Tuesday, November 19, 2019
Alkermes plc and Rodin Therapeutics, Inc. (Rodin) today announced that they have entered into a definitive agreement under which Alkermes will acquire Rodin, a privately held biopharmaceutical company focused on developing novel, small molecule therapeutics for synaptopathies. This transaction builds on Alkermes' experience in central nervous system (CNS) diseases and expands Alkermes' CNS development efforts into a wide range of neurodegenerative disorders.
Rodin has been working to develop first-in-class, orally-available, brain-permeable therapeutics for synaptopathies by designing molecules that target specific histone deacetylase (HDAC) complexes. Selective inhibition of the HDAC−co-repressor of repressor element-1 silencing transcription factor (CoREST) complex is believed to reactivate neuronal gene expression, strengthen existing synapses and promote the creation of new synapses, while minimizing known class-based hematologic safety concerns.
"Synaptic loss and dysfunction are associated with certain clinical symptoms regardless of the underlying pathology. The platform that Rodin has developed may offer potential utility across a broad spectrum of neuropsychiatric, neurodegenerative and neurodevelopment disorders, such as Alzheimer's disease, Huntington's disease, frontotemporal dementia and depression. In addition, this novel science could have potential applicability in oncology and hematological disorders," stated Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "Based on the compelling research and the significant progress that Rodin has made to advance its chemistry and understanding of selective HDAC inhibition over the last several years, we are excited to enter this interesting area of research and development at this time."
Synaptic dysfunction is a pathological feature in many neurodegenerative and neuropsychiatric diseases, and synaptic loss correlates closely with cognitive decline. HDACs are a class of proteins involved in chromatin remodeling and gene expression and have been shown to regulate synaptogenesis and synaptic plasticity. Currently available HDAC inhibitors with known prosynaptic effects are associated with dose-limiting hematological toxicities, precluding their use in the treatment of chronic neurologic conditions.
Rodin has demonstrated strong prosynaptic effects with development candidates in multiple preclinical models. Selective inhibition of the HDAC-CoREST complex in these models resulted in increased spine density and synaptic proteins, and improved long-term potentiation at doses that may allow for chronic treatment. Rodin has also studied numerous biomarkers that may help inform the potential clinical development programs for candidates that emerge from its selective HDAC inhibitor platform.
"Rodin's targeted approach to strengthening synaptic integrity is backed by a robust translational strategy and may have potential across multiple diseases which are characterized by impaired neuronal and synaptic function," commented Adam Rosenberg, Chief Executive Officer of Rodin. "With its proven ability to develop novel medicines for the treatment of CNS disorders, we believe Alkermes is ideally suited to advance this exciting new approach to neurologic diseases and bring potential new treatment options to patients that may benefit from Rodin's synaptogenic platform."
"Building on our broad experience in psychiatry, we believe this transaction will allow us to explore a wide array of neurodegenerative diseases and synaptopathies, which have been areas of significant interest to us as we have advanced our internal pipeline of medicines for CNS disorders. HDAC inhibitors are powerful epigenetic regulators that have therapeutic potential to address some of the most disruptive clinical symptoms that accompany neurogenerative diseases," commented Richard Pops, Chief Executive Officer of Alkermes. "This investment is reflective of our longstanding commitment to bring new and innovative therapeutic options to patients living with chronic CNS diseases where the unmet medical need is high."
Alkermes intends to advance Investigational New Drug (IND)-enabling activities for lead preclinical assets in the Rodin development candidate portfolio, potentially prioritizing those ahead of future clinical development of Rodin's initial clinical candidate. Alkermes also plans to continue Rodin's preclinical research program focused on the subset of frontotemporal dementia patients with an inherited mutation of the progranulin gene (FTD-GRN) and exploratory work in hematological disorders and oncology.
Alkermes expects to incur approximately $20 million of incremental Research & Development (R&D) expenses in 2020 related to the advancement of Rodin's development candidates. Alkermes will provide its complete 2020 financial expectations in February 2020.
