ADC-1013 is a human, monospecific, agonistic, IgG1 antibody intended for immunotherapy of cancer. The drug candidate targets the co-stimulatory receptor CD40, which is expressed on, for example, antigen-presenting dendritic cells. The dendritic cells reside in blood vessels and various tissues where they discover and digest proteins from viruses, bacteria or cancer cells. Next, the digested proteins are presented to so-called T-cells which are activated and kill the infected cells or the cancer cells. ADC-1013 activates CD40 on dendritic cells, enabling them to activate T-cells more effectively and thereby increasing the immune system's attack of the cancer. This is the primary mechanism of action of this drug candidate. In addition, since some cancer cells express CD40 on the surface, ADC-1013 may also act through a secondary mechanism of action by directly killing cancer cells.
The figure illustrates the cancer immunity cycle, describing how the immune system attacks tumors. The primary mechanism of action of ADC-1013 is activation of dendritic cells by the stimulation of the co-stimulatory receptor CD40. Dendritic cells that are activated by stimulation with ADC-1013 can effectively instruct the T-cells to find and kill tumor cells in the whole body. Since some tumor cells express CD40 on the surface, ADC-1013 may also act through a secondary mechanism of action by directly killing such tumor cells.
Preclinical studies indicate that agonistic CD40 antibody therapy can be used for treatment of several tumor types such as lymphoma, melanoma, hepatocellular carcinoma, osteosarcoma, renal cell carcinoma, breast cancer, colorectal cancer, lung cancer and bladder cancer.
A phase I study of ADC-1013 was initiated in April 2015. The study is conducted at five centers in the UK, Denmark and Sweden and will enroll up to 50 patients with metastatic cancer who will receive ADC-1013 by intratumoral or intravenous injection. It is a so-called open study, where both doctors and patients are aware that ADC-1013 is administered. The objective of the study is to identify the maximum tolerated dose and evaluate the safety. Furthermore, pharmacokinetics (drug turnover in the body), anti-tumor activity and mechanism of action of the drug candidate will be studied.
In August 2015, Alligator licensed all rights and further development of ADC-1013 to Janssen Biotech. Alligator will continue to sponsor the clinical phase I trial initiated by the Company in April 2015, whereas Janssen will sponsor all further development of ADC-1013, under the designation JNJ-64457107. On the 9 October 2016, an additional clinical phase I study strated dosing. This study includes dose escalation with JNJ-64457107 administered intravenously and is sponsored by Janssen.