Royalty Report: Drugs, Pharmaceuticals, Therapeutic – Collection: 4454

The Licensor granted the Licensee an exclusive, worldwide, royalty-bearing license to MBX-8025 and certain other PPAR compounds (the PPAR Products) with the right to grant sublicenses to third parties to make, use and sell such PPAR Products.

MBX-8025 is a selective agonist (a substance that stimulates a response by binding to a receptor) for the peroxisome proliferator-activated receptor delta (PPARd), a nuclear receptor that regulates genes involved in lipid storage and transport (particularly in fatty acid oxidation) and insulin signaling and sensitivity. In preclinical studies in rodents, dogs and primates, MBX-8025 demonstrated a variety of beneficial effects on the lipid profile and other metabolic parameters. MBX-8025 treatment increased peripheral oxidation of fatty acids leading to reduced levels of triglycerides (TGs) and low-density lipoprotein (LDL), while raising high-density lipoprotein (HDL). MBX-8025 inhibited fat mass accumulation, resulting in attenuation of body weight gain in rodent models of obesity.

MBX-8025 has potential therapeutic application for disorders linked to deficits in lipid storage, handling and utilization, many of which result in metabolic disorders. To date, it has been in development as a first-in-class treatment that effectively addresses all three lipid disorders associated with mixed dyslipidemia (abnormal lipid levels in the blood) as well as a majority of the cardiovascular risk factors that define metabolic syndrome. The future development program will focus on high unmet need indications in dyslipidemia as well as in high unmet need specialty and orphan diseases.

The 8-week Phase 2 study investigated MBX-8025 at doses of 50 or 100 mg/day in moderately obese patients with mixed dyslipidemia. The study demonstrated that treatment with MBX-8025 led to significant reductions in total LDL (~20%) and selective depletion of the small dense atherogenic (promotion of arterial plaque formation) LDL particles, resulting in an exceptional improvement in the LDL particle size profile. It also decreased TGs (~30%) and raised HDL (~12%). This unique combination of effects significantly decreased the atherogenic risk of patients’ lipid profile. When administered in combination with atorvastatin (Lipitor®), MBX-8025 provided a comprehensive improvement in all lipid and cardiovascular risk parameters without side effects seen in other combination lipid therapies.

In addition, MBX-8025 addressed other aspects of metabolic syndrome, including improvements in insulin sensitivity and trends toward decreased waist circumference and body fat. Over half of the patients that entered the Phase 2 study meeting the criteria for metabolic syndrome no longer met the criteria at the end of the study.

The product seladelpar is for the treatment of primary biliary cholangitis (PBC), an autoimmune disease that causes progressive destruction of the bile ducts in the liver. Seladelpar is a potent and selective agonist of PPARd, a nuclear receptor that regulates genes important for lipid, bile acid/sterol and glucose metabolism and for inflammation in liver and muscle.

Under the terms of the agreement, the Licensee has full control and responsibility over the research, development and registration of any PPAR Products and is required to use diligent efforts to conduct all such activities.

The Licensee shall grant the Licensor a worldwide, exclusive, irrevocable license under the agreement in all information that is controlled, developed or acquired by the Licensee which relates to a PPAR compound or PPAR product and in all patents that are filed.

Luteolin is the active ingredient in LutiMax.  Luteolin is a Super-Nutrient from a class of naturally occurring molecules known as bioflavonoids.  Luteolin neutralizes free radicals such as superoxide, the hydroxyl radical, and other reactive oxygen compounds to help reduce oxidative stress and may help reduce inflammation, regulate hyperactive immune systems, and promote healthy carbohydrate metabolism.