Technology Platform


GDEPT (Gene Directed Enzyme Prodrug Therapy)


Gene Directed Enzyme Prodrug Therapy (GDEPT) is a technology where a short acting gene therapy is used to convert a small molecule prodrug into an active drug within a target tissue. GDEPT is a onetime treatment designed to destroy an unwanted tissue. The conversion of the prodrug into the active drug is catalyzed by an enzyme, which is temporarily introduced into the target tissue via a gene carried by a non-replicating vector. Endogenous enzymes do not have the specificity of the introduced non-mammalian enzyme. The vector is first administered and after an incubation time of 2 days, the prodrug is then administered. A number of GDEPT systems are undergoing clinical development, with solid tumours being the typical target tissue. Elk's GDEPT system is a repurposed therapy. The CTL102/CB1954 GDEPT therapy completed a number of cancer trials before being applied to the unique orthopaedic problem of aseptic loosening. In the aseptic loosening application, the GDEPT therapy simply needs to remove sufficient interface tissue to allow the prosthesis to be re-fixed to the bone. The exciting aspect of this approach is that the tissue removal is achieved without the use of surgery or general anesthetics.

GDEPT Therapy

 

  1. A non-replicating Ad5 adenovirus Vector (CTL102) is administered into the joint space tissue (interface tissue) by injection. CTL102 carries the E coli NTR Gene into the interface tissue. The vector is not taken up by the bone.
  2. The E coli NTR Enzyme is expressed within the interface tissue cells.
  3. Small molecule Prodrug CB1954 administered into interface tissue 2 days after CTL102 administration.
  4. Prodrug converted into active drug within interface cells expressing NTR enzyme.
  5. Active drug kills cells, breaking up interface tissue, allowing it to be flushed out of joint space via inserted needles. Following the non-surgical removal of the interface tissue, the prostheses can then be re-attached to the bone with orthopaedic cement.

Elk’s platform technology is protected by a strong intellectual property portfolio of granted patents.