ABCA1

LA JOLLA, Calif., May 28, 2024 (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 that MediciNova conducted two poster presentations at the 92nd European Atherosclerosis Society (EAS) 2024 Congress held online May 26-29, 2024. MediciNova’s Chief Medical Officer, Kazuko Matsuda, MD PhD MPH presented an update on the Company’s “STUDY PROTOCOL TO EVALUATE MN-001’S (TIPELUKAST) EFFICACY, SAFETY AND TOLERABILITY IN SUBJECTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) (Abstract # 810) “, which included Clinical background, Study objectives, Study design, Inclusion Criteria and Study status of Phase 2 clinical trial ongoing in the US. As of 25 April 2024, 33 patients were enrolled, 19 patients were randomized, 14 patients completed the study. Three subjects reported serious adverse events (SAE) and were all considered “Unlikely related” or “Unrelated“ to study drug. MediciNova’s Dr. Huicheng Qi presented “MN-002, THE METABOLITE OF MN-001 (TIPELUKAST) PROMOTES MACROPHAGE CHOLESTEROL EFFLUX (Abstract # 856)”, demonstrating positive data regarding cholesterol efflux capacity by MN-001 (Tipelukast) and MN-002. This is a collaborative effort between MediciNova and Professor Masatsune Ogura at Department of Clinical Laboratory Technology, Juntendo University and Professor Takashi Miida at Department of Clinical Laboratory Medicine, Juntendo University. Objectives of this study are to evaluate the effects of MN-001 and its major active metabolite MN-002 on cholesterol efflux capacity in THP-1 *1macrophages. ABCA1 *2 and ABCG1 *3 is known to play important roles in the reverse cholesterol transport system. Macrophages derived from THP-1 *3 cells were used to analyze the effect of MN-001 and MN-002 on ABCA1 and ABCG1 mRNA expression was measured by RT-PCR and protein expression was measured by Western blotting. Next, the effects of MN-002 on Apolipoprotein AI (ApoA1) *4 dependent and High-Density Lipoprotein (HDL) dependent cholesterol efflux in THP-1 macrophages were determined, respectively. Finally, analyzed the involvement of Protein Kinase A (PKA) in the mechanism of action of MN-002 using a PKA inhibitor. The data presented in the abstract demonstrated the following: MN-002 enhances ApoA1 and HDL mediated cholesterol efflux. MN-002 increased 44.3% in ApoA1-mediated cholesterol efflux capacity compared to the control group (DMSO). MN-002 increased 15.3% in HDL-mediated cholesterol efflux capacity compared to the control group (DMSO). MN-002 increases ABCA1 and ABCG1 protein levels in dose-dependent manner MN-002 increased ABCA1 protein expression in a dose-dependent manner compared to the control group (DMSO); ABCA1 protein increased approximately 2-fold with 10 µM of MN-002. MN-002 increased ABCG1 protein expression in a dose-dependent manner compared to the control group (DMSO); ABCG1 protein increased approximately 2.8-fold with 10 µM of MN-002. MN-002 increases ABCA1/ ABCG1/ LXR-alpha mRNA levels. MN-002 increased ABCA1 mRNA expression in a time and dose-dependent manner compared to the control group (DMSO). mRNA expression of ABCA1 increased about 3-fold with 24 hours exposure of 10 µM MN-002. MN-002 increased ABCG1 mRNA expression in a time and dose-dependent manner compared to the control group (DMSO). mRNA expression of ABCA1 by increased 5.4-fold with 24 hours exposure of 10 µM MN-002 MN-002 increased LXR-alpha mRNA expression in a time- and dose-dependent manner compared to the control group (DMSO). mRNA expression of ABCA1 increased 2.4-fold with 24 hours exposure of 10 µM MN-002. MN-002 increases ABCA1 protein level independent of PKA signaling pathway. MN-002 increased ABCA1 protein expression compared to the control group (DMSO); conditions in which a PKA inhibitor did not cancel the effect of MN-002 to increase ABCA1 protein expression. Kazuko Matsuda, M.D., Ph.D., M.P.H., Chief Medical Officer, MediciNova, Inc., commented, “We are very pleased to present our clinical trial status and positive research outcomes at the EAS Congress 2024. We have randomized almost half of the randomization goal with our ongoing Phase 2 clinical trial. With the collaborative research with Juntendo University regarding the mechanism of action of MN-001/MN-002 in lipid metabolism, we identified that MN-002, the major metabolite of MN-001 (Tipelukast), had significant positive effects on both ABCA1, ABCG1 expression.” *1 About THP-1 THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. *2 About ABCA1: ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein which in humans is encoded by the ABCA1 gene. