Commsman's Pitch for IMBARK Phase 3 to the Geron Executive Management Team

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Commsman
Posts: 12
Joined: Sat Mar 23, 2019 11:35 am

Commsman's Pitch for IMBARK Phase 3 to the Geron Executive Management Team

Post by Commsman » Thu Apr 04, 2019 9:06 am

Greetings Imetelchat Community,

Thank you for providing this safe place to post ideas and communicate about all things Imetelstat! I have been very impressed by the quality of the information that I’ve found here. I have recently been inspired by kmall’s activist approach to this investment, so I’ve decided to get more active myself. I recently sent this message to Investor Relations at Geron, and I plan to share any response I get. I also look forward to feedback from Imetelchat’s very knowledgeable contributors.

Respectfully,

Commsman




Dear Geron Board and Executive Management Team,

I became a Geron Investor in March of 2018, though I made numerous investment purchases through July of 2018. I like to think many of my purchases went directly into them ATM offering, and therefore, Geron’s general fund. I would like to start by thanking John Scarlett and the Board of Directors for the professionalism and honesty in dealing with the investors. I have listened to each investor call and have found John Scarlett’s messages to be fair and prescient. I admit to being slightly impatient when Chip would talk so thoroughly about the plan IF JNJ elected not to continue the collaboration as I thought they would be foolish not to continue. However, I have been of the opinion since EHA in June of 2018 that Geron shareholders would gain far more value in Imetelstat if they got back 100% of the rights than they ultimately would from a continued collaboration with JNJ. When the discontinuation occurred, I remained confident that the science would ultimately prevail, and that Imetelstat is indeed a very promising treatment option for so many people with serious blood cancers. After the announced appointments of Dr Gutierrez and Dr Rizo, I nearly doubled my position in Geron with renewed confidence in Imetelstat’s future success.

I am more or less a regular Joe with no official background in Hematology or Oncology, but I have researched nearly everything I can on the development and clinical history of Imetelstat. I would like to propose or offer support for an option in the IMBARK trial. While I understand the strategic importance of creating a limited niche in the MDS indication, I think it would be a mistake to play an equally conservative card in the MF indication again. The strategy of “playing it safe” is already covered in IMERGE by treating highly transfusion dependent patients who are ESA relapsed/refractory and L & H naïve! This is a smart and wise path towards proving the value of Imetelstat to MDS patients. However, I think it would be strategically beneficial to use a more aggressive strategy with MF. Considering that the only approved therapy (Ruxolitinib), has well proven to only be a palliative measure at best, and in certain subsets has proven to bestow an increased risk to the patients, I would like to propose a phase 3 structure that could yield conclusive evidence as to whether Imetelstat should become an approved therapy option!

IMBARK Phase III - Head to Head Ruxolitinib vs. Imetelstat

Randomized Study of Treatment Naïve patients diagnosed with MF

Group 1 - Ruxolitinib only

Group 2 - Imetelstat only

Group 3 - Ruxolitinib + Imetelstat

One immediate benefit is that no patients would have the risk of getting no treatment in a placebo group. They would either get the standard treatment they would otherwise get without entering the trial, the experimental treatment that shows much promise in preventing disease progression, or both the standard and the experimental treatment. From all my research, it has become clear to me that many treatment options are needed by the doctors and patients. The next benefit is that this trial design would give Imetelstat 2 out of 3 paths to proving it is worthy of FDA approval, and Meatloaf always said “2 out of 3 ain’t bad!” Considering that data that shows imetelstat’s clear efficacy in ET and Dr Tefferi’s pilot study that included earlier stage MF patients who were Jakafi naïve, I am very confident that Imetelstat will show a clear advantage over just Jakafi alone – especially if an endpoint goal is to remain progression free.

My intentions with this suggestion are meant only in the most respectful way. Please bring this idea to the experts for consideration. I realize that the actual trial design has an enormous amount of complex factors that must be planned for, but I trust Dr. Rizo and team Geron to work out these crucial fine print details. I only hope that this basic concept for the framework can prove helpful as I believe it would be a very direct path towards uncovering truth through good science. I would be remiss if I failed to reveal that my Grandmother is currently living with MF, so this is a topic that is personal to me. I kindly thank you for reading my email and your consideration of these ideas. Please keep up the good fight!

Very Respectfully,

Commsman
XXX X XXX XX
Xxxxxxx XX XXXXX

xxx-xxx-xxxx
Independent Investor

cheng_ho
Posts: 128
Joined: Sun Apr 03, 2016 11:27 pm

Re: Commsman's Pitch for IMBARK Phase 3 to the Geron Executive Management Team

Post by cheng_ho » Thu Apr 04, 2019 4:32 pm

If you read Dr. Raza's essay in the book "This Idea Is Brilliant", she suggests that Phase 3 trials be run like this (except that she has a much more ambitious and detailed plan, adding in longer-term plans for data collection and comparison between trials). Dr. Scarlett may not have bothered to read her essay, but surely he has been forced to listen to her in person.

