Prexigebersen-A

Analyses of solid tumors, including ovarian and endometrial tumors, indicate that Grb2 protein is often utilized by activated or mutated tyrosine kinases to induce tumor progression. Inhibition aiming at Grb2 has high potential for success in treatment of solid tumors.

Ovarian cancer is one of the most common type of gynecologic malignancies, with approximately 50% of all cases occurring in women older than 63 years. It is the fifth most frequent cause of cancer death in women. Around 70% of patients diagnosed with ovarian cancer will have a recurrence. Recurrent ovarian cancer is treatable but rarely curable. The average duration of survival after recurrence of ovarian cancer is less than 2 years. The 5-year survival rate for patients with recurrent ovarian cancer following standard salvage chemotherapy treatment is less than 10%. Given the poor outcomes of treatment for ovarian cancer, novel drug treatments are urgently needed.

Cancer of the endometrium is the most common gynecologic malignancy in the United States. The majority of cases are diagnosed at an early stage and are amenable to treatment with surgery alone. However, approximately 50% of advanced stage endometrial cancers will recur. Recurrent endometrial cancer is incurable with currently available standard therapies. The median survival for patients with recurrent endometrial carcinoma hardly exceeds 12 months. Novel drug treatments for recurrent endometrial carcinoma are urgently needed.Prexigebersen has received orphan drug designation from the FDA and from the European Medicines Agency for AML.

Prexigebersen-A, a modified product of prexigebersen, incorporates the same drug substance as prexigebersen but has a slightly modified formulation designed to enhance nanoparticle properties for solid tumors. Preclinical studies demonstrated that prexigebersen-A effectively penetrated ovarian and endometrial tumors. Additionally, prexigebersen-A was demonstrated to reduce tumor burden both as a monotherapy and in combination with paclitaxel, a standard of care therapy for patients with advanced ovarian or endometrial cancer. A Phase I/Ib study evaluating the safety and anti-tumor effects of prexigebersen-A in combination with paclitaxel in patients with recurrent ovarian or endometrial cancer is currently underway.

Completed and Planned Studies

Bio-Path is currently conducting a Phase 1 prexigebersen-A clinical study in advanced solid tumors. The study will first evaluate the safety and efficacy of prexigebersen-A as a monotherapy in patients with advanced solid tumors, then prexigebersen-A in combination with paclitaxel in patients with recurrent ovarian or endometrial cancer. More details for this study may be found on: https://clinicaltrials.gov/ct2/show/NCT04196257.