the wording is tricky here but important

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biopearl123
Posts: 647
Joined: Fri Jul 20, 2018 5:13 pm

the wording is tricky here but important

Post by biopearl123 » Tue Jun 15, 2021 7:54 pm

We have all seen the recent posters from EHA. Dr. Rizo's comments:

"These poster presentations further support imetelstat’s differentiated approach to potentially target the malignant stem and progenitor cells in the bone marrow by inhibiting telomerase activity,” said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. “Through this novel mechanism of action, imetelstat has the potential to alter the course of MDS and MF which distinguishes it from other treatments currently approved or in development. "

I submit this can be interpreted two ways. One is MUCH stronger than the other. One, the mechanism of action is what distinguishes it from other agents in development or approved, Two, the ability to alter (potentially) the course of the disease (MF and MDS) is what distinguishes it from other treatments currently approved OR IN DEVELOPMENT. Of course the latter interpretation is the strongest but since both Constellation and CRIS claim potential to attack the malignant stem cell and potentially alter the course of the disease and Geron must know of these claims.Therefore the former interpretation must apply. That is unfortunate if true since having the only drug in development or approved that has potential to alter the course of the disease is what we want to see here. I really dislike when we have to parse words so carefully so as to not be mislead. Thoughts? Regards to all and welcome to the new board moderator! Please introduce yourself. bp

LWS
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Re: the wording is tricky here but important

Post by LWS » Wed Jun 16, 2021 5:35 pm

There are 6 considerations for blood cancers, especially MF and MDS:

1. OS
2. TI
3. Disease modification
4. Safety
5. Effectiveness
6. Current patient need

Imetelstat does well in all of these categories medically, reinforced by the 2 EHA2021 posters.

Ryan
Posts: 114
Joined: Sat Jul 08, 2017 1:41 pm

Re: the wording is tricky here but important

Post by Ryan » Thu Jun 17, 2021 4:47 pm

Reads pretty straight-forward to me, as stated - Dr. Rizo is a distinguished doctor and a global leader in her field, not a wordsmith trying to parse words and manipulate people (patients, clinicians, investors) with her comment.

Direct words = Imetelstat has a novel MoA, is proving to alter the course of these diseases (to be triply confirmed w these Phase IIIs), and if / when so, will be a first in class drug for patients w these horrific diseases.

Quite honestly, it’s your tricky prose that is more troubling to me.

biopearl123
Posts: 647
Joined: Fri Jul 20, 2018 5:13 pm

Re: the wording is tricky here but important

Post by biopearl123 » Thu Jun 17, 2021 5:21 pm

Ryan I hope you are right. All I ask is that contributors review the other agents, approved or in development before concluding that Imetelstat is the only agent that offers disease modification. If it’s true than the market has totally undervalued Imetelstat which has been our working thesis. And yet the stock languishes in part I think because of perceived threats from other agents in development. All I am trying to do is trust but verify. I am not trying to twist anything, only to be sure we are accurately understand what the company is telling us. I would encourage them to make crystal clear clarification at which point I will stop seeking verification. bp

huntingonthebluffs
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Re: the wording is tricky here but important

Post by huntingonthebluffs » Mon Jul 19, 2021 5:30 pm

Bottomline for Constellation and Curis, even MAIA, and any others trying to enter this space, they much later to the game than Geron? I wonder are they just looking for additional “targets and hits” per ashah’s link or really trying to go head-to-head with Imetelstat. Disease modification (DM) is a very deep and wide ravine with many levels that could be claimed as DM. To Ryan’s post, I think Dr. Aleksandra Rizo’s claims were not made loosely. However, because of Geron stellar results, making claims such as DM is practically the new starting point for any competition given where Geron and Imetelstat are today in the process of gaining approval. But as LWS stated, to compete with Imetelstat, the impact of a DM claim requires doing well in several other very key areas. Rizo’s swagger isn’t likely without measuring the consequences. I believe she doesn’t need to use bluffs here but this is an extremely high stakes “game” and I don’t see her or JS flinching.

As we know, coming to the game late or even a little late can make the challenge much greater. One way to try to compensate for a late entry for small pharmas (SP) is to go out and find partners with deep pockets, IP and regulatory influence capital to finance and promote the way forward. We know that can be fraught with pitfalls for the SP. If it’s a BP coming in late they have the financing, etc. but also likely have objectives in mind that aren’t necessarily just trying to develop a better mousetrap. Competition and partnerships are generally complex and can have many different goals and objectives not obvious to most reading the associated filings. Like you (biopearl123) noted, the stock price may be languishing due to other agents in development. Or it could be a dozen other things none of which I believe are desired or instigated by JS/Geron or due to the strength of the Imetelstat position. I have tried to review the competition and can’t say I have found anything significant to sway my view of Imetelstat’s strong competitive strength but I would rather leave the “verified” up to Geron and/or people with knowledge and experience like yourself.

