ImetelChat

From a purely layman’s perspective, was wondering if I and possibly others, might be underestimating JNJ / Jansen Biotech / Geron’s grand plan here. For example, could they intend to exit the CT’s with the competitive intention of being able to replace all or most drug and surgical options currently used with MF / MDS patients?

Likely, no more than a dream of mine, but given the continued march of time, scope and patient base of their CTs currently in action, with no news forthcoming, could they be analyzing and finding the MOA along with how to apply the drug accordingly on a more comprehensive basis than just confirming Dr. Tefferi’s phase 1 results? Is it reasonable to expand just to have a more comprehensive set of confirmations or to prepare a larger base of doctors and hospitals to prescribe and administer once marketing approved?

They apparently can’t change the treatment, drug quantities administered or add & assess combo drugs without public communications. However, much study in the labs could and is likely happening based on the genetics related to the various responses, disease and prior treatment history of the patients. Given the likelihood of those efforts, could it help explain in part, the time and focus, willingly expended on bringing on new sites and adding patients to broaden the scope of their findings?

I think most surmise that they have more than ample results to confirm the phase 1 study and more. Maybe this is incorrect, but it not, possibly they aren’t just trying to keep the basic study results confidential for competitive and investment purposes; could they then be pushing this to the limits of what could be learned and applied to the diseases on both science and investment levels before they exit the CTs to confirm beyond anyone’s doubt, that Imetelstat is indeed transformative and makes most other treatments obsolete? If not, help me further understand the various material considerations to continue the expansion of the CTs over the next year or more while so many continue suffering with the disease?

Hello Hunt, I will try to give you my perspective on your questions. These are my opinions only. 1. Looking at failed Jakafi patients is a short cut to a niche and so enhances the road to approval even if in a small group of patients. 2. Once on the market however because of superior efficacy, the drug may move to first line therapy. 3. As the importance of early treatment in prolonging or stoping progression of other heme malignancies (primary polycythemia, thrombocythemia, MDS) from progressing to AML, this drug will be used more and more liberally. Millions could be saved and lives improved/prolonged from the point of view of avoiding bone marrow transplants, transfusions etc. So once the drug is approved for one indication (JAK2 failures), docs may be able to use it "off label"" especially as more data comes out. Remember that reversal of fibrosis is a big deal. Unless a malicious type substituted path slides something amazing really happened. The delay in approval and need for larger studies seems orchestrated by FDA/industry in some way especially in light of what should be grounds for approval on the basis of Dr. T's studies alone. The flaws in his original study (using palpation alone to assess spleen size and failure to objectify symptoms improvement) were pounced upon by analysts at ASH some years ago and will be addressed by the current studies. Regarding other uses. In the lab multiple cancer cell types have been impacted by imetelstat. Yet translation to the clinic has hit a lot of snags. Once the Yale study came out, once Dr. Lane's study came out there was astounding radio silence in light of what should have been breakthrough recognition of this work. That should tell us something in and of itself now that that work proceeds in the quiet silence of the Janssen labs. Transformative is a strong word. Many companies seem to use it indiscriminately. I don't think Janssen is one of them. Hope this helps. Regards, bp

Reading over my response, to clarify, I meant millions of dollars not millions of patients. Sorry that was not clear. bp

BP,

I'm not entirely sure I understand the following sentence. When time permits could you clarify? Thanks:

"Unless a malicious type substituted path slides something amazing really happened."

Hi Sargasso, sure. Let me explain. We have all seen studies that never panned out and were consigned to the "Journal of Irreproducible Results." Maybe the placebo group did better than expected or there was some fluke in the study design. Contrast this with total reversal or significant improvement in bone marrow biopsies in some patients. In a fatal disease such as MF this could only have happened two ways. Remember this is a disease where spontaneous remission does not happen. Way one: the drug works and the previously never before seen and never before described occurred. Way two: an interloper with an agenda has "tampered with the evidence" and switched slides. I am certainly not suggesting this happened at all of course, I am just making the point that it this is the only other explanation for normalization of bone marrow findings. There is no in between. In other words, the drug works, it has been proven to work and the previously impossible has now become possible. bp

BP,

Thanks for your reply. I understand what you are saying and I agree with your conclusion.

BP, thanks for your thoughts, much appreciated. Unless I am misunderstanding, I think your points support moving to obtain marketing approval as soon as possible versus expanding the CTs in time, patients, sites, etc. Wouldn’t once approved, “off label” usage and further approvals come relatively quickly? So seems to justify going for the essential approval as soon as results confirm expectations. I believe you also have concerns about media suppression, FDA, industry and analyst biases that need to be overcome, interesting thoughts and I suspect you are correct. BTW, once marketing approval comes, does the ODD marketing approval come concurrently and would that allow “off label” usage or are other actions required? Regarding the Dr. Tefferi phase 1, it was a small study so I would think anyone with MF and faking a cure or someone faking that someone was cured would not be possible? But I suspect it is like a miracle, many will suspect it did not happen regardless of the messenger.