RX-0201 (Archexin®)

Archexin® – A Potential Best-in-Class Akt-1 Inhibitor

Archexin is a unique antisense oncology drug candidate that specifically inhibits the cancer cell signaling protein Akt-1, which is highly overexpressed in cancer cells. Archexin is the only specific inhibitor of Akt-1 in clinical development. The activated form of Akt-1, which is involved in cancer cell growth, survival, angiogenesis, and drug resistance, has been shown to be present or elevated in more than 12 different human cancer cell lines, including pancreatic and renal cell carcinoma.

We believe the overall safety profile of Archexin may be superior to existing cytotoxic compounds and chemotherapeutic drugs that affect growth in both cancerous and non-cancerous cells. In two clinical trials, Archexin appeared to be safe and well tolerated at all dose levels tested with no dose-limiting toxicities. The FDA has granted Orphan Drug Designation to Archexin in the treatment of five cancers: renal cell, pancreatic, ovarian, stomach, and glioblastoma.

Rexahn is currently conducting a Phase IIa clinical trial of Archexin in patients with metastatic renal cell carcinoma (RCC). This is a multi-center study designed to evaluate the efficacy of Archexin in combination with everolimus to treat metastatic renal cell carcinoma patients. This trial is being conducted in two stages. The first stage is a dose ranging study to determine the maximum tolerated dose of Archexin in combination with everolimus. The first stage of the study was completed in 2015 and a maximum tolerated dose of Archexin was identified for further study.

The results from Stage 1 of the Phase IIa clinical trial showed that in mRCC patients that have previously received multiple anti-cancer therapies, Archexin treatment produced both stable disease (which persisted for up to 383 days) and a reduction in tumor burden. Compared to baseline CT scans, three patients experienced reductions in the size of their tumors of up to 36%. At the lowest dose level of Archexin administered (125 mg/m2/day) one patient had a 16% tumor reduction after four cycles of treatment. At the second dose level (200 mg/m2/day) one patient experienced a 36% tumor reduction after two cycles of treatment. At the highest dose level (250 mg/m2/day), which has been determined to be the maximum tolerated dose, one patient had a 32% tumor reduction following six cycles of treatment.

In the present study Archexin appeared to be safe and well tolerated at each of the dose levels tested with no dose limiting adverse events. The most commonly reported adverse event in patients taking the combination of Archexin and everolimus was thrombocytopenia.

Stage 2 of the Phase IIa clinical study, which commenced enrolling patients in 2016, is a randomized, open-label, two-arm dose expansion study of Archexin in combination with everolimus, versus everolimus alone, to determine safety and efficacy of the combination. The trial is anticipated to enroll up to 30 metastatic RCC patients who will be randomized to receive either Archexin in combination with everolimus, or everolimus alone, in a ratio of 2:1. The maximum tolerated dose of 250 mg/m2/day of Archexin – identified in Stage 1, will be administered along with 10 mg of everolimus versus 10 mg everolimus alone.

The primary endpoint of Stage 2 is the percentage of progression free patients following eight cycles of therapy. Patients are scanned (CT or MRI) for the assessment of tumor progression after every 2 cycles of therapy. Secondary endpoints include pharmacokinetic profile, incidence of adverse events, changes in clinical laboratory tests and vital signs over time, tumor response, duration of response, time to response, and response rate. Exploratory endpoints include blood levels of AKT pathway biomarkers, tumor apoptosis biomarkers, or other relevant biomarkers.

Heejeong Yoon et. al. Antitumor activity of a novel antisense oligonucleotide against Akt1. Journal of Cellular Biochemistry. 2009 (108): 832 – 838.