Iberdomide

So last week, the FDA approved...

Ibertamide, or Zenbexis, which is a new oral agent for multiple myeloma.

This is, I'm reading here from the PI, a cereblon-modulating protein degrader, or CellMod, that's approved in combination with daratumab hyaluronidase and dexmedazone for myeloma patients after at least one line of therapy.

including a proteasome inhibitor and an IBIT.

A couple notable things about this.

First, this is the first drug approved for multiple myeloma as an accelerated approval based on CR rate with minimum residual disease.

FDA put out some guidance documents for Comet a couple years ago saying, is this going to be a valid surrogate endpoint that society would value? And Apparently it was, and so this is the first drug approved based on MRD complete response rate.

This is known as a CELMOD, cereblon modulating protein degrader.

It's just an emid, I think, and I'll talk about why.

So when thalidomide and lalidomide were first used for multiple myeloma, we knew that they caused changes in cytokines.

You know, like your IL-2 levels would go up, I think, or TNF-alpha levels would go down.

So it did some stuff to cytokines.

It modulated the immune system.

So they were known as IMIDs.

And it wasn't until many years into the current IMID era that we learned the way these drugs actually work is they bind to cereblon, which is a protein in the cell that is then able to basically link up once it binds to, you know, once lalidomide binds to cereblon, it then links up to Icarus and Iolos, which are transcription factors that are necessary for the growth and development of multiple myeloma.

And this whole process of binding to cereblon and then that complex binding to say Icarus or Iolos led to the proteasome degradation.

of those transcription factors by myeloma.

That's how lalidomide, pomalidomide work.

That is how iberidamide works.

There is another drug like this, mezignamide, that does the same way.

Mezignamide data have been published in the New England Journal of Medicine, I think a year ago.

Not FDA approved.

Iberidamide is FDA approved.

We don't yet have the pivotal study published yet.

So why would the people making this call it a selmot instead of like a next generation imid? So if we look at the cereblon IC50, so this is how the concentration of the drug needed to block this pathway in 50%.