High Risk MDS Cohort in Phase 3 Trial?

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Secret Third Arm
Posts: 12
Joined: Tue Aug 28, 2018 3:26 pm

High Risk MDS Cohort in Phase 3 Trial?

Post by Secret Third Arm » Thu Jun 20, 2019 11:38 am

Some food for thought regarding the Phase 3. This was inspired by some of the discussion on Seeking Alpha, so I went back and re-listened to Dr. Fenaux's talk at EHA last week. When asked about other potential uses for Imetelstat he mentioned the promising MF data but then he said this,

"I think the first step will be to study high risk MDS as a single agent…"

So then I went back to the recently updated guidance for this year and focused in on these two things. One, this statement,

"The projected increase from the Company’s prior total operating expense guidance primarily reflects the purchase of additional inventories of drug substance, drug product and raw materials for imetelstat manufacturing from Janssen in 2019 of approximately $10 million..."

and then this remark by Andrew Grethlein (the COO),

"We expect this inventory to be sufficient to supply the entire phase 3 portion of IMerge and to serve as initial supply for future clinical trials of Imetelstat in other indications."

and lastly, from Dr. Scarlett on the 3/7/19 earnings call,

"...we have drug ready to go, obviously. The Imetelstat supply chain has been cranking away..."

Now tie that all together with press release dated 5/16/19 where the CRO costs increased suddenly,

"The projected increase from the Company’s prior total operating expense guidance primarily reflects...and expected higher clinical operational costs of approximately $5 million."

These were not 'unexpected' costs that raised the price by $5 million, so Geron made a change to the proposed Phase 3 that created an 'expected' additional cost. Is it possible that Dr. Rizo decided to add a cohort of high risk MDS patients? Think about it, the trial centers are already up and running from the Phase 2 and the clinicians are well trained in the administration of Imetelstat to MDS patients.

If high risk patients were also allowed access to Imetelstat via a separate cohort, it would be the absolute cheapest way to run a Phase 3 that confirms the Phase 2 data and also possibly expands the indications for Imetelstat. If you listen to Dr. Rizo and Scarlett, they have not said anything that would contradict such a thing happening. If anything, Dr. Scarlett has refused to answer questions regarding their regulatory strategy,

"Tom, I love your perseverance. Here is the best way to put that. I would just simply say that we consider our approach is to this. I mean, as you know this is a competitive marketplace and we consider our approach is to how we’re going to deal with regulatory agencies, potential approvals and the like. We do consider not only confidential, but as said before proprietary."

Dr. Fenaux emphasized that the Phase 2 data supported use of Imetelstat in higher risk patients when he said this,

“And interestingly, patients with worse prognosis, although they remained low risk but with worse prognosis such as abnormal karyotype like trysome 8 or even worse karyotype tended to respond better to Imetelstat in terms of transfusion independence which suggests that the drug is promising for higher risk MDS.”

As recently pointed out by another eagle-eyed Geron investor, on 5/3/19 Geron also filed an order with the SEC to keep confidential certain information from the 3/7/19 10-K regarding the CRO. Considering the timing, it certainly seems likely that the company has something they are trying to keep quiet, and perhaps that is the addition of a high risk MDS cohort,

“Geron Corporation submitted an application under Rule 24b-2 requesting confidential treatment for information it excluded from the Exhibits to a Form 10-K filed on March 7, 2019.”

When you look at the actual 10-K, along with a plethora of other items the entire Attachment A (Form Of Work Order) is redacted and confidential. Now we know from Dr. Rizo from the shareholder meeting that the Phase 3 has no changes from the Phase 2 as far as trial design, so the redacting of the work order seems interesting, although it may be standard procedure and I don’t claim to know either way.

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