Geron' s report card

[biopearl123]

Here is my assessment of Geron's response to the questions I submitted to the shareholders meeting. I continue to be optimistic regarding the Geron data. In the mid term, confirmatory MDS PIII study is highly likely at the end of 2023 and will lead to commercialization as planned in 2023 (IMHO), thanks to rolling submission filing option for approval which Geron will certainly take advantage of. The two abstracts are very relevant and supportive and I expect a Geron PR after this data is presented to EHA. Near as I can tell competition is from CURIS and CNST and is lagging and no PIII studies as far along and Geron's MDS PIII with MF IMPACT ramping up (as is Manifest II). COVID problems lessening. I think most of you saw that the bulk of the questions submitted were from the letter I wrote about a month ago. Here is how I view their responses:

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.

Grade F: Competition not addressed in any meaningful way except for Grade A for statement regarding uniqueness of Imetelstat in targeting malignant clone. Issue of differentiation clear Grade A but failure to address competition of investigational agents Grade F

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.

Grade D: hard to believe no preliminary indications exist. Geron's response is to wait for PIII data and evaluation of secondary endpoints, this will probably not happen until 2024 at best.

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. 


Grade F as to response. Not to say there are no future development plans in other indications but they are not telling except they continue to evaluate. Since we have been hearing about AML and hints of combinations for years, Grade F seems appropriate.


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

Grade A: Clear and concise answer from Dr. Rizo. Bottom line is TI even if bone marrow has not completely normalized. As yet we have no indication undetectable disease states have been reached and it could be that this is not a reasonable expectation.

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?

Grade F: not answered

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?

Grade A: Clear and concise answer. DSMB can stop for safety otherwise the study goes to completion (15 months post last patient enrolled.)

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?

Grade F: Not addressed

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

Grade A: Manufacturing ramping up and validation studies as well as supply paramount. No suggestion of needed supply for early approval. No suggestion of early approval for that matter, quite the contrary. A pretty clear time line to commercialization given.

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

Grade F: Not addressed

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?

Grade C: Not clarified, vague reference to combination therapy re ADAR1.

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?

Grade FFF. No transparency re IP

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?

Grade C minus still looking (or not).

[biopearl123]

Continued:

13. Given that Janssen has returned the license on the "second" Janssen agreement, do you feel that this non Imetelstat oligo has any potential for future development? Would you please comment on the potential for future development of drugs in the oligo class in general and does Geron have any pertinent IP in this area?

Grade F minus, no explanation needed

14. Other than an agent that might be acquired by purchase, is it reasonable to assume foreseeable company efforts will be limited to the development of Imetelstat alone?

Grade B+: answer, yes, but oh what a drug!

[biopearl123]

From my letter to the board:

"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. "

Grade: A for effort. And I mean that. bp