Imetelstat has walked through the valley of the shadow of 'FDA holds', and it has emerged victorious.
Dr. Tefferi's genetic markers and Geron's intellectual property prove that work is being done to identify both the patients that Imetelstat will be therapeutic for and those for which it is likely contraindicated.
We are one giant leap toward optimal patient selection, and the number of MF patients that can be treated is about 20-25%, perhaps more.
In addition, Dr. Tefferi has refined the treatment protocol at Mayo to effectively manage abnormal LFT and other reversible side effects. We have FDA's stamp of approval.
Orphan drug designations soon. Imetelstat will be in the hands of oncologist who will follow Dr. Tefferi's protocol.
Imetelstat did have to repeat its senior year due to the FDA hold, so prom night is delayed. But, make no mistake, there will be a prom.
We have been informed by Dr. Tefferi that he has submitted data from the Myelofibrosis IST as an abstract to be considered for presentation at the American Society of Hematology or ASH annual meeting to be held in San Francisco in December. The abstract contains safety and efficacy data from patients with MF which have been updated since his presentation at ASH 2013.
Unfortunately, updated data sets from the MDS-RARS and blast phase MF patients were not available to Dr. Tefferi at the time of the ASH abstract deadline and as a consequence he did not submit abstracts to ASH regarding the treatment outcomes in these IST cohorts.
These data sets were not available because of the extensive data entry and analysis required to update the MF IST cohort data sets in order to support the preparation of this complete response to the FDA partial hold as well as the activities required to prepare for the transfer of the IND and study sponsorship for Mayo Clinic to Geron.
We look forward to the data from the patients with MDS-RARS and patients with blast phase MF being presented or published by Dr. Tefferi at a future venue.
This year we have also initiated collaborations with a select group of academic investigators who are looking into the effects of the imetelstat in non-clinical models of MF and other myeloid malignancies such as AML.
From these studies we may gain insight into the potential mechanisms of action of our drug in these malignances as well as non-clinical data to support broader clinical development of imetelstat. We’re pleased to report that our collaborators have submitted some of these data as abstract for ASH 2014. In keeping with standard ASH embargo policy, I will not be making any further comments on any of the submitted data from the collaborators.
Sentiment: Strong Buy
Orphan drug designation coming soon.
Bottom line: Imetelstat is effective for about 25% of MF and 50% of RARS MDS patients.
CR's a first. Imetelstat is good to go.
Side effects are manageable and reversible if properly managed. Otherwise, like any powerful drug, it can of course be fatal.
Jan. Mayo closed MF Pilot.
Eighty patients had been enrolled by this time.
Mar. MF study placed on partial hold.
Oct. 23 of the 80 continue. This is 28.75 percent.
Myelofibrosis 62 patients, with 17 still on Imetelstat
Myelofibrosis that has transformed into AML, known as blast-phase 9 patients, with 1 still on Imetelstat
Refractory anemia with ringed sideroblasts 9 patients, with 5 still on Imetelstat
Still on Imetelstat today are 23 patients
We are probably looking at 71 percent total drop out with about 22 percent total efficacy.
Apples and oranges
Wild cards are RARS MDS and blast-phase MF with blast phase group almost all dropping out. Dr. Tefferi update data for RARS MDS which is holding well.
The Laboratory correlative studies portion of Tefferi's abstract suggest marker for CR/PR are developing. They should be able to use this data to help guide patient selection for the phase 2. These markers, along with care in monitoring patients during treatment, will enhance the likelihood of a successful move to market perhaps earlier than expected.
John A. Scarlett, M.D., Geron's President and Chief Executive Officer is playing his cards close, not revealing much if anything about Geron's future with Janssen other than moving Imetelstat to market for myelofibrosis.
But, we already knew this. When pressed, Dr. Scarlett would only say that Imetelstat's dose would still need to be defined, but I suspect that one of the most respected doctors on the planet, Mayo Clinic's Dr. Ayalew Tefferi, might disagree. He has already perfected Imetelstat's dosing, side effects monitoring (LFT, etc.), genetic marker matching, and is now wrapping up duration and durability. We know that Dr. Tefferi is fast track phase 3 ready right now. Sure there is more to be done, but Dr. Tefferi has this under control, beyond this, he is the authority, not Geron and not Janssen.
Piper Jaffary's Dr. Charles Duncan made a move to try to shake what might be the rest of the story from Dr. Scarlett. Imetelstat must make it to market for patients with MF, we know profit potential for this indication is responsible with orphan designation premiums and world-wide sales. But there is more.
