What research is being done to make hypomethylating agents more effective?

What other research is being done with hypomethylating 
agents to make them more effective?

I'd like to highlight,

we have a new formulation

of hypomethylating agents because patients,
you and I, get the IV injection every day.

I mean, if you can get the pill and
be at home, why would I go to the hospital.

So we succeeded to get decitabine IV.

We have a oral formulation
as effective as IV formulation.

So now we have oral decitabine
that’s being given.

Fo azacitidine, we're not there yet.

There's formulation approved for maintenance,
where a patient with chemotherapy,

who are not transplant
candidates, can get a maintenance with pills.

But these maint—these oral pills,
these pills of azacitidine

are not equivalent to the IV formulation,
unlike decitabine

where you convert one pill to an IV
infusion is given 14 days every month.

But right now we’re exploring

oral azacitidine to be equivalent
to the IV formulation or sub-Q,

and to replace the way
we give IV—azacitidine.

That is being done right now,
but we're still behind decitabine.

Now, the research is being done at two levels.

Number one is to have a better understanding
of the biology of the disease.

Again, I will say
AML is not like one disease.

It's spectrum of diseases.

And we have to dig into that to each patient
identify

his or her own biology
because this will dictate how I treat.

It's not smart to give a treatment
that fits all.

It doesn't work this way.

So the first thing is
have a better understanding of the biology.

And then if I target, that you can go
after them.

Then, I can design a treatment a la cart.

And that will bring me to the second
chapter of the research is what are the best

combination
to offer the target specific population.

So we make progress and in this sense
we have different approaches.

We have, I discussed, HMA BCL-2 inhibitors.

We have FLT3 inhibitors

to be added to HMA or, FLT3 added to HMA
 and BCL-2 inhibitors, IDH1 and 2.

The group of patients
where the outcome is really still poor,

are the group who have the complex karyotype
and the p53 mutation.

These are really, really bad for patients.

For these patients, for example,
we're exploring new agents that can target

specific p53
abnormalities of the drug called magrolimab.

And others in that sense are being explored
for these patients.

These are happening right now.

I know, for example, in CML,
there was CML transformation into

AML blast—AML or CML blast crisis,
for example, for this, which we can give

tyrosine kinase
inhibitors in combination with HMA

that we hope to further improve that.

These are happening right now
and I think the future is bright,

want to make progress
and patient will have a better outcome.