Merrimack Pharmaceuticals Presents Phase 1 Clinical Data Supporting Four Novel Antibody Therapeutic Programs at the 2014 ASCO Annual Meeting

Planning Underway for Phase 2 Studies for MM-151 in Colorectal Cancer and MM-141 in Front Line Pancreatic Cancer

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| Source: Merrimack Pharmaceuticals

CHICAGO, June 2, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced that Phase 1 clinical data from studies of MM-151, MM-141, MM-111 and MM-121 was presented at the 2014 American Society of Cancer Oncology (ASCO) Annual Meeting. Data from these studies support the clinical advancement of Merrimack's novel antibody therapeutics.

"We are excited to announce Phase 1 results for MM-151 and MM-141 - two antibody therapeutics engineered with insights from our systems biology approach. This progress continues to support our goal of transforming cancer care by developing therapeutics that target key pathways responsible for tumor growth and survival. We look forward to initiating biomarker-directed Phase 2 studies with MM-151 and MM-141," said Ulrik Nielsen, Ph.D., Co-Founder and Chief Scientific Officer at Merrimack.

  • Preliminary results from a Phase 1 study of MM-151, a novel oligoclonal anti-EGFR antibody combination, in patients with refractory solid tumors suggested clinical activity in colorectal cancer with an acceptable safety profile consistent with EGFR inhibition. Planning is underway for a Phase 2 study testing MM-151 in colorectal cancer.
  • Merrimack's MM-141, a tetravalent bispecific antibody designed to block tumor survival signals by targeting receptor complexes containing IGF-1R and ErbB3, has completed the monotherapy arm in a Phase 1 study and reports no dose-limiting toxicities. The next step for MM-141 is anticipated to be a Phase 2 study testing MM-141 in front line pancreatic cancer.
  • Merrimack also presented a Phase 1 multi-arm study of MM-111 in combination with standard of care regimens in multiple tumor types as well as a Phase 1 study of MM-121 in combination with cetuximab and irinotecan in patients with advanced solid cancers.

To access clinical posters presented at ASCO 2014, click here.

Methodology and Results:

Preliminary Results from a Phase 1 Trial of MM-151 in Patients with Refractory Solid Tumors

MM-151 is a novel oligoclonal anti-EGFR antibody combination designed to target EGFR-driven tumor growth. Preliminary data from a Phase 1 study in patients with refractory solid tumors show that MM-151 has an acceptable safety profile and preliminary signs of clinical activity in colorectal cancer.

  • A total of 69 patients have been enrolled at escalating dose levels, with the most common tumor types including colorectal cancer (28 [41%]), non-small cell lung cancer (9 [13%]), head and neck cancers (5 [7%]), and pancreatic cancer (6 [9%]).
  • The most common adverse event seen thus far was infusion related reaction (47 [68.1%]), which was managed with premedication and an optimized infusion schedule.
  • Partial responses (PR) were observed in two colorectal cancer patients and a total of eight (29% of mCRC) patients had stable disease (SD) for greater than four months.
  • Planning is underway for a Phase 2 trial to evaluate MM-151 in colorectal cancer.

Results from the Completed Monotherapy Arm of a Phase 1 Study of MM-141 in Patients with Advanced Solid Tumors

A Phase 1 dose-escalation study in patients with advanced solid tumors tested the tolerability and safety of MM-141, a novel tetravalent bispecific antibody inhibitor which targets both IGF-1R and ErbB3. MM-141 blocks and degrades complexes containing IGF-1R and ErbB3 receptors, leading to the downstream inhibition of tumor pro-survival signaling. Preclinical studies have shown that MM-141 has higher activity compared to a mixture of separate anti-IGF-1R and ErbB3 antibodies.

  • This clinical study enrolled three arms: MM-141 as a monotherapy, MM-141 in combination with everolimus and MM-141 in combination with nab-paclitaxel and gemcitabine. Data presented at the 2014 ASCO Annual Meeting detailed the completion of the monotherapy arm.
  • There were no dose-limiting toxicities observed in the monotherapy arm at any dose level. The most common adverse events that were not deemed related to MM-141 monotherapy were vomiting, nausea, fatigue, abdominal pain and dyspnea.
  • MM-141 monotherapy showed preliminary activity with disease stabilization observed in patients with Ewing's Sarcoma and parotid gland carcinoma.
  • Planning is underway for a Phase 2 study of MM-141 in combination with nab-paclitaxel and gemcitabine in front line pancreatic cancer.

