What if? Musings.

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

What if? Musings.

Post by biopearl123 » Sun Feb 07, 2021 2:59 am

Greetings to all. A couple of recent thoughts. It's still unclear as to why there was no update at ASH re the MDS P II study. While there were of course no new patients added since the last EHA presentation, I was as I am sure you were curious to know what the status of the remaining patients in study were. After all NO agent in the market or in studies has had TI's of the length associated with Imetelstat in post EPO patients. A 30% or so TI extending over a year is worthy of continued scrutiny, yet we heard nothing at ASH regarding how these patients were doing. There are two possibilities: 1. They tanked and lost drug effect and Geron did not want to report this. 2. Some or all continue to do well. If the later is true, one might think that the longer they are on drug the more potential for continued bone marrow improvement. We know that fibrosis regresses in select groups of patients. What if the regression continued? What if bone marrow actually reached total normalization. What if that had not happened by ASH and was therefore not worthy of presentation (yet)? We know Geron has specialists in minimal residual disease on staff (MRD). What if that's what they are assessing now. After all there has to be something to present at EHA this year. Maybe that's it. Or maybe the clock as run out and possibility #1 is where we are. If the answer lies behind door #2, that would be a good time to go to the EMA and ask for MA, assuming the PIII MDS study is fully enrolled. The FDA on the other had has set a VERY high bar and will probably not be amenable to reviewing the data until top line is available in 2022. Oh well. EHA would be great. What lies ahead? We know there was bone marrow reversal from recent studies as well as from Dr. Tefferi in MF so waiting for that all important "first look" baked into the study design is exciting. We also know there is activity in AML--come on already and start the study. I suspect Geron has more money now. Why? Another what if: given the recent high volume days and price of the stock to 2.30 one explanation is that the big boys decided to teach us little guys a lesson. Our Sparticus (Lazerus from YMB) started a great campaign to buy (a la Game Stop) and I think may have actually triggered the rally. At some point we either got slapped down by hedge funds/short sellers or perhaps it was Dr. Scarlett raising funds from the ATM. I think it was the latter. We will know soon. Why is that good? It might allow initiation of the AML study. This is all speculation of course. Post coitum hominem triste. After Rux comes Imetelstat, after Lus comes Imetelstat, after chemo for AML comes...Observations welcome. What if... bp

Gwikley
Posts: 100
Joined: Thu Aug 30, 2018 9:05 pm

Re: What if? Musings.

Post by Gwikley » Mon Feb 08, 2021 11:39 pm

Musings welcomed.
In another universe the company would, in response to SHAREHOLDERS queries, speak on these and other issues; clarifying, updating etc.,etc.,
But no. Spontaneous open communication between the invested public and the company theoretically handled by the IR is a feeble joke.
The interactions in the CC, when held, are totally dominated by "analyst", fund rep's etc. etc. There has never been an online discourse between a disgruntled, curious, confused or...whatever..... "Joe" investor and anyone in the company. They probably feel that is too "dangerous".


'nough said. My mini rant here is little off topic, and, ultimately unrealistic, but voiced anyway, out shear frustration.

Cheers,
Gwik

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

Re: What if? Musings.

Post by biopearl123 » Tue Feb 09, 2021 1:27 am

Pre COVID one could go to a shareholders meeting in May and ask in person. Some like Bridge did go and was quite satisfied with the reception and openness with which he was met. Nonetheless you can still submit questions for the shareholders meeting. In the past every question I have submitted was addressed in open forum. Admittedly, some areas have met with resistance such as John’s unwillingness to discuss the depth of Geron’s IP for “competitive” reasons. That could have been legit or a dodge. Don’t know, but I will try again this year and so should you. On the whole, we all face a dichotomy: many have held for a very long time only to see stock value decline on one hand and on the other a class act leadership making a strong run for the finish line with the promise of potential rewards for stockholders. Regards, bp

Gwikley
Posts: 100
Joined: Thu Aug 30, 2018 9:05 pm

Re: What if? Musings.

Post by Gwikley » Tue Feb 09, 2021 7:04 am

Thanks BP. I'll give it another shot.
Be well.

