TIMP1

- Demonstrated improvements among best reported of fibrosis-reducing compounds - - Liver stiffness results complemented by positive changes in disease biomarkers and HepQuant Duo liver function test - “These findings presented today at AASLD The Liver Meeting® confirm that rencofilstat’s novel mechanism of action represents a fresh approach to the treatment of severe liver disease.” (Patrick Mayo, PhD, Hepion’s Senior VP, Clinical Pharmacology & Analytics) Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”; previously referred to as “NASH”), fibrotic diseases, hepatocellular carcinoma (“HCC”), and other chronic diseases, today announced additional efficacy data for rencofilstat, its lead drug candidate. Additional rencofilstat efficacy data from Hepion’s ‘ALTITUDE-NASH’ clinical trial was presented earlier this afternoon by Dr. Mayo in a late-breaker poster presentation at the Liver Meeting® 2023, hosted by the American Association for the Study of Liver Diseases (“AASLD”). Dr. Mayo’s presentation indicated that 17 weeks of rencofilstat treatment was associated with significant reduction in liver stiffness (FibroScan®) in MASH subjects with advanced F3, an outcome suggesting reduction in hepatic fibro-inflammation. Ongoing hepatic fibro-inflammation leads to progressive accumulation of collagen or fibrosis, increasing liver stiffness, and functional deterioration. Determination of liver stiffness often utilizes an ultrasound-based imaging technique called vibration-controlled transient elastography (“VCTE”) of which FibroScan® is the most common platform. Physicians rely on liver stiffness measurements as a diagnostic tool to help determine whether liver health is worsening or improving, as the measurements correlate well with the extent of fibrosis in liver biopsies and are predictive of the course of disease. The predictive power of liver stiffness measurements on the course of disease is further enhanced when taken together with blood-based markers of liver disease. Liver stiffness measurements are expressed in kilopascals (kPa), and Fibroscan® scores higher than 12 kPa usually represent advanced forms of fibrosis (F3 or F4 in biopsies). Reduction in liver stiffness by rencofilstat likely indicates reduction in fibroinflammation, and reduction in risk for subsequent clinical outcome. Patients who participated in the study and received a once-daily oral dose of 225 mg rencofilstat experienced an average decline of 6.02 kPa (LSMean) from their baseline measurement. When expressed as a percentage, rencofilstat treatment decreased liver stiffness by a mean of 28.8 (95% CI, -44.3, -13.4) percent from baseline over 17 weeks (p=0.001). This change from baseline was among the highest reductions ever measured in F2-F3 MASH studies (see table below). The ALTITUDE-NASH study was a multi-center, open label study in F3 MASH subjects identified by historical biopsy or having AGILE 3+ screening score of 0.53 or higher. Subjects were randomized to one of three rencofilstat treatment groups receiving either 75 mg, 150 mg, or 225 mg soft gelatin capsules once daily for a period of 17 weeks. The objective of this study was to collect a wide range of information on rencofilstat dosing levels, safety, and efficacy to optimize designs of subsequent studies. As previously announced, ALTITUDE-NASH achieved its primary and secondary endpoints, with rencofilstat demonstrating statistically significant improvements in DSI (Drug Severity Index), hepatic reserve, risk ACE (annual risk of adverse clinical outcomes) score, liver transaminases (ALT, AST), ProC3 (procollagen C 3-terminal peptide, a measure of fibrogenesis), PIIINP (procollagen 3 N-terminal peptide), TIMP1 (tissue inhibitor of metalloproteinase), hyaluronic acid, and ELF (enhanced liver fibrosis) score. The benefits of rencofilstat administration were more pronounced in subjects with more severe disease, defined as having baseline ProC3 ≥ 37.5 ng/mL. The aforementioned blood tests, combined with the additional FibroScan® results released today, demonstrated that rencofilstat improved several key indicators of liver health and function. Comparison of rencofilstat FibroScan® results to other F2-F3 MASH studies in which the study endpoint of reduction in biopsy-assessed liver fibrosis was successfully achieved RCF=Rencofilstat, EFX=Efruxifermin, PEG=Pegozafermin, RES=Resmetirom, OCA=Obeticholic Acid PLB=Placebo, CFB=Change from Baseline, QD=Every Day, QW=Every Week, Q2W=Every Two Weeks “These latest results were presented today as a late-breaker at the annual AASLD The Liver Meeting® in Boston,” commented Dr. Mayo. “These data combined with the novel liver function, multi-omic and traditional clinical data increase our ability to predict clinical outcomes in MASH patients. Both completed Phase 2 studies in MASH subjects, the 28-day Phase 2a AMBITION-NASH trial and the 17-week ALTITUDE-NASH trial, provided exponentially more information to inform our proprietary AI and risk-mitigate the on-going 1-year Phase 2b ASCEND-NASH trial. Moving forward, the demonstrated improvement in hepatic function, decrease in liver stiffness, and multi-omics at 17-weeks in the ALTITUDE-NASH trial, predict that rencofilstat is anticipated to achieve biopsy endpoints in the ASCEND-NASH trial. The ultimate goal is to determine the optimal dose of rencofilstat in individual MASH subjects to improve