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Curis, Inc. Message Board

  • croumagnon croumagnon Jul 16, 2005 1:48 PM Flag

    Hedgehog Pathways: Fact or Fiction ??

    I am a relatively new investor to Curis although I have followed it and held its stock on and off over the years. I am beginning to think this stock and its technoology are a real undiscovered Gem at this point.

    THE STORY: is very appealing. It is not Stem cells and it is not old fashioned drugs. It seems to me that it is threading the most promising middle path by controlling the signals that our body genetrates to repair tissue. As such, these drugs can promote the signals in our body that repair tissue or, conversely, they can inhibit the signals that promote diseases including cancers. I do not fully understand all the nuances, but the concept is definitely very appealing.

    THE PRODUCT POTENTIAL: this is certainly huge. To start with they seem to be the only company capable of potentially curing peripheral nerve neuropathys which is a very debilitating disease. If the technology is real, then all sorts of applications follow including neurological disorders, cardiovascular, cancers, kidney diseases, etc.

    THE PARTNERSHIPS: extremely impressive and they include serious agreements with Genetech, Wyeth, and Otho-Biotech (J&J). My thought is that these companies would not have signed these agreements if the potential of the technology was not very real. These major companies are much more capable of doing proper DD that you or I.

    THE STOCK CATALYSTS: there are many including the various research products and partnerships they have. Ironically, perhaps the most promising catalyst is their newly discovered hair growth mechanism based on small molecules, which may prove to be much better than any of the other approaches and would be a huge blockbuster.

    FINANCIAL CONDITION: is adequate. They have about $45 million in cash and a burn rate of about $10 million per year. Therefore, they have ample cash for the next two years or so and also their milestone payments from their partnerships are flowing to the company at about $4 million or so per year.

    All in all, I think CRIS is a very good investment with a lot of promise and I think it is a very probable candidate for a takeover by big pharma repatriated money or by Genentech who seems to have a strong interest in that technology. The reward could be great and the risk is minimal. Additionally, lately we seem to be breaking out of our trading range and, once we cross $5, we should be off to the races as many funds will start buying this one in earnest.

    Any thoughts?

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    • Drew, nice find. Interesting collaboration....what kind of diseases do you see treated out of this?

    • Theoretically my opinion is yes. But they are also a theoretical threat to a lot of other biotech companies. Technology looks interesting. However, they NEVER talk about delivery of their modified ZFP. Usually when you add foreign proteins proteases eat them up. Do they have any vivo experiments or only cell lines? I would not consider them a threat unless they have tried it in an animal model and it appears to work. Keep me updated :) What do you think of the company?


      The ZFP in the Hh pathway still have to go through the SMO, to be activated or inactivated.

    • Probably worth a look-see, Drew. I would be interested in your impressions, particularly as they relate to any theoretical threat to the Curis IP.


    • LOL, i just googled SGMO. That is actually a company ticker. Gli members are zinc finger proteins. I am not worried about curis/dna approach. Looks interesting, I will browse their website in a little.


    • Here is where they make their molecules. It even has a little pic of Dr. Rubin.


    • ��Theoretically, would the zinc finger transcription factor pursuit (SGMO) circumvent the patents?��

      yes theoretically that would be the best way to inhibit the pathway. To try to make a long story short, let me try to explain a little about the Hh pathway. The Gli family are transcriptional activators and repressors. An activated gli is a full length protein, a repressor is a cleaved form of a member gli. Here is the catch!!!!! Ok I am a biochemist and have not studied many pathways in detail, but what I can tell is that is that most pathways create a cascade of signals amplifying the original signal. The Hh pathway seems a little different. IT SEEMS LIKE ALL GLI-HH SIGNALING GOES THROUGH THE SMO!!!!!!! So, the current theory is that a gli family has to go through SMO. If the SMO is activated by agonist, or inactivated by an antagonist then this should in theory create an active or inactive form of a Gli member. I guess there could be some sort of mutation that might cause a Gli member not able to be cleaved??? But then that also causes problems how would you inhibit a mutated Gli member? Also, for a gli member to enter the nuclease it requires other proteins. But it still has to go through the SMO. It is easier to target a membrane bound protein then a transcriptional activator/repressor. There is a patent by somebody in NY that is pending that is aimed at targeting the Gli family. It is still pending and not approved yet.

      Does that help?

    • Hi Drew,

      <<SNIP>> to cheaply activate or inactivate the pathway it seems like curis has that well covered.<<SNIP>>

      Theoretically, would the zinc finger transcription factor pursuit (SGMO) circumvent the patents?


      p.s. Over a considerable period time now I have read the both data you unearthed and the questions you posed. I am hopeful you have quite a career in front of you.

    • Drew, you are beautiful- thanks for the explanation

    • ��Drew, can you elaborate on your comment " I can tell you curis holds all the rights for chemical modulators(turning off and on the pathway)"? do you mean to say all medical applications of the HH pathway will have to go through Curis? thanks Drew- Stock��

      Stock, curis has a number of patents that can turn off or on the pathway. They have patented methods of how to create molecules that can do this. This is the key. The molecules are considered ��small molecules��, and easy to synthesize. They also have a few patents that deal with the natural Hh protein. They patented the natural Hh protein, but what they did was added or took off certain functional groups (��Lipid modifications��) to protein that changed the characteristics of the natural protein.


      Yes, to cheaply activate or inactivate the pathway it seems like curis has that well covered.

    • "By the way i_s_d_hh, are you a molecular biologist?"

      Studying Biochemist...

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