WE ARE APPROVED

[lausanne]

Wow! This has brought some serious nostalgia and I can't resist from writing a few words. I do recall the Turtle islands (and several such) discussions 10 years ago (Even Irishtrader was participating back then I guess). Since fishermangents's unfortunate passing, kinda lost interest. I had been a very silent admirer of several of you folks in this forum (biopearl,Hoosier,CKTC,Kmall, IrishTrader52, and many more). Thank you all for the invaluable contributions. My thoughts are also with Fisher, with whom I had some conversations. It has taken a while for to get us here, but then the history of science is like this. Better days are ahead. Onwards we go!

Cheers everyone.

[KTArsenal]

Congratulations, everyone.

I wouldn't have hung in there as long as I have without this board to quiet the storm(s) that appear suddenly on my brain's radar, and quite often in the past five years.

I also know my gallows humor and dark comedy isn't for everyone, and I can sometimes go overboard with all of it; definitely not on this board, but on other social media and online financial message boards. So if I offended, I'm sorry.

I apologize to you, good and consistent imetelchat authors, but I do not apologize to them.

Thanks again, as always, for having me in the first place.

How cool is this!!! Cheers

[biopearl123]

Always welcome, KT, I thought your “stuff” was pretty funny (for the most part). Don’t worry, I always have the red pencil.

[KTArsenal]

"After Life" (starring Ricky Gervais, dark humor at its best) is one of my all-time favorite shows, ranking right up there with Gilligan's Island, 3rd Rock From The Sun, and Wheel of Fortune.

That last show was a typo.

[biopearl123]

Yup, still funny.

[00pf5272]

Many thanks to all especially BP, KMAIL. Keep having to say, ''we're approved.''

[00pf5272]

Many thanks to all especially BP, KMAIL. Keep having to say, ''we're approved.''

[LWS]

Someone once said at Mayo Clinic about Rytelo (Imetelstat), "Tantamount to a Cure".

With this approval we can reinterpret that statement. Tantamount has many meanings (similar to is one, looks like is another, more or less is a third) and cure can mean temporary or complete (Partial Remission, Complete Remission or no symptoms for 5 years). That statement looks much better now, with the FDA on board with ODAC's overwhelmingly positive recommendation, and the future very promising.

Let's give Dr. Tefferi (Dr. T) full credit for taking the time and making the effort to discover the potential of Rytelo for blood cancers. He was right-on-the-mark. Rytelo would have never made it without his inputs. .

Rytelo = Royal Telomerase Inhibitor

[biopearl123]

LWS, I think we all are aware of your unbridled enthusiasm for Geron and Imetelstat. Interpret as you will, no patient as yet can be considered a cure, tantamount or otherwise. That is not to say there have not been superlative results in many patients. As to the comments made by Dr. Teferri over 10 years ago, it should be noted that he did walk them back and Dr. T seems to have disappeared from those in the medical community who carried the banner forward (and still of course, do) for Imetelstat. There will be many more who do as more patients are exposed to the benefits of this drug. I think Dr. T’s (and many of our own) initial feelings of hope and enthusiasm were driven by the incredible slides that accompanied his initial reports in MF showing normalization of previously heavily fibrosed bone marrow samples. As various combinations are explored the hope for cure remains. Patients do read this site, and should have as balanced a view of the possible, as possible. Let’s try to stick with the data and with patient and physician experiences as they become available. For now there is lots to celebrate and to hope for.

[LWS]

bp --Correct me if I am wrong.

I believe some of the early ET patients were considered cured by Rytelo. The market was not there for commercialization, since there were other methods (perhaps not as good). In some cases, there was at least the appearance of a cure. I took this statement 'out of the mothballs' as a vindication of Dr. T. If he had said "no go" at the time, there would be no Rytelo today. Let's hope for some cures in combinations. Certainly, we can look forward to PRs and CRs. Rytelo should be an important component in the Cancer Moonshot (NIH).

================

From bp --Interpret as you will, no patient as yet can be considered a cure, tantamount or otherwise.

[Ryan]

Wait,
Dr. Tefferi did state tantamount to a cure and it was further written in a brochure put out by the Mayo Clinic.

The reason he said tantamount to a cure is because in his trial

Dr. Tefferi says. "Some patients treated with Imetelstat have reverted back to normal bone marrow." Imetelstat works by inhibiting telomerase activity in tumor cells, which leads to cell death.

I’ve never seen specific quotes “walking his statements back”
Considering his career is in the clinic and his stature, I don’t think there are tea leaves to be read about him not taking the decade long slog of Ph II and III.
Even his data and data warehousing methods weren’t particularly made for corporate research, so Geron took the ball, and with Rizo / Feller not to mention Zeidan and the football team number of pro clinical researchers, ran with it quite ably.

So back to the point, I don’t see why there needs to be a red line in using the statement tantamount to a cure. Honestly, the front line treatment trials and with what appears to be happening behind the scene in MF even not as front line… Dr Tefferi could be proven right after all.

https://newsnetwork.mayoclinic.org/disc ... treatment/

[kmall]

Ryan - Good point and just imagine results with a healthier patient group over the course of these trials. I would expect numbers would be even more impressive. It will be interesting to see where this lines up 2-3yrs down the road. -Kmall

[biopearl123]

If he is proven right I will be the first to celebrate. Medicine tends not be a world of absolutes, and as to modifying his initial enthusiasm, I heard it myself about 8 years age when he was answering questions at an Italian heme conference on (on video). Cheng Ho heard the same presentation and pointed it out to me. No drug is perfect but Imetelstat is a major advance. I will stick with Drs. Santini ,Mascarenhas et.al. for now.

