Combination of the anticancer drug PM1183 with PARP inhibitors and doxorubicin results in a synergistic effect against breast cancer cell lines and a SCLC mouse tumor model, respectively.
The anticancer candidate plitidepsin binds to eEF1A2, a novel therapeutic target in multiple myeloma, and shows activity in patient-derived tumor mouse models from a wide range of solid tumors and hematological cancers.
The new antibody-drug conjugate (ADC), MI130004, shows in vivo potent and long-lasting anticancer effects in breast tumors overexpressing HER2
Philadelphia, April 14, 2015: PharmaMar announces that it will present several abstracts at the American Association for Cancer Research (AACR) Annual Meeting 2015, which will take place in April 18-22 in Philadelphia. This year this important cancer forum will highlight the theme "Bringing Cancer Discoveries to Patients", which underlines the important bridge that connects research discoveries and new treatments. PharmaMar abstracts will underscore advances recently made by the Company that have uncovered new targets and therapeutic approaches and how these discoveries can slow down and in some cases block tumor progression in several tumor models.
The studies presented by the Company include the discovery of a new therapeutic target of plitidepsin, the protein eEF1A2. The drug candidate plitidepsin specifically binds to eEF1A2, inducing tumor cell killing in solid and hematological cancers. In addition, combination studies of the breakthrough drug molecule PM1183 with either PARP inhibitors or doxorubicin will be presented to highlight the synergistic effect in relevant preclinical models. Finally, a study showing the in vivo efficacy for the new ADC MI130004 in breast tumor models overexpressing HER-2 will be presented, which strongly suggest the clinical potential of this product candidate.
"Our priority remains improving lives and treatment outcomes for patients with cancer. We are committed to the discovery of new targets and innovative therapeutic options." says Carmen Cuevas, PhD, R&D Director at PharmaMar. "The new data we are presenting on PM1183 demonstrate that we are identifying new mechanisms of action."
Studies to be presented at AACR 2015
PM1183 The anticancer therapy PM1183 selectively targets activated transcription, as previously shown at the EORTC-NCI AACR 2014 (abstract #47) and blocks the DNA repair pathway called nucleotide excision repair (NER), eventually leading to an accumulation of DNA errors and cell death. Synergistic combination of PM1183 and PARP inhibitors in breast cancer tumor cell lines (Abstract #2520). Poster presentation, Session Experimental and Molecular Therapeutics - Combination Chemotherapy 1, Monday, April 20th, 1:00 PM - 5:00 PM, Poster section 27
Lead author Juan Fernando Martinez-Leal, PhD will be at the AACR to address the media
Building on its mechanism of action targeting DNA repair, PharmaMar is presenting the synergistic activity of PM1183 in combination with PARP inhibitors, which targets a different DNA repair. These data are encouraging as the combination therapy of PM1183 with PARP inhibitors may be used to increase tumor cell killing in breast cancer. Combination of PM1183 with doxorubicin induces a synergistic antitumor activity in SCLC tumor xenografts (Abstract #2542). Poster presentation, Session Experimental and Molecular Therapeutics - Combination Chemotherapy 1, Monday, April 20th, 1:00 PM - 5:00 PM, Poster section 27
Lead author Pablo Avilés, PhD will be at the AACR to address the media
The data from this study in mice bearing SCLC tumors show that the combination of PM1183 with the chemotherapeutic doxorubicin induces synergistic antitumor activity. These data have provided the rationale for the start of a clinical study with this combination treatment in patients with SCLC.
Plitidepsin (Aplidin®) The phase 3 study evaluating the efficacy of plitidepsin with dexamethasone in patients with refractory/relapsed multiple myeloma is close to completion and the drug is currently being investigated in the clinic in a subtype of T-cell lymphoma. Plitidepsin shows antitumor activity in patient-derived tumor xenografts and hematologic malignancies (Abstract #5252). Poster presentation, Session Experimental and Molecular Therapeutics - Novel Targets 1, Tuesday, April 21st, 1:00 PM - 5:00 PM, Poster section 30
Lead author Heiner FiebigL, MD, PhD will be at the AACR to address the media
Data from this study show the antitumor activity of plitidepsin in 23 different tumor types, both solid and hematologic cancers. The broad anticancer activity of plitidipesin across different tumor types is opening new avenues for future clinical studies in different tumor types eEF1A2 is a new target for anticancer therapy (Abstract #5430). Poster presentation, Session Experimental and Molecular Therapeutics - New Targets 2/Novel Assay Technologies, Wednesday, April 22nd, 8:00 AM - 12:00 PM, Poster section 31
Lead author Luis Francisco García-Fernández, PhD will be at the AACR to address the media
This study further describes how plitidepsin directly interacts with the novel target, the protein eEF1A2, which was recently identified. This protein is overexpressed in tumors, including multiple myeloma. The data support the role of this protein as a novel molecular target in cancer.
ADC MI130004 A recent breakthrough of the Company is the development of a new ADC, MI130004, which combines the HER2-targeting monoclonal antibody trastuzumab with the marine-derived anticancer agent PM050489. MI130004, a new antibody-drug conjugate, induces a strong, long-lasting antitumor effect in HER2-expressing breast tumor models. (Abstract #2480). Poster presentation, Session Immunology - Antibodies/Antibody Derivatives, Monday, April 20, 1:00 PM - 5:00 PM, Poster section 25
Lead author Carmen Cuevas, PhD will be at the AACR to address the media
The data underscore the potent and long-lasting activity against HER-expressing breast tumors in mice and the effect in survival. The positive results show great promise for this product.
INFORMATION:
About PharmaMar
PharmaMar is a world leader in the discovery and development of marine-based anticancer drugs with a rich pipeline of drug candidates and a strong R&D program. PharmaMar, which is headquartered in Madrid, is a subsidiary of Zeltia, S.A., which has been listed on the Spanish Stock Exchange since 1963 (MSE: ZEL) and on Spain's Electronic Market since 1998. Currently the most advanced clinical programs are PM1183, a novel anticancer agent that prevents tumor progression through different mechanisms of action, including DNA binding to block its replication, inhibition of activated transcription and proteins involved in DNA repair, and the modulation of the tumor microenvironment; and plitidepsin, an anticancer drug that targets eEF1A2 leading to increase in apoptotic death. PM1183 is currently in late-stage development for small-cell lung cancer, BRCA1/2-mutated breast cancer and platinum-resistant ovarian cancer. Plitidepsin is in a phase 3 trial with dexamethasone for refractory multiple myelomaand in a phase 1 study in triple combination with bortezomib for this same indication.
Disclaimer
This document is a press release, not a prospectus. This document does not constitute or form part of an offering or invitation to sell or a solicitation to purchase, offer or subscribe shares of the company. Moreover, no reliance should be placed upon this document for any investment decision or contract and it does not constitute a recommendation of any type with regard to the shares of the company.
Contact:
PharmaMar Media Relations:
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Phone: +34 91 846 6108
Mobile: +34 608 93 36 77
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Phone: +34 914444500
