Soyean Bio Announces Key Clinical Trial Progress for DB103, a First-in-Class mGlu2/3 Receptor Agonist for Schizophrenia Treatment

VCBeat News (WeChat ID: biobeat1) has learned that on May 23, 2019, at the newly convened 74th Annual Meeting of the Society of Biological Psychiatry (SOBP), Dr. Joshua Kantrowitz from Columbia University presented, at the Forum on New Drug Development for Mental Disorders in the 21st Century, the clinical trial results from Jeff Lieberman’s team. The study utilized biomarkers to assess the dosage and target engagement of DB103 (Pomaglumetad Methionil).

Due to the scarcity of new-mechanism drugs launched over the years, the demand for novel therapeutics in the field of schizophrenia has become increasingly urgent. Glutamate and its related signaling pathways have long been regarded as highly promising drug targets; however, there are no successful precedents for glutamate receptor agonists to date.

Suoyuan Biomedicine’s DB103 is a prodrug of LY404039, a partial agonist of metabotropic glutamate II/III receptors (mGlu2/3R). To evaluate the extent of DB103 binding to its drug target, mGlu2/3R, at different doses, Dr. Jeff Lieberman, a renowned expert in psychiatry from Columbia University, and his team conducted a clinical trial involving 100 healthy volunteers. The trial was designed as a three-arm, randomized (1:1:1), double-blind study. The three arms were: 1) low-dose DB103 (40 mg BID); 2) high-dose DB103 (160 mg BID); and 3) placebo.

This clinical trial simulates the synaptic dysfunction of schizophrenia through ketamine-induced glutamate release, and uses functional magnetic resonance imaging (fMRI) to detect the effects of the mGluR2/3 partial agonist DB103 at different doses on ketamine-stimulated glutamate release in the prefrontal cortex.

The team led by Jeff Lieberman has accumulated extensive expertise in glutamate and neuroimaging. They discovered that pharmacoBOLD fMRI, a technique leveraging Blood Oxygenation Level Dependent (BOLD) contrast via functional magnetic resonance imaging, can monitor intracerebral glutamate levels and serve as a biomarker to evaluate the pharmacodynamic effects of DB103. A total of 81 volunteers completed the full course of this clinical trial. The results demonstrated that, compared with placebo, DB103 significantly inhibited ketamine-induced fMRI BOLD activity in a dose-dependent manner.

These encouraging results also established the dose of DB103 capable of activating the primary target (mGlu2/3 receptors), providing a critical basis for selecting effective doses in future clinical studies of DB103 for the treatment of schizophrenia.

Suoyuan Biomedicine has multi-faceted collaborations with Jeff Lieberman’s team, including another ongoing clinical trial of DB103 for the treatment of prodromal schizophrenia. In addition, Suoyuan Biomedicine’s international multicenter clinical trial of DB103 in patients with early-stage schizophrenia was approved by China’s National Medical Products Administration (NMPA) at the end of 2018, and Phase I clinical trials have been successfully initiated.

DB103 is a prodrug of LY404039, an agonist of metabotropic glutamate II/III receptors (mGlu2/3R). Currently, no new drugs targeting this receptor have been marketed globally, making DB103 a first-in-class therapy. Originally developed by Eli Lilly and Company for the indication of schizophrenia, DB103 has completed more than 30 clinical trials. In 2015, Eli Lilly transferred the global rights to DB103, including all rights to development, manufacturing, and commercialization, to Denovo Biopharma LLC, a wholly-owned subsidiary of Suoyuan Biomedicine.

Suoyuan Biomedicine (Hangzhou) Co., Ltd. is a leading precision medicine enterprise that develops Class 1 new drugs through a rapid and efficient model. Registered in the Hangzhou Economic and Technological Development Zone, China, the company has its clinical operations center in Beijing and a wholly-owned subsidiary, Denovo Biopharma LLC, located in San Diego, California, USA.

Suoyuan Biomedicine licenses new drugs from major international pharmaceutical companies that have demonstrated safety in late-stage clinical trials and shown efficacy in subsets of patients. Leveraging its proprietary biomarker platform technology, the company identifies predictive biomarkers from residual clinical samples. By using these newly discovered biomarkers as companion diagnostics to screen patients, Suoyuan Biomedicine can re-initiate clinical trials in sensitive patient populations, thereby optimizing efficacy, safety, and tolerability, and increasing the success rate of new drug development. This approach enables the development of innovative drugs at lower costs and in shorter timeframes. Suoyuan Biomedicine holds global rights to DB102, DB103, and DB104, three first-in-class innovative drug candidates that have advanced to late-stage clinical development.

The Phase III clinical trial of DB102 (enzastaurin) for the treatment of previously untreated high-risk diffuse large B-cell lymphoma (DLBCL) is underway in China and the United States. DB104 (liafensine) is an antidepressant drug acquired from ARMI/BMS. Suoyuan Biomedicine is currently in negotiations with several international pharmaceutical companies to acquire similar late-stage innovative drugs, leveraging its biomarker platform technology to conduct personalized innovative drug development in the same manner.