RESEARCH FIELD
3D011
Back3D011
3D011 is an in-house discovered tyrosine kinase inhibitor (TKI) prodrug that will be developed as monotherapy and in combination with other agents for the treatment of solid tumors. We received IND approval from the NMPA in January 2021, and we initiated this Phase I clinical trial in February 2022. On June 7, 2022, a U.S. patent for 3D011 was granted by the United States Patent and Trademark Office. On December 28, 2022, a European patent for 3D011 was granted by European Patent Office. As of the date of this report, we are conducting an open-label, single-arm Phase I dose-escalation and dose-expansion clinical trial in patients with advanced solid tumors.
Multi-target Anti-angiogenesis Small Molecule Prodrug
Abnormal neovascularization, a hallmark of solid tumors, plays a key role in tumor progression. ABT-869 (Linifanib) is an oral multi-target drug, which significantly inhibits angiogenesis-related kinases including VEGFRs, PDGFRs, CSF1R, c-KIT and FLT1/3. Clinical trials of ABT-869 has demonstrated anti-tumor efficacy comparable to similar products, but also high systemic toxicity. To improve its pharmacokinetic characteristics and reduce its systemic toxicity, we have designed a prodrug - 3D011, which is formed by linking ABT-869 and a specific pentapeptide (Asp-Glu4) with a linker (dodecylic acid). 3D011 is stable in vitro, but the linker and the specific pentapeptide could be degraded in vivo by tissue-specific proteases and hydrolases, releasing the active molecule ABT-869 (Linifanib) at the tumor site. Preclinical studies have demonstrated that 3D011 has anti-tumor activity comparable to ABT-869 and less toxicity at the same dose. A series of pre-clinical studies of 3D011, including in vivo and in vitro pharmacokinetic studies, pharmacokinetic/toxicokinetics studies, and safety pharmacology studies have been completed to support clinical trials in patients with advanced tumors.
