Monday, May 5, 2025
5/5/2025
Intratumoral immunotherapy with formulated resiquimod for metastatic melanoma - PROJECT SUMMARY Malignant melanoma is one of the most aggressive types of skin cancer, causing a large majority of skin-cancer related deaths worldwide. The combination of anti-PD-1 and anti-CTLA-4 is FDA approved for metastatic melanoma and shows better efficacy than any single agent alone. Unfortunately, the incidence of high-grade immune-related adverse events (irAEs) due to anti-CTLA-4 is approaching 50%. There is a pressing clinical need to develop therapeutic agents that may enhance the therapeutic effect of anti-PD1 therapy without significantly increasing toxicity in cancer patients. CureBiotech is aimed to develop an efficacious intratumoral immunotherapeutic drug that can treat metastatic melanoma by itself and in combination with anti-PD1 therapy. Resiquimod is a toll-like receptors (TLR) 7 and 8 agonist. It is a second generation imidazoquinoline that is 100 time more potent than imiquimod (Aldara). Using a phase I SBIR grant, CureBiotech has developed two proprietary hydrogel based injectable formulations for resiquimod. The formulations were designed to confine resiquimod locally in the tumor to decrease systemic cytokine release symptoms;; and to be penetrate better fibrotic tumor stroma to allow a stronger host immune response. Our preliminary data demonstrates that resiquimod treatment not only inhibited melanoma growth, but also suppressed lymph node metastasis. Resiquimod increases the number of intra-tumoral CD45+ leukocytes and enhances the proliferation and function of tumor antigen recognizing CD8+ effector T-cells. Resiquimod shows synergistic effect in inhibiting melanoma growth when combined with anti-PD1 therapy. This SBIR phase II project is aimed to 1) study PD/PK of the formulated injectable resiquimod in melanoma mouse models;; 2) optimize dose/frequency/timing of formulated resiquimod in combination with anti-PD1 therapy for melanoma;; 3) perform non-clinical IND enabling studies using formulated injectable resiquimod. The deliverables proposed in this SBIR grant represent the jumping stone towards (i) submission of FDA IND application of an injectable resiquimod formulation and (ii) attracting private equity funding to support Phase I clinical trial of injectable resiquimod in patients with metastatic melanoma. CureBiotech has the business development expertise, proper intellectual property and scientific and personnel capability to achieve these aims quickly and meticulously. Results from this proposal will lay a solid foundation for FDA IND submission that will ultimately bring a novel and effective therapy to clinicians and patients in their fight against melanoma.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).