Replies to post #121 on Biotech Values

[DewDiligence]

rph: Interesting question about the possibility of negative ramifications from non-IV administration. Would like to hear from the biology cognoscenti on this subject. In any case, I am not aware of any indication from the company itself that GENR seriously intends to pursue alternative formulations such as nasal or transdermal.

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Did you listen to today’s webcast. The revelation that GENR is submitting the phase 1/2 Squalamine data to an independent review panel makes me think this was requested by one or more prospective partners. In other words, the Squalamine data was so good that prospective partners wanted to be sure it was real!

[Biowatch]

squalamine delivery

As far as I know, it has only been people speculating on various GENR message boards that have brought up the possibilty of nasally or transdermally delivered squalamine as the next pathway that GENR will follow. Although this would be a more user-friendly method of administration than intravenous or intraocular injection, it would take years to develop and test a new method of administration.

I am not a medicinal chemist, and not an expert on drug delivery, but one would have to develop a new formulation method and test it before it could reach the market (i.e., reach the market and generate sales.) Typically, large pharmaceutical companies wait until the patent on a particular drug (and its approved formulation) is about to expire, or when they are facing competition from similar drugs before they pursue alternative methods of administration.

Yes, the chemical structure of squalamine means that it is highly water-soluble. In addition, its core ring structure is that of the classic steroid, and all I know is that many steroids are given by injection.

My feeling, based in part on what I quote below, is that intravenous administration is preferable to the intraocular injection (needle stick in the eyeball) method being pursued by the current potential competition. Developing alternative delivery methods should be considered, of course, but at the moment intravenous seems reasonable.

I have not looked at the chemical structures of other drugs in clinical trials. That would be worth doing.

Most of the work being done on alternative delivery methods seems to be in the pre-clinical stage, so is years away from reaching the market.

The Fall 2003 newsletter from the Foundation Fighting Blindness had a synopsis of news from the May meeting of the annual meeting for the Association for Research in Vision and Opthamology (ARVO). This included the following (written by Tom Hoglund; all typographical errors are my own):

>>Pharmaceutical Therapies and Drug Delivery

Dr. Rong Wen from the Foundation's Research Center at the University of Pennsylvania is testing a new and powerful survival factor called Oncostatin M (OSM). This substance provided long-term rescue of photoreceptors in an RP animal model. OSM joins a long list of promising drug therapies for RP. Unfortunately, advancing these drugs to clinical trials has been hampered by a lack of a safe and effective drug delivery method. MOST DRUGS CANNOT CROSS THE BLOOD/RETINA BARRIER AND SO THEY MUST BE DELIVERED DIRECTLY INTO THE EYE. [emphasis added] ARVO devoted three sessions to drug delivery.

Several groups presented work on delivering drugs through the sclera. The sclera is the white of the eye and is thought to be porius enough to allow even large proteins through to the retina. Various approaches were presented including drug patches that sit in the eyelid or eyesocket and rest against the sclera.

Another transcleral approach, called iontophoresis, which relies on electrical current to pass drugs through the sclera, showed promising results with delivering drugs to the retina. Placed under the eyelid along the outside corner of the eye, an electrode 'patch' transmis small electrical pulses that help transmit the drug to the retina. Transceral drug delivery does not require invasive procedures to deliver the drug and may prove valuable for certain types of drugs.

Researchers from Neurotech presented results with their implantable drug delivery system calles Encapsulated Cell Techmology (ECT) (see story page 1). In collaboration with The Foundation, the ECT device with CNTF slowed vision loss in animal models of RP. In more recent work, Neurotech evaluated cell lines that produced high and low amounts of CNTF for over a year. The study bodes well for effective long-term delivery of CNTF in patients.

Althogh it is difficult to condense all of the research presented at ARVO into a brief article, this thumbnail sketch should convey a sense of the many scientific avenues toward finding treatments and cures for the entire famile of retinal degenerative diseases.<<