Corporate Overview. September 2018

Transcription

1 Corporate Overview September 2018

2 Forward Looking Statements To the extent that statements contained in this presentation 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, future revenues 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 potential for Merrimack s product candidates to provide clinical benefit, the timing of availability of clinical trial data, the anticipated achievement and receipt of milestones and the availability of funding sufficient to fund Merrimack s operations. Such forwardlooking 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 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 product 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 August 7, 2018 and other reports Merrimack files with the SEC. 2

3 Merrimack: A Passion for Outthinking Cancer Pipeline Clinical-stage oncology company focused on biomarker-defined cancers; nine wholly-owned clinical and preclinical programs Biomarker Focus Personalized studies designed around a fundamental understanding of cancer pathways and drug metabolism Data-rich 2018 Two clinical data readouts anticipated in 2H 2018; robust discovery engine to repopulate pipeline as assets mature Financial Position Cash runway anticipated into at least Q1 2020; experienced management team focused on prioritized pipeline and efficient use of cash 3

4 Data-rich wholly-owned programs 3 clinical trials 1 unified focus robust clinical and preclinical pipeline two readouts expected in 2H 2018; one in Ph. 2 biomarker-defined cancers 4

5 Executive Leadership Team Richard Peters, MD, PhD President & Chief Executive Officer Daryl Drummond, PhD Head of Research Ellen Forest Head of Human Resources Jean Franchi Chief Financial Officer INDUSTRY EXPERIENCE INCLUDES: Jeff Munsie General Counsel Head of Corporate Operations Sergio Santillana, MD, MSc Chief Medical Officer 5

6 Board of Directors Gary Crocker Chairman of the Board President and Managing Director Crocker Ventures, LLC George Demetri, M.D. Board Member Professor of Medicine, Harvard Medical School Faculty Member, Dana-Farber Cancer Institute James Quigley Board Member CEO Emeritus Deloitte John Dineen Board Member CEO Emeritus GE Healthcare Richard Peters, M.D., Ph.D Russell Ray Board Member Board Member President & CEO Managing Director Emeritus Merrimack Stifel Healthcare Investment Banking Ulrik Nielsen, Ph.D Board Member CEO Emeritus, Torque Therapeutics Co-Founder, Merrimack 6

7 Scientific Advisory Board Peter Blume-Jensen, M.D., Ph.D. Founder and President, Acrivon Therapeutics George Demetri, M.D. Senior Vice President, Experimental Therapeutics, DFCI Director, Center for Sarcoma and Bone Oncology, DFCI Professor of Medicine, Harvard Medical School Co-Director, Ludwig Center at Harvard Douglas A. Lauffenburger, Ph.D. Ford Professor of Bioengineering Head of Department, Biological Engineering Massachusetts Institute of Technology Lee N. Newcomer, M.D., M.H.A. Former Senior Vice President, Oncology and Genetics UnitedHealthcare Peter Sorger, Ph.D. Otto Krayer Professor of Systems Biology Program Head, Therapeutic Science Director, Laboratory of Systems Pharmacology Harvard Medical School Josep Tabernero, M.D., Ph.D. Head of Medical Oncology, Vall d Hebron Barcelona Hospital Director, Vall d Hebron Institute of Oncology (VHIO) Head of Research Innovation, Catalonian Cancer Centers Network 7

8 Diversified Pipeline Shaped by Three-Pronged Strategy 1. Understand the Problem A Clear Understanding of Cancer Pathways Cancer pathways (Systems Biology) Drug metabolism (Systems Pharmacology) 2. Design Specific Solution Treatments designed with pharmacological properties to match disease need Engineered antibodies Antibody-directed nanotherapeutics 3. Test Solution in Homogeneous Populations Biomarker-driven clinical strategies with clear clinical rationale Biomarker-enriched clinical trials 8

9 Our Pipeline: 9 programs, 3 clinical trials, 1 unified focus.

10 Clinical Pipeline PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MM-121 (seribantumab) Monoclonal antibody targeting HER3 Description: HRG+, non-small cell lung cancer (NSCLC) Study Name: SHERLOC study Status: Enrollment completed; top-line randomized Phase 2 data anticipated second half of 2018 Description: HRG+, HR+, HER2- metastatic breast cancer Study Name: SHERBOC study Status: Enrolling patients MM-310 Antibody-directed nanotherapeutic (ADN) targeting EphA2 Description: Solid tumors Status: Enrolling patients; Phase 1 safety data anticipated second half of 2018 Growth factor pathway Cellular proliferation/repair 10

