Alzheimer's Disease, Alzheimer, Degenerative Disease discussed on Breaking Biotech


What's up everybody? Welcome break in biotech. Thank you for being with me here today. My name is Matt and you like the Channel. You can help it out. By clicking the like or subscribe button you can also help out the channel by leaving a review. Wherever you listen to this podcast. So I'm glad to be back and thanks again. Everybody I really do appreciate support. I've been getting the numbers have been growing quite substantially lately. So please continue to tell friend today. We're going to talk about cassava sciences and Alzheimer's Disease Cassava. Themselves are quite a small company. But they've seen a pretty substantial increase in valuation lately so we're GONNA touch on their pre clinical data the face to a data. They released late last fall. And then we're going to move on to my suspicions for the upcoming data released that they're going to have. And then we're GONNA finish up with a twenty nineteen recap and then a portfolio review for the last week. So that's the plan for today and with that let's just get right into it. So Cassava Sciences Ticker Symbol S. A. V. A. They closed on Friday the tenth of January eight dollars and fifteen cents a share giving them evaluation of one hundred and forty million dollars and like I said I think it was about a month ago. They were trading about one dollar in change so they have increased quite a bit lately but I think there is some good justification for that. But we'll talk about that a little bit later. The companies formerly known as pain Therapeutics Ticker P. T. i. e. and they were trying to develop a drug called Moxie which is an extended release oxycodone and they were developing this as a means to deter abuse in patients but they ran into a lot of trouble with the FDA just not seeing eye to eye on how this drug would be beneficial to patient so the company ended up dropping development of the drug. They rebranded themselves as a neuroscience company with a focus on Alzheimer's disease so the company in their pipeline have a single molecule as well as a diagnostic test related to Alzheimer's disease. But in this talk today. I'm just going to talk about their molecule and its potential in Alzheimer's disease but before we get into that we first need to touch on Alzheimer's disease and so for those who don't know Alzheimer's is a chronic nerve degenerative disease symptoms of the disease include things like disorientation language problems mood swings of motivation as well as behavioral issues the risk factors so this disease. Because we don't really know what causes it. They include things like family history history of head injuries. Depression hypertension. So it's all this conglomerate of things that we don't know why they contribute to it but we do know that they do one of the issues with Alzheimer's diagnosis is often delayed. Because the symptoms are mistaken for normal aging. We know that the disease mechanism is not understood. Very well I touched on this and other video so put a playlist together for everybody who wants to look at that. I've talked a lot about Baijian in their attempt to effect Alzheimer's by modifying Amyloid Beta. And how that hasn't worked out very well but for our purposes today. This is interesting because it's a different mechanism. So we know that amyloid Beta is able to bind to receptors on neurons. And somehow this leads to hyper phosphorylation of Tau and what we're GonNa see later is that you can alter this relationship through chemical means and this might lead to an improvement in the disease. So we're GONNA touch on that but there are multiple different hypotheses around how Alzheimer's develops and we still don't really know. What the primary mechanism is the treatments. That exist today. Don't alter the course of the disease. But they do effect this symptoms that are present so dinette. Brazil which has been approved for a long time isn't a CDL as inhibitor. And that seems to prevent a lot of the negative effects of Alzheimer's other treatments that have been around for a little while now. Amanda Dean and maintain our an MD a receptor antagonists and these also seem to help patients as well. Now when it comes to the size of the market of Alzheimer's currently twenty six point six million people worldwide. They're diagnosed five. Point eight million people here in the USA and this number seems to be increasing as the demographics are such that. The baby boomers are now in that age where it's more common to get diagnosed with Alzheimer's disease. I have here on the right. An estimate of the revenue that's been generated from previously approved Alzheimer's drugs. The one of most notable importance is air set and that reached a peak of three point. Five billion dollars in sales and that was in two thousand nine and two thousand ten. The sum of all four of these drugs in the revenue was six point. Five billion dollars in two thousand nine. So there's obviously a huge market potential here for a disease modifying drug and another thing. We need to consider that a drug that can change the course of the disease. Mike Garner premium even more than what was charged by the company that developed air said. So let's talk about cassava scientists main molecule. Which IS P T? I one to five. And this is a drug. That's able to bind to a protein called a when it's in a special confirmation and I'll talk about that in a second. But the role filament a is to act as a scaffold protein and this is a very important function because often proteins are just hanging around in. The site is all randomly and they need to be brought together in order to mediate. The deduction of a signal so filming is one of various different scaffold. Proteins IN THE CELL. And it's been characterized as bringing ninety different proteins together to mediate the function of a signal through a cell. And I know it's very broad but you think about all the different pathways. The different ways that cells can communicate through these means so film and just one version of that and the hypothesis is that amyloid Beta outside of the cell binds