MDS study updated

[biopearl]

So to continue my thoughts on the updated MDS trial. (See previous note). As noted the study has been extended to 2019 top line and 2020 for completion. What does this tell us? Well for starters it is safe to surmise that enrollment will be resumed as planned in first half 2017. Since they only have 30 patients in the 2/3 arm you have to wonder why they are not continuing to enroll now to save time. Interestingly the study says it is still recruiting (not suspended like the MF trial). This suggests (unless someone is inordinately lazy and has not changed the trial layout) that they are continuing to recruit but not enroll. That way there could be a large infusion of patients ready to roll when the study does resume administration of drug. Why extend by almost a year? To prove longevity and other secondary endpoints. But probably not for primary endpoints which should be reached long before then ("consistent with the Tefferi NEJM findings"). That means that we should not get discouraged as J an J could and probably will file purely on the basis of the primary end points, with more data to follow after approval. My question is, are thirty patients enough for the FDA? Could J and J be thinking of filing before resumption of study and is that why there is this inexplicable delay built into the design? Truth is I have no idea and wonder if anyone can help us understand this better. At least the study looks like it will go on as planned. bp

[biopearl]

The value of the recent update. So by telling us the MDS trial will extend into 2020 and thereby confirming the continuation of the trial I think we can do some numbers. If G has about 120 M in the bank just an estimate at this point (spending down to support studies) and no debt. They are assured of 65 M milestone in 2017 when the MDS trial goes to phase III. This will give them 185 plus the 5M from the oligo license. Call it 190 and subtract an estimate of 20 M spend on study support, could be more. (Doubt much from AST which will have no sales and little from Australia via the bladder cancer urine telomere license). So, 170 M cash in 2017 or about 1.20sh or so in cash. At the current price of around 2.00/share the enterprise value would be about 80/sh cents by next year. The company will have more cash than it will have enterprise value. These numbers should be fine tuned but I am just thinking out loud. Since it now appears we will not have a drug on the market in 2017 the only income is in milestones which will keep the company going until drug approval. If J and J truly expects 1B, and 200M belongs to G than it looks like about 1.20//sh excluding other milestones. At 20:1 PE thats 24/sh in 2018 from MDS. I think Hoosier and others did this math before and I have not looked back at his note but now I think the likelihood of the 65 M in 2017 appears strong. On top of this could be milestones/and license payments. A surprise (solid tumors--go Yale, MM--go JHU) always possible. bp

[Fishermangents]

Bio, your figures make a kind of sense as far as I can see. I like those short and simple calculations for getting an idea. Let's see if people like Hoosier or Phill could comment on it.

Regarding the pushing to 2020: as you said on SA, it is probably to get more data on durability of CR and PR responses (and maybe/probably also on OS, given the severity fo the disease).

I also like CKTC views (SA, today) on the extension:
"First, the MDS trial update shows two timelines have been pushed back. The Estimated Primary Completion Date has been pushed from June 2018 to April 2019. This is the date when final data necessary to support the primary outcome measure will be collected. The Estimated Study Completion Date (end of study) has been pushed from May 2019 to April 2020. This is the date when final trial data is expected to be collected. Certain data in the MDS trial will be collected from each patient for up to two years from the start of trial enrollment. So some quick math shows they are currently expecting to enroll the final patient sometime by April 2018. These are current estimates and actual timelines can change. It’s important to note final data is not necessarily required for sufficient information to file for approval. So even with the recent delays and schedule changes, a 2019 filing in MDS is still consistent with the timeframe recently released by J&J in its 3rd quarter presentation.
Regarding the MF Frontline trial, J&J just published in its 3rd quarter presentation the expectation of a planned filing by 2019. When J&J publishes a filing timeline, it’s been my experience it is committed to the trial. Can that change, of course? But if it plans to file for MF Frontline sometime in 2019, that trial will need to start in short order.
As to the MF R/R trial, even though the estimated filing date has been pushed from 2017 to 2018, our expectation that the filing will be made on the back end of the Phase 2 trial is still intact. Give the current MF R/R trial delays, a 2018 filing can only be possible using the Phase 2 data. This means our original theory that some type of accelerated filing designation will be awarded still holds. Can this also change, of course? But if the 2018 timeline remains intact, accelerated approval will be the only way to accomplish it."

