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Merrimack Pharmaceuticals, Inc.

Partner : Baxter International Inc. ex US

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PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) TO SEE THE OUTCOME OF THIS EVENT.

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June 17, 2014
Merrimack Pharmaceuticals Announces Oral Presentation of Additional Data Results in Phase 3 NAPOLI-1 Study at the ESMO 16th World Congress on Gastrointestinal Cancer
Company to Host Investor Conference Call at 8:00 a.m., ET, June 26, 2014
CAMBRIDGE, Mass., June 17, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced that results of the successful Phase 3 NAPOLI-1 study in metastatic pancreatic cancer will be communicated in an oral presentation at the European Society for Medical Oncology 16th World Congress on Gastrointestinal Cancer (ESMO GI) held from June 25th to 28th, 2014 at The International Convention Center of Barcelona in Barcelona, Spain. The data will be presented by Andrea Wang-Gillam, M.D., Ph.D., Assistant Professor of Medicine, Division of Oncology, Washington University School of Medicine, and the co-chair of the steering committee for the NAPOLI-1 study. The presentation will include additional efficacy and safety data from the three arm study of MM-398, a nanoliposomal irinotecan, in patients with metastatic pancreatic cancer who have received prior gemcitabine-based therapy.

"We are honored that the findings of MM-398 in combination with 5-fluorouracil and leucovorin in patients with post-gemcitabine pancreatic cancer from our NAPOLI-1 study have been accepted for oral presentation at ESMO GI," said Eliel Bayever, M.D., Vice President of Clinical Development at Merrimack. "We look forward to updating the medical oncology community with more comprehensive results of our study in treating this devastating disease. We are especially grateful to the patients, their families and caregivers, the investigators, and the research community for their commitment to this important study."

Oral Presentation:

NAPOLI-1: Randomized Phase 3 Study of MM-398 (nal-IRI), with or without 5-Fluorouracil and Leucovorin, versus 5-Fluorouracil and Leucovorin, in Metastatic Pancreatic Cancer Progressed on or Following Gemcitabine-based Therapy (Abstract #O-0003)
Session II: Cancer of the pancreas and bile ducts
Wednesday, June 25, 2014, 5:00 p.m. CEST
Poster viewing time: Thursday, June 26, 2014, 10:30-11:00 a.m. and 4:30-5:00 p.m. CEST
CCIB, Exhibit Hall
Merrimack to Host Conference Call

Merrimack will host an investor conference call and webcast at 8 a.m., Eastern Time, on Thursday, June 26, 2014 where Dr. Wang-Gillam will review the data presented at ESMO GI. Investors and the general public are invited to listen to the call by dialing (877) 564-1301 (domestic) or (224) 357-2394 (international) five minutes prior to the start of the call and providing the passcode 61076181.

A press release detailing the results presented at ESMO GI will be issued after the oral presentation on June 25. Slides accompanying the call and a listen-only webcast of the call can be accessed in the Investors section of Merrimack's website, http://investors.merrimackpharma.com, and a replay of the call will be archived there for six weeks.
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Source: press release, 6/17/14. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=855045

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Geoffrey M. Grande, CFA, Investor Relations, gave guidance for upcoming milestones. He stated, "A recap of the clinical milestones we anticipate in the near term, in Q2 we expect top line data from our phase-III study of MM-398 in pancreatic cancer, and our phase-II study of MM-121 in triple negative breast cancer. At ASCO, we anticipate the presentation of full biomarker data for our phase-II program of MM-121. We also expect to initiate phase-II studies for MM-302, MM-151 and MM-141 this year."
Source: Q4 2013 earnings conference call, 2/27/14.

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Merrimack Updates Guidance on Availability of Top Line Data for MM-398 Phase 3 Clinical Trial to Second Quarter of 2014

Merrimack now expects to report top line data for NAPOLI-1, its Phase 3 clinical trial of MM-398 in advanced pancreatic cancer, in the second quarter of 2014. Merrimack previously disclosed that top line data was expected in the fourth quarter of 2013 or the first quarter of 2014. This change is based on a blinded assessment of overall survival events across the entire trial, which are occurring later than forecasted. As previously disclosed, Merrimack met its enrollment target for the trial in August 2013.
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Source: press release, 11/07/13. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=805246

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August 28, 2013

Merrimack Reaches Patient Enrollment Goal in the Phase 3 NAPOLI-1 Study of MM-398 in Late Stage Pancreatic Cancer
A Study of MM-398 Both as Monotherapy and in Combination With 5-FU and Leucovorin in Patients With Advanced Gemcitabine-Refractory Pancreatic Cancer

CAMBRIDGE, Mass., Aug 28, 2013 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) announced today that the enrollment goal has been reached in the NAPOLI-1 trial. NAPOLI-1 is a randomized Phase 3 study of MM-398, with or without 5-fluorouracil (5-FU) and leucovorin (LV), versus 5-FU and LV, in patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy.

