Re: ER today
The source of quotes below is the SA-transcribed earnings conference call.
At the end of the company conference call an analyst asked a question about the Regeneron collaboration which included, ALN-APP, that could possibly have applications to Alzheimer's disease(=AD). To this question, JM stated:
[[thanks for asking the question of Regeneron and APP. We are obviously excited about amyloid precursor protein(=APP) as we've characterized before. It is our lead CNS program. Akshay, do you want to comment further on?]]
AV said: [[I think it will be our first time being in the CNS space and we continue to believe that the work is going well. Our primary target is in cerebral amyloid angiopathy(=CAA), which we've discussed before where it's a genetically validated target for the inherited form of the disease. And many believe it's very heavily implicated in the wild-type or more sporadic form of the disease, which affects hundreds of thousands, if not millions around the world. And with respect to the broader question, I think, APP A-beta and Alzheimer's as we've had recently from Pfizer continues to be an ongoing discussion and debate.
And it'll be very interesting to see how the various experts at regulatory agencies and elsewhere, evaluate the aducanumab data set. I think it could be very important in further fueling the need to have A-beta suppressing agents. And what better than to turn the tap off or substantially turn the top off and reduce the production of the protein as we've done with TTR. And we would be optimistic that would have a profound impact on the nature of disease, but as you know, much more to be learned in that.]]
JM responded: [[Yes. And obviously, we were pleased to see that there might be some light at the end of the tunnel for aducanumab and approaches targeting the amyloid hypothesis and Alzheimer's. And that's obviously good for medicine and patients. And that could also be instructive for our program as well, which is good.]]
I think AD is a complex system of a high degree. So are CAA and dementia. Greater than 80% of AD patients has CAA and 100% has dementia. Compared to them, ATTR is relatively simple. But there are similarities between ATTR and AD. Mutations in their trigger molecules destabilize their normal conformation, which leads to aggregation of trigger molecules. These aggregations produce irreversible end products, such as CAA for which a majority is caused by APP, inflammation, BB barrier breakdown, dementia, not in the stated sequence in the progression of AD, It will be difficult to reverse all of them at once, but burden of some can be reduced by drugs. Since ALN-APP attacks the trigger APP and Aducanumab attacks the middle man, called amyloid plaque, the combination of RNAi against APP and Aducanumab may have beneficial effects in patients in early stages, but would have minimal effects in the late stages of the disease. The strategy taken by Alnylam to attack CAA first is very wise, in my opinion.