ImetelChat

1 Aug 2017

IMerge
Substantial results are observed in the 13 patients subgroup (non-del5q and naïve to HMA): 53.7% achieved 8+ weeks of TI. The non-del8q subgroup represents approximately 85% of all the MDS patients. It seems the imetelstat will beat Best Available Therapy in this group. 20 new patients will be added to confirm these findings. They will be observed at least another 6 months. Enrolment starts in Q4 of this year.

Some quotes from Dr. Scarlett:
"Based on the results to date in Part 1, JnJ believes the lower risk MDS population has been identified for whom imetelstat is particularly beneficial."
"We and JnJ believe that the results from the 13 patients subset are very promising and suggest that imetelstat could offer lower risk MDS patients a much needed alternative to progressing the HMA's and/or Lenalidomide."

IMbark
- will proceed unchanged
- Clinical benefit and survival benefits have been observed in the R/R MF subgroup
- The expect a 'meaningful impact' on OS in R/R MF subgroup
- median survival has not reached in both 4.7 and 9.4 arms, because still more than at least 50% of the patients are still alive
- in Q3 2018 they expect to have 'sufficient data on survival benefit to take further development decisions.
- After completion of the IMbark Primary Analysis JnJ must take the continuation decision

My conclusion: JnJ is closing in on how best to apply imetelstat in R/R MF and MDS. Interactions with the FDA are ongoing. Part of those interactions will be a refinement of the IMerge protocol for Part 2 (Phase 3). It seems that survival benefit and TI improvement have been proven. The next year will need to bring confirmation of these observations based on more data.

Happy to see your opinions.

Repost from sdrawkcabeman (YHMB, yesterday)

Drug development is an exercise in strategic planning. Tracing the root of the Imet program, we see the strategy being continually refined and the drug proven to be active repeatedly across multiple conditions, and this quite stunning and clear signal in the MDS subset is yet another feather in Imet’s cap.

The non-del q pop is the greater majority of MDS pts. The 1/3 T.I. is expected per the previous guidance, but what a pleasant surprise to have an unexpected update w/concrete #s, albeit w/out durability #s. Also, to see greater than 50% in the subset are achieving T.I. and w/greater durability, it emphasizes Imet’s continued strategic development.

Re the changes in Imerge Part 2 w/the new subset, we could see any number of configurations of trial arms and differential approval timelines. This could be an impetus for the expedited program altogether. I’ll be listening for clarity on trial arms on the CC.

Let’s get something straight about this delay, b/c you know the trolls on the board will try to make hay with it. The objective is to get a drug approved. If you have about 1/3 benefitting, and also about 1/3 from the best available, it’s a strong result and certainly w/that precedent for approval; but now having an additional 50% response in the subset with stronger durability gives even more impetus to Imet’s approval. So the delay is, well, a delay; but strategically it puts Imet in a stronger position. Put yourself in Janssen’s shoes: you find a stunning signal for 50% response in a subset, do you ignore the amazing signal, or do you want to show the FDA that you are knowledgeable about your drug and know how best to help pts? The finish line is approval, and you’d rather not have the FDA doubt where you might otherwise demonstrate a stronger raison d’etre. This is a delay derived from positive developments, not a delay for lackluster results, etc.

There is the inconvenience of the mechanics of now having to find pts who have not been treated with HMA and Lenalidomide. But only 20 such pts, anyways. The PR also indicates the Imerge P3 will be pegged to Imbark’s primary analysis. The continuation decision on Imbark will be made Q3 2018, unless they have median OS numbers sooner; and that’s a good thing. Yes, again, the delay, but the delay means longer OS, and OS is king. Also, there’s to be an internal review in Q1 2018, and we will be privy to any protocol changes then as now. The last mile is surely the longest...

sdrawkcabeman, YHMB 01 Aug 2017

another great comment from Hoosier (SA):

1) Contractually, Janssen could've postponed the primary analysis as long as they desired. Thus, by agreeing to the 3Q18 cut-off date, Janssen is showing some consideration / compassion for Geron's position.

