What is the future of immunotherapy in amyloidosis?

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What is the future of immunotherapy in amyloidosis?

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In some sense, it's here already

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And what I mean by that is that some of the medicines that we use in treating multiple myeloma that are considered a mere therapy or we use in amyloidosis already. So the classic one is daratumumab, which of course is now approved in amyloidosis.

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So that is a form of immunotherapy and we're using it now 2021.

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It's interesting to think about other more advanced immunotherapies that also could be relevant to amyloidosis

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things like CAR-T. So that's something that's extremely hot in multiple myeloma and other forms of cancer are extremely promising. We're still figuring out how best to do that, but clearly there's a role for that.

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And multiple myeloma has not been tested in amyloidosis. And given the issues that some patients with amyloidosis have, with heart trouble and other things like that, it makes CAR-T a little bit a little bit dicey.

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But that's something that could be relevant. And then all the other immunotherapies that are being looked at in multiple myeloma

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could also be relevant, and they haven't really been looked at yet.

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So for example, the bispecific molecules, which is just another way of basically turning on one's immune system to help to fight cancer, which in this case could be the amyloidosis

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and lots of other immunotherapies or immunotherapies that are being developed which are almost certainly relevant to amyloidosis. Also, it's just a question of doing the trials to to figure that out, to prove that they work.

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And then also much like I said earlier, for

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the treatment of amyloidosis and not just grabbing things that we use for myeloma and giving them to patients with amyloidosis, rather, we need to do this carefully. So, for example, again, CAR-T, we really need to think long and hard about that, whether whether it would be safe to do a CAR-T in somebody with amyloidosis, what significant cardiac involvement?

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Probably not. So we just need to be judicious and careful about doing that,

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Are there any drug trials for amyloidosis?

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are there other drug trials for amyloidosis. Yes. And this is an area where things have become very interesting and exciting. So really big picture. There's two categories of things that are being tested in amyloidosis currently. First is basically myeloma therapy so plasma cell directed drugs.

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And this is a lot of this is looking at medicines that we know worked in multiple myeloma already. They've not been tested in amyloidosis. They should because any drug that kills plasma cells should work in amyloidosis as well as it should in myeloma. But as we've said, dosing is a little bit different, responses are a little bit different.

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And so we need to do those trials in amyloidosis to see how effective and safe these different myeloma drugs are in that related but unique condition of amyloidosis.

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But that's category number one of plasma cell directed therapy. But then category number two, which is really not relevant to multiple myeloma, is a whole separate avenue of research looking at drugs that actually help to break down amyloidosis that's in organs already.

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And the idea behind this is that, as I mentioned earlier, when we use myeloma, but medicines that we borrow from multiple myeloma to treat amyloidosis, we kill plasma cells, we suppressed, light chains, and that's good. But the problem is that that does nothing to clear the amyloidosis that's already deposited in the heart, in the kidneys, in the different organs.

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And unfortunately, that's what often makes amyloidosis life threatening, which is that these organs are already

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terminally damaged. And controlling the light chains isn't enough. The heart's already long, already end stage and and patients succumb due to heart disease. And so there's a lot of interest. And the other thing is that we know that it takes months, two years for that protein to disappear, that the name of the game in treating amyloidosis is suppress.

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The bad light chain proteins stop the attack of that light chain protein on, let's say, the heart or the kidneys, and then the organs can heal. So the body's natural healing mechanisms can, we think, break down that bad protein and then organ function gets better in some cases and then patients improve.

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But that takes too long and it doesn't happen frequently enough.

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So there's a lot of interest at looking at new medications to help that process along. And so there are a couple that have been developed. One is called NEO D 001. So by this company called Prevena that was one that we and other groups were involved in doing clinical trials with a couple of years back. Those trials didn't pan out, unfortunately, in that the drug was unsuccessful, probably coming back now in clinical trials.

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So fingers crossed will hopefully work.

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And then there's another one that we have in trials currently called CAEL-101 one so it’s C A E L dash 101.

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a drug where the idea is that it's a monoclonal antibody. So a drug that is structured much like daratumumab or other drugs of that class that we use to treat lots of different forms of cancer these days.

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But this drug is structured so that is given intravenously goes into the body and it actually sticks to amyloid that's deposited in different organs already. It sticks in the heart, it sticks in the kidneys, maybe in different organs, too. And as it does that,

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we think that it turns on cells called macrophages where macrophages are immune cells that are normal.

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We all have them. But what happens after that CAEL-101 drug binds to the amyloidosis, let's say in the heart, is that that acts as a targeting mechanism for the macrophages to then come in and chew up the amyloidosis and help to degrade it, to emphasize this is experimental early phase clinical trials are promising. It's in clinical studies now hopefully will pan out.

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But that's an extremely promising and important avenue of research for amyloidosis currently, because we really need drugs that can break down that protein because that's what, again,

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what can cause

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can cause people to pass away from this disease. And what even for those that are surviving and it's what causes them to feel awful. And so we need these medications that can help to break down those bad proteins, which in turn helps those organs to work better.

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And if those organs work better, then people don't die of this disease and they feel better. So that's where it's really critical, a critical and exciting area of research for that. So again, very different from what we're doing in myeloma, because that concept of amyloid protein sticking in different organs is not relevant to most people with multiple myeloma who don't have that.