A Fully Integrated Cancer Company.

Transcription

1 A Fully Integrated Cancer Company. Jefferies Global Healthcare Conference June 3, 2014 Robert Mulroy, President and CEO

2 Forward Looking Statements To the extent that statements contained in this presentation are not descriptions of historical facts, they are forwardlooking 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 presentation, Merrimack s forward-looking statements include statements about the potential effectiveness and safety profile of Merrimack s product candidates, including MM-398 either alone or in combination, the expected timeline for seeking regulatory approval for the MM-398 combination regimen, Merrimack s ability to translate clinical data into future clinical success, anticipated milestones, including the initiation of new trials, the timing of availability of clinical trial data, the status of and enrollment in clinical trials, the timing of availability of clinical trial data, Merrimack s commercialization plans and strategies and the ability to enter into business development transactions. 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, availability of funding sufficient for Merrimack s foreseeable and unforeseeable operating expenses and capital expenditure requirements, 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 Annual 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. 2

3 Investment Highlights MM-398 Achieves Ph3 Endpoint in Pancreatic Cancer Combo arm achieved mos of 6.1 months, HR=0.67, p-value=0.012 Preparing to file NDA Core commercial team preparing for launch MM-121 BM+ data in Ovarian, Breast & NSCLC Pre-specified biomarkers identified 30-50% of patients most at risk of progression BM+ patients showed statistically significant improvement in PFS Technology Leadership Systems biology R&D engine driving new insights into cancer Six novel therapeutics in clinical development with companion Dx Nanoliposomes improve drug deposition and exposure Multispecific antibody capabilities engineering novel agents 3

4 A Superior Approach to Drug Discovery Gene Protein Network Network dynamics govern cell decisions Systems dynamics is a way to evolve our understanding of cancer and our ability to develop targeted therapies Predictive models enable more precise targeting and the development of diagnostics Simulations inform the engineering of drugs and the understanding of their pharmacodynamics Paired with deep technological expertise, this approach enables rapid development of new therapies with a strong clinical rationale 4

5 Drugs Engineered to Specific Cancer Biology PC Phase1 Phase 2 Phase 3 MM-310 undisclosed MM-131 undisclosed DX-929 Nano-imaging agent MM-302 nano-doxorubicin MM-151 EGFR MM-141 IGF1R-ErbB3 MM-121 ErbB3 MM-111 ErbB2-ErbB3 MM-398 nanoirinotecan 5

6 Merrimack s Antibody-targeted Nanoliposomal Drug Platform vs. ADCs 30,000+ drug molecules per nanoliposome Many types of drugs Many options for targeting antigens 2-4 drug molecules per antibody Few drugs possible Very few antigens have proven possible 6

7 NanotherapeuticsDesigned for Protected Delivery and Prolonged Exposure Preclinical Data MM-398: Sustained intra-tumor levels t 1/2 (h) AUC (µg*h/ml) CPT MM Clinical Data PK analysis of patients show extended circulation 70-fold higher AUC in the blood vs. irinotecan Local activation of MM-398 in tumor (AACR 2014) 5-fold higher levels of SN-38 in the tumor compared to blood 7

8 MM-398 Nanoliposomal encapsulation of irinotecan Engineered for increased drug deposition, local activation of SN- 38 and prolonged cytotoxic effects Recently achieved positive phase 3 results in combination arm in pancreatic cancer Next step is to file NDA in 2014 Has orphan drug designation Additional studies ongoing in CRC, Ewing s sarcoma and glioma Imaging diagnostic also in development 8

9 Pancreatic cancer is difficult to treat Tumor Associated Macrophages (TAMs) Associated with poor prognosis Dense stroma Drug penetration barrier Extracellular matrix proteins Complex intracellular signaling pathways Hypoxic micro-environment (Wilson & Hay, 2011) Suppresses cytotoxic drug activity gemcitabine 9

