– MM-310 is an antibody directed nanotherapeutic (ADN) targeting the EphA2 receptor, which tumor surveys suggest is present in 50-100% of major tumor types including prostate, ovarian, bladder, gastric and lung cancers
– MM-310’s novel ADN design was developed to maximize the delivery and local activation of a newly engineered chemical entity of docetaxel as a prodrug
– MM-310 had superior antitumor activity compared to traditional docetaxel (100 days versus 40 days of full tumor regression) while significantly decreasing drug-related side effects in preclinical models
CAMBRIDGE, MA, USA I April 21, 2016 I Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) today 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. The posters can be accessed on Merrimack’s website.
“We designed MM-310 to deliver a large and sustained chemotherapy payload of Merrimack’s newly engineered docetaxel prodrug within a protective nanoliposome to the tumor site while minimizing exposure to healthy tissues, with a goal of overcoming one of the greatest challenges in cancer treatment,” said Walid Kamoun, Ph.D., Research Team Lead at Merrimack. “We also used our systems approach to choose the EphA2 target as a means of enhancing MM-310’s ability to be taken in by tumor cells and to penetrate deep into the tumor core. We are excited by MM-310’s preclinical data set and look forward to future clinical evaluation of this latest therapeutic candidate from our ADN platform.”
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.
“In an analysis of the docetaxel dose-response relationship, the data strongly suggest that the ability to deliver a higher dose of the traditional chemotherapy may lead to higher therapeutic response but also to higher toxicity. In our preclinical models, MM-310 was associated with fewer hematologic toxicities than free docetaxel and was shown to induce tumor regression or controlled tumor growth,” said Daryl Drummond, Ph.D., Vice President of Discovery at Merrimack. “We believe these data support clinical evaluation of MM-310 across multiple tumor types.”
Methodology and Results:
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.
About Merrimack
Merrimack is a fully integrated biopharmaceutical company that views cancer as a complex engineering challenge. Through systems biology, which brings together the fields of biology, computing and engineering, Merrimack aims to decrease uncertainty in drug development and clinical validation, and move discovery efforts beyond trial and error. Such an approach has the potential to make individualized treatment of patients a reality. Merrimack’s first commercial product, ONIVYDE® (irinotecan liposome injection), was approved by the U.S. FDA on October 22, 2015. With four additional candidates in clinical studies, several in preclinical development and multiple biomarkers designed to support patient selection, Merrimack is building one of the most robust oncology pipelines in the industry. For more information, please visit Merrimack’s website at www.merrimack.com or connect on Twitter at @MerrimackPharma.
SOURCE: Merrimack Pharmaceuticals
Post Views: 154
– MM-310 is an antibody directed nanotherapeutic (ADN) targeting the EphA2 receptor, which tumor surveys suggest is present in 50-100% of major tumor types including prostate, ovarian, bladder, gastric and lung cancers
– MM-310’s novel ADN design was developed to maximize the delivery and local activation of a newly engineered chemical entity of docetaxel as a prodrug
– MM-310 had superior antitumor activity compared to traditional docetaxel (100 days versus 40 days of full tumor regression) while significantly decreasing drug-related side effects in preclinical models
CAMBRIDGE, MA, USA I April 21, 2016 I Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) today 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. The posters can be accessed on Merrimack’s website.
“We designed MM-310 to deliver a large and sustained chemotherapy payload of Merrimack’s newly engineered docetaxel prodrug within a protective nanoliposome to the tumor site while minimizing exposure to healthy tissues, with a goal of overcoming one of the greatest challenges in cancer treatment,” said Walid Kamoun, Ph.D., Research Team Lead at Merrimack. “We also used our systems approach to choose the EphA2 target as a means of enhancing MM-310’s ability to be taken in by tumor cells and to penetrate deep into the tumor core. We are excited by MM-310’s preclinical data set and look forward to future clinical evaluation of this latest therapeutic candidate from our ADN platform.”
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.
“In an analysis of the docetaxel dose-response relationship, the data strongly suggest that the ability to deliver a higher dose of the traditional chemotherapy may lead to higher therapeutic response but also to higher toxicity. In our preclinical models, MM-310 was associated with fewer hematologic toxicities than free docetaxel and was shown to induce tumor regression or controlled tumor growth,” said Daryl Drummond, Ph.D., Vice President of Discovery at Merrimack. “We believe these data support clinical evaluation of MM-310 across multiple tumor types.”
Methodology and Results:
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.
About Merrimack
Merrimack is a fully integrated biopharmaceutical company that views cancer as a complex engineering challenge. Through systems biology, which brings together the fields of biology, computing and engineering, Merrimack aims to decrease uncertainty in drug development and clinical validation, and move discovery efforts beyond trial and error. Such an approach has the potential to make individualized treatment of patients a reality. Merrimack’s first commercial product, ONIVYDE® (irinotecan liposome injection), was approved by the U.S. FDA on October 22, 2015. With four additional candidates in clinical studies, several in preclinical development and multiple biomarkers designed to support patient selection, Merrimack is building one of the most robust oncology pipelines in the industry. For more information, please visit Merrimack’s website at www.merrimack.com or connect on Twitter at @MerrimackPharma.
SOURCE: Merrimack Pharmaceuticals
Post Views: 154
