I don’t want to argue, only give you one example. I was investing in company which run phase 3 trial with two doses of the drug. It turned out that higher dose did not work but lower dose was perfectly OK. What FDA said? You need to run a new trial with lower dose only.
With Apaziquone, pre-specified primary endpoint of the trial was not met. 6, 12, and 18 months data is just a post hoc analysis. It can help to formulate a new hypothesis which will need to be proved in a new trial. I don’t know any precedent where FDA accepted post-hoc efficacy data for approval. Sorry, forgot that I don’t want to argue.
This analyst is worse than fortune tellers
"Benjamin has a -9.3% average return when recommending SPPI, and is ranked #3036 out of 3602 analysts."
"which start investors thinking about the possibilities"
One possibility with present management is that they could announce enrollment but will not enroll as they did with Marqibo and most likely with Apaziquone multi-instillation trial. Everything will look OK for a while.
You are wrong.
"The threonine-790 to methionine (T790M) point mutation is found in approximately 50% of all patients at the time of acquired resistance to EGFR TKI therapy"
Read Oncogene. 2009 August ; 28(Suppl 1): S24–S31.
I recommend to read an article published in Pharmacological Research 87 (2014) 42–59
Name Target PubChem CID Cancer indications
FDA-approved ErbB kinase inhibitors
Afatinib ErbB1 10184653 NSCLC
Erlotinib ErbB1 176870 NSCLC
Gefitinib ErbB1 123631 NSCLC
Lapatinib ErbB1/2 208908 Breast
ErbB kinase inhibitors in clinical trials
AZD-9291 ErbB1 Not assigned NSCLC
BMS-599626 ErbB1/2/4 10437018 Glioma
Canertinib ErbB1/2 156413 NSCLC/breast
Dacomitinib ErbB1/2/4 11511120 NSCLC/gastric/head and neck/glioma
Icotinib ErbB1 44609731 NSCLC
Neratinib ErbB1/2 9915743 Breast/NSCLC
Poziotinib ErbB1/2/4 25127713 NSCLC/breast/gastric
TAK-285 ErbB1/2 11620908 Advanced solid tumors
Vandetanib ErbB1/VEGFR/RET 3081361 Thyroid/NSCLC/head and neck
WZ4002 ErbB1 44607530 NSCLC
This list is not complete. It does not include some most promising third generation TKIs.
Listen to their 1astQ CC:
"Our focus will be on a fast-to-market development strategy, capitalizing on the robust activity identified in breast cancer patients who failed previous HER2-directed therapies and those with the specific receptor mutations."
Based on data presented at ASCO, we know that drug has no effect on specific receptor mutations which is T790M. This mutation is a major cause of resistance to first and second generation TKIs. Learn more about neratinib. Chemically not much different from poziotinib, way ahead of poziotinib in clinical trials, showed very similar preclinical profile but could not inhibit T790M receptor in patients. It was a good chance for poziotinib to differentiate. Did not work. And guess what? It was tested in "breast cancer patients who failed previous HER2-directed therapies and those with the specific receptor mutations".
"Obvious clinical evidence suggesting that poziotinib may overcome acquired resistance secondary to EGFR T790M mutation was not captured in this study"
Now you can forget about poziotinib. It won't be better than neratinib.
Yes, their strategy is clear. To buy cheap shares, to replace failed CEO and to give the company a fresh start or to sell it. Both scenarios are good for them and for shareholders. For some biotech companies, just recruiting a new CEO with focused business plan is enough to start long term growth. Raj had his chance, but he blew it.
"If they were experts at running something as complex as a biotech company they world be a biotech company." If they can make more money by being a hedge fund, why would they want to be a biotech company? Their job is making good investments. What they see is that company they invested in has a CEO which is incapable of running and presenting the business. Raj lacks integrity. Spectrum is in biotech sector, has a decent revenue but is valued as a generic company. And it is a CEO's fault. Something needs to be done.
"A procedure to minimize bleeding is out of SPPIs hands; SoC is SoC"
One thing they can try is to prolong period of time from TURBT to instillation. In their previous studies, some patients were waiting less than 30 min and majority were waiting longer than 2 hrs. They can try a second instillation a day later. Minimizing bleeding is better than excluding patients from analysis after treatment. How will it work in real life?
Bleeding is one of the symptoms of bladder cancer and is a normal consequence of TURBT surgery. Therefore, in most cases blood will be present. Question is how much blood is acceptable for Apaziquone not to be neutralized. Spectrum needs to say what concentration of blood they consider as bleeding. The more I think about it, the more I realize that this approach might be flawed. They need to focus on development the procedure that minimize bleeding and analyze all patients, not excluding anyone. Another possibility is that Raj said it without thinking.
"How's it possible for somebody not to know by now?"
Study is double blind. Nobody suppose to know what patient is taking, drug or placebo. It will be known only after unblinding.
"Wouldn't it be fine for our side if it also worked on diabetic retinopathy!" It should be fairly large study. Where they get money from?
They are waiting for a pre-specified number of exacerbations to unblind and finish the trial. It seems like they are one exacerbation short by now.
from the last CC.
It was mentioned that bleeding patients will be excluded from analysis. Wonder how they are going to decide who is bleeding and who is not? What concentration of blood in urine will be determined as not acceptable?
"Will Spectrum start a P3 in another indication to satisfy the AA requirements for Marqibo?"
You mean, not ALL?
"Or will Spectrum be able to use the OPTIMAL 60 P3 study in DLBCL to meet its requirement"
FDA said to run study in ALL. DLBCL is not ALL.
"Or will the FDA let Marqibo remain on the market without a P3 study"
It is the most important question. I would like to know what was the problem with enrollment.