Therapeutic Focus
At ProdIgY Biotech
We are pioneering IgY-based antibody therapeutics to revolutionize the treatment of liver diseases through microbiome modulation. Our cutting-edge research and technology harness the unique properties of avian-derived antibodies to selectively neutralize harmful microbial components while preserving beneficial gut flora. By targeting the gut-liver axis, we aim to develop first-in-class, non-invasive therapies that address the root causes of alcohol-associated hepatitis (AH).
Gut – Liver Axis
The gut-liver axis forms a critical connection between the digestive system and liver health. The liver is the first organ encountered after gut content absorption via the portal vein, exposing it to microbial metabolites, toxins, and nutrients. In turn, the liver regulates gut homeostasis by producing bile acids, Immunoglobulin A (IgA), and antimicrobial molecules.
Alcohol-Associated Liver Disease
Chronic alcohol consumption not only harms the liver directly but also disrupts the gut microbiome, leading to intestinal dysfunction that worsens liver injury. Alcohol shifts the gut microbiome into a dysbiotic state, characterized by a loss of beneficial bacteria and an increase in harmful, pro-inflammatory microbes.
This imbalance, along with alcohol itself, weakens the intestinal barrier and increases gut permeability—a phenomenon often referred to as a “leaky gut.”
As a result, harmful microbial byproducts, such as endotoxins and bacterial metabolites, enter the bloodstream and reach the liver via the portal vein, triggering inflammation, immune activation, and disease progression.
Alcohol-Associated Hepatitis: Unmet Medical Need
Alcohol-Associated Hepatitis (AH) is the most severe and acute manifestation of late-stage Alcohol-Associated Liver Disease (ALD), a condition with no FDA-approved treatments to date. Affecting more than 350,000 patients annually in the U.S. It is a significant cause of hospital admissions, with a staggering 1% of all U.S. hospitalizations in 2010 linked to AH.1
Prognostic models like the Model for End-stage Liver Disease (MELD) and Fibrosis-4 (FIB-4) scores are used to gauge the severity of the disease, which assess the risk of mortality in the next 90 days.
Current treatment options, such as corticosteroids, offer limited short-term benefits. While they can reduce the risk of death within 28 days, they do not improve survival for the following 6 months.2 This lack of effective treatment, combined with a high rate of readmissions, one-third of patients are readmitted within 90 days.3 This places an immense financial burden on healthcare systems.
Role of Cytolysin in Alcohol-Associated Hepatitis
89% of AH patients with cytolysin (+) E. faecalis died within 6 months compared to 4% of patients with cytolysin (-) E. faecalis (p<0.0001)4
Microbial profiling of ALD and AH patients reveals shifts in bacterial and fungal species compared to healthy controls. Many of these associations worsen disease in animal models and some have great prognostic value in AH patients.4,5
The most compelling finding is cytolysin, a two-subunit exotoxin produced by Enterococcus faecalis, and its association with high short -term mortality. Additionally, its presence exacerbates liver inflammation and induces hepatic injury in mouse models of ALD.
PRO-AH-001
Emerging research confirms that gut-derived bacterial toxins, particularly cytolysin, are key drivers of alcohol-associated hepatitis (AH) severity. PRO-AH-001 is the first targeted therapy designed to eliminate both the toxin and its producer, Enterococcus faecalis, reducing liver inflammation and improving patient outcomes.
Unlike broad-spectrum antibiotics, PRO-AH-001 offers selective microbial targeting, removing harmful bacteria without disrupting the balance of the gut microbiome. Its non-systemic action ensures efficacy within the gut, avoiding the risks of immune suppression or systemic side effects. Preclinical studies published in Hepatology demonstrated that oral administration of PRO-AH-001 significantly reduced ethanol-induced liver disease in microbiota-humanized mouse models.5 Highlighting its potential impact, this research was selected for the cover of the July 2023 issue of Hepatology.
PRO-AH-001 represents a new frontier in microbiome-targeted liver therapeutics, offering a safe, innovative, and highly specific approach to treating AH.
Pipeline
Alcohol-Associated Hepatitis (AH)
PRO-AH-001Alcohol-Associated Hepatitis (AH)
PRO-AH-002Primary Sclerosing Cholangitis (PSC)
PRO-PSC-001Metabolic Dysfunction-Associated Steatohepatitis (MASH)
PRO-MSH-001References
- Jinjuvadia, R., & Liangpunsakul, S. (2015). Trends in Alcoholic Hepatitis Related Hospitalizations, Financial Burden, and Mortality in the United States. Journal of Clinical Gastroenterology, 49(6), 506–511.
- Louvet, A., Thursz, M. R., Kim, D. J., Labreuche, J., Atkinson, S. R., Sidhu, S. S., et al. (2018). Corticosteroids reduce risk of death within 28 days for patients with severe alcoholic hepatitis, compared with pentoxifylline or placebo: A meta-analysis of individual data from controlled trials. Gastroenterology, 155(2), 458–468.e458.
- Han, S., Yang, Z., Zhang, T., Ma, J., Chandler, K., & Liangpunsakul, S. (2021). Epidemiology of Alcohol-Associated Liver Disease. Clinics in Liver Disease, 25(3), 483–492.
- Duan, Y., Llorente, C., Wang, L., et al. (2019). Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature, 575, 505–511.
- Cabré, N., Hartmann, P., Llorente, C., Kouno, T., Wang, Y., Zeng, S., Kim, H. Y., Zhang, X., Kisseleva, T., Iyer, S., Kudumala, S., & Schnabl, B. (2023). IgY antibodies against cytolysin reduce ethanol-induced liver disease in mice. Hepatology, 78(1), 295–306.