Perhaps Scarlett doesn't have much to say!! I hope he and Huh are not regretting getting rid of some of the gem scientists from Geron (of course, driven by their own greed of getting hefty compensation packages!!). Executives all over the USA are known to ask for higher compensation and bonuses from the board when they bring about staff reductions and thus (temporary) savings, without having any idea of how those long-serving employees handle losing their jobs. I hope Scarlett and Huh are not such ruthless executives or are they?!!
End, I wanted to end this discussion as this is not a platform to go too deep into it. Also, neither am I nor you are a cell biologist or a geneologist/genomic expert to comprehend this complex issue well. However, the following is what I like to add to our discussion.
I have faced myself a bone-marrow disorder and Sloan-Kettering did some genomic study, which frankly, I did not quite understand. However, one thing they told me clearly that what causes gene mutations is still not fully known or even well-known, although the scientists are now able to know what genes are responsible for certain neoplasm disorders. The science is still advancing. In my case, my exposure to any nuclear radiation while visiting an operating nuclear reactor 12 years before the disorder was observed should not be the cause; the only thing I suspected that may be responsible for the mutation should be of chemical nature (like use of excessive antibiotic medicines to counter sinus and perhaps abdominal infection). However, the SK physicians and scientists disagreed with me. In any case, in my view, what causes mutations must be understood well before we can conclude confidently whether Imetelstat can bring lasting recovery to patients suffering from hematological cancers. And that may be too far-fetched.
Thus, the FDA's quest for knowing this, if it's, may be too far fetched and should allow Geron to start its Ph 2 and give the accelerated approval for the clinical use of Imetelstat ASAP so that suffering patients can have a decent choice to fulfill their optimism to live. If any serious side effect does develop, let the patient decide if he is willing to take the risk or not. And, I am pretty sure, all desperate patients will not hesitate doing that. All the hematologist treating the patient has to do is to warn him of likely side effects, like it's being done for all prescription medicines and surgical procedures. Therefore, I just can't understand FDA's delay.
End, you have provided a good layman's explanation of the neoplasm disorder (under Joanie's response in here). Scientifically, gene mutation causes the onset of inbalance and the disease spreads as cancer cells produced by the mutation multiply a lot faster than the normal ones in the blood. The process of cancer-cell multiplication is terminated when the telomeres at the ends of the chromosomes are stopped from growing. I understand, by depriving them of the telomerase. My understanding is that Imetelstat is effective in doing this. Thus, with growth of cancer cells curtailed, the proportion of normal cells in the blood grows again and the blood becomes normal when all cancer cells die. However, my puzzle and questions are related to what happens to the gene-mutation process? Was that just a one-time occurrence that disappears when all cancer cells die? Does Imetelstat work only in obliterating supply of telomerase to cancer-cell telomeres or goes beyond that and repairs also damage to chromosomes? Irish's post below suggests that it does that too! But, then, the question remains as to how it does that, and if that process causes any other undesirable side effect? Does the LFT abnormality have anything to do with such a side effect and why? I think that is where the FDA's concern may lie. A detailed genomic study may also be in order. All this study is apparently too much for the current scientific-investigation capability and staffing of Geron because its management seems to be focused elsewhere! Therefore, I consider it inept. Luckily, we have Mayo and Tefferi to help in this regard; but, collaboration with a resourceful and compatible partner may become a necessity. This is neither Scarlett's nor Huh's cup of tea!!
Since this a Yahoo board, I think it will be wise to go no further deeper into this matter. Thanks for your detailed reply.
Imet, you're simply repeating what End2War already brought up on this board early yesterday and this thing has been chewed up very well already if you care to go through responses and discussions under the post by ETW!!!
So... there are several types of JAK2 mutations!! Imetelstat effectiveness thus may depend on the mutation type, I guess, And, it does get complicated!
I can see now why a detailed specific study may be required to determine how Imetelstat restores chromosome function and also to assess what else Imetelstat does. Does it cause other unwanted effects? Could these effects be long-term for patients who may have a long life ahead of them? Perhaps, the scientists at the FDA and Mayo are trying to get a handle on this before they develop specific protocol requirements to begin the Ph 2. This, then, becomes an understandable reason for delaying the trial. To me, it looks like, Geron did not go deep enough in its study of ET/PV/MM trials to save costs and that may have upset the FDA and is now perhaps falling on Mayo to develop a better understanding to which Tefferi may have concurred. In a nutshell, Geron scientists of the past developed a wonder drug; but the current management can't handle it well!!!
All this leads me to continue believing that Geron perhaps resorted to cutting corners. Drastic staff reductions to save costs while paying hefty remunerations to executives resorting to half-hearted policies may be to blame, and not the FDA!!!
Thanks, End. You're a gem on this board!!! Please, tell me if i am wrong in my assessment.
Thanks, End, for the specific details and your prompt response. No body, including myself, is as sincere as you are.
However, I am also looking for response from Irish about the %ge of MF patients in general who have JAK2 mutation and among those 22 Mayo patients (not 33 as I stated before). I will be very happy if you know the answers and respond. .
