Rakuten Medical and Merck KGaA, Darmstadt, Germany have signed a multi-year agreement under which Merck provides cetuximab to Rakuten Medical for the manufacturing of ASP-1929, an investigational antibody-dye conjugate, being studied for the treatment of recurrent, locoregional head and neck cancers. based on the agreement, Rakuten Medical may use cetuximab to produce ASP-1929 for clinical trials and commercial sales.

ASP-1929 is a novel anti-cancer approach based on near-infrared photoimmunotherapy or NIR-PIT. [1]

Cetuximab is the antibody component ASP-1929.

Earlier this year, during the World Economic Forum in Davos, Rakuten Medical and Merck, memorialized their intent to join forces to explore ways to help patients conquer cancer.

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“Rakuten Medical is excited to partner with Merck KGaA,” noted Hiroshi Mikitani, Chairman and Chief Executive Officer of Rakuten Medical.

“We’re committed to partnering with world-class companies such as Merck in order to carry forward its mission to conquer cancer.”

A different approach
Near-infrared photoimmunotherapy or NIR-PIT is a hybrid cancer therapy that directly kills cancer cells as well as producing a therapeutic host immune response. The approach is different than conventional immunotherapies, such as immune-activating cytokine therapy, checkpoint inhibition, engineered T-cells, and suppressor cell depletion. These therapies do not directly destroy cancer cells but rely exclusively on activating the immune system. In contrast, NIR-PIT selectively destroys cancer cells, leading to immunogenic cell death that initiates local immune reactions to released cancer antigens from dying cancer cells. These are characterized by rapid maturation of dendritic cells and priming of multi-clonal cancer-specific cytotoxic T-cells that kill cells that escaped the initial direct effects of NIR-PIT.[1]

ASP-1929 MOA
ASP-1929 links cetuximab and a light activatable dye, IRDye® 700DX. The investigational agent is based on the company’s Illuminox™ technology platform. Cetuximab, an antibody, targets and binds specifically to the epidermal growth factor receptors (EGFR), which are overexpressed in several solid tumors, including head and neck cancer, esophageal cancer, lung cancer, colon cancer, and pancreatic cancer.

After binding to EGFR-expressing cancer cells, ASP-1929 is locally activated by non-thermal red light (690 nm) illumination emitted by an investigational laser device system. Pre-clinical data indicate that the illumination of ASP-1929 induces a biophysical process that compromises cell membrane integrity, leading to cancer cell death and tumor necrosis.

ASP-1929, has achieved Fast Track designation from the FDA and Sakigake Designation from the Japanese Ministry of Health, Labour, and Welfare and is currently under investigation in a global phase III clinical trial for recurrent head and neck cancer.

The Illuminox™ platform which forms the technology backbone for ASP-1929, is an investigational platform based on a cancer therapy called near-infrared photoimmunotherapy or NIR-PIT, which was developed by Hisataka Kobayashi, M.D., Ph.D., and a team from the National Cancer Institute (NCI) in the United States.[1]

Clinical trials
Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy – NCT03769506
Phase 1b/2, Open-label Study of ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors – NCT04305795

[1] Kobayashi H, Furusawa A, Rosenberg A, Choyke PL. Near-infrared photoimmunotherapy of cancer: a new approach that kills cancer cells and enhances anti-cancer host immunity [published online ahead of print, 2020 Jun 4]. Int Immunol. 2020;dxaa037. doi:10.1093/intimm/dxaa037

Feature Image. Courtesy: © Rakuten Medical (Aspyrian Therapeutics) 11189 Sorrento Valley Rd. #104, San Diego, CA, 92121, USA.

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