TFDA Approves SyneuRx's Schizophrenia Trials in Taiwan as part of its Global Schizophrenia Trials

　　On March 8th, 2021, SyneuRx announced that the Taiwan FDA has granted its IND applications of two phase IIb/III clinical trials: ClozaBen® (SND12) for the treatment of refractory schizophrenia in adults, and NaBen® (SND13) as an add-on therapy for adult schizophrenia. The two candidate drugs were previously granted Breakthrough Therapy Designations (BTDs) by the US FDA. These two Taiwan-based trials are part of the ongoing SND12 and SND13 global trials. It is estimated that the interim analysis of SND13 will be conducted by the end of 2021, and the trial will finish enrollment in 2022 if the interim analysis does not recommend to adjust the sample size. For the SND12 trial, the interim analysis is expected to take place in 2022.

　　There have been no schizophrenia drugs with novel mechanism of action for nearly three decades. All of the standard treatments modulate the dopaminergic and serotoninergic neurotransmissions to improve positive symptoms such as hallucination and delusion. There is currently no drug available to treat the negative symptoms and cognitive impairment of chronic schizophrenia. Patients are considered as refractory if they fail to respond to at least two classes of antipsychotics. And yet, there is a large number of patients, more than 40% of schizophrenia, who are treatment refractory. To date, clozapine is the only drug available to treat refractory schizophrenia. However, if a patient is refractory to clozapine or is suffering clozapine-induced severe neutropenia, a potentially fatal side effect, he/she will be left with no treatment. For such unmet medical needs, new schizophrenia drugs with new mechanism(s) are urgently needed.

　　NaBen® has a novel mechanism of action, which inhibits the D-amino acid oxidase (DAAO) to improve NMDA receptor function. Findings from early phase clinical trials show that NaBen® can treat a broad domain of symptoms, including negative symptoms such as social withdrawal and apathy, cognitive symptoms like memory and attention impairment, and additionally, enhancing the efficacy of other drugs for positive symptoms. To improve the efficacy of NaBen®, SyneuRx developed a novel Ω crystal form of benzoic acid that exhibited superior bioavailability and physiochemical properties than all other crystal forms, demonstrating its potential to be a potent and efficacious new drug. Moreover, benzoate in other crystal forms are not stable, and will eventually convert to the Ω crystal form, the proprietary form owned and protected by the patents of SyneuRx.

　　Three major mechanisms of action (MOA) currently drive the development of NMDA modulator drugs. Neurocrine Biosciences focuses on developing a DAAO inhibitor, Roche and Boehringer Ingelheim center on GlyT-1 inhibitors, and Concert Pharmaceuticals spotlights deuterated D-serine to activate the NMDA receptors. All of the three mechanisms were pioneered by Dr. Emil Tsai, the founder of SyneuRx, and documented in his proof-of-principle research from 1998-2010. We believe that each indication/condition may have its unique and best-matched MOA to modulate its functions. Even when targeting the same MOA, say DAAO for example, the candidate drugs need to not only display the right pharmacological qualities, but also satisfy safety requirements.

　　SyneuRx is the first pharmaceutical company in the world being granted BTDs from the US FDA for the drugs in schizophrenia and refractory schizophrenia. It is uncommon to have BTDs in CNS area, and to date, there are only 6% BTDs assigned to the CNS indications. Apart from our company, only SEP-363856 from Sunovion received BTD for schizophrenia drug development. The global schizophrenia drug market was more than USD $20 billion in 2011; however, with the patent cliff and the availability of generics, the market shrank to less than USD $10 billion more recently. It is expected that after the launch of schizophrenia drugs with a novel mechanism, the market will resume to be above USD $20 billion.

　　‘‘Our SND12 and 13 investigational therapies are novel, patient-centered NMDA treatments, aiming to improve the quality of life of the patients and their families. The NMDA therapy can improve social and cognitive abilities of those who suffer from schizophrenia.’’ said SyneuRx’s Chairman and CEO, Emil Tsai, MD, PhD, MAS.

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.

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