Geron / JP Morgan
A clear and thorough description of the data to date in essential thrombocythemia. I think the transparency provided is a reflection of the fact that the data appear rather strong, albeit in small numbers. The company also appears focused: the discussion was all imetelstat, all the time. No mention of any legacy stem cell baggage whatsoever. Some notes below
Presentation
- 90 million cash on hand as of December 31, 2012... expect to burn 33 million in 2013
- Imetelstat is the lead compound. It is a 13-mer oligo complementary to the telomerase RNA template, with a thio-phosphoramidate backbone to prevent degradation by nucleases. It has also been lipidated to increase penetration
- IC50 = 0.5 - 10 nM to inhibit telomerase in cell free system
- long half life (41 hr) and abundant distribution particularly to bone marrow, spleen, liver
- Proof of concept trial of imetelstat in essential thrombocythemia, which is an overproduction of platelets through malignant megakaryocytes
- in the trial, plan was for weekly IV dosing until hematological complete response (CR; as measured by platelets falling), and then moved onto maintenance treatment at the physician's discretion
- 14/14 patients achieved hematologic response, with 13/14 showing CR (normalization of platelets maintained for at least 4 consecutive weeks in the absence of thromboembolic events) with a mean time to response of 6.1 weeks (5.1 to 14.1 weeks range); the 14th patient showed PR
- 13/14 patients remained on therapy, 6 more than 1 year; median time on therapy 8 months
- frequency of administration reduced in maintenance phase for 11 of the 13 patients who achieved hematological CR; 5 patients eventually titrated down to every 6 week dosing
- the company also measured JAK2 V617F mutation's allele burden (% of cells carrying the JAK2 V617F mutation).... 7 of 14 enrolled patients had the JAK2 mutation, and 86% (6 of 7) of these achieved partial molecular response (defined as 60-90% suppression of malignant clones carrying JAK2 V617F)
- in comparison, jakafi shows 14% of patients showing >20% decrease in JAK2 V617F allele burden (this is in myelofibrosis i believe, but I need to double check these numbers so take it with a grain of salt... also a sicker population in MF than in this ET trial)
Q&A
- myeloid malignancies are the ones where most patients have short telomeres, hence their initial focus
- some suggestion that short telomeres may also play a role in early phase CLL, NSCLC and bladder cancer
- they eventually want to optimize a diagnostic in order to measure telomere length as part of the enrollment criteria for their registration trial