Irish, are you sure that that mutation occurs in MOST MF patients (worldwide)? Do you know if the JAK2 mutation occurred in most MF patients in the Mayo trial? If it' occurred in most MF patients in the Mayo trial, why are there only 5 CRs and PR's out of 33 patients? What other factors affect effectiveness of Imetelstat besides the JAK2 mutation? .....( I know I am asking you for too much, but I would like to know if you have answers to these questions. Thanks in advance.)
Ryan, I can't agree with you that the FDA is unaware of the proposed Geron's Ph 2 trial because 1. Geron must have consulted the FDA prior to the hold to determine protocol and initial planning that has gone on since well before the hold. 2. After the hold, Tefferi himself must have talked to the FDA about expansion of the investigation and, finally, 3 I do not think Geron/Scarlett did not tell the FDA about this plan in their on-going effort to lift the partial hold. By not allowing the partial hold, the FDA is deliberately delaying Geron's Ph 2 MF trial!
Cabo's success and strong probability of multiple applications. The company also is involved in collaborations with several major pharmas. All going on reasonably well. Like Imetelstat, Excel developed Cabozintinib after years of efforts and decided to concentrate on it a couple of years or so back while trimming down efforts on other fronts, having concluded that it will be its wonder drug. In my view, the SP must revert back to $7-$8 level by early 2015 and will go much higher if success in several Cabo trials is attained.
He was hired to look for partnerships for various Geron programs during Okarma's time. Instead, he may have managed to convince the board to divest out of stem cells, have Okarma fired, shrink the company to a one-product oncology-only outfit, get rid of other executives and scientists apparently with an intent to sell it to a large pharma, and place him as the COB!! Before he was taken as the COB, he squeezed $1m compensation for the work he did as a non-board member and as a consultant for a period of less than a year. What really he has done remains a mystery because Geron management never had and has a habit of telling what and why to its shareholders. My understanding as above is based on my reading of what occurred during the last few years or so.
(contd)...Remember that Mayo board had also to approve it. On the other hand, it was purely Scarlett's responsibility to make sure that adequate data is collected during the ET/PV/MM trials, which, apparently, he failed to do. Also, he prematurely declared failures of the solid tumor trial in a way that really hurt Geron's reputation. Furthermore, the BioTime deal he worked up was certainly short-sighted, although the decision to divest from the stem-cell portfolio must have been the board's decision of which he too is a member. Thus, in my view, he has screwed up a lot. If you give $2.3M compensation to be a CEO of a clinical-stage small outfit with only one drug, and nothing else in the pipe line, and which employs only some 40+ personnel, the board should be able to find a much smarter and capable person than Scarlett to take that position. Just look at ACTC in this respect which was able to find a much better replacement as its CEO, and with a much lower compensation than $2.3M!!
Also, Huh, being a physician and one who worked at Sloan-Kettering, has not delivered what he should have. Thus, in my view, Geron management needs changes in case Imetelstat success blows out gloriously to handle all that goes with it at the company. (More later.) Thanks.
There are two aspects of my assessment: 1. Success of Imetelstat as an effective oncologic drug 2. Company management.
On the first aspect, Mayo's findings through its MF trial are solid and show that patients with a certain mutation get either CR or PR while the other may get CI or no significant improvement. Precise study of where and how it's effective must be on-going not just at Mayo but also in other labs & inst'ts. Perhaps all these must also be looking at Geron's data when it developed the drug. This is a tedious scientific process and may take long; but, for clinical applications, all it needs at present is to verify if the drug is likely to bring about cure to critically suffering patients without major side effects or not and if the Benefit:Damage ratio is acceptable or not. Mayo's findings are clear and encourage its clinical usage. Geron's multi-center trial, when in hand, is most likely going to prove the same. Yes, before its actual clinical use, certain limiting conditions will have to be established. But, that will be a part of the trial investigation and research that will be conducted in labs all over the globe. The success of Imetelstat appears now to be certain, if adequate protocols are followed, and is likely a wonder drug because no other drug so far has attained its succeess. And, when, in the future, it is tried, perhaps in combination with other appropriate drugs or medical conditions, its wider applications are very likely. In short, success of this drug is not in doubt.
On the second aspect, Geron's idea of going to Mayo for the MF trial should not have been Scarlett's single-handed decision. It is a policy matter and not an administrative one; i.e., it must be the board decision and not an executive decision. Therefore, Scarlett, an executive, shouldn't be given full credit for that decision, if any, as some suggest on this board. My view is that Tefferi had a lot to do with initiative to begin the MAYO trial. (contd)
nom, a suggestion: Look at EXEL and its prospects for your investment. I am not a pusher for the stock; it's just an honest suggestion. Just keep track of the stock before jumping in.
Maine, just come to senses from your apparently drug-affected mindset of stereotype worthless negative comments, giving no constructive useful comments and responses. If this continues for another day, I will be forced to put you on the Ignore list permanently.
Maine, let me remind you of Will Durrant. He stated in his Story Of Civilization, "One who knows what he knows and knows what he does not know. " The latter part of the phrase is worthy of your close attention!
Maine, no negative news about Imetelstat, just more positive (like chromosome repair for JAK2 mutation cases). The drug is great, but the Geron management is just too short-sighted to handle the success of the drug and must be replaced. Imetelstat success is a credible conjecture, isn't it?