SAGE-718 is an oral investigational drug. It works by modulating a receptor in the brain called the NMDA receptor, and it modulates that receptor through positive allosteric modulation. In Huntington’s disease and also a number of different neurodegenerative diseases, we see changes in NMDA functioning. And in Huntington’s in particular, we see that changes in this functioning correlate or track with changes in cognition...
SAGE-718 is an oral investigational drug. It works by modulating a receptor in the brain called the NMDA receptor, and it modulates that receptor through positive allosteric modulation. In Huntington’s disease and also a number of different neurodegenerative diseases, we see changes in NMDA functioning. And in Huntington’s in particular, we see that changes in this functioning correlate or track with changes in cognition. And so the idea with SAGE-718 is perhaps that by restoring aberrant or abnormal NMDA tone, you may be actually able to improve cognitive impairment early in Huntington’s and therefore have some meaningful effects for patients.
There is a lot of data to support this therapeutic hypothesis, and that includes both preclinical translational as well as clinical data. So on the translational side, one of the benefits of working in the Huntington’s space is that there are very well-established databases of patient data, patients who are followed for a number of years non-interventionally. One of those databases is the TRACK-HD sample that we actually had the opportunity to work with. What we found in that sample was that patients early in Huntington’s disease have lower levels of an endogenous or naturally occurring modulator of the NMDA receptor called 24S-hydroxycholesterol, and actually that these changes or these lower levels were correlated with changes in cognitive functioning over several years. So this was actually our reason to believe that there might be a linkage.
But then we took this a step further and actually treated a subset of patients with Huntington’s with SAGE-718, and were able to demonstrate an improvement in cognition. So we actually were able, over the course of two weeks, to improve scores on a number of tests, tests that actually measure aspects of cognition that are really important to everyday functioning, things like executive functioning and multitasking. And now what we announced at the conference is a comprehensive clinical trial program to further interrogate these effects.
