Drug Farm Reports Positive Preclinical Findings Showing DF-003 Reduces Kidney Inflammation and Fibrosis
Drug Farm has 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, held in Denver, Colorado, highlighting the potential of ALPK1 inhibition as a therapeutic approach for kidney diseases associated with chronic inflammation and tissue damage.
The research provides new insights into the role of primary cilia, specialized cellular structures found on kidney tubular epithelial cells, in connecting bacterial pathogen recognition with inflammatory signaling and fibrotic changes in kidney tissue. According to the study, these structures may play an important role in coordinating innate immune responses that contribute to the progression of chronic kidney injury.
Importantly, treatment with DF-003 reduced histologically assessed kidney fibrosis in a rat model of obstructive kidney injury and suppressed inflammatory responses in primary human kidney epithelial cells. The findings were supported by complementary experiments involving human kidney organoids, genetically modified animal models, and pharmacological inhibition of ALPK1.
Together, the results provide preclinical evidence that ALPK1 is involved in the mechanisms underlying renal inflammation and fibrosis. They also strengthen the scientific rationale for investigating DF-003 beyond its existing development focus in ROSAH syndrome, potentially expanding its future application to broader kidney disease indications.
Although the findings are encouraging, the research remains at the preclinical stage. Further studies will be needed to establish the compound’s safety, efficacy, appropriate dosing, and potential clinical benefits in people with chronic kidney disease.
Research Presented at ASN Kidney Week 2026
The findings were presented in a scientific poster titled “Primary cilia couple host-pathogen sensing to chronic kidney disease progression.” Dr. Amandine Viau presented the research during the poster session “CKD: Mechanisms of Injury and Fibrosis – 1” at ASN Kidney Week 2026.
The presentation took place on Thursday, October 22, 2026, from 10:00 a.m. to 12:00 p.m. Mountain Daylight Time at the Colorado Convention Center in Denver, Colorado.
The full dataset was also reported as published on bioRxiv, an online preprint platform, under the DOI 10.64898/2026.04.24.720658.
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, alongside other collaborating research institutions.
The collaborative investigation examined how kidney epithelial cells respond to bacterial pathogens and non-infectious tissue injury, focusing on the relationship between primary cilia, innate immune signaling, and the development of fibrosis. By combining different experimental systems, the researchers sought to determine whether these mechanisms represent a shared biological pathway contributing to chronic kidney damage.
Understanding the Role of Primary Cilia in Kidney Disease
Chronic kidney disease is characterized by persistent kidney damage and a progressive decline in renal function. In many patients, ongoing inflammation and the accumulation of fibrotic tissue contribute to the loss of healthy kidney structures and the deterioration of the organ’s ability to filter blood and maintain physiological balance.
Kidney fibrosis involves the excessive accumulation of extracellular matrix components, including collagen, within damaged tissue. Although fibrosis can develop as part of the body’s response to injury, sustained fibrotic activity can disrupt normal tissue architecture and impair kidney function.
Inflammation is another important contributor to CKD progression. When kidney cells encounter infectious agents or tissue damage, they can activate signaling pathways that recruit immune cells and stimulate the production of inflammatory mediators. If these responses persist, they may contribute to additional tissue injury and promote fibrotic remodeling.
The Drug Farm-supported study investigated primary cilia as potential coordinators of these processes. Primary cilia are small, antenna-like structures extending from the surface of many cells. They participate in sensing and responding to signals from the surrounding environment and can influence several cellular signaling pathways.
The researchers found that primary cilia on kidney tubular epithelial cells could interact directly with uropathogenic Escherichia coli (UPEC), bacteria associated with urinary tract infections that can reach the kidneys and cause pyelonephritis.
This interaction was associated with inflammatory responses in kidney cells, suggesting that primary cilia may contribute to the recognition of bacterial pathogens and the initiation of immune signaling within renal tissue.
The study further indicated that primary cilia participate in responses to both infectious and non-infectious kidney injuries. This observation is significant because chronic kidney disease can arise from multiple causes, and shared inflammatory and fibrotic mechanisms may offer opportunities for therapeutic intervention across different disease settings.
DF-003 Demonstrates Antifibrotic Activity in an Animal Model
One of the principal findings was that oral treatment with DF-003 reduced kidney fibrosis in rats subjected to unilateral ureteral obstruction (UUO).
