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.
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 (ClinicalTrials.gov: NCT02379741) of ADC-1013 was completed in March 2017. The study was a dose-escalation study involving intratumoral and intravenous administration of ADC-1013 at five clinical sites in Sweden, Denmark and the UK (ClinicalTrials.gov: NCT02379741). The study was sponsored by Alligator and included 24 patients and ten different tumor types. In January 2019, the results were published in the International Journal of Cancer, https://doi.org/10.1002/ijc.32141.
The results show that the agonistic anti-CD40 antibody ADC-1013 is safe and tolerated at clinically relevant dose levels. Furthermore, the pharmacodynamic effects and the preclinical data support the further clinical development of ADC-1013 against cancer and demonstrate the potential of ADC-1013 as a combination therapy with PD-1 targeted therapies.
In August 2015, Alligator outlicensed the global development and commercialization rights of ADC-1013/JNJ-64457107 to Janssen Biotech Inc. In October 2016, Janssen Biotech started a second phase I clinical study (ClinicalTrials: NCT02829099). This study is ongoing.