The goal of this project is to deliver an affordable immunotherapy to treat advanced cervical cancer in low- and middle-income countries (LMICs) and low-resource settings in the U.S. A longer-term goal is to treat earlier stages of cervical dysplasia and assess immunity to the causative agent, human papillomavirus (HPV). The heavy burden of suffering and death from cervical cancer disproportionately falls on women in resource poor settings. Overcoming barriers to treatment, i.e. lack of infrastructure, trained specialists, specialized equipment, cold chain, and financial resources, requires a paradigm shift in the approach to treatment that can be achieved by the innovative immunotherapeutic agent proposed here. IFx-Hu2.1 (SN63/016,700) is a cream-based therapeutic immunomodulator that will be optimized for stability and performance. Our IFx-Hu2 family contains a plasmid DNA (pDNA) bulk drug substance, which can be produced for a fraction of the cost of current immunotherapies. The pDNA encodes a complex bacterial antigen, Emm55. When expressed on the tumor cell surface, Emm55 attracts antigen presenting cells and other cells of the innate immune response. Non-self-epitopes such as tumor and HPV antigens are then exposed in such a way as to set up multi-antigenic cellular and humoral adaptive immune responses. Emm55-based therapies induce personalized, multivalent, systemic, and sustained immune responses and have the potential to treat a broad range of cancers through enhanced tumor recognition, immune activation and epitope spreading. Intralesional injection of IFx-Hu2.0 has an established safety profile in multiple animal studies and is currently being tested in Phase 1 human clinical trials for cutaneous melanoma, Merkel cell carcinoma and cutaneous squamous cell carcinoma. Our preliminary clinical data corroborate pre-clinical observations, showing the activation of T- and B-cell immune responses and tumor reduction, with no short or long-term adverse effects. We propose to optimize the IFx-Hu2.1 formulation for temperature stability using established methods and models. In vitro evaluation, to include standard quality control methods and a human vaginal epithelium carcinoma model, will be followed by in vivo uptake, expression, and disease progression studies in a mouse model of cervical cancer. Room temperature storage and self-administration will circumvent onerous clinic visits, improve prognosis and preserve fertility. IFx-Hu2.1 cream formulation will provide a non-toxic cancer therapeutic treatment with minimal supportive care requirements, featuring unique delivery, and high applicability/impact to underserved populations. The data obtained by completing these studies will position Morphogenesis, Inc. to submit an Investigational New Drug application to conduct a clinical trial for women in a local community hospital (low-resource setting) and in South Africa (LMIC). These trials will be the objective of an SBIR Phase 2 proposal.

This proposal optimizes IFx-Hu2.1, a therapeutic, cream-formulated immunomodulator, for temperature stability. The optimized formulation will be a non-toxic, affordable, commercially viable immunotherapy that is amenable to self-administration. These attributes are necessary to overcome barriers to treating advanced cervical cancer in low- and middle- income countries and low-resource settings in the U.S.