Date: 2016-04-21
Type of information: Preclinical data
phase: preclinical
Announcement: presentation of results at the 2016 American Association for Cancer Research (AACR) Annual Meeting
Company: Merrimack Pharmaceuticals (USA - MA)
Product: MM-310
Action
mechanism: antibody directed nanotherapeutic. MM-310 is an antibody directed nanotherapeutic that encapsulates a newly engineered form of the highly potent chemotherapy docetaxel as a prodrug in an ephrin receptor A2 (EphA2)-targeted liposome.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 21, 2016, Merrimack Pharmaceuticals announced positive data from preclinical studies evaluating MM-310, an antibody directed nanotherapeutic (ADN) that encapsulates a newly engineered form of the highly potent chemotherapy docetaxel as a prodrug in an ephrin receptor A2 (EphA2)-targeted liposome. Preclinical data on MM-310 were presented in an oral presentation and three poster sessions at the 2016 American Association for Cancer Research (AACR) Annual Meeting.
Key findings show that MM-310 demonstrated superior antitumor activity in multiple models compared to free docetaxel and also showed that EphA2 targeted liposomes entered and delivered the cytotoxic to the tumor cell while minimizing exposure to healthy tissues, significantly decreasing traditional docetaxel drug-related side effects, such as neutropenia, in preclinical models. EphA2 receptors are associated with poor prognosis and are shown to be overexpressed in several solid tumors, including prostate, ovarian, bladder, gastric and lung cancers.
MM-310 preclinical data include:
Several preclinical models of breast, lung and prostate cancer were used to examine the differences between MM-310 and free docetaxel. In preclinical testing, MM-310 had a significantly longer half-life than free docetaxel, with prolonged exposure at the tumor site.
Treatment with MM-310 at a dose less than one half of the maximum tolerated dose led to full tumor regression for up to 100 days with no evidence of regrowth post-treatment as compared to free docetaxel-treated tumors with a time to progression of approximately 40 days. In chronic tolerability preclinical studies, MM-310 was found to be 4-7 times better tolerated than free docetaxel, with a maximum tolerated dose of at least 120 mg/kg, compared to 20 mg/kg for free docetaxel and no detectable hematological toxicity.
Preclinical data support the hypothesis that encapsulation of a docetaxel prodrug in a stable and long circulating, targeted liposome may protect against docetaxel-induced hematologic toxicity in in vivo models. Preclinical data confirmed that MM-310 administered weekly at 40 mg/kg induced less hematologic toxicity than free docetaxel administered weekly at 10 mg/kg.
In a sampling of approximately 200 tumors, EphA2 was found to be expressed in tumor cells, myofibroblasts and tumor-associated blood vessels. EphA2 overall prevalence was found to range from 50 - 100% across multiple indications. In cell models, a high level of specificity was observed in the MM-310 EphA2-targeted liposome, with a more than 100-fold increase in liposome cell association when compared to non-targeted liposomes. EphA2-targeted liposomes were shown to bind to and penetrate EphA2 positive cells, while non-targeted liposomes showed minimal binding.