[Fishermangents]

Btw: Dr.S. always said that trials were to be financed from the milestone payments' cash flow. And if JnJ is a real partner they will ensure that Geron will not be suffocated by lack of cash while the trials are going on. I am sure they will have a mutual understanding on that.

[sargasso]

BP,

I appreciate your post. There seems to be a fair amount of pessimism at the moment on the SA board about GERN. Based on what? The drop in the share price? Why should I be concerned about the day to day or week to week share price of this company? Of what relevance is that to me as long as the basic story remains intact? As far as I can see nothing has changed to justify this pessimism. In any case, below is the best explanation I have found concerning recent events. This post makes sense to me. What do you or others think of the below analysis?

NewYorkSackExchange

I think of the MF R/R Phase 2 as attempting to meet three goals:

1) verify dose (mostly done - probably 9.4 every 3 weeks)
2) verify population (perhaps requiring a pause if, similar to Tefferi's results, not all subgroups showing efficacy) - (in progress!)
3) get approval if efficacious - (later)

The approval intent with the phase 2 seems clear based on the JNJ timeline as others have stated.

If my theory is accurate, everything so far makes perfect sense:

A) At 12 weeks they have verified Dr. Tefferi's 9.4 as the correct dose. No surprise there.

B) At 24 weeks I speculate they will reveal they have essentially verified Dr. Tefferi's subgroup where Imetelstat works (U2AF1, SF3B1, JAK2, etc?) and doesn't work (ASXL1, CALR, IDH, etc?)

C) For (B), they probably have seen data supporting this population target change already (confirming what Dr. Tefferi saw in his trial) and that is why they suspended the trial - to give time to modify the trial going forward (including verifying the adequacy of the logic/support/changes with the FDA) so they are only selecting from the appropriate population, modifying the site approvals, and of course making sure the data in the meantime continues to support this alteration

D) Assuming my guess is right, and efficacy in subpopulation is sufficient, they will continue the trial in the 2nd QTR with the modified population (which would mean they might still be hitting perhaps as high as 70% of the MF population, but could be less). *This shouldn't be a surprise to anyone who has paid attention to Geron's slides and Tefferi's speeches where it is clear Imetelstat appears to work in some types of MF and not in others.*

E) After *hopefully* finalizing all these changes and re-opening the trial, they will dose the rest of the 60-70 patients in the targeted population at 9.4 - combining that data with the initial data for patients at 9.4 who already fit the targeted population (perhaps yielding 90-100 total patients at 9.4 in the targeted population). This will be hopefully sufficient for approval (goal 3 outlined above) if sufficiently efficacious.

Again, just my guess. But makes sense to me. Again I don't expect MF R/R 9.4 dose to have as good of results as MF Phase 2 by Tefferi due to the 9.4 dose in Tefferi's initial including those with weekly the first 4 weeks....also because the R/R is a tougher population. But by carving out the portion of the population where Imetelstat doesn't appear to work (ASXL1, CALR, IDH, etc?) we may ultimately see very nice results in the targeted population where they would seek approval.

- this theory IMO would also support the:

1) 12 week not meeting target disclosure (tougher population and not working in certain subgroups - Scarlett's conservatism knowing there is likely a population adjustment and a pause would lead him to want to say this specifically IMO)

2) the odd 160 sample in the trial revision (need more than planned in 9.4 to get adequate subgroup coverage)

3) The move up of the MF frontline trial (they would now know the population to target that trial already)

http://seekingalpha.com/article/4009764 ... sing-signs

[biopearl]

Hi Sargasso, there does seem to be a lot of pessimism as you note and the stock is in the basement. It is indisputable that there was some 12 week expectation that was not met although it may have been "approached". Clearly they are seeing something and want more time to evaluate. Knowing that multiple cell divisions are required to reach apoptosis in the presence of drug is not surprising but why the MDS study was pushed out is not clear. If indeed the preliminary findings are consistent with those reported by Mayo they must have several patients that have achieved TI and they have data they plan to present, both good pieces of news. I also think they have not filed for approval as yet. If they have fibrosis reversal in MF and TI in MDS and they also presumably now have molecular marker data (we will present at a future conference etc.) then these should be positives and the only reason for delay of filing for approval is they must not think the data strong enough at this point (how could that be?) . We will know a lot on Thursday when the abstracts are released and Geron gives an update as well. Lets just wait until then. I am sure Scarlet will be in the hot seat with analysts questions and unhappy investors to placate. The truth is out there. bp