Merrimack Pharmaceuticals Presents Promising Phase I Clinical Data
for Novel Agent to Treat HER2-positive Breast Cancer and
Preclinical Data on Companion Diagnostic
CAMBRIDGE, Mass., Dec. 10,
2012 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (NASDAQ:
MACK) today announced Phase I clinical trial results for MM-302,
the company's novel agent for the treatment of advanced HER2
positive (HER2+ or ErbB2+) breast cancer. The findings demonstrated
preliminary safety and tolerability. A study of its potential
companion imaging diagnostic was shown to predict treatment
response in preclinical models. Data were presented at the 2012
CTRC-AACR San Antonio Breast Cancer Symposium, Dec. 4-8, 2012 in San
Antonio, Texas.
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MM-302 is a nanotherapeutic encapsulation of the anthracycline
chemotherapy agent doxorubicin with anti-HER2 antibody fragments
attached to its surface. Anthracyclines have known cardiotoxicities
which historically have restricted their use in combination with
HER2-targeted therapies.
"We are highly encouraged by these results. MM-302 was
engineered to be a more effective treatment than free doxorubicin
and to address the safety concerns associated with the traditional
chemotherapy," said Ulrik B.
Nielsen, Co-Founder and Chief Scientific Officer, Merrimack
Pharmaceuticals. "We've encapsulated doxorubicin in a liposomal
membrane that is designed to travel through the blood to the tumor
cell with limited uptake into normal tissue such as heart tissue.
When it arrives at the tumor cell, the antibodies on the outside of
the encapsulated medicine bind to the HER2 receptor and pull the
medicine inside the cell, allowing the chemotherapy to be delivered
locally within the tumor."
Merrimack is developing an image-based companion diagnostic,
MM-DX-929, to predict response to liposomal chemotherapeutics, such
as MM-302. A preclinical study presented at SABCS showed that tumor
uptake of MM-DX-929 correlated well with treatment response to
MM-302.
METHODOLOGY AND RESULTS
A Phase I Study of MM-302, a HER2-targeted Liposomal
Doxorubicin, in Patients with Advanced, HER2-positive (HER2+)
Breast Cancer (Abstract #: P5-18-09)
- To evaluate the safety and tolerability of MM-302, 34 patients
with histologically confirmed HER2+ metastatic breast cancer were
enrolled. Patients had received a median of seven prior
therapies. The study used a standard 3 + 3 dose escalation
design to determine the Phase II dose of MM-302. Patients
were enrolled across five dose levels ranging from 8
mg/m2 to 50mg/m2 given every 4 weeks.
- Overall MM-302 was well tolerated. The most frequent adverse
events were fatigue (47%), nausea (41%) and decreased appetite
(31%). Four patients had grade 3 or 4 toxicities. No dose
limiting toxicities were observed and none of the patients treated
thus far has had a decrease in cardiac ejection fraction.
- Of the 22 evaluable patients in this heavily pretreated patient
population, 12 patients achieved stable disease (SD) and two
patients achieved a partial response (PR), resulting in a clinical
benefit rate of 64%. One of the patients who achieved a PR
had a 100% regression of their target lesion.
A Novel 64Cu-Liposomal PET Agent (MM-DX-929) Predicts
Response to Liposomal Chemotherapeutics in Preclinical Breast
Cancer Models (Abstract #: P4-02-05)
- Preclinical models bearing BT474-M3 mammary and subcutaneous
tumors were injected intravenously with MM-DX-929 prior to dosing
with MM-302. PET/CT imaging was performed at 16 hours post
MM-DX-929 injection, and tumor uptake was evaluated. Response to
treatment was quantified as tumor volume changes measured over a
2-month period by MRI.
- Tumor deposition of MM-DX-929 correlated well with treatment
response to MM-302 (Spearman correlation coefficient of -0.891 and
a p-value of 0.0004). MM-DX-929 accumulation in tumors prior to the
start of the MM-302 treatment successfully predicted improved tumor
growth inhibition following MM-302 treatment.
- These findings support further development of MM-DX-929 as a
potential diagnostic imaging agent to identify patients who are
most likely to respond to liposomal therapies.
About Merrimack Pharmaceuticals, Inc.
Merrimack Pharmaceuticals is a biopharmaceutical company
discovering, developing and preparing to commercialize innovative
medicines paired with companion diagnostics for the treatment of
serious diseases, with an initial focus on cancer. Merrimack
applies Network Biology, its proprietary systems biology-based
approach to biomedical research, throughout the research and
development process. Merrimack currently has five therapeutic
oncology candidates in clinical development.
Forward-Looking Statement
To the extent that statements contained in this press release
are not descriptions of historical facts, they are forward-looking
statements reflecting the current beliefs and expectations of
management made pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements include any statements about Merrimack's
strategy, future operations, future financial position and future
expectations and plans and prospects for Merrimack, and any other
statements containing the words "anticipate," "believe,"
"estimate," "expect," "intend," "may," "plan," "predict,"
"project," "target," "potential," "will," "would," "could,"
"should," "continue," and similar expressions. In this press
release, Merrimack's forward-looking statements include statements
about the safety and tolerability of its drug candidates and its
ability to translate clinical and preclinical data into future
clinical success. Such forward-looking statements involve
substantial risks and uncertainties that could cause Merrimack's
clinical development programs, future results, performance or
achievements to differ significantly from those expressed or
implied by the forward-looking statements. Such risks and
uncertainties include, among others, the uncertainties inherent in
the initiation of future clinical trials, availability of data from
ongoing clinical trials, expectations for regulatory approvals,
development progress of Merrimack's companion diagnostics and other
matters that could affect the availability or commercial potential
of Merrimack's drug candidates or companion diagnostics. Merrimack
undertakes no obligation to update or revise any forward-looking
statements. Forward-looking statements should not be relied upon as
representing Merrimack's views as of any date subsequent to the
date hereof. For a further description of the risks and
uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks
relating to Merrimack's business in general, see the "Risk Factors"
section of Merrimack's Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission (SEC) on November 14, 2012 and other reports Merrimack
files with the SEC.
SOURCE Merrimack Pharmaceuticals, Inc.