Keeping perspective

[biopearl123]

As more data accumulates I think it’s important to keep some perspective here. I am going to put at the top of the list the fact, (and I think we can say fact factually, since the data speaks for itself), that patients who respond to treatment in L/R MDS live longer and live better. Not only that, a heme picture that shows a rise in hemoglobin of 5 (!) grams in previously transfusion dependent patients has never been achieved before. Many allusions as to what is going on in the bone marrow have been made but replacement of malignant cells with normal cells is occurring. That’s what’s happening. As a result patients (those who respond) of course feel better, don’t need transfusions anymore, don’t need to go to the transfusion center, don’t drain the blood supply, aren’t subjected to the ongoing risks of transfusion (iron overload, blood borne diseases that get past screening) and they live longer. The latter should be in neon. The gold standard. It’s pretty hard to prove longevity in a disease that already has a pretty good longevity (lower risk) as opposed to those with a short life expectancy, because it just takes more time for Kaplan Meir curves to show a meaningful difference in the former. That is why the AML study only has a timeline of 4 months to ORR, you just don’t have to wait that long for patients to show effect if they are not going to live long from the onset of the study. A looooong time ago Geron thought they could show effects in prostate cancer and spent about 40M to make some very happy small company wealthy and then realized they could not show the effects they thought they could because many prostate patients just lived too long to prove Imetelstat made a difference. Well we are talking decades ago and I only mention it out of interest, to recall the days when Okarma was flailing and failing and throwing the company’s money away. The point is one of the posters to be presented at ASH will show longevity and there is little doubt that we will in the future see confirmation of the same in MF. Imetelstat is different. It is selective and it kills malignant cells and presumably spares normal cells. (How this will translate to pediatric AML is a worrisome question to me since kiddos are certainly still showing lots of normal telomerase active cells early in life but no doubt this will be addressed with dose schedules and a whole lot of thought. This is what we have, this is what telomerase is. Keep. Perspective. The fempoptosis thing is a whole new and exciting area. But I must ask, how is it possible that Scarlett is STILL talking to investors? How is it possible that the FDA does not grant priority review? Are these examples of willful ignorance? Undue caution? A failure of imagination? I don’t think its a question of the emperors new clothes. It’s something else. I am working on trying to figure out what. Regards, bp

[kmall]

Bp - excellent synopsis on where we stand today!!
Thank you for keeping things in perspective.

I would like to address two points you made at the end.

I've been scratching my head that Geron has been in talks with the FDA and having intermittent meetings with, since October 2019 - I'm sure most readers here remember Jenny Z?

With that said, Gerons Regulatory team, clinicians and management have been in constant communication with the FDA for over FOUR years and the company gets sidelined with standard review and a PDUFA date of June 16, 2024 ???

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

How is this even possible?....Geron had to have known that priority review was off the table.

As you pointed out, the data clearly surpasses Luspatercept in every way. Why was Luspatercept granted priority review....and approved 3 months later?.......it's HANDS DOWN inferior in comparison to Imetelstat.

https://news.bms.com/news/details/2023/ ... fault.aspx

Don't even get me started on Imetelstat vs. JAKafi.


2nd point - the endless investor conferences which certainly don't favor long term retail investors, many of whom have been here longer than the CEO and 95% of current employees on the Geron roster. Like many others here, I've been sitting on my pile and accumulating when possible, not day trading - rinse and repeat - in hindsight a HUGE mistake - however, driven by fear of losing out and being on the sidelines during a cataclysmic event - Partnership/BO - and possibly paying higher capital gains in the end, I've been shackled to this investment for the same reasons I started a position here - science/medical aspect of Imetelstat and telomerase and of course as an investor, the potential for an investment which actually pays off. Nothing in life is guaranteed - except the death and taxes thing, but for investors like myself, and there are many of us, we get beaten down everytime an institutional "investor" gets an underwriters option at a super low price. Where I'm from, it should go the other way....but that's not how the street works, and it's reflected in the CEOs actions by rewarding himself with a 20+% pay raise this year, while we all got a 50% haircut. -Kmall

