CRSPR

[muskateer]

Is Chrspr an existential threat to imetelstat or are they treating different types of diseases? Thank you,

[biopearl123]

The short answer is probably yes but not for a long time. The more pressing existential threat is Constellation Pharma and its BET inhibitor. It checks a lot of boxes: 1. spleen 2. symptoms 3. anemia 4. bone marrow. It has been tested alone and in combo with Rux. The results are impressive. I would like to get some other thoughts besides my own on this. Initial BET inhibitors did not look like a threat because of narrow therapeutic window but newest agent appears to have overcome this. Where does Imetelstat fit into the treatment scheme? It looks like it is being pushed to a place at the end of the algorithm when all else has failed. It is being positioned to be the agent that prolongs life and it does but when bone marrow fibrosis improves/resolves with another agent, that too will probably impact the natural history of the disease. I found ASH lacking in that if I wanted to go to ASH all I really had to do was to go to EHA. Virtually all of the clinical data was previously presented. For Geron to say that all ten abstracts were accepted is technically true but there was that little disclaimer in the majority of the abstracts that the data was "old". It would have taken no effort to update the MDS TI data which was not updated since Feb 2020 and presented at ASH. The opportunity to shore up the statement from Dr. Rizo that this data represented the longed TI from any agent to date was avoided. I am afraid to ask why. The pre ASH PR looked exactly like the post ASH PR. Whats up with that? bp

[Edward]

Wouldn’t stopping the cancer proliferation with Imetelstat be worth doing right off the bat, followed by (or concurrent with) symptom management? Or will Constellation’s drug handle that well enough by itself?

[biopearl123]

Edward, yes we had all hoped to see Imetelstat used as front line therapy. The reasons for not doing so are murky at best and we have not seen adequate explanation for the absence of front line evaluation or combination therapy even though at least two strong preclinical studies suggest a promising role.

[ashah]

Front line treatment are a beast to design, execute and fund.
Once a drug is approved, even if later than the front line, its use in the treatment protocol earlier than the approval is not ruled out.
If I were on GERN mgmt, I would have voted for last line Rx for trials anyway.
What is disappointing is "known non-exploration" of using Real World Data vs Imet Clinical Trial data. Of course, this may have been discussed with the various EU/US regulatory agencies and we just don't know.
In anyway, perhaps with more robust P2 or P3 interim data we can have conditional approval as salvage treatment...which sees earlier adoption in the patients once the onc's understand the drug and its effects better.

[Edward]

Is it a lower or higher bar to demonstrate improvement in patients who are treatment refractory? Could be one argument for the study designs to date. At least in my field, if someone comes in with mild symptoms we know they’re a lot less likely to show a big treatment effect. Or maybe its a higher bar and they’re intentionally trying to show imet works in dire cases of advanced illness - hoping the rest will follow from there?

But yeah, I hope we’re not boxing ourself into the salvage indication through lack of data supporting imet as a front-like treatment.