Letter for Shareholder Meeting from biopearl

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biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Letter for Shareholder Meeting from biopearl

Post by biopearl123 » Sat Mar 27, 2021 8:45 pm

March 27, 2021

Dear Dr. Scarlett and Members of the Board,

I write to you as a Geron shareholder (I do not hold shares in any other biotechs other than the historical Geron spin offs) and also as moderator of the Imetelchat internet site. I would like to submit the following questions for consideration and discussion at the upcoming shareholders meeting:

In the past Dr. Scarlett has done an excellent job differentiating Luspatercept from Imetelstat. This comparison has been very reassuring to shareholders. As other potential competitors emerge (with an “E”), can you please differentiate in as much detail as possible agents such as Pelabrisib? During last year’s stockholders meeting the effect of this agent on bone marrow fibrosis was brought up and there is now more mature data. Can you comment in detail as to the differences in MOA, toxicities etc? Issues to please touch on: A. Does Imetelstat show evidence for genotoxicity? B. Given the reported fibrosis reversal , improvement in anemia and TSS with Pelabrisib (and in combination with Rux) would you consider this a leading competitor? Please address the ability of this agent to achieve TI in MF and its potential use in MDS. C. Is genotoxicity a potential therapeutic effect of Pelabrisib or could it add some long term risk of the development of AML? D. I realize Pelabrisib is currently being evaluated with Jakifi for front line therapy and is looking at a very different population than Geron in MF. Can you discuss the differences in study designs and why Consellation might be considering expanding their study enrollment numbers? E. Does iron overload in transfusion dependent MF carry the same risks as in MDS? F. Selectively targeting the malignant clone has alway been an attractive and unique feature of Imetelstat. Do you feel this effect remains unique to Imetelstat? I realize you may not wish to discuss another company’s product but careful differentiation with this agent and other competitors, would probably be very reassuring to shareholders such as myself.

2. Is there enough data to make any comments as to whether transformation to AML has been positively impacted in either MDS or MF? I noted that mortality data with specific causes of death did not seem to be included in the EHA or ASH presentations.

3. Can you please give guidance in detail, as to the future development plans of the company beyond the current PIII studies. This has frequently been an area of opacity that deserves light. 

4. Is is reasonable to conclude that the patients with extended TI are in complete remission?

5. Can you give us a rough idea as to how many blood transfusions could be saved with approval of Imetelstat in lower risk MDS in the US and worldwide?

6. The DSMB met recently and indicated the study could continue without modification. Does this confirm that there was no evidence for a futility signal? Conversely should the DSMB find a highly statistically different beneficial drug effect, do they have the authority to recommend stopping the study for efficacy? What are the moral implications of continuing the study should superiority be found? Could this occur before full enrollment?

7. I know you are reluctant to discuss the approval process. Please reconsider and contrast the FDA process with the EMA, specifically the EMA has issued guidance that MA can be considered under circumstances that Geron has clearly met. Beyond that is earlier approval possible in Japan or England post Brexit?

8. It appears that manufacturing is proceeding full speed ahead and production probably exceeds current study demands. Can you elucidate why this might be?

9. There appears to be continued effect in some patients even if the agent is stopped. Can you comment?

10. Imetelstat appears to have multiple effects beyond targeting telomerase. One such appears to he an effect on the Wnt/beta-catenin pathway and ADAR1 expression among others. Can you comment as to how this might affect the choice of agent in combination particularly as it relates to the emergence of resistant cells with other single agents? Can you please discuss clonal drift as a general process and strategies to combat the emergence of resistant clones?

11. I have always been under the impression the Geron has an extensive IP in the area of the telomere. Yet other telomerase inhibitors appear to be in development by other companies. In the past Dr. Scarlett has been reluctant to discuss Geron’s IP in shareholders meetings. I am asking that Dr. Scarlett reconsider so shareholders might better understand what they own. Specifically if Dr. Scarlett could address the research being done with 6 thio dG by MAIA, that would be appreciated. My reading of a Geron patent is that this research (performed by some that have had former associations with Geron) should be covered by Geron’s IP. Is this not the case? If applicable will Geron defend the patent or consider a license? Or is it just not covered?

12. In the past the possibility of a European partner (or any partner for that matter) has been raised. Can you apprise us as to your current thinking (and progress if any, in this area?) In light of current progress would you prefer to remain an independent company?

My thanks to Dr. Scarlett, Dr. Rizo and the Geron Board and staff for all the hard work done, now made even harder by COVID. There are many fans who read the Geron Imetelchat board which was started by a patient with MF who could not avail himself of Imetelstat treatment and subsequently died. It is my hope that the flow of accurate, timely and honest information will give patients that are still alive and can benefit from Imetelstat, the hope, and treatment, they deserve. I am sure they share in my best wishes to you for the success of Geron.

Sincerely,

ashah
Posts: 60
Joined: Wed Jan 09, 2019 1:32 pm

Re: Letter for Shareholder Meeting from biopearl

Post by ashah » Sun Mar 28, 2021 5:30 am

Very comprehensive letter BP.
Thank you, on behalf of many of the GERN stakeholders!

cheng_ho
Posts: 202
Joined: Sun Apr 03, 2016 11:27 pm

Re: Letter for Shareholder Meeting from biopearl

Post by cheng_ho » Mon Mar 29, 2021 6:51 pm

Will this be another virtual meeting? It would be pretty dangerous to ask about 6-thio-dG in person ;)

He'll evade the question anyway, but better to ask two years late than not at all. Stockholders deserve an answer.

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