Targeted Therapy with HDP-101: Overcoming Drug Resistance in Multiple Myeloma

A new type of antibody-drug conjugate (ADC) is being tested for blood cancers. Most ADCs use a few toxic compounds that target fast-growing cells, but this new ADC, called an ATAC (antibody-targeted Amanitin conjugate), uses amanitin, a toxin that works differently. It attaches to a part of the cell that makes proteins and stops it from working, which can be effective even in slow-growing cancers.

The study looked at HDP-101, an ATAC that targets a protein called BCMA, which is found on certain types of immune cells and cancer cells. HDP-101 was tested on cancer cells in the lab and in animals and showed strong effects at very low doses. It did not harm normal cells or cancer cells that did not have the BCMA protein. In animal models, HDP-101 caused tumors to shrink and in some cases disappear after a single dose.

Tests in monkeys showed that HDP-101 was well-tolerated and safe, with only minor and temporary effects on liver enzymes and a certain chemical in the blood. The drug stayed in the blood for about 12 days, and the free toxin was found at very low levels.

The study concludes that HDP-101 is a promising new approach for treating multiple myeloma, a type of blood cancer, because it works in a different way than other drugs. It could help overcome resistance to other treatments and improve outcomes for patients. The first human trial for HDP-101 is expected to start soon.

Several authors of the study are employed by Heidelberg Pharma GMBH and have stock options in the company. Other authors have various connections to different pharmaceutical companies.