11 Preclinical Pipeline TARGET DISCOVERY TARGET VALIDATION LEAD DISCOVERY LEAD OPTIMIZATION PHARMACOLOGIC PROFILING IND FILING MM-161 Monoclonal antibody targeting FGFR IIIc-Isoforms ATRi Nanoliposome targeting ATR TRAIL Ligand fusion targeting Death Receptor 4 and Death Receptor 5 BCL 2 /BCL XL Nanoliposome targeting BCL 2 /BCL XL Immuno-oncology Undisclosed STIMULI Multispecific TNF superfamily receptor agonists for immune stimulation Growth factor pathway Cellular proliferation/repair Immuno-oncology 11

12 MM-121 MM-121 (seribantumab) Seribantumab is an innovative fully human monoclonal antibody that blocks HER3 12

13 MM-121 (seribantumab): Overview Robust data package Safety: 727 patients treated in previous clinical trials; well-tolerated as a combination therapy Biomarker-positive patients: Retrospective analyses in breast, non-small cell lung and ovarian cancer showed heregulin positive (HRG+) subgroups had statistically significant hazard ratios of 0.26, 0.35 and 0.37, respectively, for PFS U.S. Orphan drug designation received for the treatment of heregulin (HRG) positive non-small cell lung cancer Potential commercial opportunity Non-Small Cell Lung Cancer: Initial planned indication: Combination with chemotherapy for HRG+ NSCLC following platinum-based therapy, with prior immuno-oncology therapy allowed Advanced Breast Cancer: Initial planned indication: Combination with hormone therapy in patients with HRG+, HER2- metastatic breast cancer after prior treatment with CDKi Additional Indications: ~50% of solid tumors are HRG+ Companion diagnostic Heregulin positive status: prognostic and predictive value Partnered with Leica for development of HRG-ISH IVD kit for PMA and commercialization Single assay with established cut points for both breast and lung cancer 2016 Merrimack Pharmaceuticals, Inc. All rights reserved

14 Biological Rationale For Targeting HER3 Heregulin Induces Drug Tolerance/Resistance HRG-driven loss of sensitivity: CDK4/6i and mtorci Enhanced immune evasion: upregulated checkpoint ligands (PDL1) Isotype Control Non-treated sample HRG-treated sample Loss of sensitivity: chemotherapies Loss of sensitivity: antihormonal therapies Fulv - HRG Via HRG-increased cell cycle progression CDK2 pcdk 2 Via activation of alternative signaling pathways mediating drug tolerance HRG positive cells protected against effects of standard of care HRG negative cells that are susceptible to standard of care Merrimack Pharmaceuticals, Inc. All rights reserved. 14

15 MM-121 Blocks Heregulin (HRG)/HER3 Signaling HRG/HER3 drive tumor cell resistance Key Biomarker HER3 Seribantumab displaces HRG from HER3 Therapeutic Diagnostic HER3 Therapeutic: Seribantumab (MM-121) Potentially first to market Fully human IgG2 Blocks heregulin binding to HER3 Down-regulates HER3 Diagnostic: Heregulin Superior technology using RNA in-situ hybridization Pathologist-scored assay Cut-point established in Phase 2 15

16 Heregulin Identified As Predictive Biomarker For MM-121 Conclusion from previous development program: Seribantumab combines well with cytotoxic and targeted therapies Focus development on HRG+ patients in solid tumor indications with highest prevalence and highest unmet need Breast Cancer Ovarian Cancer Non-Small Cell Lung Cancer Prevalence: 45% Prevalence: 38% Prevalence: 54% HRG+ (Archived tissue) HRG+, HER2-low (Pre-Rx biopsy) HRG+ (Pre-Rx biopsy) Progression-free survival exemestane MM exemestane paclitaxel MM paclitaxel erlotinib MM erlotinib Time (months) Time (months) Time (months) Hazard ratio (TRT vs. CTR) P-value Hazard ratio (TRT vs. CTR) P-value Hazard ratio (TRT vs. CTR) P-value

17 Heregulin Companion Diagnostic Overview Fully automated RNA in situ hybridization assay Run on a Leica autostainer, the market leader for automated RNA tissue staining assays Amenable to many sample types Core needle biopsies Fine needle aspirates Surgical resections Age of formalin fixed paraffin embedded (FFPE) tissue block does not affect performance HRG Pathologist scored Well-defined scoring system Visualization of HRG in tumor vs normal tissue Scoring in tumor cells correlated best with clinical outcomes High inter-pathologist scoring concordance High sensitivity & specificity 17 HRG splice variants activate ErbB3 receptor, all variants are detected 17