10 MM-398 Ph3Study Design Primary Endpoint: Overall Survival Secondary Endpoints: Progression Free Survival Safety and Adverse Event Profile Metastatic Pancreatic Cancer Received prior gemcitabine-based therapy N = 405 (planned): 417 (actual) RANDOMIZATION Global Principal Investigator: Daniel D. Von Hoff, M.D., F.A.C.P. Arm A: MM mg/m2 IV q 3 weeks Arm B (control): 5-FU/LV 2000 mg/m2 IV over 24 hours/200 mg/m2 l+dracemic form, q weekly X 4 Arm C: MM FU/LV MM mg/m2 IV, q 2 weeks 5-FU/LV 2400 mg/m2 IV over 46 hours/400 mg/m2 l+dracemic form 1:1:1 randomization for paired-wise comparison against 5-FU/LV control arm 10

11 MM-398 Ph3Top line Results MM-398 in combination with 5-FU/LV Median OS 6.1 months HR=0.67; p-value= month improvement over control arm Statistically significant improvement in PFS also observed Control arm 5-FU/LV Median OS 4.2 months MM-398 monotherapy Median OS 4.9 months HR=0.99, p-value=

12 MM-398 Ph3Top line Safety Most common Grade 3 or higher adverse events in the combination arm Neutropenia (14.5%) Fatigue (13.7%) Diarrhea (12.8%) 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 In general, patients on the monotherapy arm experienced a higher level of adverse events at this dose and treatment schedule compared to patients who received the combination of MM-398 with 5-FU and leucovorin 12

13 Pancreatic Cancer Landscape Extremely high unmet medical need with few clinical options 73% mortality within one year 6% 5-year survival Unacceptably high recurrence rates post adjuvant treatment (ACS Cancer Facts and Figures 2014) Front line treatment in Pancreatic Cancer FOLFIRINOX: 11.1 mo. vs. GEM mo. (Conroy, NEJM) Abraxane-GEM: 8.5 mo. vs. GEM mo. (Impact, 2013) GEM monotherapy: 5-6 mo. (various) Gemcitabine is the mainstay first line treatment and a significant proportion of patients treated with gemcitabine will be eligible for further treatment. Second line treatment (post-gem) No approved regimens other than 5-FU & leucovorin 13

14 MM-398 Path Forward & Next Steps Regulatory Path: Hold Pre-NDA meeting with FDA Plan to submit NDA in 2014 Commercial Next Steps: Core commercial team preparing for potential launch Activities initially focused on US Geographic clustering allows pancreatic cancer physicians to be effectively targeted by a small, focused field force Expansion/Development: Diagnostic-led expansion into other indications Geographic Location Pancreatic Cancer US ~45,000 EU ~60,000 Japan ~30,000 China ~100,000 Patients Diagnosed Annually* *Decision Resources Report on Pancreatic Cancer. Ma et al. [Trend and prediction on the incidence of pancreatic cancer in China] Feb;34(2): Chinese. 14

15 MM-398 Diagnostic Approach with Ferumoxytol* Pre FMX MRI 24 hours post FMX MRI Presented at AACR 2014 grow 6 patients 23 lesions 5 different tumor types Best Change in Tumor Lesion Size stable *The use of Ferumoxytol(Feraheme, AMAG Pharmaceuticals) in the pilot study mentioned above is for clinical investigational studies only and has not been approved by the FDA. More FMX uptake shrink 15

16 MM-121: Addressing ErbB3-Driven Cancers MM-121 is a monoclonal antibody targeting ErbB3 About ErbB3-Driven Cancer Promotes resistance to therapies and worsens patient outcomes Spans many solid tumors Works in conjunction with other pathways Not a traditional oncogenic pathway where it is primary driver of the cancer # patients MM-121 Designed to Target Biomarker Positive (BM+) patients Unmet need BM+ BM- Response Biomarker positive patients appear to respond worse to standard-of-care (SOC) than biomarker negative patients Biomarker positive patients on MM-121 may respond better than biomarker positive patients on SOC alone 16

