Mitazalimab: Clinical drug candidate

Mitazalimab (previously ADC-1013) is an agonistic – or stimulatory – antibody that targets CD40, a receptor in the dendritic cells of the immune system, which are the cells that detect enemies such as cancer cells. Mitazalimabs activation of CD40 enables dendritic cells to stimulate the immune response’s weapons more effectively – in this case, T cells – allowing the immune system to selectively attack the cancer. Mitazalmiab has been optimized using Alligator’s unique FIND technology, with the aim of improving binding affinity. This makes it possible to achieve efficacy with very low doses. In preclinical experimental models, mitazalimabhas been shown to induce a potent tumor-targeted immune response and provide long-lasting tumor immunity. In addition, preclinical data have demonstrated how ADC-1013 can be used against multiple types of cancer.

1. The dendritic cell presents the target molecule CD40 on its surface.
2. Mitazalimab binds to CD40 and starts signaling to activate the immune systems´ beneficial T cells.
3. The T-cells are activated to kill the tumor cells.

Project status

To date, the clinical program has comprised two Phase I studies. The first study was conducted by Alligator with a focus on intratumoral administration. The results showed that clinically relevant doses of mitazalimab are well-tolerated. Further promising safety and tolerability data from a second Phase I clinical study with mitazalimab in cancer patients was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2019. The results showed that the adverse effects were mostly mild and transient. The study comprised a total of 95 patients. Doses of up to 1200 μg/kg i.v. with no premedication, and up to 2000 μg/kg with premedication proved safe and tolerable. The results also gave signs of clinical activity. Partial response was observed in one renal cancer patient, while 10 patients showed disease stability for at least six months.

Next step in the development of mitazalimab is the submission of a Phase II clinical trial application (CTA) which is planned for December 2020. The study (OPTIMIZE-1) is an open-label, multi-center trial assessing the clinical efficacy of mitazalimab in combination with chemotherapy (mFolfirinox) in patients with metastatic pancreatic cancer. The OPTIMIZE study will be performed at several clinics in Europe, with inclusion of the first patient H1 2021.