"We are grateful to the patients and their families for volunteering for the study, and to the doctors, nurses, and medical teams for their outstanding care. We hope that MM-398 is able to make a difference to these patients and look forward to presenting the final study analysis," said Eliel Bayever, M.D., Vice President and Medical Director of MM-398. "To our knowledge this is one of the largest controlled studies ever conducted in this patient population, which has very few treatment options."

Currently, there is no approved treatment for patients with metastatic pancreatic cancer after gemcitabine has failed, nor is there a clear consensus on the standard of care in this patient group. Limited data suggest that without effective treatment, these patients are expected to live only a few months once they have progressed on first line therapy. Metastatic pancreatic cancer is almost uniformly fatal, with a 73 percent death rate within one year of diagnosis (American Cancer Society) and a 5-year overall survival rate of approximately six percent in the United States (National Cancer Institute).

NAPOLI-1 was designed to enroll approximately 405 patients at over 100 sites in North America, South America, Europe, Asia and Australia. As recently as July 2013, a data safety monitoring board reviewed the available data from NAPOLI-1 for safety and recommended that the trial continue. The Global Principal Investigator is Daniel von Hoff, M.D., F.A.C.P. of TGen, University of Arizona, Mayo Clinic and Scottsdale Healthcare.
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Source: press release, 8/28/13. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=787582

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Robert J. Mulroy President & Chief Executive Officer, gave guidance for data from the NAPOLI-I trial of MM-398 for pancreatic cancer. He stated, "With respect to study execution, we remain on track to complete enrollment in Q3 this current quarter. We are very near the end of our enrollment effort and expect to be announcing the achievement of our enrollment target in the weeks ahead. With respect to data, we expect to report top-line data later this fall in the fourth quarter of 2013 or potentially the first quarter of 2014 depending on event range."
Source: Q2 2013 earnings conference call, 8/08/13.

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Merrimack anticipates the following upcoming milestones:

Completion of enrollment and announcement of top-line data for the NAPOLI-1 study, MM-398's global Phase 3 clinical trial in gemcitabine-resistant pancreatic cancer;

Announcement of top-line data from four MM-121 Phase 2 clinical trials focused on:
Second line hormone receptor positive breast cancer in combination with exemestane,
Second line wild type EGFR non-small cell lung cancer in combination with erlotinib,
Neoadjuvant HER2 negative breast cancer in combination with paclitaxel, and
Second line platinum resistant/refractory ovarian cancer in combination with paclitaxel; and

Transition of multiple Phase 1 programs into Phase 2 opportunities to address large, unmet patient needs.
More
Source: press release, 8/08/13. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=783855

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NAPOLI-I - A Randomized, Open Label Phase 3 Study of MM-398, With or Without 5-Fluorouracil and Leucovorin, Versus 5 Fluorouracil and Leucovorin in Patients With Metastatic Pancreatic Cancer Who Have Failed Prior Gemcitabine-based Therapy
Estimated Enrollment: 405
Study Start Date: November 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
More
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01494506?term=MM-398&rank=2

Compound/DeviceSpecialtyIndicationCompound ClassTarget
ONIVYDE (MM-398) Pancreatic cancerOncologyPancreatic cancerTopoisomerase I InhibitorTopoisomerase I-DNA covalent complexes

Mechanism of action: ONIVYDE (MM-398) is a liposomal formulation of the hydrochloride salt of the semisynthetic camptothecin analogue irinotecan with potential antineoplastic activity. During the S phase of the cell cycle, irinotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery. MM-398 is designed to rely on the natural blood flow of the tumor to direct the therapy directly to the site of the cancer and minimize exposure to non-target cells. Also, liposome encapsulation of this agent promotes efficient drug delivery into the cytosol from the endosome compartment of the cell.

Phase of Development: III

Event Type: Data: Phase III trial results

Dates: 2014-06-26

Results:

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Final Results of NAPOLI-1 Study Confirm Overall Survival and Progression-Free Survival Benefit for the ONIVYDE® Regimen for Patients with Metastatic Pancreatic Cancer
- ONIVYDE® in combination with fluorouracil (5-FU) and leucovorin establishes a new standard of care for patients with metastatic pancreatic cancer who have progressed on gemcitabine-based therapy
- Disease control achieved in twice as many patients treated with ONIVYDE in combination with 5-FU and leucovorin (52%) compared to 5-FU and leucovorin alone (24%)
CAMBRIDGE, Mass., Oct. 11, 2016 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) today announced final results from the pivotal Phase 3 NAPOLI-1 study validating the use of ONIVYDE® (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin, which represents a new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) following treatment with gemcitabine-based therapy. The final NAPOLI-1 results were presented in a poster discussion session and a separate analysis of NAPOLI-1 safety-over-time data was presented in a poster session at the European Society for Medical Oncology 2016 Congress in Copenhagen.