Of course, re-designing the trial (instead of just zombie-ing along with the original Janssen plan that convinced JNJ to bail) would mean having to re-submit it to the FDA. And most of all, it would involve Scarlett having to show up occasionally... so you're essentially telling Scarlett that you hate him and want to completely destroy his lifestyle.

Complimenting Scarlett on his honesty is a good touch... using humor to keep things light is essential in these dark times when our best science is kept away from patients by the patent/FDA system.

biopearl123
Posts: 299
Joined: Fri Jul 20, 2018 5:13 pm

Re: Commsman's Pitch for IMBARK Phase 3 to the Geron Executive Management Team

Post by biopearl123 » Thu Apr 04, 2019 10:23 pm

Cheng, I think that fast track status conveys the privilege of more frequent meetings with the FDA and ongoing guidance regarding study design. This also allows for rolling submission of data. Even if the study design does not change from the original Janssen PIII, the FDA could confer an accelerated approval track. I do wonder if the DSMB, when (if) they see clear evidence for achievement of primary endpoint (8 week TI), might call for an "unplanned" interim analysis. Study study design as outlined and confirmed by Dr. S does not have a planned interim analysis unlike the MF study which did and resulted in the dropping of the low dose arm. bp

Commsman
Posts: 12
Joined: Sat Mar 23, 2019 11:35 am

Re: Commsman's Pitch for IMBARK Phase 3 to the Geron Executive Management Team

Post by Commsman » Mon Apr 15, 2019 3:01 am

Cheng Ho,

Thank you for your comment, and thank you for suggesting such a good read in “This Idea Is Brilliant”, Compiled by John Brockman! I am absolutely flattered that you would suggest that the option I put forth and support for IMBARK PHASE III embodies the ideas of Dr. Azra Raza in her essay "The Cancer Seed and Soil Hypothesis"! I must confess to having been ignorant of this absolutely brilliant proposal to use pan-omics in clinical drug development, so I did indeed find and read Dr Raza’s essay, and I agree it is truly brilliant. This, of course, is suggesting a fundamental paradigm shift in drug development in which patients and good drug therapies ultimately win much sooner by using meta-data models in the trial design (pan-omics). Indeed, this sounds very much exactly like what Dr. Steven Lane is doing RIGHT NOW in Australia! Truthfully, I recognize that I may not have been the first person to think of this suggested trial design for IMBARK PHASE III and that’s why I said “I would like to propose or offer support for…”, but thank you for the very kind compliment. I don’t care whose idea it is, but I do think “This Idea Is Brilliant”.
: - D

The 2nd paragraph of your reply is simply beneath you, dude. I’ve read a lot of information from you over the past year+, and I truly respect that you are extremely intelligent and well-informed. You’ve also been instrumental in helping me to become more well-informed myself and for that I thank you. John Scarlett himself has said numerous times that he(they) are consulting with various “Key Opinion Leaders” about pursuing and researching their options with the intention of announcing their plan regarding whether or not to pursue MF as an approved indication for an Imetelstat Therapy, so it seems like this is the perfect time to be advocating this proposed MF Trial design. I am one of the few members of your community that still has compassion for the fact that you have had to witness in full detail nearly two decades of The History of the Development of Imetelstat. I could think of very few more twisted forms of torture. I am hopeful that you can remain a positive influence in the development of Imetelstat and clinical trial science in general, but you need to stop alienating your community members with the severe negativity.

I’ve listened to Scarlett at every opportunity, and he was up front and truthful when he tapped the ATM last year, and when he announced in August that he wouldn’t tap the ATM any more BEFORE the JNJ decision. In retrospect, that might have been a mistake, but he did do what he said he would do! Chip also well laid out the plan IF JNJ didn’t continue, and he has stuck to that plan and timeline more than enough for my satisfaction to say he has been honest. He didn’t sugar coat it then, and I feel confident he won’t sugar coat it in the future. I am also hopeful that we will see a much more assertive and relaxed Chip going forward as he will no longer be yolked by the collaboration agreement.

I also agree that the medical research system needs to be improved, as the current FDA approval system regarding Medicine sometimes does more harm than good. Surely, good SCIENCES will win in the end! Again, thank you for your comments. I hope you can once again elevate the dialogue as you have in the past.

Respectfully,
Commsman

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