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

Re: What if? Musings.

Post by biopearl123 » Wed Feb 10, 2021 12:49 am

Gwickley, Pretty sure I have posted return letters here that I have received from Geron IR in response to my questions in the past. They have taken pains to respond and even followed up with clarifications after the last investor's meeting. I think it is worthwhile for you to compose a letter to them. It is highly likely you will receive a response. The current format for the meetings does not allow for venting/cross examination in real time but does allow for written responses that can be submitted before and during the meeting. This assumes that they do not change the format. Having personal interaction over Zoom or by phone would be preferable in my view but does open the door to disgruntled shareholders to vent which can be time consuming and perhaps counterproductive. But maybe not a bad thing given the frustrations of many including yourself. In any case it is unlikely that our comments would change the course of the company chosen by management, but from an informational standpoint have been useful (at least to me) in the past. Let us know how it goes. Regards, bp

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

Re: What if? Musings.

Post by biopearl123 » Sun Feb 14, 2021 6:42 pm

Gwickley, here is an example of the letter I wrote to Geron IR before the last shareholders meeting, with their responses. I posted this after I received it last year. The shareholders meeting really is a reasonable place to try to get information and potentially air grievances. At this point, given the challenges of COVID, the ongoing successful enrollment and the class leadership team, I can’t find too much to complain about. Anyway hope this helps.

Thank you for your interest in Geron. We have provided answers to your questions below:

1. When you assumed the helm at Geron you commented that the best time to sell a small biotech was when the company had accumulated good PII data. Since that now appears to have occurred, in conjunction with the approval of two PIII studies, do you still hold the same opinion?

The ideal partner for us would bring not only funding for our current program, but also the ability to potentially expand imetelstat into multiple indications, as well as provide an opportunity to have imetelstat commercialized globally. Building and cultivating relationships with potential partners who could meet these criteria will take time and effort and achieving such a partnership is uncertain and typically a lengthy process.

2. Do you feel that enough data has been collected to make some comment as to whether the potential transformation to AML in both the MF and MDS study groups has been impacted by treatment with Imetelstat via disease modification?

No. We need to collect more data in order to have a better understanding.

3. Given the FDAs guidance regarding using RWD as an acceptable control and given their guidance regarding OS as the ultimate end point in conjunction with the establishment of on target surrogate indicators (h-TERT or telomere shortening) why were we not granted AA in the MF study? Can you make some specific comments about the TN group in the MF study?

Janssen decided to look at RWD to validate the importance of the OS observations from the IMbark Phase 2 clinical trial. The RWD analyses conducted in collaboration with the Moffitt Cancer Center provided strong support for us to move forward with a randomized controlled Phase 3 clinical trial with OS as a primary endpoint.
The use of RWD is an evolving concept for the FDA. RWD, so far, has been used solely to support supplemental approvals (sNDAs). We are not aware that RWD has ever been used as the primary means to obtain an NDA approval.
As such, our clinical plans in MF do not include an assumption for accelerated approval. We are very excited to have an opportunity to potentially demonstrate OS in a randomized controlled Phase 3 clinical trial in MF patients who are refractory to a JAK inhibitor. To our knowledge, this would be the first trial in refractory MF to use OS as a primary endpoint, and it’s quite a differentiator for imetelstat in this poor prognosis patient population when compared to approved treatments or those in development.

4. Did the analysis of RWD from Lake Success and the lately added Italian study support the existing data of the control arm RWD OS determination?
See answer to question 3

5. What value creating events can we anticipate over the coming year? This is especially important since PIII data will not be forthcoming for years. It appears that the only clinical data we might expect in continued evidence for durability in the PII MDS study. Could continued durability data support AA status?

For the IMerge Phase 3 clinical trial in lower risk MDS, we expect to complete enrollment in the first quarter of 2021 and expect top-line results in the second half of 2022. For the planned Phase 3 clinical trial in refractory MF, we expect to open the trial in the first quarter of 2021; complete enrollment in the second half of 2022; conduct an interim analysis in the first half of 2023, which could support registration of imetelstat in refractory MF; and conduct a final analysis in the first half of 2024. A summary of these development priorities can be seen in our latest corporate slide deck, which is available in the investor section of our website.