"The final results of the NAPOLI-1 study provide a high level of clinical evidence establishing the ONIVYDE regimen as a meaningful treatment option for patients with metastatic pancreatic cancer," said Prof. Li-Tzong Chen, M.D., Ph.D., corresponding author, Investigator on the NAPOLI-1 trial and Director, National Institute of Cancer Research, National Health Research Institutes in Tainan, Taiwan. "Pancreatic cancer is a devastating disease with a poor prognosis. In a patient population with few treatment options, the ONIVYDE regimen provides an opportunity for extended overall survival while maintaining baseline quality-of-life and represents a new standard of care. We thank all of the patients, caregivers and investigators who participated in this pivotal study."

The extended data cutoff occurred at final database lock in November 2015 after 382 OS events that had occurred in the intention-to-treat (ITT) population. In this extended analysis of NAPOLI-1, the previously described overall survival advantage was maintained for ONIVYDE in combination with 5-FU and leucovorin versus 5-FU and leucovorin alone: 6.2 months versus 4.2 months (p=0.039, hazard ratio (HR) =0.75, 95% CI: [.057 - .99]). Findings also showed that one in four patients treated with the ONIVYDE combination regimen survived one year or more, a significant milestone. This was represented by a 26% probability of survival at one year for patients receiving ONIVYDE in combination with 5-FU and leucovorin versus 16% for patients who received 5-FU and leucovorin alone. Furthermore, disease control was achieved in twice as many patients treated with ONIVYDE in combination with 5-FU and leucovorin (52%) compared to 5-FU and leucovorin alone (24%). The demonstrated improvements in overall survival for the ONIVYDE combination regimen were achieved with little or no impact on quality of life over 12 weeks despite the addition of a second chemotherapeutic agent to 5-FU and leucovorin, a therapy recognized as a well-managed treatment for metastatic pancreatic cancer.

Results from a separate analysis of the NAPOLI-1 data evaluating the incidence and prevalence of gastrointestinal toxicities and neutropenia during the course of treatment with ONIVYDE plus 5-FU and leucovorin showed that the majority of these adverse events occurred early in treatment with decreased incidence and severity thereafter. Dose reductions or dose delays were commonly used to manage these adverse events and may account for the decreased incidence and/or severity that was observed.

The primary Phase 3 NAPOLI-1 data were the basis of the US Food and Drug Administration (FDA) and Taiwan FDA approvals of the ONIVYDE® (irinotecan liposome injection) combination regimen in October 2015. They were also the basis of the European Union's Committee for Medicinal Products for Human Use (CHMP) positive opinion issued in July 2016. The ONIVYDE combination is designated as a category 1 treatment option in the 2016 National Comprehensive Cancer Network (NCCN) guidelines for pancreatic adenocarcinoma in the United States as well as a category 2B status in the 2015 European Society for Medical Oncology (ESMO) clinical practice guidelines in the European Union.
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Source: press release, 10/11/16. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=992958

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NAPOLI-1 Data Demonstrates ONIVYDE® Regimen Maintains Quality of Life While Improving Overall Survival in Patients with Metastatic Pancreatic Cancer
The addition of ONIVYDE (irinotecan liposome injection) to fluorouracil and leucovorin significantly improves median overall survival and progression-free survival in patients with metastatic pancreatic cancer following gemcitabine-based therapy without compromising quality of life at 12 weeks when compared with fluorouracil and leucovorin alone
Quality of life analysis was presented at ESMO 18th World Congress on Gastrointestinal Cancer
CAMBRIDGE, Mass., June 30, 2016 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) today announced a newly presented analysis of the Phase 3 NAPOLI-1 data shows patients treated with ONIVYDE® (irinotecan liposome injection), also known as "nal-IRI," in combination with fluorouracil (5-FU) and leucovorin, maintain similar baseline quality of life at 12 weeks despite the addition of a second chemotherapeutic agent when compared to 5-FU and leucovorin alone. These findings were presented in an oral session by Dr. Richard Hubner, an investigator on the NAPOLI-1 trial and a Consultant Medical Oncologist at Christie NHS Foundation Trust, at the European Society for Medical Oncology (ESMO) 18th World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Previously reported Phase 3 NAPOLI-1 data demonstrate that the ONIVYDE combination regimen significantly improves overall survival and progression-free survival when compared to 5-FU and leucovorin alone1. ONIVYDE in combination with 5-FU and leucovorin was approved by the U.S. Food and Drug Administration (FDA) in October 2015 for the treatment of patients with metastatic adenocarcinoma of the pancreas whose disease progressed after gemcitabine-based therapy. It is the first and only FDA-approved therapy in this setting and was recently designated category 1 status by the National Comprehensive Cancer Network.