Take a look at what academia is #$%$ these days:
Steven E. Artandi†, Stanford University, USA
Telomerase in the 'Immortal' Germline
Dirk Hockemeyer, University of California, USA
Elucidating Telomerase Function in Human Tumor and Stem Cell Biology using Genetically Defined Cell Models
Expect more cancer indications, likely in combination wtih what Janssen has on the table, specifically Imbruvica combinations. For example: AstraZeneca, Pharmacyclics and Janssen partner on immuno-oncology combination trials with IMBRUVICA® for haematological cancers.
But, beyond haematological cancers, expect more. All of Geron's preliminary work points toward brain cancer, and I suspect this is what reallly got Janssen's attention.
I look for a 15-20 pps buyout before, during, or after the phase 2.
If that narrows it down. This is based on 25% of the MF market.
It is estimated that nearly 23,400 new cases of primary malignant brain and central nervous system (CNS) tumors will be diagnosed in the United States in 2014; of those, approximately 2,240 will be diagnosed in children ages 0 to 14 years and 540 will be diagnosed in adolescents ages 15 to 19 years.
Brain tumors are the leading cause of death from solid tumor cancers in children; brain and CNS tumors make up approximately 21 percent of all childhood cancers. The incidence rate of brain and CNS cancers in children has been relatively stable since the mid-1980s, but the death rate has dropped over this period.
The causes of most brain and CNS cancers are not known. However, factors that may increase the risk of developing certain types of brain tumors include exposure to radiation, exposure to vinyl chloride, and having certain genetic syndromes. There are no screening tests for brain and CNS cancers. Standard treatments for adult brain cancer include watchful waiting, surgery, radiation therapy, chemotherapy, and targeted therapy.
Newer treatments for adult brain cancer, such as biological therapy and proton beam radiation therapy are being studied in clinical trials.
Assuming that incidence and survival rates follow recent trends, it is estimated that $4.9 billion will be spent on brain cancer care in the United States in 2014.
Sentiment: Strong Buy
MF is not the only game in town.
Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells.
Sentiment: Strong Buy
Yes, when the market connects 1 + 1, it'll happen.
They are just waiting on Tefferi's real update, not the abstract.
Here you go Ohmtaxi.
Do you understand why the Mesoblast/Osiris data is relevant to the ATHX board now?
Competition is a good thing, and Multistem and Prochymal have a key common effect, increase in IL-4 and IL-10. This is good because Multistem is 1/4 the cost per dose with more cells.
Co-localization of transplanted MAPC and resident CD4+ splenocytes is associated with a global increase in IL-4 and IL-10 production and stabilization of the cerebral microvasculature tight junction proteins. (MAPC were obtained from Athersys, Inc. (Cleveland, OH).
Additionally, Prochymal up-regulates the production of beneficial anti-inflammatory cytokines, specifically interleukin-10 and interleukin-4.
I have been in since they were a stem cell biotech back in the day, but not nearly as long as some of the founders on this board. I think the end of the road is near. I agree with many others that the job of John A. Scarlett, M.D. is to put Geron in as mint condition as possible and sell it. The Mayo Clinic trial and surviving the FDA hold is a green light for any pharma to make their move. Porches and more underwater photography for Scarlett in his retirement coming soon.
Camelia Iancu-Rubin, Ph.D., et al.
4582 Imetelstat (GRN163L), a Telomerase Inhibitor Selectively Affects Malignant Megakaryopoiesis in Myeloproliferative Neoplasms (MPN)
Monday, December 8, 2014, 6:00 PM-8:00 PM
West Building, Level 1 (Moscone Center)
We conclude that GRN163L-mediated inhibition of telomerase affects normal megakaryopoiesis by blocking the terminal maturation of CD34+/CD41+ MK precursors, providing a possible explanation for GRN163L’s propensity to induce thrombocytopenia in patients with normal bone marrow. By contrast, GRN163L treatment inhibited the ability of MPN CD34+ cells but not normal CD34+ cells to form CFU-MK colonies and drug treatment reduced the numbers of malignant MK generated. We propose that the amelioration of fibrosis observed in a clinical trial of MF patients treated with GRN163L might be due to, at least in part, two potential modes of action: 1) inhibiting malignant MK progenitors cells and 2) preventing terminal MK maturation thus depleting the pool of mature MKs which are the major source of fibrogenic cytokines in MF.
Naysayers crawling out of the woodworks.
Get ready for FDA Fast Track, Breakthrough Therapy, Accelerated Approval.
Get ready to run with the big dogs.
Sentiment: Strong Buy