Today the EMA Approves Modification to Imetelstat PIP

[Commsman]

Just today, Nov 13, 2023, the European Medicines Agency approved a modification to the Imetelstat Paediatric Investigation Plan to allow imetelstat to be administered to children between the ages of 28 days and 18 years with MDS, JMML, or AML. Why, and why now?

This comes out just on the heels of the exciting news break that imetelstat kills AML progenitor cells via a scarcely understood process called ferroptosis, I believe this development portends some very exciting times in the very near future. AML is the 6th deadliest cancer in men, and the 8th deadliest cancer in women. Essentially a near term death sentence, AML represents a vast market with a huge unmet need. With so much promise in AML, I believe the world will finally take notice and give Imetelstat the attention it deserves.

Cheers to all fans of Imetelstat! May we finally bring this life saving medicine to all the patients who desperately need it.

[biopearl123]

Thanks for posting this Commsman. I always wondered years ago why Geron had to go through the trouble of getting approval for pediatric MDS (or was it MF) when virtually no children got that particular disease. I asked Geron about it then and was told it was just a requirement from the EU. Now things are a little clearer and we can certainly expect a new study in pediatric AML which has many differences when compared to adult AML:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290074/

[Commsman]

https://www.ema.europa.eu/en/medicines/ ... p03-20-m01

Here is a link to the EMA Approval Document. Near the bottom just under the field "DECISION" is the pdf document that was adopted by the EMA on Nov 13, 2023.

[Commsman]

Excellent point biopearl. Pediatric AML is a soul crushing form of cancer that gets a massive amount of media attention. We've all seen the pictures of little kids with bald heads in the news and research donation solicitations. If I'm reading these very early signs right, I think imetelstat may show "disease modification" at an unprecedented level in AML. I sure hope the AML Community takes notice of Imetelstat. If so, we could see investigator led trials get funded and executed very quickly.

[Zhears]

The dates are a little confusing here

The decision was made in dec 2022
https://www.ema.europa.eu/en/documents/ ... lan_en.pdf

so what are we seeing here?

[mck]

I can see all of the documents referenced, but is Imetelstat use in the pediatric population still deferred until 2035?

[kmall]

Does anyone here know what "modification" was made?

From what I can tell - looking at all of this on my phone - in travel mode at the moment......a "modification" was "approved." Apparently the decision for this modification was made Dec 2022 and it looks like that decision to a "modification" was "approved" yesterday???

It clearly states at the bottom that completion of the PIP is October 2035.

Also of note:

"Information provided by the applicant (Geron):
The product is not authorised anywhere in the European Community."

Although promising, from what I can read here, it looks like they most likely lowered the participant age to 28 days from something that was higher (ie: 6 months) - simply a guess on my part of course.

Thanks for any clarity on this. -Kmall

[Commsman]

Essentially, the EMA has adopted the proposed changes to the Pediatric Investigational Plan to allow a clinical trial for children with MDS, JMML and AML to commence as of Nov 13, 2023. The trial will have several stages where imetelstat is used in combination with 2 different chemotherapeutics and in monotherapy for children in the EU between the ages of 28 days and 18 years.

The timing of this approval right on the heels of the "eureka" discovery of Imetelstat induced ferroptosis in AML is interesting to say the least.

[kmall]

Commsman - copy all of that......do you happen to know the exact "modification" made?

PIP has been in place for at least 2yrs or longer....what change has taken place.

And the "eureka" moment was actually at last years ASH - abstract 201......for some reason, the doctors involved in that abstract have decided to do a public service announcement. Perhaps Australias - Therapeutic Goods Administration or TGA - is eyeballing this for approval?

As Bp has pointed out, as of now Geron has not made any public endorsement of that video. I think this is all positive, but it's premature to see how Dr. Lanes video and yesterday's EU modification are connected at this point. Both happened last year. Of course.....I would LOVE to be wrong on this. -Kmall

[Commsman]

@ kmall - I don't know the exact changes made which is why I haven't said anything. I suspect the changes were to include the indications of MDS, JMML, and AML. I think previously approved conditions for Imetelstat investigations in EU children were brain cancer (which I believe was revoked at some point) and MF which biopearl says is nearly non-existent in children. It's pretty hard to fully understand the EMA document other than that it is a formal green light to investigate imetelstat in children for MDS, JMML, and AML which I think is a good thing. Perhaps the timing was purely by chance, but I think it's possible the IMPress trial which has been active in France and Germany (in addition to Australia) may have helped push this over the line for EU children. Whatever the case, I think it's a very exciting development. I've long thought that (paradoxically) imetelstat would be more effective in high risk MDS and AML than in low risk MDS. I didn't know anything about ferroptosis, but my reasoning is that these more active cancers would speed themselves to their end more quickly when deprived of telomerase. I also think John Scarlett has been hesitant to go after AML for a long time as AML is such a difficult nut to crack. However, I think time may prove that imetelstat efficacy in AML will prove to be a major catalyst for adoption of Imetelstat to finally make an impact in the treatment of AML as well as numerous other cancers.

