A Fully Integrated Cancer Company.

Transcription

1 A Fully Integrated Cancer Company. Jefferies 2015 Healthcare Conference June 2, 2015 Robert Mulroy, President & 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, and similar expressions. In this presentation, Merrimack s forward-looking statements include, among others, statements about the New Drug Application that Merrimack submitted to the FDA, the market opportunity and potential eligible patient populations for its investigational therapeutics, Merrimack s plans to commercialize MM-398, the potential timing and amounts of payments under its partnership with Baxter, the sufficiency of data from Merrimack s Phase 2 clinical trial of MM-302 to support an application for accelerated approval by the FDA, the potential effectiveness and safety profile of Merrimack s investigational therapeutics in certain patient populations or subpopulations, Merrimack s ability to develop predictive diagnostics, the timing of initiation and completion of new clinical trials, the timing of availability of clinical trial data and Merrimack s 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, 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 Quarterly Report on Form 10- Q filed with the Securities and Exchange Commission (SEC) on May 7, 2015 and other reports Merrimack files with the SEC. 2

3 A Fully Integrated Cancer Company Systems Foundation Precision Diagnostics Clinical Translation Integrated Medicine Targeted Therapies 3

4 Recent Progress/Highlights MM-398 NDA Filing Robust Ph3 data in post-gem pancreatic cancer Fast Track rolling NDA submission completed in April Preparing for US approval and launch targeting ~19,000 patients Baxter Partnership Entered into a $970M Ex-US partnership for MM-398 $250M near term funding expansion/commercial Development plan for 1L pancreatic and gastric MM Ph2 BM+ patients w/ HRs between Registration path planned in breast and lung cancer Targeting >300,000 HRG+ BC & NSCLC patients MM-302 Launched Ph2 3L HER2+ breast cancer trial Designed for potential Accelerated Approval application Targeting ~8,000 US patients post T-DM1 4

5 Systems-Based 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 5

6 Systems-Driven Clinical Insights Resistance Exposure Synergy Network Dx uanatomy Dx 6

7 Drugs Engineered to Specific Cancer Biology PC Phase 1 Phase 2 Phase 3 MM-310 undisclosed MM-131 c-met & EpCAM DX-929 Nano-imaging agent MM-151 EGFR MM-121 ErbB3 MM-302 nano-doxorubicin MM-111 ErbB2-ErbB3 MM-302 MM-141 nano-doxorubicin IGF1R-ErbB3 MM-398 irinotecan liposome injection nanoliposomes antibody-targeted nanoliposomes mab bi-specific antibodies oligoclonal MM-398 MM-302 MM-310 MM-121 MM-141 MM-131 MM-151 7

8 Rational Development of Integrated Medicines Systems Diagnostics Network Inhibitors Targeted Cytotoxics MACK IM Regimens Network Activation: Dx121 Dx Dx141 Dx Deposition: FMX Dx

9 Nanotherapeutics Designed for Protected Delivery and Prolonged Exposure Nano Target Payload MM-398 MM-302 MM-310 Macrophages HER2 TBA Tumor Antigen 80,000 CPT-11; locally activated SN-38 30,000 Doxorubicin; Internalized TBA cytotoxic; Locally activated MM-398: 300-fold Increase in Exposure t 1/2 (h) AUC (µg*h/ml) CPT MM

10 MM-398 Overview Nanoliposomal encapsulation of irinotecan Combination achieved OS endpoint in Ph3 post-gem metastatic panc cancer trial Fast Track and Orphan Drug designations Patients with high unmet need No clear standard of care Rolling NDA submission completed in April; preparing to commercialize in US Ex-US partnership with Baxter 10

11 MM-398 Ph3 Results Met clinical endpoints with MM FU/LV combination Overall Survival: 0.67 HR (p=0.012) PFS: 0.56 HR (p=0.0001) Overall treatment response: 16% vs. 1% (p=<0.001) 12-week PFS rate: 57% vs 26% CA19-9 tumor marker response: 36% vs 12% Acceptable risk/benefit profile Most frequent grade 3+ AEs include neutropenia, fatigue, and GI effects 1) Protocol-defined primary analysis data cut (14Feb2014, after 305 events). Survival follow-up is ongoing and the final results will be reported once all patients are off treatment and at least 90% events have taken place. 2) Protocol-defined primary analysis data cut (14Feb2014, after 305 events). Per protocol population was defined as patients who received at least 80% of the protocol defined treatment during the first 6 weeks of treatment and did not have protocol deviations related to inclusion/exclusion criteria, receiving prohibited therapies or not receiving treatment as randomized. Overall Survival Proportion # at risk: Overall Survival Proportion Intent to Treat (ITT 1 ) Population Median OS, Months (95% CI) MM FU/LV 6.1 ( ) 5-FU/LV 4.2 ( ) Unstratified HR: 0.67 ( ) p = Stratified HR: 0.57 ( ) p = Per Protocol Time from randomization (PP 2 ) (months) Population Median OS, Months (95% CI) 0.9 MM FU/LV 8.9 ( ) FU/LV 5.1 ( ) Stratified HR: 0.47 ( ) p = Time from randomization (months) 11