[biopearl123]

Kmall, right on. So odd that Geron went through submitting tranches of data as they were available to “hasten” the approval process. Fast track? What a euphemism! Total borscht. I did want to mention that with the data emerging about lengthening life, that the life extension clock starts for the treatment group when imetelstat treatment starts. (Second line or greater.) What we don't and can't know where even great longevity effects might occur (and reduction in transformation to H/R MDS and AML) is the glaring question of what would happen to longevity, H/R,,AML transformation rates, symptoms, anemia, transfusions (total) QOL (the list goes on) if finally treatment was just started commensurate with the actual diagnosis, when there was “darkness upon the deep” (e.g. day one?), Genesis. And G-d said let there be light. Are we so afraid to ask the question? We understand myeloproliferative diseases as smoldering processes that should be left alone until symptoms emerge. What if that’s not true? What if once recognized, those as yet malignant preclinical clones should actually be attacked? What if there was no drug that could do that previously and now there is? Must we accept the thesis that doing so only encourages the emergence of more resistant clones? But now we have fempoptosis, might be time to re ask the basic questions…Just musing here…

[LWS]

bp & kmall --- I believe we are making similar points. ODAC is looking at the same successful trials and scientific evidence that we have been following. Since they are experts in the field of oncology, I don't see how they could not approve the NDA in a timely matter.

The other part of this (from an investors point of view) are market forces (hedge funds, naked shorts, etc.) and 'gray area' business practices at Geron or their rivals that have not been in patients' best interests (another subject).

From a medical and scientific point of view, these are my conclusions. This may not be in the same certain category as "death and taxes" but (IMHO) it is close to happening (from EAP to NDA approval) in a timely manner, with strong and solid recommendations from ODAC and the FDA.

My conclusions:

Imetelstat is a 'miracle' blood cancer medicine that uniquely modifies that group of diseases, kills cancer stem cells (in 2 ways), brings about transfusion independence, extents life, improves life (fatigue, etc.), and will effectively treat (PRs, CRs, possible cures) some cancers in combinations. AML is now in focus as the next step beyond ET, MDS and MF. Imetelstat's safety profile is very good for such a powerful medicine, with few side effects that are reversible and manageable.

[kmall]

LWS - One of the main obstacles for momentum in the SP has been the CEOs willingness to dilute the stock immediately following a major company event which could implement a breakout. It's my belief, and my belief ONLY, that he prefers a lower SP for institutional investment, inducement grants to entice new employees and managements/BOD yearly stock option awards......once again, everyone wins but the small guys who have been here a while supporting patients and this company. -Kmall

[KTArsenal]

JS and company want the SP low for key hires, probably definitely, but they also know that it helps to shake the financial tree free from retail, because we don't invest millions of dollars and aren't welcome at their dinner table with the clothes we wear.

[Zhears]

I share the same maddening frustration about the share price. I also think that many of us have become too fixated on approval being the end of a long road. Which, unfortunately, it isn't.

The share price doesn't care about science, only future profit. Currently, thats all guesswork and still a year away until they will be reporting on that, assuming approval of course.
So why has JS diluted so many times? Does he have any other choice? The shorts will attack after the news anyway, so if he doesn't sell then he would have to sell later at an even lower cost.
I am still hopeful for a buyout in Q1 next year, but JS has to plan incase that doesn't happen, hence more investor conferences, more dilutions on the horizon. Costs can only go up, and sales forces aren't cheap.

It's worth evaluating JS past actions against hoping for the best, and planning for the worst.

So the $4-5 price tag, i think is realistically pricing in more dilutions.

[LWS]

History Lesson for Imetelstat (IMET has come a long way since ET)


Dr. Sergei Gryaznov (Dr. G, now at MAIA), formerly Geron's (NASDAQ: GERN) Chief Scientist in Nucleic Acid Chemistry, is the named inventor of GRN163L, also known as Imetelstat.
===============================================
As I remember, Imetelstat (GRN163L) was invented at Geron for ET (before Mayo Clinic and Dr. Tefferi (Dr. T) got involved with MDS research) by Dr. G. Imetelstat (IMET) in most cases, I believe, created a CR (complete remission) or a complete cure for ET. However, at the time, ET was being treated successfully in other ways, so as a commercial product, it was thought to not be viable (perhaps that is being reevaluated now).

