Merrimack Announces Encouraging Clinical Data From Expanded Phase 1 Study of MM-302 for the Treatment of Advanced HER2-Positive Breast Cancer

Planning Underway to Advance MM-302 Into Phase 2

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| Source: Merrimack Pharmaceuticals

CAMBRIDGE, Mass., Dec. 13, 2013 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced Phase 1 clinical trial results for MM-302, a novel HER2-targeted liposomal doxorubicin for the treatment of advanced HER2-positive breast cancer. Primary objectives for the trial are to assess the safety of MM-302 as a monotherapy and in combination with trastuzumab, as well as to determine the Phase 2 dose for MM-302. Data were presented at the 2013 San Antonio Breast Cancer Symposium, Dec. 10-14, 2013 in San Antonio, Texas.

Anthracyclines, particularly doxorubicin, have been an effective component of breast cancer treatment for decades, though their use is ultimately limited by cardiac toxicity. These cardiotoxic effects limit the use of traditional anthracyclines in combination with targeted therapies, such as trastuzumab, for treatment of HER2-positive breast cancer. MM-302 is specifically designed to address this issue by delivering doxorubicin to tumor cells overexpressing HER2, while minimizing uptake into normal cells, including those of the heart.

In this ongoing Phase 1 study, patients treated with MM-302 showed no signs of clinical decline in cardiac function. The most common adverse events were fatigue, nausea and decreased appetite; the rates of these events were consistent across MM-302 as a monotherapy and in combination with trastuzumab. Results from the trial also showed that patients treated with MM-302 as a monotherapy at doses of 30, 40 and 50 mg/m2 had an estimated progression free survival (PFS) of 5.6 months (95% CI: 2.8-10.9 months) and a clinical benefit response rate of 37%. Of note, 5 of 9 patients who had not been previously treated with anthracyclines had a PFS of greater than 9 months.

"We are pleased with the data for this trial and the preliminary safety profile for MM-302, particularly in regards to cardiac toxicity," said Ulrik Nielsen, Chief Scientific Officer at Merrimack. "These results are encouraging for the development of our nanoliposomal technology platform, and an important step towards successfully establishing the safety and activity profile of MM-302 in the HER2-positive breast cancer population."

A Phase 2 study for MM-302 is being planned in patients with HER2-positive breast cancer.

METHODOLOGY AND RESULTS

Assessment of Safety and Activity in an Expanded Phase 1 Study of MM-302, a HER2-targeted Liposomal Doxorubicin, in Patients with Advanced HER2-positive (HER2+) Breast Cancer (Abstract #P4-12-29)

Safety of MM-302

  • To evaluate the safety and tolerability of MM-302 both as a monotherapy and in combination with trastuzumab, 47 patients with histologically confirmed HER2-positive metastatic breast cancer were included in the analysis. Patients received a median of 4 prior therapies for metastatic disease.
  • The study first used a standard 3 + 3 dose escalation design for the monotherapy to determine a potential Phase 2 dose of MM-302. Patients were enrolled across 5 dose levels ranging from 8 mg/m2 to 50 mg/m2 given every 4 weeks. Expansion cohorts were performed at 40 and 50 mg/m2 for a total of 12 patients at each dose. Additional patients were then enrolled in arms receiving MM-302 plus trastuzumab.
  • Overall, MM-302 was well tolerated. As a monotherapy, the most frequent all-grade adverse events were fatigue (65%), nausea (59%) and decreased appetite (41%). The addition of trastuzumab did not appear to increase the incidence of adverse events observed with the monotherapy alone.
  • Neutropenia was the most common Grade 3/4 adverse event occurring in 7 patients (6 in the monotherapy arms and 1 in the combination arm). One dose limiting toxicity was observed (febrile neutropenia) and the dose was subsequently withheld; the patient went on to continue study treatment for 3 additional cycles.
  • No clinically significant declines in left ventricle ejection fraction (LVEF) were observed in patients treated with MM-302 or MM-302 plus trastuzumab, including 8 patients who had been treated with lifetime cumulative doxorubicin in excess of 500 mg/m2.

Activity data

  • Data was presented on 47 patients treated in the ongoing Phase 1 trial. Of the 27 evaluable patients who were treated with 30, 40 and 50 mg/m2 of MM-302 as a monotherapy, 1 patient achieved a complete response (CR), 3 patients achieved a partial response (PR), and 6 patients experienced stable disease (SD), resulting in a clinical benefit rate of 37%. Estimated progression free survival (PFS) was 5.6 months (95% CI: 2.8-10.9 months).
  • In anthracycline-naïve patients treated with MM-302 as a monotherapy, 4 of the 9 patients achieved a CR or PR and 5 of the 9 patients had a PFS of 9 months or more.
  • Of the 13 evaluable patients who were treated with MM-302 and trastuzumab, 4 were anthracycline-naïve. Of the 4 anthracycline-naïve patients, 2 achieved a PR and 1 experienced SD.

Imaging

  • Tumor deposition and biodistribution of MM-302 was assessed in a subset of patients using 64Cu-labeled MM-302 and positron emission tomography (PET)/computed tomography (CT).
  • Accumulation of 64Cu-labeled MM-302 was observed in metastatic lesions, including in the brain and bone.

About Merrimack

Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack applies its systems biology-based approach to biomedical research throughout the research and development process. Merrimack currently has six targeted therapeutic oncology therapeutics in clinical development. For more information, please visit Merrimack's website at www.merrimackpharma.com.

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 potential effectiveness and tolerability of MM-302 as a monotherapy and in combination with trastuzumab in certain patient populations or subpopulations, its ability to develop a predictive diagnostic or imaging agent and its ability to translate clinical 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 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 8, 2013 and other reports Merrimack files with the SEC.

Investor Contact:

Geoffrey Grande, CFA
Merrimack
617-441-7602


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