Vuong Trieu
Oncotelic/Mateon Therapeutics, USA
Title: Trabedersen-Drug Development using phosphorothioate antisese platform
Biography
Biography: Vuong Trieu
Abstract
Using the PS antisense platform we were able to target TGF-β2 without impacting on the β1 and β3, thus avoided the toxicity related to β1 knockdown. OT-101 lifts the immunosuppression in the tumor allowing the body to recognize the tumor as foreign. Once that is in place- everything else is easy. For example- checkpoint inhibitor given to pts that don’t recognize the tumors as foreign would have no benefits.
The antisense platform has the potential of replacing small molecules and mAbs as it is a single platform with abundance of clinical safety data and requiring minimum testing for backbone toxicity- much the same way mAb was so attractive as a platform. This has allowed for rapid drug development such as Milasen- developed from lab to patient in less than year. FDA has approved many antisense drugs recently including: Fomivirsinen, Macugen, Mipomersen, Nusinersen/Spinraza, Exondys, Luxturna, Inotersen, and Patisiran. One especially high profile early failure is Oblimersen (Genesense, Genta). Poor management of Oblimersen tainted the field especially PS DNA backbone primarily because clinical trials proceeded for more than a decade including multiple phase III trials- despite marginal efficacy data due to wrong target, wrong tissue, and wrong indication. The determinants for successful PS antisense development drawing on our Trabedersen development experience are as follow: 1) Appropriate target without compensatory mechanisms. 2) Clear clinical efficacy across multiple indications. 3) Avoidance of the dreaded pCG island. 4) Target tissue should be the underlying tissues and not blood.