PROTAC is a proteolysis-inducing molecule that offers prominent advantages over traditional anti-cancer inhibitors. However, as a large molecular weight high potency API, its manufacturing is complicated due to highly toxic intermediate impurities. In this case study, Wuxi STA enabled a PROTAC candidate to IND filing in 13 months.
At the start of the project, the API research team immediately synthesized a few lab-scale batches. With these materials, pre-formulation and tox studies could proceed in parallel with continuous optimization of API processes and analytical methods.
Later, a confirmation API batch was produced for formulation development. At the same time, a non-GMP 1-kg batch was produced. After the formulation development was completed, this 1-kg non-GMP batch was used to produce the demo drug product.
Parallel to the formulation development, our drug product analytical team, besides providing continuous support, was simultaneously developing the analytical method for the drug product.
Finally, with the optimized process, 10 kilograms of GMP API were manufactured. A small portion was used to make an engineering batch. Once it was proven successful, this GMP API batch was formulated into a GMP injectable drug product. After the final release testing, the IND application was submitted in the 13th month.
This PROTAC drug candidate required 25 synthesis steps, and some of the toxic intermediates were dangerous if left as impurities in the final drug product. Yet, our experts overcame the challenges and successfully developed injectable drug products. From discovery to pre-clinic testing, our API and drug product teams streamlined their work in parallel and eventually concluded this PROTAC project in 13 months
