Some coverage in China This was published today at pharmacub.com a chicness site. Good to see THTX’s PDC get some coverage in china. Note the original article was translated by google so there are some misspellings.
1. TH1902
SORT1, also known as neuroblastatic receptor 3, is a membrane binding receptor that belongs to the VPS10P receptor family. SORT1 plays a different role in transporting and sorting various ligands within cells, including neurohypertensives, granuloid precursors, and lipoprotein E. On the other hand, an increase in SORT1 has also been observed in many types of human cancers, such as breast, ovarian, pancreatic and melanoma, and pituitary adenoma. In particular, SORT1 is expressed on 59 percent of TNBC and can also be a therapeutic target for TNBC.
Thera technologies has developed the PDC drug TH1902 for THERT1 receptors. In the structural form of the drug, TH1902 should be regarded as a conventional conjugate drug form. At present, TH1902 has entered the clinical Phase I study, plan Q4 to release early safety and efficacy data. In early 2021, the FDA also awarded fast-track certification for TH1902 single-drug treatment standard therapy for refractor-positive sortilin-positive recurrent advanced solid tumors.
The peptide molecules in TH1902 target the SORT1 protein expressed in a variety of cancers, and the lysable Linker links polypeptides to toxic loads of dositsa.
n terms of mechanism of action, TH1902 applies the "key theory" to conjugate drugs and competitively binds to the target SORT1.
Another similarity between PDC drugs and ADC drugs is the precise release of payloads, reducing exposure to normal tissues, and improving tolerance and efficacy. In a sense, conjugate drugs are also like a class of drug delivery techniques. Preclinical research data from TH1902 do illustrate this nature.
From the results, TH1902 is composed of docetamol and peptide molecules in a 2:1 ratio through Linker( succinic acid), through sorting protein dependence mechanism into cells, can effectively bypass the P-pg excretion pump (MDR1) action, improve intracellular concentration, achieve better tumor migration and growth inhibition.
For TH1902, the value of peptide molecules is like albumin in albumin yew alcohol, which can be said to open up a new delivery technology. By reducing the accumulation of normal tissues and reducing side effects, it not only improves drug tolerance, but also expands the treatment window of the drug. The stable source and cost advantage of polypeptide molecules compared with albumin naturally need not be said, if TH1902 shows similar potential of clinical data, it is not impossible to expand the application to yew alcohol.
https://med.sina.cn/article_detail_103_2_104428.html