PharmaMar results for antitumoral compounds and their mechanism of action at EORTC-NCI-AACR emphasize an innovative pipeline of targeted therapies
•Targeting of eEF1A2 by antitumor drug Aplidin® reveals novel mechanism of action driving therapeutic efficacy
•A newly developed antibody-drug conjugate (ADC) combining a marine-derived agent with trastuzumab shows potent antitumoral activity in breast tumors overexpressing HER2 grown in mice
•Antitumoral activity of investigational drugs with different molecular targets in the pipeline highlights their potential in several tumor types
Barcelona, Spain, November 20, 2014: Zeltia announces that its pharmaceutical company PharmaMar, will present various abstracts at the annual symposium on Molecular Targets and Cancer Therapeutics of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR), Nov 18-21, 2014 in Barcelona. This symposium is an important forum to discuss new advances in targeted therapies for cancer and novel therapeutic strategies, such as immunomodulators and combination treatments. PharmaMar data that will be presented during the course of this event demonstrate promising compounds with targeted therapeutic profiles, and innovative strategies in the development of immunotherapies.
"Our compromise is to provide the clinician with a toolbox of first-in-class and innovative drugs. Our efforts are helping uncover how our compounds exert their antitumoral activity to optimize their efficacy and safety in patients", says José María Fdez Sousa-Faro, President of PharmaMar who will attend the symposium.
Two remarkable studies uncover how the antitneoplastic drug Aplidin® might exert its antitumoral activity in cancer cells (Abstract #334; Nov 20, 18:08 am and #345, Nov 20, 18:10 am). Biological and biophysical data using cancer cells resistant or sensitive to Aplidin® show that eukaryotic elongation factor 1A2 (eEF1A2) is physically bound to the drug Aplidin®. This direct interaction of Aplidin® with eEF1A2 mediates the efficacy of the drug against cancer cells, which involves oxidative stress and final apoptosis. Aplidin® gained orphan drug designation by the Food and Drug Administration (FDA) and the European Commission (EC) for the treatment of multiple myeloma (MM) and acute lymphoblastic leukaemia (ALL). Patients with MM have been shown to have increased amounts of eEF12A.
Following the line of investigation at PharmaMar, another abstract will show the mechanism of action of the antitumoral compound PM01183 (Abstract #47, Nov. 19, 18:08 am). The results show that in various human tumor cell lines, such as colon, lung, and cervical cancer, as well as sarcoma the drug specifically inhibits active--not basal--transcription by inducing degradation of the enzyme RNA polymerase II via the proteasome (a protein degradation system in the cell). PM01183 is an antitumoral drug that has demonstrated clinical efficacy in patients with platinum-resistant/refractory ovarian cancer. Furthermore, building on the efforts of PharmaMar to understand the mechanism of action of the drug candidates and products in the pipeline, data will show efficacy of Yondelis® and PM01183 in cells derived from patients that lack specific factors of the DNA repair mechanism NER (nucleotide excision repair) (Abstract #57, Nov. 19, 18:08 am). They have different profiles compared to other DNA binding agents, such as cisplatin and mytomycin C, highlighting a different mode of action driving their antitumoral activity.
Preclinical data on a newly developed antibody-drug conjugate (ADC) describe the structure, which combines the monoclonal antibody trastuzumab with the antitumoral agent PM050489, an inhibitor of microtubule assembly through a novel mode of action, and the antitumoral activity in tumor cell lines and mice bearing breast tumors with different trastuzumab sensitivity (Abstract #502, Nov, 21, 9:08 am). The ADC showed potent efficacy in vivo against tumors that are able to uptake the marine-derived compound PM050489.
"We are very excited to present our new therapeutic approach for ADCs using marine compounds, as they are showing a promising therapeutic profile in animal models compared to standard treatment", pointed out the Director of R&D at PharmaMar Carmen Cuevas who is spearheading the research projects.
Finally, data from antitumoral studies of the investigational compound, PM060184, in patient-derived xenograft tumors in mice show efficacy at low doses in several tumor types, including breast, NSCLC and pancreas (Abstract #55, Nov. 19, 18:08 am). Early results in vitro also demonstrate substantial antitumoral activity of three marine-derived compounds against a broad panel of human tumor cell lines (Abstract #58, Nov. 19, 18:08 am).