Results from a Phase 1, multi-arm study of MM-111 in combination with standard of care regimens in multiple tumor types

MM-111 is a bispecific antibody designed to inhibit HER3 (ErbB3) signaling in HER2-positive tumors. Preclinical research has shown that MM-111 restores sensitivity to chemotherapy and HER2-targeted treatment. MM-111 was tested in a Phase 1 study in combination with a variety of standard of care HER2-targeted regimens, namely: 1) capecitabine, cisplatin and trastuzumab; 2) lapatinib with or without trastuzumab; 3) paclitaxel and trastuzumab; 4) lapatinib, paclitaxel and trastuzumab; and 5) docetaxel and trastuzumab. The study enrolled patients with multiple HER2 positive tumor types, including breast, bladder, colorectal, gastric, esophageal and ovarian cancers. Each arm in the study was designed to run as a separate Phase 1 trial to address safety and tolerability of MM-111, and utilized a "3+3" design with standard dosing of the standard of care regimen.

  • A total of 86 patients with advanced HER2+ cancers were enrolled in the study.
  • The combination of MM-111 with standard HER2-directed therapy was generally feasible with standard doses for the HER2 directed therapies. Only Arm 1 required a reduction in the dose of capecitabine to 800 mg/m2 as a result of dose limiting toxicity.
  • Adverse events reported for MM-111 in combination with the standard of care HER2-targeted regimens were similar to adverse events reported for the regimens alone, which included diarrhea, fatigue, decreased appetite, neutropenia and hypokalaemia.
  • Across all dosing regimens, the overall clinical benefit rate, defined as complete response, PR and SD for at least four months, was 55% in 86 evaluable patients.
  • The combination of MM-111 and standard of care HER2 directed regimens showed clinical activity across a variety of advanced solid tumors with objective responses being observed in multiple HER2-positive tumor types.
  • MM-111 is currently in a biomarker stratified Phase 2 study testing MM-111 in combination with trastuzumab and paclitaxel in patients with advanced gastric, esophageal and gastroesophageal junction cancers.

Results from a Phase 1 Study of MM-121 in Combination with Cetuximab and Irinotecan in Patients with Advanced Cancers

This Phase 1 trial assessed the safety, tolerability and pharmacokinetic properties of MM-121 in combination with cetuximab or with cetuximab and irinotecan in patients with advanced solid cancers. MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin.

  • Patients were dosed in a standard "3+3" design with escalating doses of MM-121 and cetuximab in two groups without (n=34) or with biweekly irinotecan (n=14).
  • The most common adverse events from across the entire study included fatigue, hypomagnesemia, diarrhea and hypokalemia.
  • Across all dosing regimens, 18/48 (37.5%) of patients achieved a best overall response of SD or PR, 14/48 (29.2%) had SD, 4/48 (8.3%) had a PR. Of the four patients who had PR, two had KRAS wild-type colorectal cancer, one had cholangiocarcinoma and one had NSCLC.
  • One colorectal cancer patient previously treated with cetuximab and irinotecan achieved a PR on the MM-121/cetuximab/irinotecan combination. One head and neck cancer patient who previously received cetuximab achieved a durable response of SD on the MM-121/cetuximab combination.
  • Phase 2 doses were established for the combination of MM-121 and cetuximab and MM-121, cetuximab and irinotecan.
  • Further studies with these combinations are being evaluated.

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 seeks to gain a deeper understanding of underlying cancer biology through its systems biology-based approach and develop new insights, therapeutics and diagnostics to improve outcomes for cancer patients. Merrimack currently has six oncology therapeutics in clinical development and three additional candidates in late stage preclinical development. For more information, please visit Merrimack's website at www.merrimackpharma.com.

Forward-Looking Statements

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," "hope" and similar expressions. In this press release, Merrimack's forward-looking statements include statements about the potential effectiveness and tolerability of its investigational therapeutics in certain patient populations or subpopulations, its ability to develop a predictive diagnostic, the initiation of future clinical studies, 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, 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 May 6, 2014 and other reports Merrimack files with the SEC.

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