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Halozyme Therapeutics, Inc. Message Board

  • fezziwig2008 fezziwig2008 Aug 7, 2012 10:08 AM Flag

    Let's Just Say Cellulite has Investors Interested...

    Everyone know someone(s) "afficted"!

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      Halozyme Therapeutics, Inc.
      (Nasdaq: HALO), a biopharmaceutical company developing and commercializing
      products targeting the extracellular matrix (“Matrix”), announced the
      presentation of new pre-clinical findings on the controlled modification of
      the Matrix with HTI-501 at the European Society for Dermatological Research
      (ESDR) and Japanese Society for Investigative Dermatology (JSID).

      HTI-501 is a new recombinant human lysosomal proteinase under
      development at Halozyme that could provide an effective dermatologic
      treatment by targeting and degrading the fibrous components of the Matrix
      in a highly controlled fashion. This Matrix targeting new molecular entity
      is being explored as a potential solution for therapeutic, as well as
      aesthetic, dermatology indications for which surgery may be impractical,
      such as cellulite and certain forms of scarring.

      HTI-501 works by a process called enzymatic subscision, which involves
      degradation of fibrous septae (or cords) in a controllable and predictable
      manner to release skin tissue from the fibrous cords and smooth out the
      surface contour, which could be especially beneficial in aesthetic
      dermatology indications. Other proteinases such as collagenases are not
      generally feasible therapies for aesthetic dermatology, due to their
      persistent degradation of surrounding tissue that may create safety
      concerns or require use of sub-potent dosing regimens. As a strictly
      pH-dependent enzyme, HTI-501 may be capable of exerting its activity in a
      tightly regulated fashion.

      Key findings were as follows:

      – HTI-501 was identified as a member of the lysosomal proteinase family
      capable of degrading insoluble collagen in vitro at pH 5-6, but
      catalytically inactive at physiologic pH of 7.4.

      – By injection of pH indicators of increasing buffer strength, the study
      established that temporal-spatial pH control of the extracellular
      environment from 1-20 minutes post injection could be achieved.

      – The efficacy of HTI-501 on fibrous septae in rodent and porcine models
      was established by release of hydroxyl-proline and histologic
      evaluation in comparison with bacterial collagenase.

      – HTI-501 administration resulted in significant hydroxyproline release
      at pH 5 compared to bacterial collagenase, but not at pH 7.4.
      Importantly, skin interstitial pH returned to neutrality within 20
      minutes of the administration of HTI-501.

      “Due to strict pH dependence for enzyme activity, lysosomal proteinases
      have been largely neglected as potential therapeutic proteins due to their
      inability to digest proteins outside the lysosomal compartment in the
      cell,” said Gilbert Keller, PhD, Halozyme’s Technical Leader in
      Dermatology. “By bringing this intracellular environment to the
      extracellular matrix in a temporal fashion, our platform for controlled
      modulation of the dermal matrix may provide a novel mechanism for tightly
      controlled pharmacologic subscision of collagenous interstitial matrix.
      Additional pre-clinical studies are continuing on our lead candidate,

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