Cytotoxicity of Synthesized EPD (EPD-S), A Natural Sesquiterpene Lacton, and its Future Clinical Efficacy
Background
Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with paclitaxel and cisplatin. Although initial a favorable response, relapses are common and prognosis stays poor.
A plant, Calomeria amaranthoides of the family Asteraceae, endemic to Australia, has been collected in the Blue Mountains (NSW). Asteraceae are known for their natural active compounds, including sesquiterpene lactones (SL’s) which are known for their potential as anti-cancer agents.
This new anti-cancer drug, Eremophilanolides-1-(10)-11(13)-dien-12,8β-olide or EPD, has been proven a very interesting anti-cancer drug. It has exhibited potent cytotoxic effects towards ovarian cancer and other cancers, like melanoma, sarcoma, colon, thyroid, leukemia, breast, but not towards normal cells.
Technology
Most of the experiments have been performed “in vitro”, using the IC50
tests on ovarian cancer cell lines, but also on other cancer cell lines. A
study with nude mice showed that EPD did better than cisplatin, used as
a positive control.
Since EPD has been synthesized by Syncom, (Groningen) (EPD-S) it hasbeen studied by Oncolines and Oncolines Profiler by The Netherlands Translational Research Center (NTRC, Oss, The Netherlands).
Not only has EPD-S been proven cytotoxic on its own, it also has shown strong synergism with paclitaxel and cisplatin in resistant ovarian cancer
cell lines and other cancer cell lines. EPD, in combination with cisplatin, was studied in cell lines with a BRCA1 mutation. In comparison with
olaparib (medication for patients with BRCA1 mutation), showed EPD-S
much stronger chemosensitivity. EPD –S is blocking the pathway of NF-kβ, with apoptosis as result.
Value Proposition
The global Ovarian Cancer market size alone is expected to gain market
growth in the forecast period of 2020 to 2025, with a CAGR of 9.0% in the forecast period of 2020 to 2025 and will expected to reach USD 2382
million by 2025, from USD 1684.4 million in 2019 (https://www.marketwatch.com/).
Team
Dr Caroline van Haaften is the sole inventor of the technology, and she
currently holds the position as Head of Carocell Nederland B.V.
Key benefits
- Strong synergism with paclitaxel and cisplatin.
- Application in high risk children (for asthma/allergy) as primary/secondary prevention strategies.
Applications
- Novel anti- cancer drug for ovarian cancer treatment.
- Might be applicable to other cancer types.
Patent status
This technology is subject of several international patent applications for both EPD and EPD-S alone, as well as in combination with other drugs (Paclitaxel, cisplatin, olaparib):
AUS: P85397AUOO (GRANTED); P103934AUOO (GRANTED); one filed
NL: P92032NLOO (GRANTED), P103934NLOO (GRANTED); one filed
EP: P109498EPOO (GRANTED)
US: P92032USOO (GRANTED); P85397USOO (GRANTED); P109498USOO (PUBLISHED)
CN: P85397CNOO (GRANTED)
JP: P109498JPOO (PUBLISHED)
CAN: Priority application filed