17 MM-121 Ph2 Studies: HRG is the Key Biomarker Patients with HRG respond poorly to standard-of-care MM-121 appears to restore sensitivity in HRG positive patients Optimal benefit is observed in HER2 low patients (0+ and 1+) MM-121 This is important to measure in ovarian cancer (~50% of HRG positive patients are HER2 2+) This is NOT important to measure in HER2 negative breast cancer and NSCLC (very few patients are HER2 2+) 17

18 Clinical Testing of Diagnostic Hypothesis Archived Biopsy Platinum-resistant Ovarian Cancer (N=220) Ovarian cancer 140 Paclitaxel + MM-121 Paclitaxel 80 Archived ER/PR+ Metastatic Breast Cancer (N=115) ER/PR+ mbc 59 Exemestane + MM-121 Exemestane 56 Archived Biopsy EGFR wt NSCLC (N=129) EGFR wt NSCLC 85 Erlotinib + MM-121 Erlotinib 44 18

19 MM-121 PFS Data in Biomarker (BM) Defined Population Progression-free survival BM+ Paclitaxel Paclitaxel + MM-121 Ovarian BM+ BM- BM- BM+ BM- BM- Progression-free survival BM+ Exemestane Exemestane + MM-121 Breast Time (weeks) Time (weeks) Progression-free survival BM+ BM+ Erlotinib Erlotinib + MM-121 Lung Study BM+ BM- N HR Prev. N HR Ovarian % Breast % Lung % BM- BM Time (weeks) 19

20 HRG is pervasive & Orthogonal to Other Mechanisms of Disease Ovarian cancer Breast cancer Bladder cancer Cervical cancer 41% 56% 46% 71% Colorectal cancer Head and Neck cancer Liver cancer 36% 99% 55% Prostate cancer 48% SOC Combos Pancreatic cancer Melanoma Uterine cancer Indications 57% 40% 28% HRG expression data from The Cancer Genome Atlas Percentages based on observed threshold for MM-121 benefit in ovarian cancer

21 MM-111 HER2-3 bispecific Ab Engineered against hyperactive HER2/HER3/HRG trimer Demonstrated superior signaling inhibition to current agents in preclinical studies Global Ph2 trial in gastric cancer underway Diagnostic approach: Stratifying based on HER2 and other biomarkers Wholly owned MM Multiple Combinations Phase 1 HER2+ Patients in Multiple Solid Tumors 42% ORR 52% CBR Presented at ESMO 2012 * Indicates patient ongoing at time of presentation The toxicity profile of the MM-111 combinations was consistent with that generally observed in patients receiving the underlying HER2 therapy. 21

22 MM-111 Ph2 Second Line Gastric Study Applied learning from MM-121 Ph2 program Increased confidence in ErbB3 as a target and in its role across solid tumors Added a second independent primary objective for biomarker positive population Updated Study Design Enroll 120 HER2+ FISH+ Patients Focuses resources on biomarker-driven data, increases number of patients studied in this population and is a faster path to proof of concept for MM-111 Data anticipated in 2015 Documentation of HER2 Expression HER2 3+ OR HER2 2+ AND FISH+ 1:1 RANDOMIZATION Experimental (60 patients) Paclitaxel + Trastuzumab + MM-111 Comparator (60 patients) Paclitaxel + Trastuzumab 22

23 progression free survival (PFS) (months) best change in tumor burden (% change) MM-302 ErbB2 Abtargeted nanotherapeutic encapsulation of doxorubicin Engineered for local accumulation & retention (10x) and maximal potency/cell uptake Designed to address cardiotox issues of combinations Diagnostic approach: PET/MRI imaging with copper labeled molecule Wholly owned Phase 1 Monotherapy Presented at SABCS December 2013 N 27 Complete Response (CR) 1 Partial Response (PR) 3 Stable Disease (SD) 6 ORR (CR + PR) 15% CBR (CR + PR + SD) 37% PFS: 5.6 months (95% CI: 2.8, 10.9)

