This is the first post about squalmaine and ohrp on this board. In the short term todays share price is how the the market sees squalamine drops but in the long run only the data counts

I think that the evidence is there that the drops work with a high degree of certainty.  And the drops should work from what we know; that is the drops work considering the rabbit data and Genaera data.  All that's left is for us to do is to see the DATA IN HUMANS.

Now AF and others are cynical about eye drops working. They would give OHRP a low probaility of success.  But they have no evidence.  Zilch.   Undeniably, the drops have worked in the first patient they were given to. 

   

Last edited by Admin (5/10/2014 12:58 am)

Thank you for doing this!!  Any thoughts about how next week might look?

What could go wrong?   Well the worst case is that the data is inconclusive since even the possibilty of side effects was minimized.  Now the problem with that is that if we assume that QID obviates the need for ALL injections in PDR and hence in wet amd,, then logically BID should obviate the need for about half of the injections in PDR and hence in wet amd  Now 50% fewer injections mean about 3 less injections since 6 are expected and that would show a statisticall significance.

When I analyzed squalmaine IV, the response was linear with dose pretty much, since the rate of letters lost was linear with the number of letters gained.  So if 80mg IV per week gave a gain of 10 letters, the only way that gain could be kept was by continuing the 80mg per week dose. And if 40mg per week would gain say 6 letters, again the only way that gain could be kept (at steady state) was by giving 40mg per week and not 20mg per week which resulted in no gains at all, because the rate of diseas progression was faster than the rate of disease elimination..

This may be due to squalamine not binding up vegf as Eylea does so well but instead binding up calmodulin, which leaves vegf floating around just outside the cel  And that keeps NO levels high but the problem is if squalamine levels fall suddenly, then all the vegf is ready to pounce on the vegf receptors immediately and trigger angiogenesis.  So if squalamine levels fall by 50% in 4 days (one half life), then up to 50% calmodulin become free.  Even when Eylea levels fall by 50%, it may take longer than that to produce the vegf and thus extend the time between Eylea doses to a few months.
 
So the other problem is that the eldelrly patients were underdosing their eyes, skipping doses, ..etc.  Squalamien works best if given twice day since even missing 12 hours will drop the squalamine level by  8% or so. 

Last edited by Admin (5/10/2014 9:12 am)

The Genaera report of Oct, 2003 showed no significant difference in response with dosing 25 vs 50 mg/m**2.  Slide titled: "No Notable Difference in Visual Acuity Response in Study Eye By Dosing Group at 2 Months"   That may be PK related.

What would concern me is if BID did not show sufficient response for sufficient number of patients to lead to a significant separation between dosed and placebo.  If there is additional complications from misdiagnosed AMD, plus normal variability this could fail statistically.  It's powered for 1.5 injection difference, but it doesn't take much variability among 30 dosed people to remove that.  That's why I was asking for a hard mean and p value based on previous data.

The depth of the selloff is concerning in itself.  

Admin wrote:

I think this is the bottom.  First a fire has been lit under Dr. T and Sam to get the share price up.  Alll the options were at $10+ and OHPR has never revalued options down before. So the pressure is on.  And most importantly, the investors in the shelf who are cozy with directors, possibly being the main shorts above $10, or now down a few dollars. And they are not happy!  Theyt have lost some of their profits on shorting this down. And if they didn't short, they are more unhappy.

The company is moving faster now and listening more. I know the DME study had originally called for BID dosing and that was changed to QID dosing likely on the advice of the clnicians who began understanding the difference between steady state and saturation based on Dr. Elman's work. Over the years, I tried to press this point to Ohr with no luck.

And most of all, the data is probably closed as of next week and will go to the statistician.  At that point, news leaks out.   The only problem right now is the headwinds of negative world events, the burrsting of biotech,  the end of QE,...etc. It may be a bumpy ride after results come out.  I don't know. All I know is that nearly nobody out there thinks squalamine works.  But all the science I've learned says it does work. 

If this keeps dropping then something is wrong.  

bill wrote
"The Genaera report of Oct, 2003 showed no significant difference in response with dosing 25 vs 50 mg/m**2.  Slide titled: "No Notable Difference in Visual Acuity Response in Study Eye By Dosing Group at 2 Months"   That may be PK related.

What would concern me is if BID did not show sufficient response for sufficient number of patients to lead to a significant separation between dosed and placebo.  If there is additional complications from misdiagnosed AMD, plus normal variability this could fail statistically.  It's powered for 1.5 injection difference, but it doesn't take much variability among 30 dosed people to remove that.  That's why I was asking for a hard mean and p value based on previous data.

The depth of the selloff is concerning in itself"

Yes your right, it's was PK related.  They are talking about gains 2 months after the LAST DOSE. It may have been 1 month after the last dose, but regardless, squalamine levels decrease by 50% every 4 days, so that by 3 to 4 weeks later, the gains will come down significantly. 

Also they seemed to have the result that the 25mg/m2 and 50mg/m2 gave similar results all through the monthly followups, although I believe that the 50mg/m2 gave signficantly better weekly gains during the first month.  I had asked OHR to put that data up on their website 2 years ago, because it's gone from the internet.

As far as QID vs BID, that may have caused anxieity because the dose this is a 3rd protocall now.  They could have used the Dr. Elman approach but I think they didin't want to HAVE TO see the patients the week after starting them out and that's why they gave them an initial injection which should hold them until the first monthly followup. This seems like it will be SOP to give the patient the first injection as the basis of any protocall unless the doctor wants to see the patient in the following week, except perhaps for wet amd because it has the slowest rate of growth..    DME has very high levels of vegf, comparable to PDR; only wet amd seemed to be the outlier with low levels from the papers I saw and even then some wet amd patients had very high levels..  It was RVO that had the highest due to the acute nature of the blockage, so I wonder how Dr. Wroblewski is fairing.  Anyway, squalamine blocks calmodulin so it shouldn't be a stoichiometric issue with vegf levels.  But who knows?

The sell off is concerning. . And stop losses of longs are being triggered (and to continue playing this great game of speculation we need stop losses) and shorts are reflexively selling too.  The sell off I think is an opportunity in the making because emotions work both ways, to overvalue and undervalule the object of our analyis. We always end up with emotional reasoning influencing rational thinking at the top and bottom of markets.   The question is, what is the value of OHRP eventually going to be.?  It's not like we are buying a house, a loaf of break,..etc something tangible. Therefore we have to be careful

 

Last edited by Admin (5/10/2014 8:08 am)

The worst indicator I see is the heavy volume in the selloff for the last 3 days.  A 1 mth or weekly chart of price and moving avg volume shows this well.  As of Apr 30, 1.3M shares were short. That's almost 10% of the float and up 14% from Apr 15.   The numbers get updated May 15.  Be nice to know if Marcin still has his position as well.