12 Post-Gemcitabine PanC Opportunity Positive Post-Gemcitabine Metastatic Patient Dynamics Patients receive gemcitabine in all lines of therapy Differentiated from secondline therapy ~19,000 eligible patients in US Post-gemcitabine treatment rates growing Significant Worldwide Opportunity Annually (000 s) Diagnosed Incidence A B C US EU28 JP First-line Second-line Third-line Total Eligible

13 % Share* % Polled Oncologists* New Standard of Care Opportunity Current 2L Practice Oncologists View of MM % 2% Other 8% Gem/Tarceva 80% 80% 20% Gem Mono 60% 60% 40% 20% Gem/Abraxane 20% Capecitabine 40% 20% 60% 37% 3% 20% 0% 20% FOLFOX 10% FOLFIRINOX 0% Superior to Some or All Equivalent Slightly Inferior MM-398 regimen viewed more favorably than FOLFOX across dimensions of efficacy, safety and dosing* *Source: Clarion TPP Analysis, July,

14 Best Change in Tumor Lesion Size MM-398 Diagnostic Approach with Ferumoxytol * Pre FMX MRI 24 hours post FMX MRI Presented at ICSB 2014 and AACR 2014 grow 9 patients 31 lesions 6 indications *The FDA has approved ferumoxytol (Feraheme, AMAG Pharmaceuticals) for intravenous use as an iron replacement product for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). The use of ferumoxytol in the pilot study mentioned above has not been approved by the FDA and is for clinical investigational studies only. More FMX uptake stable shrink 14

15 MM-398 Path Forward & Next Steps Regulatory Rolling NDA submission completed in April Received Fast Track and Orphan Drug designations; have requested Priority Review Commercial Expansion Experienced team preparing for US launch Geographic concentration of pancreatic cancer centers enables focused commercial team Third-party market research shows favorable oncologist impression of MM-398+5FU/LV profile Planning trial initiations in front-line pancreatic and HER2-negative gastric ISTs in glioma and Ewing s sarcoma Deposition diagnostic development 15

16 MM-302 Design Integrates Proven Therapeutic Approaches in HER2+ MBC MM-302 antibody liposome conjugate: delivers a large chemotherapy payload 1. HER2 target validated in HER2+ MBC 2. Doxorubicin approved chemotherapy with greatest activity in HER2+ MBC 3. Liposomal Encapsulation aims to avoid cardiotoxicity of doxorubicin 16

17 Significant Need for Improved Treatment Options in Late-line HER2+ MBC Number of Patients (per year in US)* Standard of Care Therapy 1 st Line 2 nd Line 3 rd, 4 th Line or greater 8,800 7,500 8,500 Pertuzumab + trastuzumab + taxane T-DM1 No clear SOC Median PFS 18 months 1 10 months months 3 Clinical Outcome ~30% progress in 12 months ~20% don t respond ~30% progress in <6 months ~55% don t respond Rapid progression ~90% don t respond 1 CLEOPATRA, Baselga, et al EMELIA, Verma, et al TH3RESA, Krop, et al 2014 *Taken from Decision Resources, 2014 report 17

18 MM-302 Shows Promising Ph1 Activity MM-302 Phase 1 Efficacy (MM-302 alone, with trastuzumab and with trastuzumab and cyclophosphamide) Overall Median PFS (n=62) 7.6 mo Greatest activity in anthracycline-naïve patients (n= 25 in anthracycline-naïve patients) ORR = 24% (6/25) PFS = 11 mo Overall population received a median of 4 prior lines of therapy Includes only patients dosed at therapeutic doses ( 30mg/m2) Data Presented at AACR

19 MM-302 HERMIONE Trial: Potential Registration Path in HER2+ MBC Randomization 1:1 (250 patients) Patient population HER2-positive MBC Anthracycline-naive Prior exposure to pertuzumab and T-DM1 Experimental Arm MM-302 (Q3W) Herceptin (Q3W) Control Arm Chemo of Physician s Choice Herceptin (Q3W) Primary endpoint: Progression- Free Survival Study is designed to support a potential application for accelerated approval in the U.S. and conditional marketing authorization in the E.U. Currently enrolling US sites: Patients with HER2+ locally advanced and metastatic breast cancer No restriction on number of prior lines of therapy Anticipate 70 sites in US, Canada and EU Chemotherapy of physician s choice: one of gemcitabine, capecitabine or vinorelbine Primary endpoint: Hazard Ratio of (8 mo experimental arm vs. 5 mo control arm ) 19

20 # patients MM-121: Addressing ErbB3-Driven Cancers MM-121 is a monoclonal antibody targeting ErbB3 Wholly owned 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 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 20

