2B3-201 (GSH-PEG liposomal methylprednisolone, now ENX-201 at EnhanX Biopharm Inc.) for acute relapses of multiple sclerosis has completed a Phase I clinical trial in healthy volunteers.

2B3-201 is being developed for patients suffering from acute and chronic neuro-inflammatory diseases, with an initial focus on patients with acute multiple sclerosis relapses. 2-BBB has completed a double-blind crossover Phase I study with 2B3-201 in healthy male and female volunteers, studying the product in comparison to current methylprednisolone treatment and placebo. (British Journal of Clinical Pharmacology, May 2018

Medical need and existing treatment

Neuro-inflammation is associated with a wide range of CNS diseases, including multiple sclerosis (MS), optic neuritis, non-infectious uveitis, acute disseminated encephalomyelitis (ADEM), neuro-myelitis optica (NMO), as well as neuropathic pain, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease.

The standard of care for acute relapses of neuro-inflammation in MS is a high-dose (1000 mg) methylprednisolone, an anti-inflammatory glucocorticoid drug. The therapeutic effect of a single injection of methylprednisolone has a relatively short duration, requiring daily injections for 3 consecutive days. In addition, this therapy is associated with many undesirable side effects, resulting in a substantial medical need among MS patients with acute relapses for a product with an improved safety profile and more convenient dosing regimen compared to the current standard of treatment drug Solu-Medrol®.

Benefits of 2B3-201

Based on a comparison of efficacy and safety parameters, methylprednisolone is 2-BBB’s preferred glucocorticoid treatment option with proven use in neuro-inflammation. By encapsulating methylprednisolone into liposomes, a lower total dose can be given resulting in at least the same efficacy and reduced side effects with a single administration. 2-BBB is extending this benefit even further by using the G-Technology® to safely enhance the delivery of methylprednisolone to the brain, without the acute psychiatric side effects caused by peak concentrations associated with administration of the free drug.

In preclinical proof-of-concept studies in a model of MS, 2B3-201 was shown to be more effective when compared to non-targeted PEG liposomal methylprednisolone, while free methylprednisolone at the same dose was completely ineffective. Compared to free methylprednisolone, 2B3-201 had a favorable pharmacokinetic profile and optimal distribution to the brain.  (Journal of Controlled Release, December 2012; Journal of Neuroimmunology, September 2014