We aren’t privy to many material and substantial things about the Geron/Imetelstat landscape or competition only what is required by law. However, while one doesn’t expect competition to cheer Geron on in its quest for Imetelstat approvals, there are a few obvious behaviors that contribute to the mysteries we have with Geron/Imetelstat timeframes to commercialization. One of the most obvious mysteries to me is that we have many frontline KOL’s, researchers and several mega-investors cheering Geron and Imetelstat’s results, yet there doesn’t seem to be any BP’s providing even a smell of catalytic interest or support nor do they seem to be in JS’s focus at the moment. Rather they seem to be in a hurry to grab attention by trying to create their own fracas in a historically quiet space. Why is that? I don’t think it is just because so many of us old people are now living long enough to finally run into hematological cancer, that it’s becoming a profitable space. Could it simply be the size, scope and implication of the prize if Imetelstat was to win this race? And now in the face of competition, Geron’s organization / infrastructure buildout and Phase 2 watershed results appear to have put them in the position to promote their own way forward? I think that is a big concern for BP. Size matters here and BPs aren’t going to take it laying down. However, dare we say, their leverage is waning and that will begin to show in the share price and ever-increasing noise / late entries in the telomerase inhibition space as well as associated industry attention.

biopearl123
Posts: 647
Joined: Fri Jul 20, 2018 5:13 pm

Re: the wording is tricky here but important

Post by biopearl123 » Mon Jul 19, 2021 8:12 pm

Hi Hunt, nice post! Both (if I remember correctly) Curis and CNST have claimed DM or at least fibrosis reversal. We know from John's experience that claims that may be construed as other than intended (or even directly intended) can result in a trip to the lawyers conference rooms. So I would think the competition would be circumspect. Your point as to the outward ennui of BP is important and mysterious. John made at least 10 presentation to various potential partners. If they all thought Geron would be too expensive, that is a vote of indifference or an unreasonable valuation by the Geron board. Geron could craft a partnership with less $ up front and a longer term royalty payout over time based on sales in order to get a deal done. But they haven't. The recent B-cell ALL article posted here and elsewhere is interesting but was also funded by Geron with no apparent BP collaborators. Most of the EU activity this year seems focused on the pediatric requirements for approval (for a drug that has no utility in pediatric patients in MF and MDS which would be exceedingly rare in this population). Perhaps a prelude to a B-cell ALL pediatric combo study as suggested by the authors? bp

huntingonthebluffs
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Joined: Wed Feb 24, 2016 12:00 am

Re: the wording is tricky here but important

Post by huntingonthebluffs » Sun Jul 25, 2021 12:23 am

Thanks again biopearl123, for taking this deeper and wider as usual! I continue to believe the reason we don’t have a partner, etc. as Dr. John Scarlett has said, the terms are not reflective of Geron/Imetelstat’s value and I suspect the starting point of the stock price will need to be considerably higher as well. When that watershed time comes based on “progress”, things will likely change rapidly. I think we all know the bounds on the timeframes for the rapid changes to begin.

Secondly, so here is where, at least for me, it really gets “tricky”. What exactly is the definition of “disease modification” with regards to myeloid malignancies? And maybe secondly, what are the accepted cancer biomarkers (or collection of alterations) that are accepted as myeloid cancer related and what “reduction level” can be viewed as DM? I suspect Dr. Scarlett and Dr. Rizo are making assumptions and driving stakes regarding where they believe the bar is set to claim DM and, in that realm, their stated belief is that Geron/Imetelstat is unique and stands alone regarding DM. Since bone marrow fibrosis can be reduced by more drugs than Imetelstat, I suspect JS/AR know that by itself that will not be regulatorily accepted as claimed by CNST and CRIS as DM.

I am out of league as usual but believe further vetting is required here. For starters, from what I’ve read, DM claims would vary based on the disease target. I suspect quantification of DM likely exists somewhere, but I did not find and FDA/EUA documents specifying a way to quantify DM. “Both the FDA and EMA have previously accepted disease modification-related terminology in areas such as MS” years ago but in today’s environment “there is a clear regulatory trend toward a simpler wording”. Geron/Imetelstat being able to breakout above the simpler wording and claim DM, likely has been discussed at length with the regulators and possibly revolves around the points made by LWS above and also possibly includes nondisclosed items as well.

https://www.ncbi.nlm.nih.gov/pmc/articl ... 1/#s5title

So I continue to think that because of Imetelstat’s CT results and JS/AR’s DM claim, it is likely that competitors now believe it necessary to “systematically referring to disease-modifying therapies” however, the regulatory bodies will conclude that their claims will ultimately show they are “not sufficiently supported by the submitted data”. Thus, allowing Geron/Imetelstat to stand alone regarding DM.

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