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. ABCA1 is an integral cell membrane protein that protects against cardiovascular disease. *3 About ABCG1 The primary function of ATP-binding cassette transporter G1 (ABCG1) is to efflux cholesterol to spherical high-density lipoproteins (HDL). ABCG1 also effluxes cholesterol to low-density lipoproteins (LDL), liposomes and cyclodextrin and it exports sphingomyelin, phosphatidylcholine and oxysterols to HDL and albumin. *4 About Apolipoprotein AI (ApoA1) Apolipoprotein A-I (Apo A-I) is a major protein that has specific roles in the lipid metabolism. It promotes cholesterol efflux by accepting fats from cells to the liver for excretion. AboutNAFLD,Type2DiabetesMellitus(T2DM),andHypertriglyceridemia NAFLD is considered the hepatic manifestation of metabolic syndrome; studies have reported that 50% of patients with metabolic syndrome also have NAFLD. There is sufficient clinical and epidemiological evidence supporting the assertion that NAFLD is strongly associated with an increased prevalence and incidence of cardiovascular disease, T2DM, chronic kidney disease, and malignancy. The presence of dyslipidemia (hypercholesterolemia, hypertriglyceridemia, or both) is reported in 20 - 80% of NAFLD cases. AboutMN-001 MN-001 (tipelukast) is a novel, orally bioavailable, small molecule compound thought to exert its effects through several mechanisms to produce its anti-inflammatory and anti-fibrotic activity in preclinical models, including leukotriene (LT) receptor antagonism, inhibition of phosphodiesterases (PDE) (mainly 3 and 4), and inhibition of 5-lipoxygenase (5-LO). The 5-LO/LT pathway has been postulated as a pathogenic factor in fibrosis development, and MN-001's inhibitory effect on 5-LO and the 5-LO/LT pathway is a novel approach to treat fibrosis. MN-001 has been shown to down-regulate expression of genes that promote fibrosis including LOXL2, Collagen Type 1 and TIMP-1. MN-001 has also been shown to down-regulate expression of genes that promote inflammation including CCR2 and MCP-1. In addition, MN-001 was found to inhibit triglyceride synthesis in hepatocytes by inhibiting arachidonic acid uptake. 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 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, 2023 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: David H. Crean, Ph.D. Chief Business Officer MediciNova, Inc info@medicinova.com

This review paper summarizes numerous research studies that address the role of kidney cholesterol and lipid accumulation in the development and progression of chronic kidney disease (CKD).ZyVersa’s Cholesterol Efflux Mediator™ VAR 200 is in development to reduce renal cholesterol and lipid accumulation that damages the kidneys' filtration system in patients with glomerular diseases, including diabetic kidney disease, focal segmental glomerulosclerosis, and Alport Syndrome. WESTON, Fla., Oct. 11, 2023 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of renal and inflammatory diseases, announces publication of a paper in the peer-reviewed journal, Nature Reviews Nephrology, that summarizes data highlighting how lipid accumulation in the kidneys contributes to CKD development and disease progression. In the review paper titled, “Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease,” the following key points were made: Lipids and lipid-related enzymes have a major role in modulating the function of the kidney’s filtration system, and lipid accumulation can drive CKD irrespective of circulating lipid levels and use of systemic lipid lowering drugs like statins.Although several lipid types, including cholesterol, triglycerides, fatty acids, and phospholipids, are dysregulated in the kidney and contribute to CKD progression, dysregulation of cholesterol metabolism is one of the hallmarks of kidney injury in CKD. Cholesterol accumulation occurs in association with impaired transport of cholesterol out of the kidney.Accumulation of fatty acids triggers kidney cell damage by promoting inflammation and fibrosis. The paper includes a brief overview of Cholesterol Efflux Mediator™ VAR 200 (hydroxy-propyl-beta-cyclodextrin), highlighting that it reduced cholesterol accumulation and cell death (apoptosis) in podocytes in vitro, and provided protection from kidney disease progression in mouse models of diabetic kidney disease, FSGS, and Alport Syndrome. The authors concluded this section by stating that VAR 200, which is in development for patients affected by several forms of kidney disease, provides therapeutic potential for diseases characterized by ABCA1 deficiency. To read the article, Click Here. “The numerous studies summarized in the paper published in Nature Reviews Nephrology reinforce the importance of addressing kidney accumulation of cholesterol and lipids to help attenuate progression of chronic kidney disease, which affects over 35 million adults in the United States,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “Currently, over 130,000 patients with kidney disease progress to renal failure each year, and more than 800,000 patients are living with renal failure requiring dialysis or transplant to sustain life. We are hopeful that protection against kidney injury, fibrosis, and disease progression seen with VAR 200 in animal models of diabetic kidney disease, FSGS, and Alport Syndrome will translate to humans. Our first clinical trial with VAR 200 in patients with diabetic kidney disease is planned to begin in early 2024.” To review a white paper summarizing the preclinical research with VAR 200, Click Here. About Cholesterol Efflux Mediator™ VAR 200 Cholesterol Efflux Mediator™ VAR 200 (2-hydroxypropyl-beta-cyclodextrin, 2HPβCD) is a phase 2a-ready drug in development to ameliorate renal lipid accumulation that damages the kidneys’ filtration system, leading to kidney disease progression. VAR 200 passively and actively removes excess lipids from the kidney. Preclinical studies with VAR 200 in animal models of FSGS, Alport syndrome, and diabetic kidney disease demonstrate that removal of excess cholesterol and lipids from kidney podocytes protects against structural damage and reduces excretion of protein in the urine (proteinuria). The lead indication for VAR 200 is orphan kidney disease focal segmental glomerulosclerosis (FSGS). VAR 200 has potential to treat other glomerular diseases, including orphan Alport syndrome and diabetic kidney disease. About ZyVersa Therapeutics, Inc. