Rencofilstat Produces Positive Outcomes in Translational Study on Idiopathic Pulmonary Fibrosis
- Rencofilstat shifted protein profiles of IPF tissue towards normalized expression more robustly than standard-of-care drugs
- Rencofilstat monotherapy altered levels of 8-28% of proteins identified in PCLuS, 2-4 times greater than nintedanib or pirfenidone
- Rencofilstat in combination with nintedanib altered levels of 16-42% of proteins, 2.7-7.8 times more than nintedanib alone
- Rencofilstat in combination with pirfenidone altered levels of 12-46% of proteins, 1.3-2.2 times more than pirfenidone alone
- Majority of rencofilstat's effects on overlapping proteins were opposite to disturbances reported in large IPF studies
- Rencofilstat's normalizing actions spanned important classes of proteins
- None.
– Proteomics analysis showed that rencofilstat improved aberrant protein profiles in IPF tissues –
– Superior effects of rencofilstat alone and in combination with pirfenidone and nintedanib –
EDISON, N.J., Sept. 14, 2023 (GLOBE NEWSWIRE) -- Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis (“NASH”), fibrotic diseases, hepatocellular carcinoma (“HCC”), and other chronic diseases, today announced positive results from a translational research study in which Hepion’s lead drug candidate, rencofilstat, was administered to diseased human lung tissue from patients with idiopathic pulmonary fibrosis (“IPF”).
Proteomic quantitation of nearly 2,000 proteins showed that rencofilstat shifted protein profiles of IPF tissue towards normalized expression more robustly than the two standard-of-care drugs, nintedanib and pirfenidone, and with strong combinational effects especially when co-administered with nintedanib.
In this study, FibroFind Ltd. (Newcastle, UK) obtained diseased lung tissue from two individuals undergoing lung transplantation for end-stage IPF, a deadly fibrotic lung disease. Precision cut lung slices (PCLuS) were made and individually incubated in culture with rencofilstat, nintedanib, pirfenidone, or combinations of the compounds for four days. Proteomics analyses were conducted on lung tissues at the end of treatment by PhenoSwitch Bioscience (Sherbrooke, Canada) and identified 1,953 unique proteins in the samples. The changes in abundance of the proteins produced by the drug treatments relative to vehicle control were determined and compared to abnormal protein profiles in IPF lungs reported in multiple proteomics studies over the past 5 years.1–3 These analyses demonstrated:
- Rencofilstat monotherapy altered levels of between 8 and
28% of the 1,953 proteins identified in PCLuS depending on dose and donor. This represented changes 2 - 4-times greater than nintedanib or pirfenidone in PCLuS from the first donor, and 2-fold greater than nintedanib in the second donor; - Rencofilstat, in combination with nintedanib, altered levels of 16 -
42% of the 1,953 proteins depending on donor, which represented 2.7 - 7.8-fold more than nintedanib alone; - Rencofilstat, in combination with pirfenidone, altered levels of 12 -
46% of the 1,953 proteins depending on donor, which represented 1.3 - 2.2-fold more proteins altered by pirfenidone alone; - Among three studies reporting differentially expressed proteins in IPF lungs compared to normal controls,1–3 up to
41% of the reported differential proteins were also found in the current PCLuS study to be altered by rencofilstat alone or in combination. Furthermore, the majority of rencofilstat’s effects on the overlapping proteins (increased or decreased abundance) were opposite to the disturbances reported in the large IPF studies, which is consistent with disease-normalizing actions of rencofilstat; - The normalizing actions of rencofilstat monotherapy and combinations spanned many important classes of proteins, including multiple isoforms of collagens, laminins, integrins, keratins, and MHC antigens. Additional, notable proteins whose abundance was positively shifted by rencofilstat included TIMP3, nidogen, surfactant protein C, cathepsin B, myeloperoxidase, lysozyme, mimecan, and asporin; and
- Cyclophilin B protein, a primary target of rencofilstat, was reported to be elevated in IPF lung tissue,1,2 suggesting a pathogenic role, and rencofilstat alone and in combination in PCLuS decreased tissue levels of cyclophilin B.
“The technological advances in recent years in proteomics and other “omics” methodologies have blown the doors wide open on the scope and complexity of molecular changes in diseases like IPF, helping us to understand why so many narrowly targeted drug candidates have failed to have therapeutic effects,” commented Dr. Daren Ure, Hepion’s Chief Scientific Officer. “Rencofilstat’s suppression of fibrotic collagen production through cyclophilin B inhibition is one well-established mechanism, but inhibition of additional cyclophilin isoforms likely helps to explain rencofilstat’s robust effects in the present study. Rencofilstat alone shifted protein profiles more extensively than nintedanib and pirfenidone in most instances, and rencofilstat combinations were superior to every monotherapy, which is very encouraging. The old dogma in drug development about narrowly targeted drugs needs to adapt to emerging insights on complex diseases, and rencofilstat is one such candidate that is advancing that new paradigm of systems-targeting drug.”
Dr. Robert Foster, Hepion’s CEO remarked, “As our Phase 2b NASH clinical trial progresses, we continue our nonclinical research on cancer and other fibrotic indications such as IPF with the aim of expanding our understanding of rencofilstat’s therapeutic and commercial potential. The new actions of rencofilstat that continue to be uncovered complement and strengthen the anti-fibrotic activities that we have seen in many experimental models of NASH, and the numerous positive outcomes in previous NASH clinical trials. The new findings in human IPF samples provide a good foundation for advancing rencofilstat in fibrotic diseases, which potentially also includes IPF.”
REFERENCES
| 1. | Konigsberg IR, Borie R, Walts AD, et al. Molecular Signatures of Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2021;65(4):430-441. doi:10.1165/RCMB.2020-0546OC |
| 2. | Tian Y, Li H, Gao Y, et al. Quantitative proteomic characterization of lung tissue in idiopathic pulmonary fibrosis. Clin Proteomics. 2019;16(1):1-11. doi:10.1186/S12014-019-9226-4 |
| 3. | Åhrman E, Hallgren O, Malmström L, et al. Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. J Proteomics. 2018;189:23-33. doi:10.1016/J.JPROT.2018.02.027 |
About Hepion Pharmaceuticals
The Company's lead drug candidate, rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental disease models and is currently in Phase 2 clinical development for the treatment of NASH. In November 2021, the U.S. Food and Drug Administration (“FDA”) granted Fast Track designation for rencofilstat for the treatment of NASH. That was followed in June 2022 by the FDA’s granting of Orphan Drug designation to rencofilstat for the treatment of HCC.
Hepion has created a proprietary Artificial Intelligence deep machine learning (“AI/ML”) platform designed to better understand disease processes and identify patients that are rencofilstat responders. This AI/ML has the potential to shorten development timelines and increase the observable differences between placebo and treatment groups. In addition, Hepion’s AI/ML can be used to drive its ongoing NASH and HCC clinical development programs and identify other potential therapeutic indications for cyclophilin inhibition with rencofilstat.
Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission.
For further information, please contact:
Stephen Kilmer
Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580
skilmer@hepionpharma.com
