Tis 17 maj / År 40 / Nr 1 2022

Priming the Immune System to Fight Cancer

Immunicum AB (publ) has established a unique immuno-oncology approach for the treatment of cancer through the development of allogeneic, off-the-shelf cell-based therapies. Ilixadencel, the Company’s lead product, is currently being evaluated as an immune-activating therapy in clinical trials for the treatment of a range of solid tumour indications.

One defining characteristic of cancer cells is their ability to “hide” from the immune system and thereby avoid detection and subsequent destruction from immune cells. Recent discoveries in the oncology field have allowed researchers to develop therapeutics and add-on treatments that reactivate the immune system.

Targeting solid tumours
Immunicum’s approach is to create off-the-shelf cell-based therapies that boost the patient’s own immune system to fight cancer. As such, ilixadencel, is manufactured from the dendritic cells of healthy donors that have been activated to produce factors that stimulate the immune system.

Injecting ilixadencel directly into the tumour triggers a local inflammatory reaction, similar to that seen in a viral infection. This inflammation destroys tumour cells and activates the immune system against the tumour, recruiting the patient’s dendritic cells to engulf the fragments of tumour cells and the range of neoantigens (mutated antigens that are specific to the tumour). The dendritic cells then alert other immune cells in an adaptive systemic response that is personalised to the individual patient’s tumour.

“We believe that we have created an off-the-shelf agent that has potential as a therapy against a wide range of solid tumours and that requires no genetic manipulation making it simpler to manufacture, store and administer”, says Immunicum CEO Carlos de Sousa.

Combination approaches
Immunicum is currently assessing ilixadencel’s potential in a variety of solid tumours including renal cell carcinoma, hepatocellular carcinoma, gastrointestinal stromal tumours (GIST), head and neck squamous cell carcinoma, non-small cell lung cancer and gastric adenocarcinoma.

“Cancer treatments are increasingly focused on combination approaches. We believe that our approach could be used as a backbone therapy along with checkpoint inhibitors, chemotherapy and tyrosine kinase inhibitors (TKIs), such as sunitinib. One additional benefit is the excellent safety and tolerability of ilixadencel that has been demonstrated in several clinical studies to-date”.

Current key Phase Ib/II study
Ilixadencel first moved to clinical trials in 2012. The completed Phase I/II open-label study in patients with newly diagnosed metastatic renal cell carcinoma was presented in a number of papers and posters. This trial was followed by the MERECA open-label Phase II controlled study evaluating ilixadencel plus sunitinib compared with sunitinib alone in metastatic renal cell carcinoma. MERECA closed enrolment in January 2018 and positive results were disclosed during the third quarter of 2019.

“Beyond the positive news from MERECA, we now have another key Phase Ib/II study in place, known as ILIAD, which combines ilixadencel with checkpoint inhibitors, including Keytruda® (pembrolizumab), in head and neck cancer, gastric cancer and non-small cell lung cancer. The study is ongoing in the United States and will expand into Europe in the Phase II part of the study supported by our collaboration with Pfizer and Merck KgaA”, explains Carlos de Sousa.

Preclinical development programs at Immunicum include opportunities based on the IMM-2 (formerly Subcuvax-Adenovirus) and IMM-3 platforms (formerly CD70) that are currently in research and preclinical evaluation.