A repost of a message I left on SA please discuss and critique

[biopearl123]

Can we go back and talk about the science? Can I start by recommending Dr. Raza's article in the 2014 Advances in Genetics and Genomics. In it the point is made with a bubble graph (reference kindly provided by richrohel above, via youtube) that MDS with ringed sideroblasts carries a unique genetic mutation that confers a very different disease and prognosis. If you look at the bubble graph, there is a cluster of MDS subtypes with MOS between 1 and 3 years but with the RS mutation at about seven years MOS. The morbidity in this very low risk group of RS is in blood transfusion requirement and iron toxicity with a low risk of development of AML. Also note the 5 del q mutations have a much better prognosis also and less risk of development of AML. MDS is heterogenous. There is risk from iron toxicity in the very low and low risk, high transfusion requirement group and there is risk of transformation to AML in the high risk groups who may not live long enough to see the iron toxicity of the lower risk groups. So far I can only find one drug that targets that malignant stem cell and that is Imetelstat. It has been implied that by doing so the risk of transformation to AML may decrease. In targeting groups that are not 5 del q and excluding RS which will get plenty of attention from luspatercept, the remaining genetic abnormalities have a much worse prognosis, much worse by a factor of years. We have seen CR and PRs not to mention major reduction in TR in MDS with Imetelstat in the smaller programs and resulting TI in many. This is all good stuff. The market has been unkind to Geron after the Janssen walk. But the science should be strong enough to stand on its own regardless of the business decision Janssen made. Del has made the point that the Arrowhead deal brings strong new technologies and four potential drugs that do not appear to be related to MDS (at least not yet). When I look at current treatment strategies and the plea from the medical community for better drugs I think Geron must receive some very close scrutiny at this point. I know we are all waiting for ASH and watching Geron get punished in the mean time. Also I wish to convey my admiration for Dr. Scarlett and his understated leadership style. These are very strong abstracts. I felt they warranted a plenary session they were that strong but there is nothing like a phase III study getting the attention (lustatercept). Yet when one looks carefully at the very limited population targeted by this drug (even with the very impressive results and kudos to them for it) one can't help but see the much broader potential application that Geron might bring to this terrible set of diseases. bp
12 Nov 2018,
biopearl

[Ryan]

Basically agreeing - Seems everything is pointing in the right direction except the timeline. Which is admittedly brutal.

I don't think there is much to try to interpret about Dr. Raza, cause we'll hear from her in a couple weeks. As well as Dr. Steensma, who surprisingly disagreed with Dr. Raza's Dec 2017 comments in a response on Twitter.

Regarding the plenary session, I too believe Imet deserves one - when there is Phase III data, it will receive one.

[karagozoglu12345]

My apologies for diverting focus from the science. No worries though this will be my last post here as I feel criticism of Geron management for the most part is not welcome on this board. Interestingly, even though those who want to focus exclusively on science can't help but interject the discontentment with business side: In the words of Biopearl "meantime watching Geron punished". Market does not "punish", it merely reacts.

Good science bad management!

From the get go they messed up the JandJ partnership by not requiring to focus on earlier stage patients (to replicate the great results from Tefferi/Mayo pilot study) in the agreement. According to Teffferi Imet produced significantly better results than any other drug available for MF by controlling root cause of the disease for earlier stage patients. It was a huge mistake to focus on late stage patients (unproven result) rather than earlier stage patients (proven result).

They are messing up the share price currently by: 1) Not giving investors assurance that they will take all possible measures to speed up the transfer of the trials from Janssen to Geron. 2) Not assuring investors that if survival data turns out compelling they will file for NDA without going to Phase III for MF (Was this not the intention of Janssen? What changed? 3) Not providing concrete parameters on when in the future will be a cut off date to call survival data a success. We already know after discontinuing Jakafi patients live 9-14 months. Scarlett is irresponsibly nonchalant about this issue and all he says is at some point in the future they will discuss the results with experts to decide whether Phase III is warranted. It then translates they have no intention to file regardless of the MOS data and that best-case scenario is starting Phase III. 3) Not mentioning anything about the compassionate use of Imet that Janssen included in their list and later deleted. Was that a mistake? If not, why not start the compassionate use program under Geron umbrella now if at all possible or at least lay out plans to offer in the near future for the sake of patients! 4) Not even mentioning about their plans regarding the Imet combo for AML in any of the CC’s so far.