Development of ablative therapy for the destruction of cervical neoplasia

PROJECT SUMMARY Cervical intraepithelial neoplasia (CIN) is caused by the sexually transmitted Human Papilloma Virus (HPV), which infects 14 million women in the US every year and is the most common viral infection of the reproductive tract. Over 3 million US women are infected with oncogenic types of HPV that most commonly lead to CIN, and up to 1 million women are diagnosed with CIN each year in the US. CIN is a precancerous lesion that, if left untreated, can develop into cervical cancer. There are about 604,000 new cervical cancer cases and over 342,000 attributable deaths in 2020. This constitutes 9% of the global burden of cancer among women. Despite improvements in screening and vaccination, the rates of cervical cancer have increased globally by 45% in the last 30 years. Current treatment strategies against CIN are defined by the World Health Organization and include both ablative (cryotherapy) and excisional (loop electrosurgical excision and cold knife conization) procedures. While both have proven beneficial in treating CIN, they are associated with different limitations: cryotherapy lacks effectiveness and is limited because of the logistic constraints associated with gas cost, procurement, and storage; excisional procedures carry the risk of adverse obstetric outcomes. The need for capital equipment and the shortage of providers with the skills to use it, result in up to 80% of women diagnosed with CIN never receiving the recommended treatment. This issue of undertreatment also specifically affects black women in the US. There is thus, an unmet need for a simple, effective, and affordable technology capable of deploying treatment at point-of-care as soon as the woman is diagnosed with CIN. Gynion will address this unmet need with the Clarablex™ gel which is formulated with Trichloroacetic Acid (TCA) as the active ingredient and indicated for the destruction of oncogenic HPV and CIN. Clarablex does not require capital equipment. It will be provided in prefilled syringe cartridges and will be available for immediate use at any cervical cancer screening facility. TCA has been successfully used as a low-viscosity “water-like” solution in clinical trials as a chemical ablative agent against CIN lesions. Clarablex has an improved proprietary formulation that has a gel-like viscosity, enabling precise application to the target tissue and predictable ablation depth. This improves efficacy, enhances safety, prevents accidental spillage and damage to healthy tissue, and simplifies the procedure. The formulation is delivered with a single-use applicator that safely applies Clarablex topically on the surface of the cervix and chemically destroys neoplastic lesions during a quick 10-minute procedure. The treatment has a cost of goods of less than $10 per treatment. Preliminary research demonstrates the ability of the Clarablex to ablate cervical tissues up to 7-8 mm penetration, which is expected to be sufficient to treat even high-grade CIN lesions. The proposed SBIR Phase I study will focus on developing the cervical applicator, refinement of the gel formulation with optimized flow characteristics, and conducting ex vivo exposure studies on human uteri to demonstrate the potential effectiveness. Phase II project will assess the toxicologic and clinical safety of Clarablex.