What are some promising investigational agents and novel therapies for relapsed/refractory patients?

What are some promising investigational agents and novel therapies in the relapsed and refractory setting?

classes of drugs that are very interesting for multiple myeloma is the bispecific antibodies and the car T-cells. We'll have a few more that I'll get to as well.

for the bispecific antibodies. Of course we have teclistamab that's approved, but we have several others also in the pipeline.

So we have the BCMA targeted ones. We have elranatamab, alnuctamab, the Abbvie one, Regeneron. So there is a lot more in the pipeline. We have talquetamab, that's targeting GPRC5D. So that's another treatment target. And then we have cevostamab which targets FCRH5 so patients can respond to another bispecific with another target, even though they have been treated with, say, a BCMA one upfront or earlier.

Then we have the car T cells. These have been around for a now a few years. The BCMA targeted ones. We have car T cells with other targets also GPRC5D We're also now having a trial here with dual CAR-T, so we infuse two CAR-T, BCMA targeted and a grpc5d targeted at the same time.

And then we also have CelMoDs. So these are immunomodulatory drugs and they have somewhat the same targets as the IMiDs. So as lenalidomide or pomalidomide the new ones are iberdomide and mezigdomide. Those are very promising, very good results. And also what we're doing now is we're combining these in smart ways. So we're combining the already approved drugs with the bispecific antibodies.

For instance, we have CelMoDs in combinations with approved drugs also coming with bispecific antibodies. And then for the car T cells so far they have been a one and done treatment. But we're also looking into maybe maintenance after CAR-T.

So there is both very interesting new treatment options and new combinations and new ways of using them.

the question is what are some of the novel therapies that are being tested in a relapsed setting? And again, I mean, I think the it's the era of immunotherapy. Now we are able to use the patient's own immune cells to eradicate myeloma. We can either take the immune cells out of the body genetically modify them and make them a myeloma killer.

So that's called car-t cells or we can just give an antibody that will bring the myeloma cells and the immune cells next to each other and destroy the myeloma cells. These are the bispecific antibody Engagers. We have two approved car T cells in America right now, which is very exciting. And we have one bispecific T cell Engager also just got approved a month ago in America.

So that's really great news.

Talvey and Elrexfio received FDA approval in August 2023 for myeloma patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti Cd38 monoclonal antibody.

I think we just need to learn about them more. So what we're seeing here, data at ash is about different bispecific that are available and probably will get approval soon. different target for bispecific.

The target that we've been using now for a long time is BCmA B-cell antigen present on myeloma and normal plasma cells.

But there are other targets that are, you know, very exciting because they're different.

So we are you know, the results are being presented and they look very promising. So I think that's really important. The other thing is, can we generate a myeloma killer immune cells that are not from the patient and they can be used. So because it's sometimes hard when you have a patient who's relapsing and you have to, you know, way to collect the T cells from them and then send them for manufacturing and wait for them to come back.

Myeloma is not going to be waiting for that. So it will be nice to have off the shelf Car-T cells that are available to the patients. And there are studies being presented here about what we call allogeneic T-cells, you know, T-cells from donors that are stripped from their ability to attack the patient's normal tissues but only kill the myeloma cells. That is really exciting.

So and then there are these called trispecific, you know, not just going after one target on the myeloma cells. Let's go after two targets. And so there are you know, exciting data being presented here. So right now, you know, the only, approved, T-cell redirecting therapy is, Teclistamab, right. So there's a whole panel of other, BCmA directed therapies that are, being explored, T-cell redirecting, treatments. And I think those offer interesting opportunities, because of alternate, dosing approaches, perhaps slightly different, side effect profiles that may make them easier to administer in the outpatient setting. And so forth.

Right now, teclistamab so there are you know, exciting data being presented here. So right now, you know, the only, approved, T-cell redirecting therapy is,Teclistamab, right. So there's a whole panel of other, BCmA directed therapies that are, being explored, T-cell redirecting, treatments. And I think those offer interesting opportunities, because of alternate, dosing approaches, perhaps slightly different, side effect profiles that may make them easier to administer in the outpatient setting.

And so forth. Right now, teclistamab is administered, on the inpatient setting because of the cytokine release syndrome, that can develop, that requires inpatient management in a small percentage of patients.

Talvey and Elrexfio received FDA approval in August 2023 for myeloma patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti Cd38 monoclonal antibody.

and then, the agents targeting other myeloma surface molecules. So the GPRC5D, redirecting drugs are very, encouraging, as are, you know, FCRH5 redirecting, T-cell redirecting molecules.

Those are very exciting molecules. And I think really, it's how we utilize these agents, both in combination with, you know, two redirecting drugs or in combinations with, currently available, myeloma therapies, standard of care, myeloma therapies, or how we sequence them with, Car-T cell therapies. Those are the areas that I think are kind of the hot topics now of trying to, you know, trying to understand how to incorporate all of this into a broader myeloma treatment paradigm.

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