Patients #3 and #9 had both been on Luspatercept.

[Hoosier Investor]

Both of our ODAC patient success stories (#3 and #9) involved each patient being on Luspatercept prior to Imetelstat.

Patient #3 was on Luspatercept from Aug'22 to Feb'23 (~6 months). You can hear her comments at the 4:34:40 mark. Basically, she states that Luspatercept "helped some (she thinks) but it returned less than acceptable results". She noticed a significant improvement ~6 weeks after starting on Imetelstat, and she's been transfusion free for 8+ months. She was taking blood transfusions on a ~biweekly basis prior to Imetelstat treatment.

Patient #9 was put on Luspatercept in Jun'22. He doesn't comment specifically on his experience with Luspatercept, but he was enrolling in the Imetelstat trial in May'23 (~11 months later). Like Patient #3, he was initially treated with Placebo (2 rounds) before being switched over to Imetelstat in Aug'23. He had a total of thirteen (13) transfusions between 4/20/23 to 9/7/23. He began his Imetelstat treatment on 8/7/23 with his hemoglobin increasing from a low of 6.6 (Sep'23) to 13.1 (Dec'23) as a result of his Imetelstat treatment. His comments can be heard at the 5:07:50 mark of the video.

https://www.youtube.com/watch?v=Om-cKKBsMS4

Let's hope the FDA is aware & considerate of these two stories when considering the use of Imetelstat following Luspatercept treatment. Further, both of these stories involve US-based patients.

[biopearl123]

Great post HI, thank you. I was a little intrigued by the FDA’s assertion that implied that more patients benefited from Imetelstat who lived outside the US. The number of US patients being comparatively small and certainly not subject to much of a meaningful statistical analysis. Geron has basically stated that virtually all Lus failures will land in the Imetelstat camp. And your observations comport with this.

[CKTC]

I believe only six patients were in the trial with prior luspatercept exposure. This lack of data will be a problem for Geron once luspatercept overtakes ESAs in the frontline setting. Doctors will want to know if their luspatercept-failure patients will respond to imetelstat. Contrary to what Scarlett may claim, these patients will not simply fall into imetelstat’s lap. Doctors will not automatically offer imetelstat treatment; it’s not the only option. There’s lenalidomide, which has shown to provide 8-week transfusion independence in 20% of non-del(5) patients, hypomethylating agents, and a bunch of trial drugs that will indeed be targeting the luspatercept-failure market just like luspatercept and imetelstat targeted the ESA failure market. Doctors have no idea if these patients will respond to imetelstat. They might throw them into a clinical trial for free rather than spend $150K on a drug with unknown results. Consider this quote from the ESMO article that covered the IMerge study results:

“Reliable and practical biomarkers and patient selection criteria are much needed and, depending on the cost of the drug, one questions whether it would be feasible for patients to avoid getting hypomethylating agents or lenalidomide in the real world before they access imetelstat. With the August 2023 US Food and Drug Administration approval of luspatercept for the frontline management of anemia in patients with LR-MDS regardless of ring-sideroblast status, data would be needed in an expedited manner to see if patients treated with luspatercept respond to imetelstat or not.”

Scarlett must wise up and run a small trial in this patient population. What will Geron do if another drug wins FDA approval in this subset?

[Hoosier Investor]

Slide #20 of Geron's current (March) investor presentation conveys their current beliefs in the LR-MDS indication. The slide has a visual showing their expectations and is accompanied by the following statements.

* Imetelstat is expected to be used in the second-line regardless of frontline use with either ESAs or luspatercept.

* Imetelstat is expected to be used in the frontline in the majority of patients who are ESA-ineligible (sEPO ≥500 U/L).

NOTE: The slide is based on U.S. market research with 50 practicing community and academic hematologists.

[biopearl123]

CKTC, the expanded access protocol might provide data in Luspatercept failures. Might form the basis for a presentation at EHA.