"This quality of life analysis of the NAPOLI-1 data underscores the significant clinical benefit the ONIVYDE regimen provides to a patient population with few treatment options," said Dr. Richard Hubner, investigator on the NAPOLI-1 trial and Consultant Medical Oncologist at Christie NHS Foundation Trust. "Fluorouracil and leucovorin is recognized as a well-tolerated therapy for metastatic pancreatic cancer patients. The addition of ONIVYDE, a second chemotherapeutic agent, to this treatment regimen demonstrated significant improvement in median overall survival, progression-free survival and overall response rate2 with little or no impact on baseline quality of life at 12 weeks, as shown in this analysis. This further supports the growing recognition that the ONIVYDE combination regimen is a clinically beneficial treatment option for metastatic pancreatic cancer patients who have progressed on gemcitabine-based therapy."

Methodology and Results:

Effects of nal-IRI (MM-398) ± 5-fluorouracil on quality of life (QoL) in NAPOLI-1: A phase 3 study in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy (Abstract O-004)

Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life core questionnaire, which includes functional scales (physical, role, cognitive, emotional and social), symptom scales (appetite loss, constipation, diarrhea, dyspnea, fatigue, insomnia, nausea and vomiting and pain), and a global health and quality of life scale.

Patients completed the European Organization for Research and Treatment of Cancer quality of life core questionnaire at treatment start, every 6 weeks and 30 days post-follow-up visit. A total of 154 patients (ONIVYDE in combination with 5-FU and leucovorin, n=71; 5-FU and leucovorin, n=83) comprised the population for this analysis. Sixty-nine percent (49/71) of patients in the ONIVYDE combination regimen group and 53% (44/83) in the 5-FU and leucovorin group had evaluable data at 12 weeks. No substantial differences are identified in the percentage of patients exhibiting improved, stable or worsening quality of life in the global health status, functional scale or symptom scale scores between the two study arms. The analysis demonstrates that in the NAPOLI-1 study, evaluable patients treated with the ONIVYDE combination regimen were able to maintain quality of life over 12 weeks and there were no significant differences versus the 5-FU and leucovorin-treated patients in quality of life response despite the addition of a second chemotherapeutic agent.
More
Source: press release, 6/30/16. http://investors.merrimack.com/releasedetail.cfm?ReleaseID=977765

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Merrimack to Present New Analyses of Phase 3 NAPOLI-1 Data at the ESMO 18th World Congress on Gastrointestinal Cancer
Oral presentation on Phase 3 NAPOLI-1 data will highlight the effects of the ONIVYDE® (irinotecan liposome injection) regimen on quality of life for patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy
An analysis of the Phase 3 NAPOLI-1 safety data across patient subgroups will also be presented

CAMBRIDGE, Mass., June 21, 2016 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) today announced that it will present new analyses of the Phase 3 NAPOLI-1 data in an oral presentation and poster discussion session at the European Society for Medical Oncology (ESMO) 18th World Congress on Gastrointestinal Cancer, June 29 - July 2, 2016 in Barcelona, Spain. An oral presentation by Dr. Richard Hubner, Consultant Medical Oncologist, The Christie NHS Foundation Trust and investigator on the NAPOLI-1 trial, will compare the effects of ONIVYDE® (also known as "nal-IRI") in combination with fluorouracil and leucovorin on quality of life in patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy versus treatment with fluorouracil and leucovorin alone.

Merrimack will also present an analysis of the NAPOLI-1 safety data across patient subgroups in a poster discussion session and a trials-in-progress poster on a Phase 2 study evaluating ONIVYDE containing regimens as first-line therapy for patients with metastatic pancreatic cancer.

Oral Presentation:

Effects of nal-IRI (MM-398) ± 5-fluorouracil on quality of life (QoL) in NAPOLI-1: A phase 3 study in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy (Abstract O-004)
Wednesday, June 29, 2016, 5:53 - 6:03 PM CEST
Session: Pancreatic Cancer
Poster Presentation Time: Thursday, June 30, 2016, 11:00 - 11:30 AM and 5:10 - 5:40 PM CEST
CCIB, Exhibit Hall
Poster Sessions:

Safety across subgroups in NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy (Abstract PD-023)
Session: Pancreatic Cancer
Poster Discussion Time: Thursday, June 30, 2016, 11:00 - 11:30 AM CEST
Poster Presentation Time: Thursday, June 30, 2016, 11:00 - 11:30 AM and 5:10 - 5:40 PM CEST
CCIB, Exhibit Hall
Nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine as first-line therapy in patients with metastatic pancreatic adenocarcinoma (mPAC): A randomized, open-label phase 2 study (Abstract P-287)
Session: Pancreatic Cancer
Poster Presentation Time: Thursday, June 30, 2016, 11:00 - 11:30 AM and 5:10 - 5:40 PM CEST
CCIB, Exhibit Hall
More
Source: press release, 6/21/16. http://investors.merrimack.com/releasedetail.cfm?ReleaseID=976619