24 MM-302 SABCS 2013 Phase 1 Data CT PET merge Anthracycline Naïve Response Data 44 hr 53 min ROI ROI ROI=RegionofInterest ROI ROI ROI ROI Positron emission tomography/computed tomography (PET/CT) of patients treated with MM-302 and 64 Cu-labeled MM-302 indicates liposomal accumulation in difficult to treat metastatic lesions. Patients were imaged within the first hour and approximately 20 to 48 hours later. A region of interest (ROI) encompassing the site of a brain metastasis for patient , as determined by MRI(not shown), is shown. PET signal enhancement at 44 hours indicates 64 Cu-MM-302deposition. best change in tumor burden (% change) progression free survival (PFS) (months) N 9 CR 1 PR 3 SD 1 ORR 44% CBR 56% PFS: 10.9 months (95% CI: 1.6, NR) 24

25 Other Merrimack ASCO Data MM-151 MM-141 EGFR IGFR ErbB3 Oligoclonalanti-EGFR antibody combination Presented Phase 1 study results Next step: initiation of Ph2 study in colorectal cancer in 2014 Bispecificantibody designed to target IGF-1R and ErbB3 Presented Phase 1 study results Next step: initiation of Ph2 study in front line pancreatic cancer Also presented: MM-111 Ph1 multi-arm study in combination with standard of care therapies in multiple tumor types MM-121 Ph1 study testing safety and pharmacokinetics in patients with advanced solid cancers 25

26 Anticipated Milestones Presentation of full data for MM-398 Ph3 study in pancreatic cancer at ESMO GI in June Top line data for MM-121 Ph2 study in neoadjuvanttnbc in Q2 14 Initiation of Ph2 studies for MM-302, MM-151 and MM-141 in 2014 Business development transactions across pipeline in

27 Investment Highlights MM-398 Achieves Ph3 Endpoint in Pancreatic Cancer Combo arm achieved mos of 6.1 months, HR=0.67, p-value=0.012 Preparing to file NDA Core commercial team preparing for launch MM-121 BM+ data in Ovarian, Breast & NSCLC Pre-specified biomarkers identified 30-50% of patients most at risk of progression BM+ patients showed statistically significant improvement in PFS Technology Leadership Systems biology R&D engine driving new insights into cancer Six novel therapeutics in clinical development with companion Dx Nanoliposomes improve drug deposition and exposure Multispecific antibody capabilities engineering novel agents 27

28 Oncology Pipeline Candidate Design Target Trial (1) Preclin Ph1 Ph2 Ph3 Pre-NDA Signaling Inhibitors Nanoliposomes MM-398 MM-302 MM-310 MM-121 MM-111 MM-151 MM-141 Nanotherapeutic targeted irinotecan ErbB2 Ab targeted nanotherapeutic doxorubicin Antibody targeted nanotherapeutic Monoclonal antibody Bispecific antibody Oligoclonal antibody Bispecific tetravalent antibody Topo I inhibition / DNA replication Topo II inhibition / DNA replication Undisclosed ErbB3 ErbB3 & ErbB2 EGFR IGF-1R & ErbB3 Ph2 mono: 25% 1 yr OS 5.2 mos median OS 50% DCR Ph1 mono: 15% ORR 37% CBR N/A Ph1 combo: 39% ORR 70% CBR Ph1 combo: 40% ORR 52% CBR Ph1 mono: TBA Ph1 mono: TBA MM-131 Multispecific antibody Undisclosed N/A (1) Selected trials: MM-121 plus paclitaxel in ErbB2 (HER2) negative breast, ovarian and other gynecological cancers; MM-111 plus multiple anti-cancer therapies in ErbB2 (HER2) positive solid tumors; MM-398 monotherapy in pancreatic cancer; MM-302 monotherapy in ErbB2 (HER2) positive breast cancer 28