Minerva Neurosciences, Inc., a clinical-stage biopharmaceutical company focused on the development of therapies to treat central nervous system (CNS) disorders, announced the filing of a U.S. patent application for use of its investigational proprietary compound, MIN-117, to treat pain. MIN-117 is currently in Phase 2b clinical development as a treatment for major depressive disorder (MDD).

“In addition to providing further significant intellectual property protection for MIN-117, the pre-clinical data supporting the application suggest that this compound should be investigated beyond mood and anxiety disorders to include chronic pain, which is often a symptom of several neuro-psychiatric disorders,” said Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer of Minerva.

“Chronic pain is also one of the main reasons cited by patients with MDD who seek medical help,” said Dr. Luthringer. “In fact, there is a strong connection between chronic pain and mood disorders, which is exacerbated if mood and anxiety disorders are both present.”

Pre-clinical rat models submitted in the patent application included peripheral motoneuropathy, inflammatory pain and chemotherapy-induced peripheral neuropathic pain. Findings in these models showed that MIN-117 restored approximately 60 percent of the nociceptive pain threshold after peripheral motoneuropathy or inflammatory pain and significantly reduced, in a dose-dependent manner, chemotherapy-induced peripheral neuropathic pain.

The results obtained in these models suggest that MIN-117 may be a candidate for study in the treatment of diseases with chronic pain symptoms and may have the potential to address the urgent need for non-opioid therapeutic options for the treatment of pain. Furthermore, the currently available treatments for chronic pain are often not satisfactory and may be associated with adverse reactions, tolerance, dependence and reductions in the quality of life for patients.

The pharmacological effects of MIN-117 are thought to be largely mediated via serotonin and dopamine, two key neurotransmitters involved in several CNS disorders. With respect to serotonin, the molecule is believed to antagonize a specific subtype receptor called 5-HT1A and prevents the reuptake of serotonin. Both of these activities are known to have effects on mood and anxiety. Furthermore, the effect of MIN-117 on the pre-synaptic 5-HT1A receptors may help achieve an early reversal of depressed mood.

In addition, MIN-117 is believed to prevent the reuptake of dopamine, thus increasing the availability of this neurotransmitter in the synaptic cleft. Dopamine levels are known to be reduced in patients suffering from mood disorders.4 Therefore, an increase of dopamine in the synaptic cleft may potentially benefit patients who do not respond to existing therapies.5 Additionally, the molecule modulates the levels of the adrenergic receptors alpha-1a and -1b, which further modulate catecholamine levels in the brain.

This pharmacological profile of MIN-117 has been observed in the reversal of anhedonia in preclinical models, including the mild chronic stress-induced model. Anhedonia is among the remaining residual symptoms after treatment of a major depressive episode with currently available treatments.

MIN-117 is currently in a Phase 2b clinical trial to evaluate its efficacy in patients with a diagnosis of moderate to severe MDD with anxious distress and without psychotic features. In addition to the primary endpoint of reducing the symptoms of MDD, investigators in this trial are assessing anxiety, cognition, sexual function, sleep, validated depression biomarkers and onset of action to further define the product profile of MIN-117 as an agent that can potentially address the shortcomings of existing therapies for MDD, including slow onset of action, cognitive impairment, sexual dysfunction and anhedonia. Top-line data from this trial are expected to be available in the first half of 2019.