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com. Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities. Corporate and IR Contact:Karen CashmereChief Commercial Officerkcashmere@zyversa.com786-251-9641 Media ContactsTiberend Strategic Advisors, Inc.Casey McDonaldcmcdonald@tiberend.com646-577-8520 Dave Schemeliadschemelia@tiberend.com609-468-9325

Published data demonstrate that a deficiency in cholesterol transporter ABCA1 increases deposition of cellular cholesterol, contributing to inflammation, cell death (apoptosis), and damage to the kidney’s filtration barrier in type 2 diabetic mice and in human renal glomerular endothelial cells cultured to simulate type 2 diabetes ZyVersa’s Cholesterol Transport Mediator™ VAR 200 is in development to reduce renal cholesterol and lipid accumulation that damages the kidneys’ filtration system in patients with glomerular diseases (diabetic kidney disease, focal segmental glomerulosclerosis, and Alport Syndrome) VAR 200 mediates transport of excess cholesterol out of kidney cells passively and by upregulating cholesterol transporter ABCA1 WESTON, Fla., May 15, 2023 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces publication of an article in the peer-reviewed journal, Metabolism, which supports the mechanism of action of Cholesterol Efflux Mediator™ VAR 200 in development to treat kidney diseases. In the paper titled, “ABCA1 deficiency-mediated glomerular cholesterol accumulation exacerbates glomerular endothelial injury and dysfunction in diabetic kidney disease,” the authors reported that ABCA1 deficiency contributes to injury and dysfunction of the kidney’s filtration system (glomerular endothelium) in early diabetic kidney disease (“DKD”). They proposed that ABCA1 transporter deficiency results in glomerular cholesterol/lipid accumulation leading to inflammation and cell death. This causes structural and functional damage to the kidney’s filtration system and in turn, protein spillage into the urine (proteinuria) and DKD progression. The authors concluded that therapies which effectively reduce elevated glomerular cholesterol levels have potential to combat early DKD. To read the article, Click Here. “The research published in Metabolism demonstrating that deposition of glomerular cholesterol contributes to structural damage and dysfunction of the kidney’s filtration system in models of type 2 diabetes is consistent with data from VAR 200’s preclinical program. Our preclinical program showed similar results not only in models of DKD, but also in models of two orphan kidney diseases, focal segmental glomerular sclerosis (FSGS) and Alport Syndrome. More importantly, by mediating cholesterol transport out of the glomeruli through passive transport and upregulation of ABCA1 transporters, VAR 200 protected against glomerular injury and fibrosis, and significantly reduced protein spillage into the urine in all three kidney diseases,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “Given the unmet needs for effective treatments for kidney disease, we are hopeful that VAR 200 will demonstrate similar results in patients with kidney disease in studies planned to initiate late this year,” continued Mr. Glover. About Cholesterol Efflux Mediator™ VAR 200 Cholesterol Efflux Mediator™ VAR 200 (2-hydroxypropyl-beta-cyclodextrin, 2HPβCD) is a phase 2a-ready drug in development to ameliorate renal lipid accumulation that damages the kidneys’ filtration system, leading to kidney disease progression. VAR 200 passively and actively removes excess lipids from the kidney. Preclinical studies with VAR 200 in animal models of FSGS, Alport syndrome, and diabetic kidney disease demonstrate that removal of excess cholesterol and lipids from kidney podocytes protects against structural damage and reduces excretion of protein in the urine (proteinuria). The lead indication for VAR 200 is orphan kidney disease focal segmental glomerulosclerosis (FSGS). VAR 200 has potential to treat other glomerular diseases, including orphan Alport syndrome and diabetic kidney disease. About ZyVersa Therapeutics, Inc. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit . Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc. (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities. Corporate and IR Contact: Karen Cashmere Chief Commercial Officer kcashmere@zyversa.com 786-251-9641 Media Contacts Tiberend Strategic Advisors, Inc. Casey McDonald cmcdonald@tiberend.com 646-577-8520 Dave Schemelia dschemelia@tiberend.com 609-468-9325