As we wrote in a previous (and longer) post about RRx-001 (nibrozetone), we idly wondered, after having binge watched the trippy Apple TV sci-fi-thriller, Dark Matter, about the multiverse and the “what-ifs” in life, where our lead therapy, AdAPT-001, would have ended up if we hadn’t initially developed it in cancer.
The answer if we had to guess is in fibrosis since AdAPT-001, an attenuated oncolytic adenovirus, expresses a transforming growth factor beta (TGFβ) trap at high levels in the body. This trap binds to and eliminates the cytokine, TGFβ, the primary factor that drives fibrosis in most, if not all, fibrotic diseases. These diseases include cirrhosis of the liver, idiopathic pulmonary fibrosis, renal fibrosis, cardiac fibrosis, systemic sclerosis (SSc), sclerodermatous graft vs. host disease, Peyronie’s disease, Dupuytren’s disease, and macular degeneration to name but a few.
The potential advantage of AdAPT-001 over all other TGFβ inhibitors in development is that AdAPT-001 self-amplifies in the body — in other words, AdAPT-001 copies itself over and over along with the TGFβ trap that it carries. The result: only a small input dose of AdAPT-001 is required to produce large amounts of TGFβ trap. This is not only a much more cost-effective strategy to block TGFβ, but the anti-TGFβ effect should be longer lasting, and more continuous, compared to other TGFβ inhibitors, none of which self-amplify. We already know from clinical trial results in cancer that any safety concerns with AdAPT-001, and oncolytic adenoviruses in general, are minimal, so it should be straightforward to evaluate AdAPT-001 in non-cancer indications.
According to the TV show, and novel, Dark Matter, the number of multiverses is infinite, and so are the possibilities with the AdAPT adenoviral platform into which literally any DNA sequence or transgene can be inserted and expressed for the treatment of multiple diseases not just cancer or fibrosis. More on that in subsequent posts.