2) I suspect Janssen's recent discussions with FDA may have played a role in the decision to enroll an additional 20 patients in the IMerge trial. If it were simply a Steering Committee and/or Janssen business decision, the decision would've likely been made a few months ago.....when the IMerge Phase 3 start date was moved from mid-year to Q4.

3) Janssen just made a 'mini' continuation decision by agreeing to enroll the additional 20 patients in the IMerge trial.

4) If Janssen had chosen to go after the treatment naïve frontline MF patients, I suspect we'd be celebrating confirmation of CRs and PRs about now. The clinical and survival benefits being reported in the R/R population lead me to believe we're likely to duplicate Tefferi's CR/PR responses in a frontline MF setting. As previously stated, I believe the IMbark trial data will be presented at ASH'18.

5) What Janssen is doing with IMerge mirrors what Celgene did with Lenalidomide in MDS. Celgene's initial MDS trial with Lenalidomide realized a 27% response rate, but the subsequent data analysis highlighted better responses among the del 5q patients. Celgene realized a 67% response rate in a follow-up trial specific to the del 5q patients.....which gained them FDA approval for 5q del MDS patients. Thus, we can see Janssen taking the very same approach with the IMerge trial. This was discussed the other day, but I thought it worth repeating.

6) In the event Janssen opts 'not' to continue with the collaboration next year, Geron's contingency plan almost certainly involves partnering Imetelstat up with AbbVie/Roche's Venetoclax compound. Venetoclax trials include CLL and Multiple Myeloma which are Janssen strongholds (involving Imbruvica and Daratumumab), and the research & clinical data clearly suggests the combination of Imetelstat and Venetoclax will lead to better efficacy than Venetoclax alone. Thus, a Janssen decision to discontinue the Geron collaboration will not only flush five (5) years of work down the drain, result in a Janssen taking financial write-off of the book value of Imetelstat & production assets, leave the myelofibrosis market for Geron, but also spawn future competition in their bread-n-butter CLL and Multiple Myeloma markets. All things considered, I don't see Janssen dropping out of the collaboration. Imetelstat would have to be a complete flop for Janssen to drop, and we know that's not the case as we're seeing clinical & survival benefit in MF, and we have a 54% TI response rate in a sizable MDS patient population.

Hi Fish, although there is not a lot of posting, plenty of people use this board for information so please when you have time, can you update the news section to reflect this last PR? Best wishes, bp

Done. It is in the News and the Commercial section.

Thanks Fish, I think this board remains the gold standard. Thanks for maintaining it. bp

Hi All,

Excited to have received a login to join the board, and even more excited about the prospects of Imetelstat.

The light certainly has been turned on at the end of the tunnel, and there is not reason to think there are any roadblocks in the tunnel....

I truly believe that Janssen has been making all the correct moves, although 'methodical' is definitely not a favorable Wall Street word. It won't be long to finally see.........
Cheers, Ryan

You're welcome, Ryan!

Indeed, the latest telco seems to tell us that JnJ is closing in on its target and is carefully choosing its gateway to the market. These early biotech tunnels can be long and dangerous, and proper lighting is not always available....

Just an update based on the 19 December 2017 Geron telco, where Dr. Raza spoke about MDS and imetelstat. During the Q&A she said the following:

'Once the drug gets approved, then everybody will be using this upfront. It is not like we happily use lenalidomide or HMA's in that group'.
And:
'My personal experience with the drug has not been intense myelosuppression at all. It's reversible, manageable. It is something we see with HMA's, something we see with lenalidomide. In fact, to me it's less than with some of those agents.'

Link to this quote: https://www.youtube.com/watch?v=ZASbfsJBHp4

From her words we can almost conclude that imet indeed is beating BAT (see also the other post on Dr.Raza).