both quality and quantity of life in this patient population.” Stephen Harrison, MD, Hepion’s Consultant Medical Director, added, “The encouraging results of this Phase 2 study with rencofilstat bodes well for the ongoing success of Hepion’s drive to bring clinical benefits to individuals suffering from this serious medical condition. The initial results in the ALTITUDE-NASH study that were announced this past May indicated a significant improvement in liver function using the HepQuant diagnostic of liver function. Now, with the new non-invasive efficacy data announced today, I am further encouraged that Hepion continues to move in the right direction, and look forward to continuing with the ongoing Phase 2b ASCEND-NASH study. MASH is an incredibly tough disease to tackle, and we are always looking for predictive clinical signs of success. The results released today along with the HepQuant results indicates to me that Hepion is on the right track.” Hepion is pleased to invite all interested parties to participate in a conference call at 4:30 p.m. ET today, during which the additional rencofilstat efficacy data will be discussed. To participate in this conference call, please (800) 715-9871 (U.S.) or (646) 307-1963 (international), conference ID 8619177, approximately 10 minutes prior to the start time. The call will also be broadcast live and archived on the Company’s website at www.hepionpharma.com under “Events” in the Investors section. References Harrison, S.; Mayo, P.; Hobbs, T.; Zhao, C.; Canizares, C.; Foster, R.; McRae, M.; Helmke, S.; Everson, G. Hepatic Functional Improvement detected by HepQuant DuO within 120 days of treatment with Rencofilstat (RCF) in MASH subjects with ≥F3 fibrosis. (2023): AASLD late breaker. Harrison, Stephen A., et al. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. The Lancet Gastroenterology & Hepatology (2023): 8(12):1080-1093. Harrison, Stephen A., et al. A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. JHEP Reports (2022): 5(1):100563. Loomba, Rohit, et al. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. New England Journal of Medicine (2023): 389(11):998-1008. Harrison, Stephen A., et al. Effects of resmetirom on noninvasive endpoints in a 36‐week phase 2 active treatment extension study in patients with NASH. Hepatology Communications (2021): 5(4):573-588. Sanyal, Arun J., et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. Journal of Hepatology (2023): 79(5):1110-1120. 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. The content above comes from the network. if any infringement, please contact us to modify.

LA JOLLA, Calif., Aug. 15, 2023 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced it has received a Decision to Grant from the European Patent Office for a new patent which covers MN-001 (tipelukast) for the treatment of scleroderma and/or systemic sclerosis. This patent is expected to expire no earlier than June 2035. The allowed claims cover the use of MN-001 (tipelukast) for inhibiting or treating scleroderma and/or systemic sclerosis. The allowed claims cover oral administration, including tablets and capsules, as well as liquid dosage forms. The allowed claims cover a wide range of doses and a range of different dosing frequencies. Kazuko Matsuda, M.D. Ph.D., MPH., Chief Medical Officer, MediciNova, Inc., commented, “This new patent is based on positive results from a systemic sclerosis animal model study conducted recently. The Canadian Intellectual Property Office granted a similar patent earlier this year. We are very pleased to receive notice of this new patent which covers Europe, and we believe it could increase the potential value of MN-001.” About MN-001 (tipelukast) MN-001 (tipelukast) is a novel, orally administered, small molecule compound with multiple mechanisms of action which has been in clinical development for the treatment of chronic inflammatory and fibrotic diseases, among others, due to its anti-inflammatory and anti-fibrosis effects. Based on the finding that MN-001 (tipelukast) reduces triglycerides (TG) in the blood from our previous clinical trials, we conducted a Phase 2 clinical trial in patients with hypertriglyceridemia and NASH or NAFLD. Based on the findings from the in-vitro mechanistic study of MN-001 (tipelukast), a subgroup analysis of the Phase 2 clinical trial showed a stronger improvement in lipid profile in the NASH/NAFLD patients with a history of diabetes. Therefore, a new Phase 2 clinical trial was initiated to investigate the effect of MN-001 (tipelukast) in NAFLD patients with type 2 diabetes and hypertriglyceridemia. The molecular mechanism of action of MN-001 (tipelukast) includes leukotriene receptor antagonism and inhibition of phosphodiesterase (mainly 3 and 4) and 5-lipoxygenase (5-LO) and these multiple mechanisms are believed to reduce inflammation and prevent fibrosis. We have also confirmed that MN-001 (tipelukast) suppresses fibrosis-promoting genes such as LOXL2, Collagen Type 1, and TIMP-1 and suppresses inflammation-promoting genes such as CCR2 and MCP-1 in a fibrosis disease model study. Although the direct mechanism of action of MN-001 (tipelukast) on TG reduction in blood has not yet been fully clarified, we are conducting joint research with Juntendo University with the aim of elucidating this mechanism of action. In various animal models of fibrosis disease, MN-001 (tipelukast) has been shown to improve fibrosis on histopathological examination, and the FDA has granted Fast Track status to MN-001 (tipelukast) for the treatment of NASH with fibrosis. MN-001 (tipelukast) has also been granted Fast Track status and Orphan Drug designation for the treatment of idiopathic pulmonary fibrosis. In the past, we have conducted clinical trials for MN-001 (tipelukast) for the treatment of bronchial asthma and interstitial cystitis, and more than 600 patients have been treated with MN-001 (tipelukast) to date, confirming its good safety and tolerability profile. About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety profiles, MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in glioblastoma, Long COVID, and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2022 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: Geoff O'BrienVice PresidentMediciNova, Inc.info@medicinova.com

LA JOLLA, Calif., Aug. 14, 2023 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced it has received a Notice of Intention to Grant from the European Patent Office for a pending patent application which covers MN-001 (tipelukast) and MN-002 (a major metabolite of MN-001) for the treatment of advanced nonalcoholic steatohepatitis (NASH). Once issued, the patent maturing from this allowed patent application is expected to expire no earlier than May 2035. The allowed claims cover MN-001 (tipelukast) or MN-002 for the treatment of a patient diagnosed with advanced NASH. The allowed claims also cover the treatment of advanced NASH patients that exhibit spider angiomata, ascites, splenomegaly, hard liver border, palmar erythema, asterixis, portal hypertension, hepatic scarring, cirrhosis, or hepatocellular carcinoma (HCC). In addition, the allowed claims cover MN-001 (tipelukast) or MN-002 for reducing hepatic fibrosis and hepatic scarring in a patient with advanced NASH. The allowed claims cover oral administration, including tablets and capsules, as well as liquid dosage forms. The allowed claims cover a wide range of doses of MN-001 (tipelukast) or MN-002 and a range of different dosing frequencies. Kazuko Matsuda, M.D. Ph.D, MPH., Chief Medical Officer, MediciNova, Inc., commented, “We are very pleased to receive notice that this new patent will be granted as we believe it could increase the potential value of MN-001. We previously reported positive results from a Phase 2 clinical trial of MN-001 that enrolled NASH and NAFLD patients with hypertriglyceridemia. The U.S. FDA has granted Fast Track designation for MN-001 for the treatment of NASH with fibrosis. The U.S. Patent and Trademark Office previously granted a patent which covers MN-001 and MN-002 for advanced NASH with fibrosis and similar patents were granted in Japan, Korea, and Canada.” About MN-001 (tipelukast) MN-001 (tipelukast) is a novel, orally administered, small molecule compound with multiple mechanisms of action which has been in clinical development for the treatment of chronic inflammatory and fibrotic diseases, among others, due to its anti-inflammatory and anti-fibrosis effects. Based on the finding that MN-001 (tipelukast) reduces triglycerides (TG) in the blood from our previous clinical trials, we conducted a Phase 2 clinical trial in patients with hypertriglyceridemia and NASH or NAFLD. Based on the findings from the in-vitro mechanistic study of MN-001 (tipelukast), a subgroup analysis of the Phase 2 clinical trial showed a stronger improvement in lipid pro the NASH/NAFLD patients with a history of diabetes. Therefore, a new Phase 2 clinical trial was initiated to investigate the effect of MN-001 (tipelukast) in NAFLD patients with type 2 diabetes and hypertriglyceridemia. The molecular mechanism of action of MN-001 (tipelukast) includes leukotriene receptor antagonism and inhibition of phosphodiesterase (mainly 3 and 4) and 5-lipoxygenase (5-LO) and these multiple mechanisms are believed to reduce inflammation and prevent fibrosis. We have also confirmed that MN-001 (tipelukast) suppresses fibrosis-promoting genes such as LOXL2, Collagen Type 1, and TIMP-1 and suppresses inflammation-promoting genes such as CCR2 and MCP-1 in a fibrosis disease model study. Although the direct mechanism of action of MN-001 (tipelukast) on TG reduction in blood has not yet been fully clarified, we are conducting joint research with Juntendo University with the aim of elucidating this mechanism of action. In various animal models of fibrosis disease, MN-001 (tipelukast) has been shown to improve fibrosis on histopathological examination, and the FDA has granted Fast Track status to MN-001 (tipelukast) for the treatment of NASH with fibrosis. MN-001 (tipelukast) has also been granted Fast Track status and Orphan Drug designation for the treatment of idiopathic pulmonary fibrosis. In the past, we have conducted clinical trials for MN-001 (tipelukast) for the treatment of bronchial asthma and interstitial cystitis, and more than 600 patients have been treated with MN-001 (tipelukast) to date, confirming its good safety and tolerability profile. About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety pro MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in glioblastoma and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2022 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: Geoff O'Brien Vice President MediciNova, Inc. info@medicinova.com