[kmall]

JMML, and AML have been on the schedule since shortly after Orphan Drug Status was announced - July 2020......

https://ir.geron.com/investors/press-re ... fault.aspx

Again, only a guess here, the participant age of 28 days was most likely the modification approved yesterday. Regardless, a win for patients in the EU no matter what the modification was. The 2035 date is something that I would like clarification on. Most likely not coming from the company anytime soon, and hopefully is muted by potential approval from both the FDA and EMA far before that timeframe.

Didn't get a chance to tune into today's CC, but judging from the AH action it doesn't seem as of any groundbreaking developments have taken place? -Kmall

[biopearl123]

Kmall, my take on the 2035 thing based on nothing is that long term follow up will be required (as with CRISPR).

[mck]

2035 is the date of completion of the investigation plan. Someone mentioned that clinical trials were starting this month. Does anyone have any more information about where the clinical trials are starting for AML in the pediatric population?

[rccola335]

i brought this up a couple months ago - the EMA reviewed their orphan status for imetelstat - this is standard process before approval - someone said it didn't mean anything because it was for pediatric use

[kmall]

Mck - the only Clinical Trial underway at the moment for AML with Imetelstat that I'm aware of is the P2 IMpress CT - first patient was dosed in July of this year and eligible patients must be 18+.........as of now i don't believe a specific pediatric CT has been planned? -Kmall

https://www.geron.com/research-and-deve ... al-trials/

https://clinicaltrials.gov/study/NCT055 ... %20&rank=5

https://ir.geron.com/investors/press-re ... fault.aspx

[LWS]

TELOMERE is a planned Phase 1/2 clinical trial evaluating imetelstat in patients with relapsed/refractory AML. The trial is designed to test two distinct combinations of imetelstat and venetoclax or imetelstat and azacitidine. The primary objective of the Phase 1 portion is to identify a safe dose of each of the combinations.

=================================
Kmall --- What is the status of TELOMERE?

[kmall]

LWS - It's my understanding that TELOMERE is postponed until further data from P2 IMpress is submitted for FDA review. -Kmall

[Ryan]

I would say that every time there is a modification to this trial, a lot of flags are raised and flown, a lot of cheers and exuberance… but, I agree that this is a non-issue. It’s been stated that this is part and parcel with an application for marketing approval with the EMA.

If a new trial were being initiated, with patients (children/babies in the case) by Geron, it would be discussed in a public call and perhaps a PR.
If a new trial is initiated by a sponsor (Geron not paying), it could initiate without notice, but I think our online sleuths would find it. I do not believe this is the case.

Stock movement - I would say the market has rallied a bit, particularly biotech sector which has been woodshedded and coming off essentially 5 year lows. Other factors, AML trial publicity, but again, theee are results that have been known since the abstract release in Nov 2022. But I guess not well known.

And as I like to point out, the institutional ownership % has continued to scale up despite the stock drop (plummet). It looks like it’s up in the 70% range, and guess what % is going down… retail ownership. Retailers getting exhausted, capitulating, etc… while the fundamental story (data) hasn’t changed. Soon the institutions will have their fill / the stock supply of sellers will be much more sparse, IMO.

[mck]

Essentially, the EMA has adopted the proposed changes to the Pediatric Investigational Plan to allow a clinical trial for children with MDS, JMML and AML to commence as of Nov 13, 2023. The trial will have several stages where imetelstat is used in combination with 2 different chemotherapeutics and in monotherapy for children in the EU between the ages of 28 days and 18 years.

The timing of this approval right on the heels of the "eureka" discovery of Imetelstat induced ferroptosis in AML is interesting to say the least.

Commsman ~ do you have more specific information on these trials that are supposed to begin this month. Like where are they being done? Where can I find more information on this?

[biopearl123]

Woah cow boy , not so fast, there is no evidence that trials are starting anywhere near on the timeline you suggest.