Non-Alcoholic Steatohepatitis (NASH) - Pipeline Insight, 2024

This “Non-Alcoholic Steatohepatitis (NASH) - Pipeline Insight, 2024” report provides comprehensive insights about 100+ companies and 110+ pipeline drugs in Non-Alcoholic Steatohepatitis (NASH) pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

• Global coverage

Non-Alcoholic Steatohepatitis (NASH): Understanding

Non-Alcoholic Steatohepatitis (NASH): Overview

Nonalcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a fat buildup in the liver. It is part of a group of conditions called nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease can be divided into the isolated fatty liver in which there is only accumulation of fat, and nonalcoholic steatohepatitis (NASH), in which there is fat, inflammation, and damage to liver cells. In NASH, there is an abnormal amount of fat in the liver cells, but, in addition, in NASH, there is inflammation within the liver, and, as a result, the liver cells are damaged, they die, and are replaced by scar tissue. NASH progresses to scarring and ultimately to cirrhosis, with all the complications of cirrhosis, for example, gastrointestinal bleeding, liver failure, and liver cancer. NASH can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma with about 30% to 40% of patients developing fibrosis. NASH is not a diagnosis of exclusion and can be associated with other liver conditions such as chronic hepatitis C. NASH is classified into two types, primary; which is related to obesity and diabetes in the absence of excessive alcohol intake, and secondary; which is toxin or drug induced. Certain conditions have been associated with NAFLD and NASH. Obesity has a strong association with NAFLD. Metabolic syndrome (which comprises of obesity, type 2 diabetes mellitus or hyperinsulinemia, hypertension, and dyslipidemia) is strongly associated with NAFLD. About three-quarter of patients with insulin resistance and type 2 diabetes mellitus have fatty liver disease with a higher prevalence of cirrhosis. Other metabolic and genetic conditions that are associated with NAFLD are polycystic ovary disease, lipodystrophies, mitochondrial diseases, Weber-Christian disease and Wilson disease.

NAFL and NASH are in the spectrum of NAFLD, which involves steatosis defined as more than 5% liver fat. The mechanism of NAFLD can be explained by the two-hit hypothesis that involves steatosis (first hit), followed by oxidative stress and injury (second hit). The three main sources of free fatty acid (FFA) in the liver are plasma nonesterified fatty acids (NEFAs) from adipose tissue, de novo lipogenesis in the liver, and dietary free fatty acids from chylomicrons. The cascade of events results in mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, ineffective autophagy, and dysbiosis of the gut flora, all of which cause sterile hepatocyte inflammation. Apoptosis, necrosis, and necroptosis of the hepatocyte is the net result of eventual progression to fibrosis and liver cirrhosis.

The diagnosis of NAFLD/NASH is often incidental, detected through abnormal liver biochemical tests or imaging showing hepatic steatosis. Ultrasonography is commonly used due to its cost-effectiveness and availability. Diagnosis of NAFLD excludes excessive alcohol intake and other liver diseases. Serum ALT and AST are mildly elevated in NAFLD, with ALT usually greater than AST in a 2:1 ratio. Liver biopsy confirms NASH and stages fibrosis, but it has limitations like sampling error and observer bias. Non-invasive tests like APRI, Fib-4, NFS, and FibroScan are used to predict fibrosis severity. Lifestyle modifications are the cornerstone of treatment for obesity, aiming for 5% to 10% weight loss through calorie reduction and exercise. Lifestyle changes may include consuming caffeinated drip coffee, avoiding high fructose corn syrup, increasing omega-3 fats, and considering thiazolidinediones cautiously. Antioxidants like vitamin E can be beneficial in non-diabetic patients. Bariatric surgery is effective for morbid obesity, while statins should not be withheld in NAFLD. Liver transplantation is a last resort for decompensated cirrhosis, with the caveat of potential NAFLD recurrence.

Non-Alcoholic Steatohepatitis (NASH)- Pipeline Insight, 2024 report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Non-Alcoholic Steatohepatitis (NASH) pipeline landscape is provided which includes the disease overview and Non-Alcoholic Steatohepatitis (NASH) treatment guidelines. The assessment part of the report embraces, in depth Non-Alcoholic Steatohepatitis (NASH) commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Non-Alcoholic Steatohepatitis (NASH) collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights

• The companies and academics are working to assess challenges and seek opportunities that could influence Non-Alcoholic Steatohepatitis (NASH) R&D. The therapies under development are focused on novel approaches to treat/improve Non-Alcoholic Steatohepatitis (NASH).

Non-Alcoholic Steatohepatitis (NASH) Emerging Drugs Chapters

This segment of the Non-Alcoholic Steatohepatitis (NASH) report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

Non-Alcoholic Steatohepatitis (NASH) Emerging Drugs

Lanifibranor: Inventiva PharmaLanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce antifibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (PPAR) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARa and PPARd, and a partial activation of PPAR?. While other PPAR agonists target only one or two PPAR isoforms for activation. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of NASH. Currently, the drug is in Phase III stage of its clinical trial for the treatment of NASH.