21 MM-121 PFS Data in Biomarker-Selected Population Comparison of MM-121+SOC vs. SOC for biomarker positive patients Breast cancer Ovarian cancer Lung cancer HRG HIGH * (Archived tissue) HRG HIGH, HER2 LOW (Pre-Rx biopsy) HRG HIGH * (Pre-Rx biopsy) exemestane MM exemestane paclitaxel MM paclitaxel erlotinib MM erlotinib N= N=18 N= N= N=14 N= Time (months) Time (months) Time (months) Study Biomarker Positive Population * HER2 was low in the majority of breast and NSCLC samples, so HER2 measurements were not needed. N HR Prevalence P-value Breast % Ovarian % Lung %

22 Blocking Heregulin is a Large Opportunity in Oncology ER/PR+, HER2- Breast ER-/PR-/HER2+ Breast Triple Negative Breast ER/PR+, HER2+ Breast 45% 59% 49% 53% Bladder Cervical Colorectal Head & Neck 39% 59% 28% 97% Liver Lung, Adeno Lung, Squamous Ovarian 48% 45% 87% 33% Pancreatic Prostate Melanoma Uterine 33% 35% 34% 21% Data from TCGA, based on the observed prevalence of heregulin in ER/PR+, HER2- breast cancer 22

23 MM-121: Targeted Indications Represent Breast cancer ER+, HER2- mbc 326K Patients Annually HRG+ (~45%) MM paclitaxel HRGpaclitaxel MM-121 Eligible Patients HRG+ 36K TNBC HRG+ (~49%) MM chemotherapy chemotherapy HRG+ 6K HRG- Lung cancer EGFR w.t. NSCLC HRG+ (~54%) HRG- MM docetaxel/pemetrexed docetaxel/pemetrexed HRG+ 284K G

24 MM-121 NSCLC Trial Initiated Initiated a Ph2 biomarker-selected clinical trial in patients with heregulin positive non-small cell lung cancer (NSCLC) Merrimack s first study to prospectively select patients based on heregulin status Builds on our learnings from previous MM-121 Ph2 clinical trials completed across lung, ovarian and breast cancers Trial will enroll 120 heregulin positive patients randomized (2:1) to receive either MM-121 plus the investigator s choice of docetaxel or pemetrexed, or the investigator s choice of docetaxel or pemetrexed alone The primary endpoint of the trial is PFS Development plans for breast cancer 24

25 MM-141 Overview Dual antibody inhibitor of IGF-1R and ErbB3 Two unique mechanisms of action: Blocks oncogenic signaling induced by multiple growth factors: IGF-1, IGF-2 and heregulin Degrades receptor complexes that contain IGF-1R and ErbB3 Orphan drug status Wholly owned Global Ph2 trial in patients with metastatic pancreatic cancer who have high serum levels of free IGF-1 Anti-IGF-1R IgG1 antibody (KD=0.3nM) genetically fused with anti-erbb3 antibody fragment (KD=0.9nM) 25

26 MM-141 Ph2 Pancreatic Study Design Front-line Metastatic Pancreatic Cancer Low Free IGF-1 (~104) Observational Group* *OS data collection Screening High Free IGF- 1 (158) Safety Run-in (6-12) Interventional Group** **Mandatory tissue sample for HRG analysis Patients to receive: MM-141 (2.8 grams IV ) or placebo q2w R 1:1 Nab-paclitaxel (125 mg/m 2 IV) and gemcitabine (1000 mg/m 2 IV) weekly for 3 weeks Randomized, double-blind, placebo-controlled Primary endpoint: Progression-free survival HR 0.63, 80% power, p=0.05 Co-primary endpoint: PFS in HRG+ population HR 0.5, 80% power, p=0.05 Secondary endpoint: Overall survival MM nab-paclitaxel and gemcitabine (73) Placebo + nab-paclitaxel and gemcitabine (73) 26

27 MM-398 NDA filing acceptance Upcoming Milestones Initiation of front-line pancreatic and gastric trials Continued commercial preparation ahead of potential post-gem launch MM-121 Planning registration trials in ER/PR+ and TNBC Continued enrollment for Ph2 trial in HRG-positive NSCLC MM-302 Continued enrollment for HERMIONE trial in support of accelerated approval MM-141 Continued enrollment for Ph2 trial in IGF-1-positive 1L pancreatic cancer MM-151 Planning a Ph2 trial in CRC 27

28 Oncology Pipeline Candidate* Design Target Investigational Disease State(s) Preclinical Phase 1 Phase 2 Phase 3 MM-398 Irinotecan liposome injection Topo I/DNA replication Currently under FDA review MM-302 HER2-targeted nanoliposomal doxorubicin Topo II/DNA replication Breast MM-121 Monoclonal antibody ErbB3 NSCLC, Breast MM-111 Bispecific antibody ErbB3 and ErbB2 Gastric MM-141 Bispecific tetravalent antibody IGF-1R and ErbB3 Pancreatic MM-151 Oligoclonal antibody EGFR Colorectal MM-310 Targeted nanoliposome Undisclosed Cancer MM-131 Bispecific antibody HGF-R (c-met) and EpCAM Cancer * None of our product candidates are approved for any indication by the FDA or any other regulatory agency. Nanoliposomes Antibodies 28