Therapeutic Focus

Depression affects more than 264 million people globally and 17 million adults in the US. Depression is characterized by persistent low mood or lack of pleasure in previously rewarding or enjoyable activities. Depression is associated with significant impairments in all aspects of life, from vocational and scholastic performance, to social and familial relationships. Depression is associated with increased risk of diabetes, obesity, cancer, and cardiovascular disease, and a reduced life span.

Depression is diagnosed when a person experiences depressed mood and/or loss of interest or pleasure in daily activities for at least 2 weeks and has additional specified symptoms such as problems with sleep, eating, energy, concentration, or self-worth.

 

If not treated to remission, depression can be devastating for patients and their families. Unfortunately, the efficacy of first-line antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs, e.g. Prozac® [fluoxetine]) and serotonin-norepinephrine reuptake inhibitors (SNRIs, e.g. Cymbalta® [duloxetine]) is moderate at best. While some patients do respond well, fully two-thirds of patients fail to achieve adequate antidepressant response to first-line antidepressants. Switching to a different first-line antidepressant or an atypical antidepressant (e.g. Wellbutrin® [bupropion]) provides better efficacy to only a small minority of patients.

 

Next-line treatment options have modest additional efficacy, and often a high side-effect burden. To date, only one oral drug class, atypical antipsychotics (e.g Abilify® [aripiprazole]), have been approved to treat depression as adjunctive therapy to SSRIs/SNRIs; but, most depression patients do not benefit from adjunctive atypical antipsychotics. And troubling side-effects include weight gain, diabetes, and motoric anomalies. Newer ketaminebased antidepressants provide significant relief to a subset of patients. Yet, the drugs have modest overall efficacy, and are limited by a requirement for in-clinic parenteral administration, limited access, schizophrenia-like side-effects, abuse potential, and high cost.

More effective and safer treatment options are urgently needed for the many depression patients not responding adequately to first-line SSRI/SNRI therapy.

 

Evecxia Therapeutics is developing adjunctive EVX-101 for depression responding inadequately to first-line SSRI/SNRI monotherapy. EVX-101 will amplify the brain’s natural serotonin production, thereby synergizing with the SSRI/SNRI in promoting brain serotonin neurotransmission and augmenting the antidepressant response.

Suicidality

In 2018 more than 48,000 people died by suicide in the US; 1.4 million people attempted suicide. In young people, suicide was the 2nd leading cause of death. US suicide rates have increased 35% since 2000. Suicide has risen to epidemic levels and is a national emergency in the US. Likewise, in the European Union,
56,000 people died by suicide in 2018.

 

Unfortunately, there are no drug treatments for suicidality approved by the FDA or European Medicines Agency. New treatments for treating acute suicidal crisis and for preventing future suicides are critical for combatting the suicide emergency.

 

Evecxia Therapeutics is developing EVX-301—a proprietary 24h infusion of 5-hydroxytryptophan (5-HTP)—to treat patients in acute suicidal crisis. EVX-301 is designed to rapidly amplify endogenous brain serotonin, which, in turn, could rapidly ameliorate suicidality-related affective states and behaviors.

Other Mental Disorders

OCD

Obsessive-compulsive disorder (OCD) is a chronic and often serious mental disorder. The OCD patient experiences persistent obsessions, compulsions, or both, that interfere with all aspects of life and cause significant distress. Obsessions are unwanted, intrusive thoughts, images, or urges that trigger intensely distressing feelings. Compulsions are behaviors an individual engages in to attempt to get rid of the obsessions and/or decrease his or her distress. OCD affects over 3 million people in the US.

 

The key pharmacological treatment for OCD is the SSRIs (e.g. Prozac® [fluoxetine]). SSRIs typically work best if given in conjunction with Cognitive Behavior Therapy (CBT). Most OCD patients experience some relief following SSRI therapy; unfortunately, significant symptoms and impairment persists in almost all patients, even when combined with CBT.

 

No new OCD drug treatment has been approved for decades.

OCD appears uniquely treatable by drugs enhancing serotonin function. Amplifying serotonin neurotransmission beyond what is achievable with an SSRI could further reduce obsessions and compulsions, thereby providing additional relief and improved quality of life and functioning in OCD patients. Adjunctive EVX-101 could amplify brain serotonin neurotransmission beyond the SSRI effect, and hence become a critical new therapy for OCD.

Anxiety Disorders

There are 40 million Americans suffering from an anxiety disorder. For a person with an anxiety disorder, the anxiety is persistent, can get worse over time, and interfere with daily functioning, sometimes severely. Anxiety disorders such as social anxiety disorder (fear of being judged, evaluated, or socially ejected) and generalized anxiety disorder (excessive anxiety about life aspects, often accompanied by physical symptoms) are treatable with SSRIs. However, about half of anxiety patients treated with cognitive behavioral therapy, SSRIs, or other pharmacotherapy continue to experience clinically significant residual symptoms, and many experiences minimal or no symptom relief. Adjunctive EVX-101 could be a new treatment option for the millions of patients suffering from anxiety disorders and not helped by current treatment options.

 

Post-Traumatic Stress Disorder

More than 10 million Americans suffer from post-traumatic stress disorder (PTSD). PTSD develops in response to a traumatic event. The symptoms include persistent reexperiencing of the trauma, avoidance of reminders of the trauma, numbing of positive emotions, social withdrawal, and increased autonomic arousal. SSRIs are the only drug class FDA-approved for PTSD; but, improvements in symptoms are usually modest. PTSD is thus one of the most urgent unmet needs in Psychiatry. Adjunctive EVX-101 could present as a novel, much needed, treatment avenue for PTSD.

 

Impulse Control Disorders

Impulse control disorders are a group of disorders characterized by the repeated inability to resist an impulse, drive, or temptation to perform an act that is harmful, e.g. aggression, to the person or to others. In clinical studies, increased impulsivity and aggression tend to co-segregate with indices of brain serotonin deficiency. Conversely, enhancing serotonin function tends to abate impulsivity and aggression. Indeed, there is evidence that amplifying brain serotonin could treat impulse control disorders. As an effective drug to amplify brain serotonin function, EVX-101 could hypothetically treat core neurobiological and behavioural deficits in impulse control disorder patients, enabling them to lead fuller and more harmonious lives.