MSDC-0602K: Cirius TherapeuticsMSDC-0602K, a second-generation oral insulin sensitizer, is designed to selectively modulate the mitochondrial pyruvate carrier (MPC) while minimizing direct PPAR-gamma activation. The MPC mediates at the cellular level the effects of over nutrition, a major cause of Nonalcoholic fatty liver disease NAFLD/NASH and Type 2 diabetes. In preclinical studies, modulation of the MPC has been shown to improve insulin sensitivity, lipid metabolism, and inflammation. Currently the drug is in Phase III stage of Clinical trial for the treatment of NASH.

TERN-501: Terns PharmaceuticalsTERN-501 is a THR-ß agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-ß compared to other THR-ß agonists in development. Agonism of THR-ß increases fatty acid metabolism via mitochondrial oxidation and affects cholesterol synthesis and metabolism. As a result, THR-ß stimulation has the ability to reduce hepatic steatosis and improve serum lipid parameters including LDL cholesterol and triglycerides. In vivo NASH studies in a rodent model have demonstrated that low-doses of TERN-501 achieved complete resolution of steatosis and reductions in serum lipids, hepatic inflammation and fibrosis. TERN-501 has high liver distribution and is 23-fold more selective for THR-ß than for THR-a activation in a cell free assay, thereby minimizing the risk of cardiotoxicity and other off-target effects associated with non-selective THR stimulation. Currently, the drug is in Phase II stage of its clinical trial for the treatment of NASH.

HTD 1801: HighTide BiopharmaThe company's lead drug candidate, HTD1801, is a first-in-class new molecular entity (ionic salt of two active moieties). It is a novel orally active ionic salt of berberine and ursodeoxycholic acid, substantially reduced liver fat while improving glycemic control and other cardiometabolic biomarkers in adults with nonalcoholic steatohepatitis (NASH) and type 2 diabetes (T2DM). Currently, it is in Phase II trials for the treatment of primary sclerosing cholangitis (PSC), and nonalcoholic steatohepatitis (NASH).

Non-Alcoholic Steatohepatitis (NASH): Therapeutic Assessment

This segment of the report provides insights about the different Non-Alcoholic Steatohepatitis (NASH) drugs segregated based on following parameters that define the scope of the report, such as:

Major Players in Non-Alcoholic Steatohepatitis (NASH)

• There are approx. 100+ key companies which are developing the therapies for Non-Alcoholic Steatohepatitis (NASH). The companies which have their Non-Alcoholic Steatohepatitis (NASH) drug candidates in the most advanced stage, i.e. Phase III include, Inventiva Pharma.

Phases

This report covers around 110+ products under different phases of clinical development like

• Late stage products (Phase III)
• Mid-stage products (Phase II)
• Early-stage product (Phase I) along with the details of
• Pre-clinical and Discovery stage candidates
• Discontinued & Inactive candidates

Route of Administration

Non-Alcoholic Steatohepatitis (NASH) pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Oral
• Intravenous
• Subcutaneous
• Parenteral
• Topical

Molecule Type

Products have been categorized under various Molecule types such as

• Recombinant fusion proteins
• Small molecule
• Monoclonal antibody
• Peptide
• Polymer
• Gene therapy

Product Type

Drugs have been categorized under various product types like Mono, Combination and Mono/Combination.

Non-Alcoholic Steatohepatitis (NASH): Pipeline Development Activities

The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Non-Alcoholic Steatohepatitis (NASH) therapeutic drugs key players involved in developing key drugs.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Non-Alcoholic Steatohepatitis (NASH) drugs.

Non-Alcoholic Steatohepatitis (NASH) Report Insights

• Non-Alcoholic Steatohepatitis (NASH) Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

Non-Alcoholic Steatohepatitis (NASH) Report Assessment

• Pipeline Product Profiles
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing Non-Alcoholic Steatohepatitis (NASH) drugs?
• How many Non-Alcoholic Steatohepatitis (NASH) drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Non-Alcoholic Steatohepatitis (NASH)?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Non-Alcoholic Steatohepatitis (NASH) therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for Non-Alcoholic Steatohepatitis (NASH) and their status?
• What are the key designations that have been granted to the emerging drugs?

Key Players

• Guangdong Raynovent Biotech
• Dr. Falk Pharma GmbH
• Enyo Pharma
• Viking Therapeutics
• Sagimet Biosciences
• Terns
• Sinew Pharma
• Madrigal Pharmaceuticals
• Hepion Pharmaceuticals
• Poxel SA
• Pfizer
• CytoDyn
• Altimmune
• Oramed, Ltd
• PharmaKing
• Can-Fite Biopharma
• Cirius Therapeutics

Key Products

• ZSP1601
• ZED1227
• EPY 651
• VK2809
• TVB-2640
• TERN-501
• SNP-630
• Resmetirom
• Rencofilstat
• PXL065
• PF-06865571
• leronlimab
• Pemvidutide
• ORMD-0801
• Oltipraz
• Namodenoson
• MSDC-0602K

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