As you know, we had four abstracts that were accepted for presentation at EHA, which is scheduled to commence a week from today. The MDS abstract includes remarkable long-term durability and was accepted for an oral presentation. Three MF abstracts were accepted as poster presentations and substantiate the OS data observed in IMbark and support the planned Phase 3 clinical trial in refractory MF.

6. Can you elucidate information regarding the recent hires who were granted options?

Options granted to new hires are granted as a material inducement to employment in accordance with Nasdaq rules, and are referred to as inducement grants. We are required by Nasdaq to publicly disclose when inducement grants are made, both to executive and non-executive employees.
Inducement grants are used at the time of hiring to attract and retain talent. They also diminish the need to use cash signing bonuses, which are also sometimes used by companies to attract and retain talent in a highly competitive hiring environment.
In order to maintain employee confidentiality, we do not disclose the names of employees receiving inducement grants, except for senior executives when they are named in a press release.
As has been discussed previously, a majority of our new hires receiving inducement grants within the past year-and-a-half are research and development professionals who are responsible for advancing the development of imetelstat.

7. Can you discuss what measures are in place to improve patient retention in the new studies and is it your sense that if patients knew that improved survival (an apparent surprise) was occurring in the MF study that physicians and patients might have been more inclined to stay on drug?

As you know, outcomes in relapsed/refractory MF are dismal with historical data reporting on 14-16 months median overall survival. In our IMbark Phase 2 trial, we reported a median overall survival of 28.1 months. Furthermore, our data indicate that imetelstat improves symptoms resulting in patients feeling better, which should also influence their decision to enroll and to stay in the trial. We are confident that these data will help drive enrollment and encourage retention in the trial.

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

Re: What if? Musings.

Post by biopearl123 » Sun Feb 14, 2021 6:45 pm

Continued:


8. Are there any other drugs in the clinic that have shown disease modification and if so how does Imetelstat stack up against them? Where do you see the greatest competitive threats?

Constellation Pharma has a BET inhibitor that is being studied in MF and that they believe has disease modification because of fibrosis improvement. We have yet to see any data related to overall survival, which we believe is a strong indicator of disease modification. We’re waiting to see how their data matures.

9. Can you discuss Geron's IP in other non Imetelstat oligonucleotides and monomers and also the status of the ongoing agreement with Janssen in the area on Geron's non Imetelstat IP?

As you know from our 10-K, we have an ongoing license agreement with Janssen related to oligonucleotide chemistry. Geron’s development plans are not contingent upon this agreement, and we cannot speak on behalf of Janssen regarding how or if they plan to use this going forward. Our focus is on two Phase 3 clinical trials – the ongoing IMerge Phase 3 in lower risk MDS and the planned Phase 3 in refractory MF.

10. A previous presentation has suggested Imetelstat synergy when used sequentially with JAK inhibitors. Can you update us on your thinking as to where this might go?

At this time, we are prioritizing the two Phase 3 clinical trials – the ongoing Phase 3 in lower risk MDS and the planned Phase 3 in refractory MF. Therefore, we are currently not planning to pursue the previously announced proof of concept study in High Risk MDS and AML, or any other such studies.

11. Have any patients in any Geron studies succumbed to COVID and if so how are they dealt with statistically?

Our IMerge Phase 3 clinical trial is a double-blinded trial. We do not plan on sharing any data from the trial until we announce top-line results in the second half of 2022.

12. Is the potential for a positive change in study status such as the granting of AA off the table or could it still happen (for example if the part I of the MDS study continued to show the remarkable durability it appears is emerging?)

Our plans in lower risk MDS do not include an assumption for accelerated approval because we have an ongoing randomized Phase 3 clinical trial with registration intent.

Gwikley
Posts: 100
Joined: Thu Aug 30, 2018 9:05 pm

Re: What if? Musings.

Post by Gwikley » Mon Feb 15, 2021 5:40 pm

Outstanding BP. Thank you so much. Will re-read often.

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