to the Alpha seven NICOTINIC acetylcholine receptor. And when it does this recruits filming a on the inside of the cell altering its confirmation in mediating dysfunctional signaling one of the consequences of this pathway. Here through amyloid. Beta and this Alpha seven nicotinic receptor is that it leads to hyper phosphorylation of Tau. So this is how we go back to the amyloid hypothesis and the Tau Hypothesis. That apparently through this relationship amyloid Beta is able to affect hyper phosphorylation of Tau and lead to the deleterious effects associated with amyloid Beta. Now what does is it binds to fill them in a when it's in that confirmation that's enabled by the binding of amyloid. Beta to the Alpha seven nicotinic receptor and when P. T? I BINDS TO FILM IN. A it's able to fix. Its confirmation such that there is no dysfunctional signaling and it prevents Tau phosphorylation. There's another mechanism that involves CD fourteen. The toll like receptor four and neuro inflammation. But I'm not gonNA talk about that. The ability of one to five to effect this amyloid Beta hyper phosphorylation of Tau is probably the primary mechanism in which it has any effect at all. So that's the premise. On which the company has developed this drug further. And I'll talk about a little bit of evidence that suggests that this is true so I'm showing here some Western blot data from the lab. That developed this drug. And what they did here is they took human hippocampus. They treat it with amyloid. Beta with or without. Pti One to five for a certain amount of time and what they saw was when they treated the hippocampus with amyloid Beta. We see this big increase in Tau phosphorylation which you can see here and for those just listening to take my word for it but then when they treat it as well with PT. I one to five. We see dose dependent decrease in the amount of phosphorylation and nitro cessation of town. So this suggests that P t two five is able to disturb that relationship between amyloid. Beta the office seven nicotinic receptor and phosphorylation of Tau thus hopefully preventing Alzheimer's disease and some of the cognition effects that are associated with that. So this was just done in vitro now I WANNA move to the face to a data that they showed in late fall last year. And we'll see whether or not there was an effect in actual living humans. So the first thing they did was Pharmacokinetics looked at how the drug behaves when it's placed into humans and this drug is taken Twice daily one hundred milligram doses and what they saw here. I mean at least for pharmacokinetics. You're looking for whether or not the drug is able to stay in somebody's system for certain amount of time. You want to make sure that it is in fact absorbed in that there is an appropriate dosing schedule that can exist if there was any accumulation of the drug that occurred between day one and day. Twenty eight and that didn't seem to be the case the drug seems to behave similarly whether they're being dosed on the first day or on. Day Twenty Eight. So that's good to see we'll see that the half life is still around twelve hours either way so this dosing schedule suggests that the drug is around and if it will have an effect it should have that effect given these parameters. They're only looking here when it comes to the biomarker data at a change from baseline today twenty eight. And I'm GonNa talk about this timeline later because I think it's relevant when we get to the cognition effects that we're looking forward to seeing in the face to data but basically here what we see is the levels of Tau levels of a Beta Neuro. Filmon light chain neuro granted as well as this protein Y. K. L. Forty. And what we see across the board except for a Beta is that in the CSF as well as the plasma. There's a pretty substantial decrease in the levels of these proteins. We see that in a Beta. There's an increase in CSF as well as the plasma and it's a little bit of a strange correlation but actually an increase in the level of CSF a Beta correlates to a decrease inside of cells or inside the interstitial space. So that's actually a beneficial thing to see if you look at the individual patients here. It makes it a little easier to see the data but pretty much across the board. Every patient responded relatively well. There's two patients in the Beta frame where we see that in fact there. Csf A Beta decreased which is not a good thing that means that there's increasing amounts of a Beta inside the cells inside the interstitial space to look at the data data on its own. I'M GONNA blow this up a little bit and we can see here that except for those two patients everybody else increase the levels of a Beta in the CSF which is a beneficial thing. If you're trying to lower Alzheimer's disease looking at plasma biomarkers so the same thing but just instead of cf they looked in plasma and it was a little more mixed but in general the trend was going in the right direction. Not GonNA spend too much more time on that. And they also saw that plasma a Beta increased and I think that this relationship is less tenuous than the CSF relationship the levels of Beta inside the cell but this does go in the proper direction they also looked at cytokines given the effects of PT are one to five on neuro inflammation and these didn't see a very huge effect but did kind of go in the right direction. So that's also good to see and then they also showed this western blot data and what they were looking at specifically is in plasma. They wanted to see whether or not Tau phosphorylation or nitrous. Latian was decreased after dosing now. Western blot is not a very quantifiable way to look at these things but it does give us some insight into it but to add to take with a grain of salt since I personally did a lot of work using this technique in my in my past life but basically my issue with it especially with plasma samples is that it's tough to normalize because you need to make sure that the amount you put in is compared to a standard and hear what they used as their standard is tau when it came.

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