AST-008 as a monotherapy for cancer.
We believe AST-008 potentially can be used as a monotherapy to treat cancer. We have examined AST-008 in a colon cancer mouse model, as well as in a melanoma model.
Mouse colon cancer model. Mice were implanted with colon cancer tumors. Once the tumor volume reached approximately 100 mm3, the mice were treated with vehicle or varying doses of the mouse analogue of AST-008, referred to as mu-AST-008. The mu-AST-008 was administered by intratumoral injection every three days, starting on the ninth day after tumor implantation, for a total of five doses. The dose levels were 0.8, 3.2, or 6.4 mg/kg/injection. The mice were monitored for mortality, and tumor volume measurements were obtained twice weekly until day 40 of the experiment.
The mice treated with mu-AST-008 had a dose dependent increase in survival and decrease of tumor burden compared to mice receiving the vehicle. A complete clearance of the tumors was observed in animals receiving the 6.4 mg/kg/injection dose of mu-AST-008. In addition, no mice in the group receiving the high dose of mu-AST-008 had died at day 40 of the study, while all of the vehicle-treated animals died by day 33.
Intratumoral treatment with the mouse analogue of AST-008, referred to as mu-AST-008, reduces tumor volume and increases survival in a colon cancer mouse model in a dose dependent manner. * = p < 0.0001 versus vehicle on day 23.
We believe the results of this study demonstrate that AST-008 has potential as a monotherapy for cancer.
Clinical development plan for AST-008
We began subject dosing in the Phase 1 clinical trial for AST-008 in the fourth quarter of 2017. The Phase 1 clinical trial is the first-in-human clinical trial of AST-008 and will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of AST-008 by subcutaneous administration in healthy volunteers. The clinical trial is planned to be a randomized, single ascending dose, or SAD, and randomized, double-blind multiple ascending dose, or MAD, trial. Subjects will be recruited in five or more SAD cohorts. After the fourth SAD cohort, the first of three or more MAD cohorts will begin recruiting. We plan to dose a total at least 44 healthy subjects during this Phase 1 clinical trial. We expect this trial to be completed in mid-2018.
SNA targeting IL-4RA for atopic dermatitis
We are developing SNAs that target IL-4RA mRNA for the treatment of atopic dermatitis. The signaling of the cytokines IL-4 and IL-13 is believed to play a role in the pathogenesis of atopic dermatitis. Both of those cytokines require binding to the IL-4RA protein to produce inflammatory signaling.