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Updated Data Shows ONIVYDE® (irinotecan liposome injection) Combination Regimen Increased One Year Survival by 63% in Patients with Metastatic Pancreatic Cancer
Results based on an updated analysis from the NAPOLI-1 Phase 3 study in post-gemcitabine pancreatic cancer
Additional data to be presented at the ASCO GI 2016 conference indicate observed overall survival and progression free survival benefits for the ONIVYDE combination regimen compared to 5-FU and leucovorin alone were greatest among patients with the highest baseline CA19-9 levels
CAMBRIDGE, Mass., Jan. 19, 2016 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) today announced that an updated overall survival analysis of the Phase 3 NAPOLI-1 study of ONIVYDE® (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival in patients with post-gemcitabine metastatic pancreatic adenocarcinoma when compared to 5-FU and leucovorin alone. These updated data will be presented at the American Society of Clinical Oncology 2016 Gastrointestinal Cancers Symposium (ASCO GI), January 21-23, 2016, in San Francisco.

Analysis of the updated data supports the robustness of the overall survival benefit of the ONIVYDE combination therapy observed in the primary analysis of the NAPOLI-1 trial. Updated findings showed one in four patients treated with ONIVYDE survived a milestone of one year or more: 12-month overall survival estimates of 26% (95% CI, 18-35%) for ONIVYDE in combination with 5-FU and leucovorin, a 63% improvement when compared to 16% (95% CI, 10-24%) for 5-FU and leucovorin alone. No new safety or tolerability concerns were note in the updated analysis.

"Pancreatic cancer is a devastating disease with dismal survival," said Andrea Wang-Gillam, M.D., Ph.D., lead author of the NAPOLI-1 article and Associate Professor of Medicine, Clinical Director of GI Oncology Program, Division of Oncology, at Washington University School of Medicine, St. Louis. "These updated findings reinforce the overall survival benefit of ONIVYDE in treating patients with metastatic pancreatic adenocarcinoma who have progressed after gemcitabine-based therapy. With a significant improvement in the 12-month overall survival rate and a well-defined safety and tolerability profile, the ONIVYDE combination regimen is well-positioned to become the standard of care in the post-gemcitabine setting. This new therapy offers hope for extended life expectancy in a patient population with limited options."

Methodology and Results:

Updated overall survival analysis of NAPOLI-1: Phase 3 study of nanoliposomal irinotecan (nal-IRI, MM-398), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy (Abstract #417, Board L11)

In this analysis of updated data from the NAPOLI-1 study, the previously described overall survival and progression free survival benefits were maintained for the ONIVYDE in combination with 5-FU and leucovorin arm compared with 5-FU and leucovorin alone. This data analysis presents updated estimates of overall survival based on 378 events and includes data from all patients randomized across the three arms of the study. Twelve-month survival estimates for ONIVYDE in combination with 5-FU and leucovorin were 26% (95% CI, 18-35%) compared to 16% (95% CI, 10-24%) for 5-FU and leucovorin alone. Six-month survival estimates were 53% (95% CI, 44-62%) for the ONIVYDE combination regimen versus 38% (95% CI, 29-47%) for 5-FU and leucovorin. No new safety or tolerability concerns were noted in the updated data analysis. The most common grade 3+ adverse events occurring at a ≥ 2% incidence in the ONIVYDE-containing arms were neutropenia, diarrhea, vomiting, and fatigue.

Effect of baseline carbohydrate antigen 19-9 (CA19-9) level on overall survival (OS) in NAPOLI-1 trial: A Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy (Abstract #425, Board L19)

Carbohydrate antigen 19-9 (CA19-9) has been shown to correlate with response to therapy and overall survival in patients with metastatic pancreatic cancer. In this updated analysis of NAPOLI-1 data, patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 levels with ONIVYDE in combination with 5-FU and leucovorin or 5-FU and leucovorin alone. A total of 213 patients treated with the ONIVYDE combination regimen or 5-FU and leucovorin alone had a baseline CA19-9 measurement and were included in this analysis. Results show the observed overall survival and progression free survival benefits for the ONIVYDE combination regimen compared to 5-FU and leucovorin alone were greatest among patients with the highest baseline CA19-9 levels. These results suggest that baseline CA19-9 levels are associated with the treatment effect observed for the ONIVYDE combination regimen in metastatic pancreatic cancer patients.
More
Source: press release, 1/19/16. http://investors.merrimack.com/releasedetail.cfm?ReleaseID=950856