Dr. T ("Tantamount to a cure") discovered (to everyone's surprise) that IMET had very powerful properties that no one understood (MOA being defined to this day). Dr. G moved on to MAIA (THIO and solid cancer combinations).

Now we know about two (2) mechanisms that kill cancer stem cells with IMET, as it is being reviewed by ODAC as a 'miracle' blood cancer medicine.

1/ Ferroptosis
2/ Telomerase & Telomeres

[mistergern]

Unfortunately, as one who has taken Kmall's investment approach for over twenty years, I am now in the final stages of Grief. However, the latest news from Down Under has changed my perspective from sadness to acceptance with a dash of hope (and I'm sure it has also altered the perspectives of major investors).

Looking back to the J&J decision, it was my conclusion (right or wrong) that Scarlett had assessed the potential for Imetelstat to be profoundly greater than J&J's assessment. The MDS Stage 3 trial has, thus far, lent credence to Scarlett's faith in Imetelstat. The Aussie AML study (in my opinion) has brought Imetelstat's potential market value to a whole new level which I'm fairly sure is not yet shared by big pharma. I believe Scarlett intends to hold onto Geron until the market agrees with his assessment of Imetelstat's value and does not think that will happen until more data validates his perspective, ergo - he'd rather dilute than sell out - as of now, I (gingerly) agree with the approach.

[huntingonthebluffs]

mistergern, yes many of us here have been steadfast with our GERN stock positions. Maybe wrongly so however, I think instead of bashing Dr Scarlett and company, let’s not lose sight of the responsible parties for the most grievous offenses of incessant delays, ignoring great and unique results, roadblocks, patients in need, etc. Yes of course, it’s the “3 letter“ government agencies in the US and internationally (yes I know it’s more than 3 letters in some places). The FDA is totally responsible for committing many misdeeds in getting Imetelstat to patients.

IMHO, the FDA is very tainted and everyone knows it. Let’s call a spade for what it is and shift some of the bashing and as tax payers take some action in that regard if possible! Dr Scarlett is playing the long game. Excessive pay and benefits yes, but IMO we are where we are because of the FDA and related influencers, not JS.
And in terms of pay for performance, JS and company are being quite successful in delivering the results and quality they are most responsible for, again IMO. I can’t defend the pay raises but I also can’t deny Geron’s product, CT and related results.

Can Geron do more for the stock price, of course, but JS appears to be going for the gold. It was never as straightforward or easy as any one, JS included, expected. We, the retail investors especially, are not generally long term or as savvy as institutional investors, and as I’ve learned we frequently end up being roadkill investing in pre-commercial biotechs.

I’m reasonably sure funding a company like Geron is not straightforward either. Certainly mistakes have been made (let’s include their investment advisers here as well) and are maybe the most apparent to us as it has directly affected our wealth, but assuming we are going for the gold with JS, and live long enough, we should (not guaranteed) be richly rewarded and very proud we stayed the course.

[biopearl123]

LWS as far as I know you are the only poster on the board that refers to Imetelstat at a “miracle” medicine. Without getting into hagiography, I think we can all agree it appears to be better than anything out there now.

[LWS]

bp--- considering everything that we know from trials, conferences, publications and KOLs I believe "miracle" is an appropriate word for Imetelstat along with "remarkable, compelling, durable". "miracle" also is what JS is saying in another way, "bigger than all of us".

In retrospect it was a "miracle" from the early ET days of CRs and complete cures (Dr. G) at Geron, which was followed by Dr. T's research at Mayo Clinic.

