fibrosis – 1,” at ASN Kidney Week 2026 with full dataset published in BioRxiv (doi: https://doi.org/10.64898/2026.04.24.720658).

The presentation took place on Thursday, October 22, 2026, from 10:00 AM to 12:00 PM MDT at the Colorado Convention Center in Denver, Colorado.

The research was conducted through an international collaboration involving investigators from Université Paris Cité, INSERM, Institut Imagine, Institut Necker Enfants Malades, Institut Pasteur, Institut Cochin and Drug Farm, together with other collaborating research institutions.

Key Findings from the Preclinical Research

The study investigated how primary cilia, specialized structures extending from kidney tubular epithelial cells, coordinate innate immune responses to bacterial infection and tissue injury and contribute to renal inflammation and fibrosis.

Using kidney epithelial cell cultures, human kidney organoids, genetically modified animal models, and pharmacological inhibition of ALPK1, researchers identified a shared fibro-inflammatory signaling mechanism connecting host-pathogen interactions with CKD progression.

Key findings included:

  • DF-003 reduced kidney fibrosis in an animal model: In rats subjected to unilateral ureteral obstruction (UUO), an established experimental model of renal fibrosis, oral treatment with DF-003 reduced histologically assessed kidney fibrosis compared with vehicle treatment. DF-003 also reduced the expression of inflammatory genes, including Ccl2 and Cxcl1, and fibrotic genes, including Col1a1, Tgfb1, and Acta2.

  • DF-003 suppressed inflammatory responses in human kidney cells: In primary human kidney epithelial cells, DF-003 inhibited inflammatory cytokine responses induced by pharmacological activation of ALPK1, supporting the functional relevance of the pathway in human renal epithelial cells.

  • Primary cilia directly interact with bacterial pathogens: Primary cilia on kidney tubular cells were shown to bind uropathogenic Escherichia coli (UPEC), contributing to inflammatory responses associated with kidney injury.

  • Infectious and non-infectious kidney injuries activate overlapping pathways: Experimental pyelonephritis and ureteral obstruction induced similar ciliary changes and fibro-inflammatory signaling programs, suggesting that primary cilia coordinate responses to multiple forms of kidney injury.

  • Genetic disruption of ALPK1 reduced renal fibrosis: Genetic deletion of ALPK1 attenuated kidney fibrosis in rats subjected to ureteral obstruction, independently supporting the contribution of ALPK1 signaling to renal fibrotic responses.

  • Primary cilia regulate ALPK1-mediated innate immune signaling: The study demonstrated that primary cilia influence cellular responses to ADP-heptose, a bacterial metabolite recognized by ALPK1, which activates downstream TIFA and NF-κB inflammatory signaling.

Together, these findings identify primary cilia and ALPK1 as important components of a fibro-inflammatory pathway associated with chronic kidney injury and demonstrate that pharmacological ALPK1 inhibition with DF-003 can reduce renal inflammation and fibrosis in preclinical models.

Researcher Perspective

“These findings reveal a previously unrecognized connection between the kidney’s ability to detect bacterial pathogens and the inflammatory processes that contribute to chronic kidney disease,” said Dr. Amandine Viau, presenting author of the study. “We demonstrated that primary cilia coordinate these responses through pathways involving ALPK1, and importantly, that pharmacological inhibition with DF-003 reduces kidney inflammation and fibrosis in preclinical models. The findings identify a potentially actionable mechanism linking innate immune activation to kidney injury and provide a strong foundation for further therapeutic investigation.”

Company Statement

“These findings provide compelling preclinical evidence supporting the therapeutic potential of DF-003 in kidney disease,” said Henri Lichenstein, Ph.D., Chief Executive Officer of Drug Farm. “We are particularly encouraged by the demonstration that oral treatment with DF-003 reduced kidney fibrosis in an established animal model, together with its ability to suppress inflammatory signaling in human kidney cells. The identification of ALPK1 as a key mediator connecting pathogen recognition, kidney inflammation, and fibrosis substantially strengthens the scientific rationale for expanding our development efforts beyond ROSAH syndrome into broader kidney disease indications.”

About DF-003

DF-003 is a proprietary, first-in-class drug developed by Drug Farm’s MedChem5 platform that inhibits the activity of ALPK1 and its disease-causing variants. DF-003 has demonstrated evidence of clinical improvement across multiple symptoms of ROSAH syndrome in an ongoing Phase 1b study (NCT06395285). DF-003 is among the first AI-developed drugs advancing toward a Phase 3 trial.

In preclinical kidney disease research, DF-003 has demonstrated anti-inflammatory and anti-fibrotic activity, including reductions in kidney fibrosis in an experimental model of obstructive renal injury. DF-003 also has therapeutic potential for heart diseases based on efficacy observed in preclinical models.

DF-003 has received Fast Track, Orphan Drug, Rare Pediatric Disease, and Rare Disease Evidence Principles designations from the FDA. The discovery of DF-003 has been published in Nature Communications.

About Drug Farm

Drug Farm is a private biotechnology company developing innovative treatments targeting innate immunity for hepatitis B, heart and kidney diseases, and ROSAH syndrome. Its proprietary IDInVivo platform integrates genetics and artificial intelligence to identify and validate novel drug targets directly in living systems. Drug Farm is advancing multiple first-in-class drug candidates into clinical development.

For more information, please visit: https://www.drug-farm.com.

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