UUO is an established experimental model used to investigate renal injury and fibrosis. The procedure obstructs one ureter, disrupting normal urine drainage and triggering a series of pathological changes within the affected kidney. These changes include inflammatory signaling, tissue remodeling, and the accumulation of fibrotic material.
In this model, researchers compared animals receiving DF-003 with those receiving vehicle treatment. Histological assessment showed that the DF-003-treated animals had reduced kidney fibrosis compared with the vehicle-treated group.
The study also reported changes in the expression of genes associated with inflammation and fibrotic tissue remodeling. DF-003 reduced the expression of the inflammatory genes Ccl2 and Cxcl1, which are involved in signaling processes associated with immune-cell recruitment and inflammatory responses.
The treatment also reduced the expression of the fibrotic genes Col1a1, Tgfb1, and Acta2. These genes are associated with collagen production, transforming growth factor beta signaling, and cellular processes involved in tissue remodeling and fibrosis.
The findings suggest that DF-003’s activity may extend beyond the suppression of individual inflammatory signals. By affecting both inflammatory and fibrotic gene-expression patterns, ALPK1 inhibition may influence interconnected processes involved in the progression of kidney injury.
However, the results do not yet establish whether DF-003 can prevent long-term kidney function decline or reverse established fibrosis in humans. Additional research will be required to determine how these preclinical observations translate into clinically meaningful outcomes.
Suppression of Inflammatory Responses in Human Kidney Cells
In addition to the animal experiments, the researchers evaluated DF-003 in primary human kidney epithelial cells to investigate the relevance of ALPK1 signaling in human renal tissue.
The experiments examined inflammatory responses induced by pharmacological activation of ALPK1. Treatment with DF-003 inhibited these responses, supporting the functional relevance of the pathway in human kidney epithelial cells.
This finding complements the results obtained in the rat model. While the animal experiments demonstrated reduced renal fibrosis in a whole-organism setting, the human cell experiments provided evidence that DF-003 can suppress inflammatory signaling in cells relevant to kidney biology.
The use of primary human cells is particularly important during early therapeutic research because it can help investigators determine whether mechanisms observed in animal models are also active in human biological systems.
Nevertheless, cell-based experiments cannot fully reproduce the complexity of chronic kidney disease. Human kidney function depends on interactions among multiple cell types, immune responses, blood vessels, metabolic processes, and other physiological factors. Clinical studies will therefore be necessary to establish whether the observed effects translate into therapeutic benefit.
The research also incorporated human kidney organoids, which are laboratory-grown tissue models designed to reproduce selected features of kidney development and function. Together with the other experimental approaches, these models helped investigators examine the relationship between primary cilia and fibro-inflammatory signaling from multiple perspectives.
ALPK1 Connects Bacterial Recognition With Inflammatory Signaling
A central focus of the study was ALPK1, an innate immune signaling protein that recognizes ADP-heptose, a metabolite associated with bacterial biology.
When ALPK1 detects ADP-heptose, it activates downstream signaling involving TIFA and the nuclear factor kappa B (NF-κB) pathway. NF-κB is an important regulator of inflammatory gene expression and contributes to immune responses under a variety of physiological and pathological conditions.
The study indicated that primary cilia influence cellular responses to ADP-heptose and the resulting ALPK1-mediated inflammatory signaling. This suggests that primary cilia may help coordinate how kidney epithelial cells detect environmental signals and respond to bacterial components.
The proposed pathway provides a potential mechanistic connection between pathogen recognition and the persistent inflammatory responses that can contribute to chronic kidney injury.
The researchers also investigated whether the same pathway could be involved in kidney damage arising from non-infectious causes. Experimental pyelonephritis and ureteral obstruction induced similar changes involving primary cilia and overlapping fibro-inflammatory signaling programs.
These findings suggest that primary cilia and ALPK1 may participate in biological responses shared by different forms of kidney injury rather than being relevant exclusively to bacterial infection.
For drug development, a shared mechanism could be important because it may support the investigation of a targeted therapy across multiple disease settings. However, the extent to which ALPK1 contributes to individual CKD conditions remains to be established through further disease-specific research.
Genetic Experiments Further Support ALPK1 as a Therapeutic Target
The investigation included genetic experiments designed to assess whether ALPK1 directly contributes to renal fibrosis.