[rccola335]

Dr. Mascarenas when presenting imetelstat for MF called it "a game changer"
I have relied on the experts in the field on deciding my level of investment - after the shutdowns with Covid - Steensma and Sekres (when at cleveland clinic) did a video podcast and when talking about their treatment algorithm for MDS had imetelstat prominently in it - that was surprising because when Steensma presented Imerge data at the EHA before the continuation decision he did not seem impressed - I think as the study went and the durability became evident that was the changer

Kmall - I will be disappointed if we get to 2-3 years for MF - if that is the case then what we were told about life expectancy of MF patients after being refractory to Jakafi was incorrect (first we were told 7-12 months and then 12-14 months of life expectancy)

Listening to these recent chats that Scarlett and Kapur participated in, I would be surprised if we enter into a partnership agreement - they are selling the whole enchilada - the AML data from the impress was supposed to be available in the first quarter in 2024 but is delayed - I emailed QIMR Berghoffer a couple months ago to see if they would say how many people were being treated with imetelstat for AML (they had been open with discussing the positivity of their early treatments) they said they would have an update

last Summer the EMA was reviewing the Orphan status for imetelstat - this is standard to do prior to approval - MA

when Dr Scarlet says the shares holders will get to ride off into the sunset soon - I dont think 2-3 years - I feel within the next 8-12 months - now if Geron announced a european partner in the next couple of months - I will have been wrong

[kmall]

Rc - to clarify, my 2-3yr comment was only as far as line of treatment - Frontline?
And yes, the Needham link you posted several days ago was quite telling. Seems like they sure know something we don't. Be an interesting couple of months......I got a hunch we get a PR about the UK next? -Kmall

[LWS]

With Rytelo approved, Geron can go in many directions now with big pharma, deep pocketed backing. Here are some items to reconsider with an approved medicine. When will there be new partners or a buyout?
=================

Previous

Imetelstat is now making the medical news in many ways, including ASH2023, Oncology ADCOM (ODAC), EAP and NDA approvals (pending). Expressions of the past are being dusted off for new considerations (examples: “Bigger than all of us”; Tantamount to a cure”; “compelling, remarkable, durable”.

I don’t believe Geron will want to go it alone, or should they. In my opinion, they will be the need for several types of partners as Imetelstat gets approved and goes into production.
 
1/ Ferroptosis

2/ Telomerase & Telomeres

3/ Combinations

4/ Synergies

5/ Oral form potential

 ``````````````````````
Previous (for review & reference) 

Summary--- 3 Ways to Kill Cancer Cells

Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies.

1/ Imetelstat (telomerase, an enzyme, inhibitor) -- kills cancer cells,
2/ Venetoclax (BCL-2 protein inhibitor) -- kills cancer cells
3/ Imbruvica is a targeted medicine that works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway Imbruvica triggers the death of cancer cells

[LWS]

MDS and TI were the easiest hills to climb to get Rytelo FDA approved for something. Transfusion Independence is very important, but there are bigger fish to fry.

That was the tip of the iceberg. Now the focus will be on MF and AML, alone (IMPress) and in combinations (TELOMERE with AbbVIe, a longtime collaborator and potential partner). The immediate pressure is off now. Geron can now take the time to evaluate new combinations, new trials, new partners and perhaps a merger. The PPS has shown some surprising resistance, considering the successes and huge potential in numerous cancers and with an oral form a possibility.

[LWS]

Now that TELOMERE (AML clinical combination trial with Abbvie's Venetoclax and Rytelo) is getting back on track, it is time to take another look at the preclinical synergies (appear to be phenomenal -- near 100%).
==============

Preclinical History for Review

Reference Material

***Results (preclinical): A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. ****

Abstract 1101: Telomerase inhibitor imetelstat in combination with the BCL-2 inhibitor venetoclax enhances apoptosis in vitro and increases survival in vivo in acute myeloid leukemia

Joshua J. Rusbuldt, Leopoldo Luistro, Diana Chin, Melissa Smith, Amy Wong, Margarita Romero, Aleksandra Rizo, Jacqueline Bussolari, Fei Huang and Amy (Kate) Sasser
DOI: 10.1158/1538-7445.AM2017-1101 Published July 2017

[LWS]

There are 4 companies that likely have a major interest in Rytelo, at this point in time, based upon past history, deep pockets and other approved medicines (for possible combinations):

In Europe: Novo Nordisk & Novartis
In the USA: AbbVie & JNJ

EMA approval is coming soon (likely September or October) and ASH2024 (December) is on the horizon. This is all coming together. I am sure that there will be some surprises along the way.

============

Previous (June 11, 2024):

With Rytelo approved, Geron can go in many directions now with big pharma, deep pocketed backing. Here are some items to reconsider with an approved medicine. When will there be new partners or a buyout?

[rccola335]

I don’t know why everybody thinks we’re getting approved soon. The timeline would’ve normally been in May for us to be approved, but something is different. Geron has said more than once first quarter of 2025