ATT 11T

Aposense’s leading compound, ATT-11T is developed for the treatment of metastatic solid tumors such as colorectal cancer, lung cancer and ovarian cancer. The pro-drug is a conjugate of Aposense moiety with SN-38, the active metabolite of irinotecan, which is a highly potent topoisomerase I inhibitor. ATT-11T is in advanced pre-clinical development stage.

  • As demonstrated in the molecular simulation below, the original CPT-11 drug, that is devoid of the ATT moiety, does not penetrate into the membrane (lower panel). Upon conjugation to the ATT moiety (ATT-11T, a conjugate comprising the ATT moiety and CPT-11, upper panel), it enters the membrane very rapidly, and becomes embedded therein. This results in longer residence time of the drug within the body, its maintenance in an inactive stage, reduction of toxicity, and gradual release of the drug from the membrane depot to exert its effect on its target tissue, all these helping to improve drug performance.

 

  • ATT-11T has shown significant superior efficacy over irinotecan in multiple pre-clinical xenograft models, including colon carcinoma, melanoma, ovarian carcinoma, and small cell lung carcinoma. Moreover, ATT-11T has unique bio-distribution and pharmacokinetic profiles:
  • Pre-clinical studies in several animal species demonstrated a marked extension of the plasma half-life (t1/2) of both the pro-drug (ATT-11T) and the active metabolite (SN-38).
  • Bio-distribution studies in rodents indicated that ATT-11T forms an inactive depot of the pro-drug, from which it is slowly released, to be subsequently selectively transformed into the active SN-38 within moiety the tumor target tissue.
  • Due to its tumor targeted selectivity, ATT-11T circumvents the high toxicity of SN-38 derived drugs caused by its nonspecific cytotoxic effect on healthy tissues. Preliminary toxicology studies in rats and dogs indicated a favorable safety profile, related to the selective activation of the pro-drug at the tumor site.

 

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