We will see what ODAC brings us. The people on that committee are oncology experts. I believe that these experts are "honest brokers" and will review and endorse Imetelstat (NDA). We will soon know.
====================================

miracle defined

1/ a highly improbable or extraordinary event, development, or accomplishment that brings very welcome consequences:
"it was a miracle that more people hadn't been killed or injured"

2/ an amazing product or achievement, or an outstanding example of something:
"a machine which was a miracle of design" · "a miracle drug"

[LWS]

bp --- I stand by my comments that Imetelstat is a "miracle medicine" for various forms of blood cancer (alone & in combinations) and suggest that the ODAC will see it in a similar way with the NDA approval. Most likely, they will speak after ASH2023 in 2024. There is no point in getting ahead of their decisions, since they will have the last word. JS's comments on a new and more friendly structure are interesting.

[LWS]

There seems to be four parts to this ongoing discussion leading up to the NDA approval from the FDA:

1/ Imetelstat as a successful blood cancer medicine (trials, publications, conferences, KOLs, future combinations)
2/ John Scarlett (fireside chats, partners, "bigger than all of us", collaborators)
3/ Long-term investors (PPS, dilution, timeline, priority)
4/ FDA and ODAC (waiting for them to schedule (or wave) hearings open to the public; most important now)

[LWS]

Dates to Watch:

Piper Sandler 35th Annual Healthcare Conference
Tuesday, November 28th at 9:30 a.m. ET (Corporate Presentation)

6th Annual Evercore ISI HealthCONx Conference
Wednesday, November 29th at 10:50 a.m. ET (Fireside Chat)

ASH2023 --- December 9th - 12th (4 presentations)

ODAC (To be determined) -- Oncology Data Advisory Committee for FDA

[LWS]

The sun'll come out, tomorrow
Bet your bottom dollar, that tomorrow
There'll be sun!

Just thinking about, tomorrow
Clears away the cobwebs, and the sorrow
'Til there's none!

[LWS]

Focus on John Scarlett's most recent Fireside Chat today at 10:50 AM ET

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

Previous for reference:

Imetelstat is now making medical news in many ways including ASH2023, Oncology ADCOM (ODAC), EAP (operational) 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, there will be the need for several types of partners or collaborators as Imetelstat (and other oligonucleotides) gets approved and goes into production for immediate use and additional research for various blood cancers and beyond.

Here are five current Imetelstat topics that Geron and potential partners are thinking about:

1/ Ferroptosis
2/ Telomerase & Telomeres
3/ Combinations
4/ Synergies
5/ Oral form potential
==================
Synonyms & Similar Words for Tantamount:

comparable
similar

[LWS]

ASH2023 is in 10 tens days

==================================
Abstract #194: “Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) Across Different Risk Subgroups in Patients with Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) in IMerge Phase 3 Study”

Oral Presentation on December 9, 2023, at 2:15 p.m. PT

*****​​​​​​​​*************************

Abstract #4603: “Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study”

Poster Presentation on December 11, 2023, from 6-8 p.m. PT

​​​​​​​​​​​*******************************

Abstract #4605: “Durable Continuous Transfusion Independence (TI) With Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)”

Poster Presentation on December 11, 2023, from 6-8 p.m. PT

​​​​​​​​​​*********************************

Abstract #2440: “Durable Transfusion Independence in Lower Risk Myelodysplastic Syndrome (LR MDS) Is Associated with Better Survival: A Population Level Analysis Based on a Large US Health Insurance Claims Database”

Poster Presentation on December 11, 2023, from 6-8 p.m. PT

++++++++++++++++++++++++++++++++++++++++
Waiting for Evercore Fireside Chat with John Scarlett (11/29/2023)

11/28/2023
Piper Sandler 35th Annual Healthcare Conference
Download PDFof the presentation, Piper Sandler 35th Annual Healthcare Conference.(opens in new window)

11/02/2023
November 2023 Corporate Presentation
Download PDF

[LWS]

John Scarlett Fireside Chat (11/29/2023) now posted by Geron. We can now dissect his comments.

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

6th Annual Evercore ISI HealthCONx Conference
Wednesday, November 29th at 10:50 a.m. ET (Fireside Chat)

11/29/2023 10:50 AM ET
6th Annual Evercore ISI HealthCONx Conference
Webcast
--------------------------