TiGenix initiated in 2014 a phase 1b trial in severe Sepsis treated via intravenous injection of allogeneic stem cells (codename: Cx611). The company intends to launch a phase 2b trial in early RA in Q3-2015.
Severe Sepsis is a potentially life-threatening complication of infection where the whole body is subject to an inflammation caused by bacteria, fungi, viruses or parasites. If sepsis progresses to septic shock, blood pressure drops dramatically, which may lead to death. Patients with severe sepsis require close monitoring and treatment in a hospital intensive care unit.
As a proof-of-concept study, TiGenix initiated in December 2014 a phase 1b trial to test the mechanism of action of Cx611 in this indication. The trial is a randomized, placebo-controlled trial in which healthy volunteers will be challenged with a bacterial endotoxin to induce sepsis-like clinical symptoms. Results are expected in Q3-2015.
Sepsis is an affection of complex nature and its variable presentation has made it hard to develop therapies. Cx611 could be added into current clinical management, representing a good therapeutic and commercial opportunity in an unmet clinical need.
Wrong, JNJ touted that abiraterone was a "wonder drug" for prostate cancer in order to take Provenge off of the market.
The truth is, abiraterone does not work:
"For the abiraterone phase 3, the median overall survival for was 35.3 months for the group of men who received ZYTIGA® (abiraterone) plus prednisone, compared to 30.1 months for the group of men who received placebo plus prednisone. This difference, however, did not meet statistical significance." This is directly from Janssen (JNJ).
Now, Provenge is gone.
GERN does not have the potential value of BLUE with MF alone. It will never have the same market cap unless other major imetelstat indications are put on the pipeline by Janssen(JNJ).
GERN is heavily diluted and drowning in 158.09M shares.
GERN share numbers should be more in the range of a BLUE with 32M shares. Just taking a moment to reflect on this and how richly priced GERN is with almost 5X the number of shares as BLUE with much less current prospects.
GERN is currely valued correctly...and a little rich at that.
True, BLUE may turn out to be a dud if it is not safe.
But, if GERN is successful for MF, it is a 10 PPS stock.
There are about 10,000 patients with MF worldwide that will take imetelstat, representing a ~$500 million market. Tiered royalties ranging from a double-digit up to mid-teens percentage rate on worldwide net sales is $75 million annually. Geron would need to co-promote if it wants more.
Imetelstat a hypertension drug...I doubt this very seriously because of the effect on liver. Unless low dose works really well, which it might? All indications are a wild card except oncology. We need firm movement toward oncology beyond MF. Solid tumors. Difficult cases. e.g. "Telomerase Inhibitor Imetelstat (GRN163L) Limits the Lifespan of Human Pancreatic Cancer Cells"
Until we see some serious movement toward other oncology indications that immunotherapies prove ineffective, 10 PPS is the ceiling here.
The current trial is "Previously Treated With Janus Kinase (JAK) Inhibitor". This means Geron/Janssen will treat those patients whom oral JAK inhibitors are not working.
End of story.
Geron needs other indications to make it big time. As cited above imetelstat for pancreatic cancer, etc.
You are calculating to capture the entire MF market. This will never happen. Ok, for fun, double my estimate to $150 million annually for Geron at peak sales world-wide at 15% royalty. Maybe a wee bit more at 20%. Geron still has way too many shares out. 10 PPS is generous until more indications come online. Before this happens, GERN will be bought out. "JNJ gave 3 different diseases to use GERN drug on. -jkokao". This is how its going down. Buyout at 15-20 PPS?
