Good luck bball. I enjoyed some of your posts on the INO board as well. I typically go there and search for markbuti, or kyleramer. Even some of the pumper'/investor's bickering is intolerable there. Kyle has good info, though and does good DD. Mark has some good comments as well.
Isn't that an insider violation if you do it within a certain amount of time before a binary event?
For Urano, a scientist to go after MANF, a similar but unrelated protein, as a GENETIC therapy TO CORRECT cells in a genetic disease where the DISEASE IS CAUSED BY A MUTATION IN ANOTHER I REPEAT ANOTHER protein, wolframin, means the data with replacement therapy/treatment in animal models is better than replacing the mutant protein. It could be a dominant negative (scientists, you know what I am talking about) effect of mutant wolframin which would make any additional wolframin useless because of the dominant effect of the mutant protein.
Last part about the dominant negative is speculation on my part. First part with all caps for emphasis is speculation from Urano... Or is it... He said he had data coming out which would help him choose/decide between replacement therapy with wolframin or treatment with MANF for Wolfram's syndrome.
Looks like he chose.
All gene therapy approaches thus far to correct a mutation/gene deletion have targeted the mutant protein. Urano thinks supplying MANF via gene therapy is better than supplying wolframin to patients with mutated wolframin. Do you see that yet? I do not know of one instance where a scientist has tried to do that yet. For instance, boys with SCID by mutation of adenosine deaminase. People give them adenosine deaminase gene therapy to fix their lymphocytes. Not MANF. That's why it's a huge deal. Urano has stated he is testing different proteins in his wolframin mice. He had to like what he saw with MANF
I don't know what you mean by "A Wolfram's trial will use less MANF than an RP trial". Both are chronic diseases, so both will require repeated doses (after MANF is proven to be safe, etc). The pathogenesis of eye disease in Wolfram's is similar but not the same as RP, ZB.
RP is heterogeneous and many different mutations can cause RP. Its thought that the retina degenerates because of toxic accumulation of proteins and other things from degenerated rods and cones in the retinal pigmented epithelial (RPE) cells. It causes blindness because the retina becomes completely dysfunctional.
Wolfram's is caused by a defect in WFS1 gene (encoding wolframin). Loss of WFS1 causes blindness because the optic nerve atrophies. The retina is fine. Also, even though the Wolfram's patients have diabetes, they don't seem to get diabetic retinopathy.
I do concur that if they treat Wolfram's with MANF, it will be local eye treatment first, but not for retinitis pigmentosa. They will be treating the optic nerve dysfunction. If that is successful, they may try targeted therapy to the beta cells of the pancreas, or systemic therapy.
It will be like the Biomarin approach... Treat rare diseases because nobody else is doing it.
The only difference is, if MANF can treat retinitis pigmentosa, it may be a useful therapy for other forms or retinopathy. If it helps with retina degeneration, it may help with neuron degeneration in Parkinson's, Alzheimer's, and Huntington's. Also, if it can help with Wolfram's associated diabetes, it may help with protecting beta cells in type 1 or type 2 diabetes.
Got it. Thanks. I agree, less Wolfram's patients likely means less patients to enroll in the study. The only issue is with power analysis (getting enough patients to be able to detect statistically significant differences in the treatment. I wouldn't want to underpower the study.
Its really early. They need to pick an autoimmune disease. So that means: Alzheimer's, not a chance. EAE, model of multiple sclerosis that is induced by a vaccine (MOG peptide with complete freund's adjuvant), likely you can improve outcome there. Translating results from that model to MS have been difficult. Its not as bad as the NOD mouse model of diabetes (A good friend of mine is a prominent diabetes researcher, and he said if you stare at a NOD mouse funny for a long enough period of time, or if you spit on it, you can prevent diabetes in the mice), but its still pretty easy to prevent/reverse EAE in mice.
Hope you had some BBQ and beer this weekend, I sure did. Don't frequent message boards very frequently. Send me an email if you have questions. My screenname here is a yahoo email account. I think D-day is coming soon for both INO and AMBS. Good luck. I'm comfortable in my positions for both.
