MICure is a spin-off company to be founded by prof. dr. R.M. Luiten from the Academic Medical Center of the University of Amsterdam. The vision of MICure is to develop effective therapies for melanoma patients by inducing long-lasting anti-cancer immunity.
The challenge of treating melanoma patients
Melanoma is among the most aggressive forms of cancer, with 138,000 people diagnosed every year in the western world. The incidence has tripled over the last 40 years, faster than any other cancer, and continues to increase. Whereas early stage 1 melanoma has a relatively good prognosis, the survival rate drops dramatically to 60-70% for stage 2, and only 12% for advanced (stage 4) melanoma. This highlights the need of early intervention to prevent disease progression to advanced stages.
Surgery, interferon-α and chemotherapy are the hallmark for management of the disease. Zelboraf (targeting BRAF gene mutations), Yervoy (antibody targeting CTLA-4) and Keytruda (PD-1 antibody) have recently been approved for unresectable stage 3 melanoma and stage 4 melanoma. The problem remains however that therapy responses remain low to moderate or only transient and can be associated with major side effects. About 21% of melanoma are diagnosed at earlier melanoma stages 2 and 3, which have a high risk of disease progression. Interferon-α is not proven effective in these patients and other drugs are not indicated due to toxicity and low cost-effectiveness. Thus, no effective therapy is available for patients with resected stage 2 or 3 melanoma, despite the high risk of recurrence and disease progression.
Melanoma patients who develop vitiligo during immunotherapy have a significantly longer progression-free and overall survival than patients without vitiligo. The depigmentation in vitiligo is mediated by immune responses against melanocytes (pigment cells) in the skin. Since melanoma cells arise from melanocytes, the immunity found in vitiligo can also attack melanoma cells. Inducing vitiligo therefore provides a means to induce effective immunity against melanoma in patients.
MICure has developed the proprietary combination of monobenzone and immune-stimulating agents as new immune-modulating therapies to induce specific immunity against melanoma. This combination forms the powerful synergy between active induction of depigmentation with monobenzone and immune stimulating adjuvants imiquimod and CpG as enhancers for the immune response.
The lead product MIC therapy consists of topical combination of monobenzone with immune-stimulating adjuvant imiquimod and CpG injections. Preclinical proof of concept has been obtained in the gold standard model for preclinical melanoma therapy (Figure 1, van den Boorn et al, PLoS one 2010). MIC therapy has been shown to be highly selective for melanoma cells and melanocytes, with no severe toxicity to other tissues. MIC therapy induces specific anti-melanoma immunity that eradicates both melanoma cells and melanocytes, and protects against disease recurrence.
As part of ongoing clinical studies, an evaluation of the clinical effect of monobenzone and imiquimod as a local therapy for cutaneous melanoma metastases in advanced melanoma patients (stage III-IV) in a phase 2a trial (n=21) showed promising results of local clinical responses and the induction of immunity against the melanoma in the majority of patients. Results are currently finalized for publication.
R&D activities focus on the toxicity, feasibility and clinical efficacy of MIC therapy. Clinical research in melanoma patients is performed in close collaboration with the dermatologists, surgeons and medical oncologists at the NKI-AVL, renowned for its long-standing expertise in the treatment of melanoma patients and experience with new immunotherapeutic strategies.
MICure is looking for opportunities for partnering with pharma and investors to bring MIC therapy up to late clinical development. .
. Ontwerp en realisatie: Nico van Dijk Media