Translational Program


Thera is developing two new classes of small molecule and RNAi-based compounds for the treatment of neurodegenerative diseases.

Our SMRT development program leverages an 18 small molecule-library technology, licensed from Southern Research, and opens the way to exploring more effectively the regenerative role of MnSOD and how a dual-target approach can impact both the functional deficit and the disease progression.

We are also evaluating the potential of a gene-silencing approach with our SOD1-targeting sd-rxRNA®, acquired from RXi Pharmaceuticals, as an additional disease-modifying therapeutic option.


Lead Candidates


In our SMRT product portfolio we have 7 molecules active exclusively in neurons. From this group we have identified two lead candidates, SYN1 and SYN2, which are being optimized for development and positioned to enter clinical stage by late 2017.

The translational program is focusing initially on Amyotrophic Lateral Sclerosiswith our SMRT lead candidates and will expand to traumatic brain injury (TBI), Alzheimer’s disease (AD) and other neurologic diseases.

Our sd-rxRNA® technology (THN1) is currently undergoing lead optimization and animal proof of concept.



Discovery Program


Thera is also implementing a strong discovery program and fostering important collaboration with RXi Pharmaceuticals, MA, Flemish Institute of Biotechnology, Belgium, and University of Massachusetts, MA to advance research on our technology platform and small molecule portfolio.



 


 
 
 

 


 
 
 

 


 
 
 

 


 
 
 

TRANSLATIONAL PROGRAM

                                   

Neurodegenerative diseases are multifactorial disorders requiring a multifunctional treatment approach to obtain an impactful therapeutic effect.

                                   
  • Research&Development TRANSLATIONAL PROGRAM
                                   

Thera development program employs two new approaches to regenerative and gene silencing-based therapy.
The SMRT technology leverages the multifunctional effects of a key signal transduction brain factor, the NF-κB p65, and an important mitochondrial enzyme, the MnSOD, both essential for neuronal functioning and neurotransmission.
The sd-rxRNA® platform employs a RNA-based process that has the potential to target specific genes coding for proteins involved in the pathogenesis of neurodegenerative diseases. The sd-rxRNA oligonucleotides will potentially interferes with the translation of such genes blocking protein expression and preventing production of defective (or damaging) protein(s).

Our translational program focuses initially on ALS and will expand to traumatic brain injury, Alzheimer’s disease, and multiple sclerosis.

                                   

LEAD CANDIDATES

                                   

Thera has selected two lead chemical compounds, SYN1 and SYN2, and has already performed preliminary research to characterize their pharmacology, drug distribution, animal efficacy and safety.

SYN1 and SYN2 are chemically different molecules that act through a common chemical scaffold and share the same effect on selective activation of NF-κB p65 and on increased MnSOD expression.

Their shared mechanism of action is intimately linked to the ability to up-regulate pathways critical to cell functionality and viability (up-regulatory effect through NF-κB p65 activation) and exert a direct effect on mitochondrial deficit and neuronal network disruption (pathogenic target effect mediated by MnSOD expression). In addition to this shared effect, SYN1 is likely to promote its efficacy on SOD1 misfolding and toxic intracellular aggregates through a different part of its chemical structure.

                                   
                                   

SYN1 and SYN2 are broad-spectrum neuroprotective agents with a strong neuroprotective and neurotrophic activity, similar to regenerative cell therapy, and present convincing evidence of potential disease-modification effects.
They have a direct effect on three key pathogenic changes present in degenerated neurons and act through a) protecting motor neurons against protein misfolding and oxidative toxicity, b) inducing neuritic/axonal regeneration thus restoring the viability of the neuronal network, and c) activating modulatory/compensatory mechanisms that delay progression of symptoms and increase survival.

                                   

DISCOVERY PROGRAM

                                   

Thera is implementing a robust discovery and research program to strengthen and advance our product portfolio. We have entered collaborations with the Flemish Institute for Biotechnology (Vlaams Instituut voor Biotechnologie), funded by the Government of Flanders – Flanders Innovation & Entrepreneurship, to identify new NF-κB-based therapeutic targets and synthetize a number of hybrid compounds based on the common chemical scaffold of SYN1 and SYN2.