Shareholder’s letter

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karagozoglu12345
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Joined: Wed Oct 03, 2018 12:48 am

Re: Shareholder’s letter

Post by karagozoglu12345 » Thu May 02, 2019 3:02 am

Bp: From the CEO's letter: "While the data from the Phase 2 IMbark clinical trial presented at ASH in December suggest a meaningful survival outcome in relapsed/refractory MF patients, the clinical development path is not as straight forward as lower risk MDS". Did I miss his explanation of why has MF clinical development been characterized as murky in the previous CC's or did he possibly never provided in depth explanation in this regard? I wonder if they will ever possibly consider combo for MF to help patients cope with the symptoms while they benefit the survival advantage? If anyone cares to share any conjectures as to why has management never considered Imet as frontline therapy for MF going forward I would appreciate it. I feel it would be very unfortunate if Imet for MF is eventually shelved (JS implies this is a possibility), not only because MF patients would be left out of a potentially potent therapy alternative, but investors would also be short changed as Geron would be reduced to a single indication (i.e., MDS) company with "all eggs in one basket" and much less desirable from the vantage point of potential suitors for partnership or acquisition.

bucbeard
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Re: Shareholder’s letter

Post by bucbeard » Thu May 02, 2019 3:12 am

This is mind numbing. Is Incyte that powerful, have that much clout at the FDA or in the investment banking community, that we can't get beyond this MF obstacle, whatever it is???

How can this be explained...unreal.

biopearl123
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Re: Shareholder’s letter

Post by biopearl123 » Thu May 02, 2019 3:27 am

My personal view is that JS has a strategy with an implied message to FDA that if they don’t approve, even provisionally, on the basis of current data (after all there is 1. A comparitor arm, 2. True unequivocal OS esp in TN 3. Prior well documented CRs/PRs 4. Presumed strong support from thought leaders 5. True molecular endpoints), then he will not move to develop. Then the FDA has some ‘splainin to do, not Geron. He does not want todo a PIII in MF and who can blame him? But of course he is saying he would gladly do a P IV. Just my conjecture. He finally holds some cards and he are gonna play ‘em. bp

bucbeard
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Re: Shareholder’s letter

Post by bucbeard » Thu May 02, 2019 11:51 am

That is a very rational theory, on a situation that otherwise doesn't leave much room for rational theories. As always, thank you for sharing your mind BP.

karagozoglu12345
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Re: Shareholder’s letter

Post by karagozoglu12345 » Thu May 02, 2019 7:22 pm

Bp: Quite frankly I am worried about the future of Geron and my investment. Thank you for sharing your thoughts and I sincerely hope that you are right. For my peace of mind, could you please clarify the following for me and possibly for others who does not have a depth of insight as I:
1-I thought MF trial did not have a comparator arm except for placebo. Will FDA accept placebo as a comparator arm?
2-I recall MF Phase 2 trial showed one CR and only a few PR. Are you referring to Tefferi/Mayo results that showed much better CR's and PRs than the Phase 2? if it is the latter, would FDA accept a result from an earlier study and not consider the poorer result in Phase 2?
3-Why would FDA be compelled to approve without having to perform Phase 3 when there was very high drop out rates and very few CRs and PRs?
4- My thought, perhaps naive and misinformed, is that FDA would only approve without Phase 3 only when Phase 2 shows exceptional results and no troubling issues. The MF trial was problematic as the trial results did not meet the primary end points, and that unexpected survival advantage was not set as a primary end point, and large number of patients dropped out.
5-If, in effect, your thoughts reflect JS's plan (and, I certainly hope it does!), why, in your opinion, JS has avoided to share his plan in prior CCs? If and when a CEO has a plan which has important bearing on a company's success, it is his/her obligation to share it with the investor community. Unless of course if he/she is concerned about the competition factor in that secretly preempting competition is warranted.

Thank you in advance.

karagozoglu12345
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Joined: Wed Oct 03, 2018 12:48 am

Re: Shareholder’s letter

Post by karagozoglu12345 » Thu May 02, 2019 7:54 pm

Continued from above:
I did some reading on the role of placebo in oncology clinical trials: https://xtalks.com/placebo-controlled-o ... -fda-1557/
I admit I do not recall exactly what the comparator arm was in MF Phase 2 trial. I guess if the study was randomized it is a plus irrespective of control arm.

biopearl123
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Re: Shareholder’s letter

Post by biopearl123 » Thu May 02, 2019 10:33 pm

Kara, happy to respond but will wait until after May !6th conference call. That date unlikely to be coincidence sine EHA abstracts will be public then. bp

cheng_ho
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Re: Shareholder’s letter

Post by cheng_ho » Thu May 02, 2019 10:43 pm

kara, neither of the Phase 2 trials have placebo arms IIRC. They are using "historical controls", which are very poor as different hospitals keep records differently and the patient groups may not be comparable.