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January 8, 2015
Merrimack Pharmaceuticals Announces Oral Presentation of Additional Analyses of MM-398 Phase 3 NAPOLI-1 Study at the American Society of Clinical Oncology (ASCO) 2015 Gastrointestinal Cancers Symposium
Other ASCO GI Presentations Include Preclinical and Clinical Data on MM-141 and MM-151
CAMBRIDGE, Mass., Jan. 8, 2015 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced that additional analyses from the Phase 3 NAPOLI-1 study of MM-398 (nanoliposomal irinotecan injection), also known as "nal-IRI," in metastatic pancreatic cancer will be presented at the American Society of Clinical Oncology 2015 Gastrointestinal Cancers Symposium (ASCO GI), January 15-17, 2015 at Moscone West Building in San Francisco, CA. The data will be presented by Li-Tzong Chen, M.D., Ph.D., Director, Investigator and Attending Physician at the National Institute of Cancer Research in Taiwan.

Merrimack will also be presenting preclinical and clinical data supporting the development of MM-141 in combination with gemcitabine and nab-paclitaxel in front-line pancreatic cancer, as well as updated clinical and biomarker data from a Phase 1 trial of MM-151.

Oral Presentation

Expanded analyses of NAPOLI-1: Phase 3 study of MM-398 (nal-IRI), with or without fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) patients previously treated with gemcitabine-based therapy (Abstract #234, Board A5)
Oral Abstract Session: Cancers Of The Pancreas, Small Bowel, And Hepatobiliary Tract
Friday, January 16, 2015, 2:00 p.m. PT
Li-Tzong Chen, M.D., Ph.D., Director, Investigator and Attending Physician at the National Institute of Cancer Research in Taiwan
Poster viewing time: Friday, January 16, 2015, 12:00-2:00 p.m. and 5:30-7:00 p.m. PT

Poster Sessions

Session Title: General Poster Session B and Trials in Progress Poster Session B: Cancers Of The Pancreas, Small Bowel, And Hepatobiliary Tract
Friday, January 16, 2015, 12:00-2:00 p.m. and 5:30-7:00 p.m. PT

Effect of MM-141 on gemcitabine and nab-paclitaxel potentiation in preclinical models of pancreatic cancer through induction of IGF-1R and ErbB3 degradation (Abstract #289, Board B10)

HER3 as a potential prognostic biomarker in pancreatic cancer (Abstract #295, Board B16)

First-in-human study of MM-141: A novel tetravalent monoclonal antibody targeting IGF-1R and ErbB3 (Abstract #384, Board D3)

Session Title: General Poster Session C and Trials in Progress Session C: Cancers Of The Colon, Rectum, And Anus
Saturday, January 17, 2015, 7:00-7:55 a.m. and 12:00-2:00 p.m. PT

Safety, pharmacology and preliminary clinical activity of MM-151: an oligoclonal anti-EGFR therapeutic in patients with cetuximab-resistant CRC and other refractory solid tumors (Abstract 647, Board C39)

PEPCOL: A randomized noncomparative phase II study of PEP02 (MM-398) or irinotecan in combination with leucovorin and 5-fluorouracil as second-line therapy in patients with unresectable metastatic colorectal cancer - A GERCOR study (Abstract 751, Board E41)
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Source: press release, 1/08/15. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=890299

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June 25, 2014

Merrimack Pharmaceuticals Presents Data From Phase 3 NAPOLI-1 Study at the ESMO 16th World Congress on Gastrointestinal Cancer

MM-398 in combination with 5-fluorouracil and leucovorin shows statistically significant improvement in overall survival, progression free survival and overall response rate in patients with post-gemcitabine metastatic pancreatic cancer

Plan to file New Drug Application in 2014

Conference call to review data scheduled for 8:00 a.m. ET tomorrow, June 26th

CAMBRIDGE, Mass., June 25, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced detailed results from NAPOLI-1, a large, randomized, three-arm Phase 3 study of MM-398, a nanoliposomal encapsulation of irinotecan, in patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy. The combination of MM-398 with 5-fluorouracil (5-FU) and leucovorin extended overall survival and significantly increased progression free survival (PFS) and overall response rate compared to the control arm of 5-FU and leucovorin alone.

Top line results of NAPOLI-1 released in May showed that the combination of MM-398 with 5-FU and leucovorin achieved an overall survival of 6.1 months versus the 4.2 month survival demonstrated by the control arm of 5-FU and leucovorin alone. The primary log-rank analysis of overall survival was statistically significant (p=0.012), with a corresponding hazard ratio of 0.67.