The clinical performance is AMBS's experience with the LymPro test. The analytic performance is BD's results with the tests, as BD was the outside lab paid to verify the results (prove another lab can get the same results as AMBS.)
I think if BD gets above a 90% specificity and a 85-90% sensitivity, this will be 0.25- 0.30 after the conference.
Sensitivity= actual positives out of all positives (actual positives + false positives). This is the ability of a test to pick up true positives, i.e. tell a patient he has the disease.
Specificity=actual negatives out of all negatives (actual negatives + false negatives). This is the ability of a test to pick out true negatives, i.e. tell a patient he does not have the disease.
Risk, this is your answer to your question above about how do I justify my price target for AMBS based on the specificity and sensitivity numbers being verified by an outside lab.
This will become the gold standard test for Alzheimer's disease. A disease that right now has no gold standard test, because nobody can afford it. Remember the CPT code. That means insurances, medicare and medicaid can start paying for it.
Early diagnosis for any neurologic disease is paramount for early treatment (except Huntington's and Lou Gehrig's/ALS).
See bball's post below, and my post below it for the answer to your and eloinment's questions. Its all about who is performing the test. If AMBS is doing it, nobody believes it (See the price chart to the right showing 10 cents per share). If BD shows that AMBS is not full of horse manure, whoa nilly.
Apparently Gerald agrees with me too in his blog that the analytical performance is more important than the clinical performance
This is why I said the analyticalperformance presentation is so much more important than the clinical performance presentation.
Do we know when the analytical performance data will be presented at the conference?
Thanks in advance
You are correct, in an ideal world 99% 99% would be amazing. But if the test results (remember GW Medical Technologies original data showed a sensitivity of 83% and a specificity of a whopping 96% in a study of 72 patients- The long term results from these patients will also be presented in Copenhagen in the clinical abstract, per GC: Remember the sensitivity should go up with time as patients who originally did not meet diagnostic criteria for Alzheimer's get older, and possibly progress to disease, while the specificity should stay the same, since once your diagnosed with Alzheimer's, you don't really lose that diagnosis, unless you watched the planet of the apes movie and James Franco gives you a retrovirus to cure Alzheimer's...).
Now could this be the "new intellectual property" that AMBS recently acquired for the beefed up LymPro test:
Type this into your favorite web browser:
"Multivariate analysis of differential lymphocyte cell cycle activity in Alzheimer's disease."
It is a paper by the original authors of the LymPro test published in 2012. Instead of just using CD69, It measured 12 cell surface molecules on lymphocytes. 7 of these markers were differentially regulated on lymphocytes of Alzheimer's disease. Using these markers, a sensitivity of 91% and a specificity of 92% was obtained in a total of 32 Alzheimer's patients compared to 56 controls (26 Parkinson's patients and 30 healthy age matched controls).
the original results the scientists presented were 92 and 90% for their expanded study).
Now: if BD was able to replicate these studies, with a sensitivity over 90% and a specificity greater than that, that would be the best news for AMBS.
If the specificity is 96% like originally reported by GW, this will definitely be used by the big pharma for clinical trials, to be used as an exclusion criteria since if the test is negative, that will tell the company with 96% certainty that the patient does not have Alzheimer's disease.
Sorry, after per GC should be a period, not a colon. That may be a little confusing
This manuscript has an expanded marker list including CD28. Although CD28 was not as useful as CD69. I agree, though, that if the new IP is better than 91/92 (by BD in the analytical performance abstract) that this will be a home run test, and a test that will be the gold standard (for now) for diagnosing Alzheimer's. The reason I say for now is that better tests will likely become available in 3-4 years. Remember, there is nothing else available until then so lympro will be the best. Then I don't care what happens to Lympro. Because eltoprazine and MANF will be getting in gear/goin full swing and that is where the real money is with this company.
Lympro is a temporary money maker to get the company the money needed to progress with the rest of the pipeline. Let's see what partnership news we get by year end for MANF and possibly eltoprazine
I agree with what you said. My point was, 100 million to 1 billion, whatever, for 4 years is still temporary. But it's a big boost. After that, revenue will probably go down but will still be significant. By then other things will have progressed to the point that the market will assign value to them (eltoprazine and MANF). And something should be partnered as well, generating income that way