1. Mesenchymal Stromal Cells for Ischemic Stroke (SAMCIS) Phase 1 & 2
ClinicalTrials.gov Identifier: NCT01922908
Sean Savitz, The University of Texas Health Science Center, Houston
Study Start Date: July 2015
***When given between 3-10 days after an ischemic stroke
2. Cord Blood Infusion for Ischemic Stroke Phase 1
ClinicalTrials.gov Identifier: NCT02397018
Joanne Kurtzberg, MD, Duke University Medical Center
Study Start Date: May 2015
***The cord blood infusion must be given within 3-10 days of the stroke.
3. Safety of Escalating Doses of Intravenous Bone Marrow-Derived Mesenchymal Stem Cells in Patients With a New Ischemic Stroke Phase 1 & 2
ClinicalTrials.gov Identifier: NCT01849887
Steven C. Cramer, MD, University of California, Irvine
Study Start Date: January 2017
***Ischemic stroke in the middle cerebral artery territory, with onset 24-72 hours prior to the time that the therapy transfusion is initiated
4. Intra-arterial Autologous Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke
ClinicalTrials.gov Identifier: NCT02290483
Andalusian Initiative for Advanced Therapies
Study Start Date: April 2015
***Time of stroke onset is known and treatment can be started between day 1 and 7 of onset.
Indeed, Athersys has established that time is of the essence when it comes to stem cell therapy for stroke. MAPC must be infused no more than 24 hours post-stroke.
Gil's 24-36 hour time frame is too long, and the data suggests the damage is done if you wait more than 24 hours.
The sooner the better.
If Chugai moves forward, they better get the early time frame right before starting the trial. Gil is once again in la la land with his bogus extended time range. When will he ever learn?
The solution is NOT to wait until after 24 hours post-stroke to administer Multistem just to identify spontaneous responders because Multistem is only effective if given within 24 hours post stroke.
The only way to resolve the problem of spontaneous response is to give Multistem early (by 24 hours post stroke) and run a large trial to statistically overcome the confounding effects of spontaneous recovery.
What was true in 1995 is still true today:
"Our data suggest that the attempt to clinically “subtype” stroke by etiology will be insufficient to reliably identify patients destined for early spontaneous improvement. Further investigation in this area may allow us to select from the acute stroke population at large those patients who are most in need of therapeutic intervention and most likely to respond to such intervention. Until then, inclusion of patients destined for early spontaneous improvement in treatment trials conducted to evaluate these new therapies may be expected to confound analyses of efficacy."
-Stroke (1995) 26: 1358-1360
Ideally, we would know which patients will not respond to standard of care so that Multistem can be given immediately without waiting 24 hours to use lack of improvement as a diagnostic.
Chugai is likely probing this possibility, " They found...an ALDH1L1 gene variant..strongly associated with stroke." If such a gene marker can be linked to lack of response to standard of care, these patients can be selected for Multistem immediately.
Perhaps a formula would capture most of thes patients that will need Multistem: Age + ALDH1L1 gene variant + location of infarction + previous stroke
Changes to NCT02426086 on 2015_06_10
Before (Updated 2015_06_02)
Participants will receive imetelstat intravenously as 9.4 mg/kg every 3 weeks. Study drug will be administered intravenously until disease progression, unacceptable toxicity, or study end.
Participants will receive imetelstat intravenously as 4.7 mg/kg every 3 weeks. Study drug will be administered intravenously until disease progression, unacceptable toxicity, or study end.
In the previous trial at Mayo Clinic: "Imetelstat Sodium administered as IV over 2 hours with treatment up to 3 years until disease progression or unacceptable toxicity with the following dose & schedule: Starting doses are 7.5 mg/kg or 9.4 mg/kg from weekly to every four weeks based on indication."
APPARENTLY 4.7 mg/kg every 3 WEEKS IS ALL GOOD.
"Recent studies suggest that bone marrow–derived mesenchymal stem cells (MSC) home to and incorporate within tumor tissue." [Cancer Res 2009;69(10):4134–42]. "Human mesenchymal stem cells (hMSC) can home to tumor sites." Scientific Reports 3, Article number: 2298
On October 19, 2012 Chugai Pharmaceutical succeeded in establishing stable cell lines with the nature of colon cancer stem cells that are thought to be involved in the recurrence/metastasis of cancer.
If Multistem associates with their cell lines, they probably think they have a winner for drug delivery.