On Nov. 5, 2018, Pascal Biosciences announced the peer reviewed publication of their licensed cannabinoid-derived drug program for glioblastoma in the European Journal of Medicinal Chemistry, a peer reviewed journal.

The findings, titled: “Modified carbazoles destabilize microtubules and kill glioblastoma multiform cells,” summarize research headed by Dr. Nephi Stella, founder and co-director of the University of Washington Center for Cannabis Research. This work details the discovery of compounds based on cannabinoids, and follows their chemical optimization into potent tumor killing agents.

ST-403 is a mitosis inhibitor that blocks cell division. Drugs of this class disrupt microtubules, which are the structures that pull chromosomes apart during cell division. There are several mitotic inhibitors approved for cancer treatment, including paclitaxel and vinblastine, and they have substantial benefit on solid tumors when combined with other chemotherapeutics. However, unlike ST-403, none of these agents cross the blood brain barrier and therefore have no activity on glioblastoma or other brain cancers.

Glioblastoma multiforme is a devastating disease for patients with limited treatment options due to the high rate of recurrence and aggressive tumor growth. According to the National Brain Tumor Society, glioblastoma strikes about 15,000 patients each year in North America with a median survival rate of 12 to 17 months. Therapies to treat glioblastoma are limited to surgery, radiation and chemotherapy, and more recently tumor treating fields.

The only chemotherapeutic approved for glioblastoma is temozolomide, which was developed over 50 years ago and extends survival by only two months. Temozolomide kills tumor cells by causing DNA damage, a mechanism that is different from ST compounds. Temozolomide is now off patent protection, but previously had sales over $1B per year, so the commercial potential of ST-403 may be significant.