ImetelChat

Here comes another of my exceedingly simple questions. We are now aware that momelotinib performed poorly in clinical trials. https://endpts.com/gilead-racks-up-anot ... -in-phiii/ so my question is: what is the main competitive threat to imetelstat? Is there such a competitive threat and if so what is it, and at what stage of clinical development is this drug? Here’s another way of asking my question: how concerned should we be about the delay of bringing imetelstat to the market?

Sargasso, there will always be competition if be it for the sole reason that no drug works for everybody and for every disease. What I do know is that there is no competing drug that universally attacks the malignant clones in hematologic cancers like imetelstat does (see latest ET study which is based on clinical data. So no theory here!). Also there is no drug currently available nor in clincical development (as far as I can see) that achieves CR's in MF and ET. Only interferon has reported CR's and is being tested today (e.g. P1101). But also interferon only works for a small part of the MF patients (and only Low Risk- and Intermediate 1) and for many of them it is hard to tolerate. Then the unique thing about PRM151 is that it can clear the bone marrow from fibrosis. It is unclear if it can change the natural history of the disease (e.g. reducing alleic burden). So far it looks like it doesn't. It has been shown in the latest Phase 2/Part 1 results that can be bone marrow reduced, while the spleen remained enlargeded.

So if such a competing CR-drug is in pre-clinical investigations today, imetelstat will still have an advantage of many years. Because of the unique MoA of imetelstat (and the well protected IP surrounding it) I see it getting a strong and specific position in the market, once approved (anticipated filings 2018 and 2019 for MF R/R and MF Frontline respectively, source JnJ). That schedule seems unchanged.

Although momelotinib didn't perform well against Jakafi, there still is a subgroup of anemic MF patients that may benefit from the drug. As it is a JAK inhiobitor it will not create CR's though.

I see the future of imetelstat lying in the CR's (alone or in combo) and in the reduction of the disease at the molecular level (normalisation and stabelization of blood counts), basically bringing the disease back into earlier stages and keep it there.

Any additional views and opinions are highly appreciated.

Fisher,

Your response is appreciated. Your post is in accord with my own understanding of the competitive landscape. These continuing delays w/ regard to imetelstat are hard to take. Like any investor I wish to see a return on my investment and the sooner the better. I also wish to see this drug available to anyone who can benefit from it. In any case, knowing at present there is no real competitive threat to imetelstat gives me a certain degree of confidence in GERN. I continue to hold a rather substantial position in the stock.

Fish, nice post. I agree so far no drug apparent that targets the malignant clone. Also to evaluate combination therapy which is undoubtedly down the line will take years so there doesn't seem to be an immediate threat on the horizon and once we get a window on combination therapy it could be a quantum leap that a competitor could find hard to surpass. bp

Yes, Imetelstat has a uniquely deep response. There is response on both the morphological and molecular levels. In the Mayo pilot study, their was repair at the chromosomal level including some patients with 100% response at chromosonal level. Imetelstat has the markings of a truly transformative drug.

Hi Irish, a hug and a kiss on the cheek from bp, glad John continues to do well. For Sargasso, did find Rova T as a antibody (Stemcentrix) that targets the cancer stem cell in some solid tumors, just FYI. bp

I follow all Mayo Rochester myeloid cancer trials including MF of course.

http://www.mayoclinic.org/diseases-cond ... c-20261684