US FDA Approves SyneuRx’s IND Application for a Phase II Clinical Trial for Adult Patients with Treatment-Resistant Depression and Suicidal Symptoms

 　　　　On March 26, 2021, SyneuRx announced that its Synxyrin® (also known as SNA11) has been approved by the US FDA to conduct a phase II clinical trial indicated for adult patients with treatment-resistant depression (TRD) and suicidal symptoms.  
　　　　Major depressive disorder (MDD) is the most common CNS disease. The incidence rate of the disease is around 20.1% in a lifetime, which means every one out of five persons will be diagnosed with MDD at a certain time that requires proper treatment. TRD means MDD patients who do not respond adequately to at least two courses of appropriate antidepressant medication within an adequate time. Because most of current antidepressants act on the basis of a similar mechanism of action, i.e. monoaminergic neurotransmission, patients often have poor response to all of these medicines at the same time. Statistically, TRD patients account for 30-50% of the MDD population. 
　　In March 2009, the US FDA approved Symbyax as the first TRD drug, but Symbyax is merely a combination of a traditional antidepressant (fluoxetine) and an atypical antipsychotic (olanzapine). Hence, when the US FDA approved Spravato (esketamine) for TRD treatment in March 2019, it is usually considered as the first novel TRD drug. As the active pharmaceutic ingredient is ketamine which causes multiple side effects, the US FDA has required a drug safety program, Risk Evaluation and Mitigation Strategies (REMS), to help ensure the benefits and risks of Spravato. This has led to a decrease in the use of Spravato by patients due to inconvenience arisen from the fact that only certified health care facilities have access to this medicine. Therefore, TRD is still an urgently unmet medical need. 
　　　　Ketamine is a NMDA receptor ion channel blocker, which can antagonize the activity of NMDA receptor. Since the NMDA system is substantially associated with cognition, memory, experience-dependent learning, neuroplasticity, and CNS development, the long-term use of ketamine will lead to permanent damage(s) to the brain, such as the abovementioned functional impairment(s). Research has reported that hyperfunction of NMDA receptor may be involved in the pathophysiology of TRD; however, hypofunction of NMDA receptor may also induce depression. SyneuRx assumes that facilitating NMDA system balance is a key strategy. SNA11 acts as a partial agonist/antagonist on glycine binding site of NMDA receptor. When the NMDA receptor is over-activated, SNA11 acts as an antagonist to reduce its activity to 50%; on the contrary, when the NMDA receptor activity is under-activated, SNA11 acts as an agonist to increase its activity to 50%. Early clinical studies have shown SNA11 could also treat dementia, panic disorder, and post-traumatic stress disorder. Because of the partial agonism and antagonism characteristics, SyneuRx has planned SNA11 to treat TRD. 
　　　　Suicide is one of the top ten leading causes of death in Taiwan, and on average, ten people die from it per day. Most people who committed suicide are depressed. As all the current antidepressants have delayed response, they are not effective to prevent urgent suicidality. In 2004, the US FDA released a black box warning to alert increased risk of suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants. ‘It is not unusual to have suicidal ideation among friends and family. Not only my patients in hospitals, but also my classmates from College of Medicine died from suicide.’ said SyneuRx’s Chairman and CEO, Emil Tsai, MD, PhD, MAS. Due to the close correlation between major depression and suicide, the primary endpoints of SNA11 will measure suicidal ideation in addition to depressive symptoms. To date, there is no medicine approved for suicide prevention in TRD patients; our SNA11 is believed to bring a bright hope in this area. 
 
About SyneuRx International (Taiwan) Corp.  
　　　　SyneuRx is a global biotech company listed in Taiwan (TWSE: 6575), undergoing clinical development of new classes of drugs for multiple major CNS disease conditions and COVID-19. Several early and late phase clinical trials are currently in progress for multiple indications globally, including schizophrenia, dementia, depression, and COVID-19. 
 
Forward-looking statements 
　　　　This press release does not constitute any invitation or offer to purchase or subscribe for the stocks of SyneuRx. The forward-looking statements in the press release are neither promises nor guarantees of future performance, and are subject to various risks and uncertainties, which may cause huge deviation from the expected results in those forward-looking statements. SyneuRx has no obligation to amend or update this press release to respond to any events that occur after the publication of this article. New drug development takes a long time and high investment costs, without guarantee of success. All these unpredictabilities may put the investment at risk. SyneuRx does not encourage short-term investment. Investors should make diligent judgments and invest carefully.