Question to BP & other knowledgeable folks

[mistergern]

If Imetelstat extends the life of refractory Jakafi patients for over 30 months, and if a combination Jakafi/Imetelstat MF trial proves to be safe and effective, what would be the impact on the lifespan of the patient be if the Imet treatment started much earlier in the progression of the disease?

For the financial folks, how would a successful Jakafi & Imetestat combo affect revenues?

[LWS]

Note -- Combinations studies in progress, with more to come:

(With Incyte)-- IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in May 2022

(With AbbVie) -- TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R
AML in 2H 2022

That trial is underway (IMproveMF)

[mistergern]

LWS, I understand that the trial is underway. My question is; What do knowledgeable folks think the combo would have on the lifespan of MF patients and how significantly would this combo impact potential revenue?

[biopearl123]

No one knows in humans. All one can say is preclinical work very promising:

ASH 2020
Combination Treatment with Imetelstat, a Telomerase Inhibitor, and Ruxolitinib Depletes Myelofibrosis Hematopoietic Stem Cells and Progenitor Cells. Wang, X, et al, ASH 2019

[mistergern]

Thanks BP, from the study:

"Collectively, these data indicate that alterations of scheduling of the administration of Rux and Ime affect the efficacy of this drug combination in depleting MF HPC/HSCs. We propose that cycles of Rux followed by Ime represent a potentially effective therapeutic strategy that is capable of eliminating MF HSCs/HPCs with an acceptable profile."

I'm hoping the synergistic impact of combining these treatments is realized. Hope springs eternal!

[LWS]

IMproveMF: Planned Phase 1 Clinical Trial in Frontline Myelofibrosis

IMproveMF is designed as a two-part Phase 1 clinical trial evaluating imetelstat in combination with ruxolitinib in patients with Intermediate-1, Intermediate-2 or High-risk frontline myelofibrosis. Up to 20 patients are planned to be enrolled in Part 1of the study with the objective to identify the safe dose of the combination treatment, while efficacy data is being collected.

Part 2 is also planned to enroll about 20 patients, with the objective to confirm the dose of the combination treatment of imetelstat and ruxolitinib and further evaluate efficacy. The primary objective for Part 2 is symptom response rate, defined as the proportion of patients who achieve a >50% reduction in Total Symptom Score at 24 weeks. Secondary objectives include change in fibrosis; spleen response rate, defined as the proportion of patients who achieve a >35% reduction in spleen volume from baseline as assessed by imaging; and the number of patients achieving complete remission, partial remission or clinical improvement.

We expect the trial to start in the first half of 2022.

The way that I see this, there are issues of dosage and safety. Both medicines individually are safe. If there are no unsafe interactions in the combinations, then we should get the best of all worlds: spleen reduction, increased survival time, disease modification. Of course, we have to wait for the trial results, but this appears very promising.