Researchers found that genetic deletion of ALPK1 attenuated kidney fibrosis in rats subjected to ureteral obstruction. This observation provides an additional line of evidence supporting the role of ALPK1 signaling in fibrotic responses.
The genetic findings are particularly relevant because they complement the pharmacological results obtained with DF-003. A reduction in fibrosis following genetic disruption of ALPK1 suggests that the pathway itself contributes to the disease process, rather than the observed effects being attributable solely to an unrelated property of the compound.
When genetic and pharmacological findings point in the same direction, they can strengthen the rationale for pursuing a biological target during drug discovery and development.
In this case, the combined findings support further investigation of ALPK1 inhibition as a strategy for reducing kidney inflammation and fibrosis. Future research will need to determine the relative contribution of ALPK1 to different kidney disease mechanisms, as well as the degree and duration of inhibition required to produce a beneficial effect.
Researcher Highlights a Potentially Actionable Mechanism
Dr. Amandine Viau, the presenting author, emphasized the importance of the connection between pathogen recognition and the inflammatory processes associated with chronic kidney disease.
“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,” Dr. Viau said.
She explained that the research demonstrated how primary cilia coordinate these responses through pathways involving ALPK1. The team also found that pharmacological inhibition with DF-003 reduced kidney inflammation and fibrosis in preclinical models.
According to Dr. Viau, the results identify a potentially actionable mechanism connecting innate immune activation with kidney injury and provide a foundation for further therapeutic investigation.
The findings may help researchers better understand how cellular sensing mechanisms influence the transition from acute kidney injury or infection-associated damage to persistent inflammation and fibrotic remodeling.
They also raise questions about whether targeted modulation of these pathways could reduce tissue damage without excessively interfering with the body’s normal immune defenses. Such questions will be important in subsequent studies evaluating the safety and therapeutic potential of ALPK1 inhibitors.
Drug Farm Sees Potential Beyond ROSAH Syndrome
Henri Lichenstein, Ph.D., Chief Executive Officer of Drug Farm, said the findings strengthen the scientific rationale for investigating DF-003 in kidney disease.
“These findings provide compelling preclinical evidence supporting the therapeutic potential of DF-003 in kidney disease,” Lichenstein said.
He highlighted the reduction in kidney fibrosis following oral administration of DF-003 in an established animal model, alongside the compound’s ability to suppress inflammatory signaling in human kidney cells.
Lichenstein also noted that identifying ALPK1 as a mediator connecting pathogen recognition, kidney inflammation, and fibrosis supports the company’s plans to expand its development efforts beyond ROSAH syndrome into broader kidney disease indications.
The potential expansion could provide an opportunity for Drug Farm to investigate whether its proprietary ALPK1 inhibitor has applications in conditions characterized by persistent renal inflammation and progressive fibrosis.
However, the newly reported kidney findings are preclinical and should not be interpreted as evidence that DF-003 is an established treatment for CKD. Additional research will be necessary to evaluate its pharmacological properties, safety profile, dosing requirements, and potential effectiveness in relevant patient populations.
Implications for Future Kidney Disease Research
The findings presented at ASN Kidney Week 2026 provide a scientific basis for further investigating the relationship between primary cilia, innate immune recognition, ALPK1 signaling, and renal fibrosis.
The study’s combination of animal models, primary human kidney epithelial cells, human kidney organoids, and genetic approaches offers complementary evidence supporting the involvement of this pathway in kidney injury.
For DF-003, the reduction in fibrosis in the UUO rat model is a notable preclinical result, particularly when considered alongside the suppression of inflammatory signaling in human kidney cells and the findings from ALPK1 genetic disruption experiments.
Further studies will need to determine whether these effects can be reproduced across additional models of kidney disease and whether treatment can preserve kidney function over time. Researchers will also need to assess the compound’s safety, identify appropriate therapeutic exposure levels, and establish whether ALPK1 inhibition offers advantages over existing approaches to managing kidney disease.
If supported by subsequent research, the pathway could offer a new direction for developing targeted therapies against the inflammatory and fibrotic mechanisms that contribute to CKD progression.
For now, Drug Farm’s findings establish a promising preclinical foundation for continued investigation of DF-003 and reinforce the potential importance of ALPK1-mediated signaling in kidney inflammation and fibrosis.
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.