In combination with 5-FU and leucovorin, MM-398 also demonstrated a statistically significant advantage in PFS, with a median of 3.1 months compared to 1.5 months in the control arm (HR = 0.56, 95% CI [0.41-0.75], p=0.0001). The combination arm also showed a statistically significant difference in overall response rate compared to the control arm (16% and 1%, respectively, p < 0.001). The most common non-hematologic grade 3 and higher adverse events in the combination arm were fatigue (14%), diarrhea (13%) and vomiting (11%). Hematologic grade 3 and higher adverse events included neutropenia, which was observed in 20% of patients as determined by objective laboratory values, and febrile neutropenia, which was observed in 2% of patients.

Results of the study were presented today by Andrea Wang-Gillam, M.D., Ph.D., Assistant Professor of Medicine, Division of Oncology, Washington University School of Medicine, at an oral session at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer (ESMO GI) held in Barcelona, Spain, and was featured in the official press program. To access the clinical poster and slides presented at ESMO GI, click here.

"These positive results further strengthen our belief in the MM-398 combination and design of NAPOLI-1. Entering into a difficult disease with a history of clinical trial failures, the MM-398 combination has extended overall survival while striking an important balance between efficacy and toxicity in a setting where there is no current standard of care," said Eliel Bayever, M.D., a Vice President at Merrimack and the medical director for MM-398. "This Phase 3 success bolsters our confidence in our systems approach and continued commitment to engineering innovative therapies for difficult to treat cancers."

Merrimack expects to submit a New Drug Application to the U.S. Food and Drug Administration for the MM-398 combination regimen in 2014.

NAPOLI-1 Results

NAPOLI-1: Randomized Phase 3 Study of MM-398 (nal-IRI), with or without 5-Fluorouracil and Leucovorin, versus 5-Fluorouracil and Leucovorin, in Metastatic Pancreatic Cancer Progressed on or Following Gemcitabine-based Therapy (Abstract #O-0003)

Study results for MM-398 in combination with 5-fluorouracil and leucovorin

Patients on the combination therapy of MM-398, dosed at 80 mg/m2 Q2W with 5-FU and leucovorin, achieved an overall survival of 6.1 months versus 4.2 month survival demonstrated by the control arm of 5-FU and leucovorin alone (HR=0.67, 95% CI [0.49-0.92], p=0.01).
The combination arm demonstrated a statistically significant median PFS of 3.1 months compared to 1.5 months in the control arm (HR = 0.56, 95% CI [0.41-0.75], p=0.0001).
Safety and efficacy data for patients treated with MM-398 were consistent with previously reported top line data and results from earlier MM-398 clinical studies. Hematologic grade 3 and higher adverse events in the combination arm included neutropenia, which was observed in 20% of patients as determined by objective laboratory values, and febrile neutropenia which was observed in 2% of the patients. The most common non-hematologic grade 3 and higher adverse events were fatigue (14%), diarrhea (13%) and vomiting (11%).
The overall response rate in the combination arm was 16% versus 1% in the control arm which was statistically significant (p < 0.001).
A reduction of CA19-9 levels was observed in 36% of patients in the combination arm versus 12% of patients in the control arm. The reduction of CA19-9, a pancreatic tumor marker indicative of patient response to MM-398, was defined by a greater than or equal to 50% decrease in baseline CA19-9 levels.
Study results for MM-398 as a monotherapy

MM-398, dosed at 120 mg/m2 Q3W, had a 4.9 month median overall survival compared to 4.2 months in the control arm (HR=0.99, 95% CI [0.77-1.28], p=0.942).
Patients on the MM-398 monotherapy arm achieved a median PFS of 2.7 months versus 1.6 months in the control (HR = 0.80, 95% CI [0.62-1.04]).
Neutropenia was observed in 16% of the patients on the monotherapy arm and febrile neutropenia was observed in 4% of patients. The most common grade 3 or higher adverse events included diarrhea (21%), vomiting (14%) and hypokalemia (12%).
The overall response rate of MM-398 alone was 6% versus 1% in the control arm.
A reduction of CA19-9 levels was observed in 31% of patients on the MM-398 monotherapy arm versus 12% of patients in the control arm.
Merrimack to Host Conference Call

Merrimack will host an investor conference call and webcast at 8 a.m., Eastern Time, tomorrow, Thursday, June 26, 2014 where Dr. Wang-Gillam will review the data presented at ESMO GI. Investors and the general public are invited to listen to the call by dialing (877) 564-1301 (domestic) or (224) 357-2394 (international) five minutes prior to the start of the call and providing the passcode 61076181.