The MF trial does have some comparison available between the two dose arms, as the low-dose arm was deemed ineffective.

https://clinicaltrials.gov/ct2/show/NCT ... tat&rank=3

karagozoglu12345
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Re: Shareholder’s letter

Post by karagozoglu12345 » Thu May 02, 2019 11:36 pm

Okay, thank you.

Secret Third Arm
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Re: Shareholder’s letter

Post by Secret Third Arm » Fri May 03, 2019 3:45 pm

biopearl123 wrote:
Thu May 02, 2019 3:27 am
My personal view is that JS has a strategy with an implied message to FDA that if they don’t approve, even provisionally, on the basis of current data (after all there is 1. A comparitor arm, 2. True unequivocal OS esp in TN 3. Prior well documented CRs/PRs 4. Presumed strong support from thought leaders 5. True molecular endpoints), then he will not move to develop. Then the FDA has some ‘splainin to do, not Geron. He does not want todo a PIII in MF and who can blame him? But of course he is saying he would gladly do a P IV. Just my conjecture. He finally holds some cards and he are gonna play ‘em. bp
BP, I believe you have hit the nail smack on the head. If the FDA wants them to jump through hoops then the only card to play is to walk away. Then it's up to the FDA to explain to patients why they made it so difficult for a life saving drug to come to market.

If the FDA is unwilling to acknowledge the financial reality of what they impose on small biotechs with life saving drugs then those drugs will not see the light of day, regardless of how much fanfare they try and make about Break Through Designation, Fast Track, Orphan Drug Status, and Compassionate Use. How about some compassion for the financial predicament of these small companies with great drugs?

I think these ongoing conversations with influencers is intended to get Imetelstat approved provisionally and with a Phase 4 confirmation trial. That would blow the roof off the stock and get us a partner 'right quick'.

bucbeard
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Joined: Wed Jul 25, 2018 12:30 am

Re: Shareholder’s letter

Post by bucbeard » Fri May 03, 2019 8:21 pm

Thanks BTS for providing further color to BP's forward looking theory related to MF and FDA.

biopearl123
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Re: Shareholder’s letter

Post by biopearl123 » Sat May 04, 2019 3:42 am

Kara, to clarify re your question about the comparator arm. It was the low dose arm. There was no placebo (i.e. a no drug arm --I wish there had been, if so we would be before the FDA now in my opinion). The value of the comparator arm was not so much that it substituted for a placebo but that it insured there was no selection bias between the two groups. Hope that helps. bp

kmall
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Re: Shareholder’s letter

Post by kmall » Sat May 04, 2019 5:25 pm

Personally I think Dr. Mascarenhas rousing endorsement of Imetelstat in the MF IMbark P2 trial is what needs to be focused on. Using the term "remarkable" is quite earth shattering. I don't think a man of his credentials uses a term like that flippantly. As well, Dr. Scarlett has been extremely conservative until this past Needham Conference. Not only was his demeanor highly focused and somewhat offensive but he said "approval" when pressed on the entire Janssen walk. That was beyond HUGE !!! He is spelling it out for us - in my opinion - that they have big plans in the works. Along with the new hires and expansion of the company into NJ and in size employee wise, I believe we see a green light for MF and AML. I have a strong suspicion that he may have had a good sense of what ASH would reveal when JNJ obviously tried either low balling him or changing the original contract altogether. I have said all along that the CD bomb was business oriented. ASH proved that. Dr. Mascerenhas has been very excited when talking about the future of Imet in MF. I don't think he was there for eye candy.

Disclosure: I/we have a long positions in GERN as mentioned, and have plans to initiate as many positions as possible within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from the man upstairs). I could only hope to have a business relationship with any company whose stock is mentioned in this article. - gotta throw a little humor in this somewhere - Good luck to all here!! Kmall

karagozoglu12345
Posts: 61
Joined: Wed Oct 03, 2018 12:48 am

Re: Shareholder’s letter

Post by karagozoglu12345 » Sat May 04, 2019 11:11 pm

BP: Thanks for clarification.
KMALL: Wecome to Creeping Alpha. We are short (or waiting to dump) when we say we are long and long when we say we are short. It is boring to play it straight LOL

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