CAMBRIDGE, Mass.--(BUSINESS WIRE)--Rodin Therapeutics today announced positive Phase 1 results that provide the foundation for continued development of RDN-929, a potent and selective HDAC-CoREST inhibitor designed to increase synaptic density for the treatment of neurologic diseases.
The randomized, double-blind, placebo-controlled study assessed single ascending and multiple ascending doses of RDN-929 in healthy volunteers. The results support RDN-929 as the first reported safe, brain-penetrant, complex-selective HDAC inhibitor.
- The compound was safe and well-tolerated at all dosage levels and demonstrated favorable pharmacokinetic and pharmacodynamic properties.
- RDN-929 drug concentrations were measurable in cerebrospinal fluid (CSF) and in the predicted range targeted for future efficacy studies.
- Target engagement was confirmed with a dose-dependent increase across multiple acetylation marks.
- The sensitivity and specificity of assays used to assess biomarkers linked to synaptic and neuronal health was confirmed. Neurofilament light chain (NfL), neurogranin (Ng), SNAP25 and PSD95 were quantified in cerebrospinal fluid; NfL and Ng were also measured in plasma.
“These results confirm that our strategy of selectively inhibiting specific HDAC complexes allows us to target a potent regulator of synaptic gene expression while minimizing known class-based safety concerns,” said Adam Rosenberg, CEO of Rodin Therapeutics. “We now look forward to longer-term clinical studies that will evaluate RDN-929 in patients.”
In preclinical models, RDN-929 demonstrated strong pro-synaptic effects. Its selective inhibition of the HDAC-CoREST complex raised synaptic protein levels, increased the number of dendritic spines and improved synaptic function.
“We are gratified to see that the Phase 1 results mirror our preclinical data, suggesting that RDN-929’s safety profile may make it appropriate for long-term dosing in patients with neurologic diseases,” said J. Michael Ryan, M.D., Rodin’s chief medical officer. “Synaptic loss and dysfunction drive symptoms in many brain diseases and we believe RDN-929 can play an important role in treating the cognitive, behavioral and functional decline that follows from this synaptic degradation.”
Rodin is also sponsoring an ongoing, non-therapeutic clinical trial to assess the performance of a new SV2A PET ligand that enables measurement of synaptic density in the living brain. Data from this study will be presented at the upcoming Alzheimer’s Association International Conference (AAIC) meeting in Los Angeles on July 14-18.
Data from the SV2A PET study and the Phase 1 trial will guide Rodin’s planned clinical trials of RDN-929 in patients with synaptopathies.
About Rodin Therapeutics
Rodin Therapeutics is discovering and developing first-in-class therapeutics for synaptopathies by applying novel chemical strategies to target specific HDAC complexes and upregulate key neuronal genes. Rodin’s targeted approach to strengthening synaptic integrity, backed by a robust translational strategy, has potential across multiple diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and schizophrenia, all of which are characterized by impaired neuronal and synaptic function. For more information, visit https://rodintherapeutics.com/ and follow Rodin on Twitter @Rodintx.