Slides accompanying the call and a listen-only webcast of the call can be accessed in the Investors section of Merrimack's website, http://investors.merrimackpharma.com, and a replay of the call will be archived there for six weeks.
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Source: press release, 6/25/14. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=856551

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May 1, 2014
Merrimack Pharmaceuticals Announces MM-398 Achieves Primary Endpoint of Overall Survival in Phase 3 Trial in Post-Gemcitabine Metastatic Pancreatic Cancer
MM-398 in combination with 5-fluorouracil and leucovorin demonstrates statistically significant advantage compared to control arm

Plan to submit New Drug Application in 2014

Conference Call Scheduled for 8:30 a.m. ET Today

CAMBRIDGE, Mass., May 1, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced that the combination of MM-398 with 5-fluorouracil (5-FU) and leucovorin achieved an overall survival of 6.1 months, a 1.9 month improvement over the 4.2 month survival demonstrated by the control arm of 5-FU and leucovorin alone. The NAPOLI-1 Phase 3 study was conducted in patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. The primary log-rank analysis of overall survival was statistically significant (p=0.012) with a corresponding hazard ratio of 0.67. A statistically significant advantage for progression free survival was also observed in the combination arm.

The most common Grade 3 or higher adverse events in the combination arm were neutropenia (14.5%), fatigue (13.7%), diarrhea (12.8%) and vomiting (11.1%). Sepsis (3.4%) was the only serious life threatening event that occurred with a more than 2% difference between the combination arm and the control arm.

"We are excited by the results of the NAPOLI-1 study because of the critical need to help patients with this devastating illness and are moving forward as quickly as possible to get MM-398 to patients," said Robert Mulroy, President and CEO of Merrimack. "Given that there have only been a handful of successful Phase 3 trials in pancreatic cancer in the past 25 years, it is gratifying to have the first positive Phase 3 trial in the post-gemcitabine setting. The results reinforce our confidence in our entire nanoliposomal pipeline. We are grateful for the dedication of the investigators, the research community and, most importantly, the patients and their families who bravely participated in this study."

The Phase 3 study also examined MM-398 in a monotherapy regimen. MM-398 had a 4.9 month median overall survival as a monotherapy, but did not achieve a statistically significant survival advantage compared to the 4.2 months in the control arm. The hazard ratio for overall survival was 0.99 with a corresponding p-value of 0.942. In general, patients experienced a higher level of adverse events with the MM-398 monotherapy dose and treatment schedule compared to patients who received the combination of MM-398 with 5-FU and leucovorin.

"This demonstration of a survival benefit from the MM-398 plus 5-FU and leucovorin combination is particularly important given that we have very few treatment options for patients in this tough clinical setting," said Daniel D. Von Hoff, M.D., F.A.C.P., global principal investigator of the NAPOLI-1 study, Chief Scientific Officer for Scottsdale Healthcare's Virginia G. Piper Cancer Center and Distinguished Professor at Translational Genomics Research Institute (TGen).

"The Pancreatic Cancer Action Network's goal is to double pancreatic cancer survival by 2020. The positive results of this trial demonstrate progress toward that goal in a disease for which additional treatment options are urgently needed to improve patient outcomes," stated Julie Fleshman, President and CEO of the Pancreatic Cancer Action Network. "These results also underscore the important role clinical trials play when patients are exploring their treatment options. We applaud Merrimack's dedication to improving the treatment landscape for this patient population, and helping us charge forward in the fight against pancreatic cancer."

This study has been accepted for oral presentation at the European Society for Medical Oncology World Conference on Gastrointestinal Cancer being held in Barcelona, Spain on June 25-28, 2014. Merrimack expects to submit a New Drug Application to the U.S. Food and Drug Administration for the MM-398 combination regimen in 2014.

NAPOLI-1 Trial Design

NAPOLI-1 (NAnoliPOsomaL Irinotecan) is a randomized, open label Phase 3 study in patients with metastatic pancreatic cancer who received prior gemcitabine-based therapy. The study evaluated two MM-398 regimens, 80 mg/m2 combined with 5-FU and leucovorin every two weeks, and 120 mg/m2 as a monotherapy every three weeks. Each arm was compared to a control arm of 5-FU and leucovorin. A total of 417 patients were randomized across the three arms. Each MM-398 regimen was compared against the control arm on the primary endpoint of overall survival. Patients were enrolled at over 100 sites in North America, South America, Europe, Asia and Australia.

Merrimack to Host Conference Call

Merrimack will conduct a live conference call and webcast today, Thursday, May 1 at 8:30 a.m., Eastern Time, to discuss these top line results and provide a summary of first quarter 2014 financial results. Investors and the general public are invited to listen to the call by dialing (877) 564-1301Call: (877) 564-1301 (domestic) or (224) 357-2394Call: (224) 357-2394 (international) five minutes prior to the start of the call and providing the passcode 37032608. A listen-only webcast of the call can be accessed in the Investors section of Merrimack's website, http://investors.merrimackpharma.com, and a replay of the call will be archived there for six weeks following the call.
More
Source: press release, 5/01/14. http://investors.merrimackpharma.com/releasedetail.cfm?ReleaseID=844390

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