18 MM-121 (seribantumab) SHERLOC Study in NSCLC PHASE 2 RANDOMIZED PATIENT ENROLLMENT COMPLETED Non-small cell adenocarcinoma of the lung 2 nd /3 rd line treatment Progression after platinum-based regimen Prior I/O allowed Heregulin (HRG) ISH screening HRG+ Randomize 2:1 (N=100) Seribantumab + Docetaxel (N=67) Docetaxel (N=33) STATISTICS: Primary Endpoint: Progression-Free Survival (PFS) PFS Assumptions: 6 months (treatment) vs. 3 months (control) 80% power, HR 0.50 assuming a 1-sided significance level of NEXT MILESTONE: Top-line readout expected in 2H

19 MM-121 (seribantumab) SHERBOC Study in mbc PHASE 2 RANDOMIZED - ACCRUING PATIENTS HR+, HER2- metastatic breast cancer HRG+ Seribantumab + Fulvestrant (N=40) 2 nd /3 rd line treatment Progression after CDKi therapy Heregulin (HRG) ISH screening Randomize 1:1 (N=80) Placebo + Fulvestrant (N=40) STATISTICS: Primary Endpoint: Progression-Free Survival (PFS) PFS Assumptions: 7 months (treatment) vs. 4 months (control) 80% power, HR 0.57 assuming a 1-sided significance level of 0.10 STATUS: Enrolling patients 19

20 MM-121 (seribantumab) Opportunity in Major Markets US, EU5, Japan (2017) Non-small Cell Lung Cancer Breast Cancer Target Patient Population Advanced/metastatic, HRG+, adenocarcinoma, 2L+, post I/O or platinum U.S. orphan drug designation Post-menopausal, metastatic, HRG+, HR+, HER2-, 2L+, post CDK4/6 inhibitor Unmet Need Patient prognosis remains poor No standard of care post I/O in a biomarker-defined subset of patients Need for later-line therapies No standard of care post-cdk4/6 inhibitor in a biomarker-defined subset of patients 2 nd Line+ ~40K ~20K Major markets: Up to ~60K patients per year eligible for MM

21 MM-310 MM-310 MM-310 is an antibody-directed nanotherapeutic (ADN) that contains a novel taxane and targets the EphA2 receptor, which is highly expressed in most solid tumor types 21

22 MM-310: Overview MM-310 encapsulates a novel taxane and targets the EphA2 receptor, an overexpressed protein in % of many major solid tumor types, including ovarian, bladder, gastric, pancreatic and lung cancers Unique mechanism of action: Targeted delivery limits cytotoxic exposure to healthy tissue Preclinical data: MM-310 demonstrated superior antitumor activity and fewer hematologic toxicities versus free docetaxel in animal models Enrollment ongoing for Phase 1, open-label study to assess safety, pharmacology and preliminary activity 2016 Merrimack Pharmaceuticals, Inc. All rights reserved

23 MM-310: EphA2-Targeted Antibody-Directed Nanotherapeutic (ADN) EphA2 targeting [~15 scfv / liposome] Lipid matrix Encapsulation Stability High prevalence in tumors Limited accessibility in healthy organs Expression in tumor and stromal cells Novel taxane [~30,000 molecules / liposome] Potent drug Broad spectrum activity Improved stabilization and release 23

24 Preclinical Activity of MM-310 Prostate Cancer Pancreatic Cancer Gastric Cancer 24

25 MM-310 Study in Solid Tumors PHASE 1 - ACCRUING PATIENTS Solid Tumors MM-310 Dose Level 1 mtpi Dose Escalation MM-310 Dose Level 2 STATISTICS: Primary Endpoint: Determine the maximum tolerated dose (MTD) and describe dose-limiting toxicities of MM-310 monotherapy Modified toxicity probability interval approach (mtpi) to determine the MTD MILESTONE: NEXT MILESTONE: Safety data and MTD expected in 2H

26 A Passion for Outthinking Cancer Upcoming Milestones

27 Data-rich wholly-owned programs 3 clinical trials 1 unified focus robust clinical and preclinical pipeline two readouts expected in 2018; one in Ph. 2 biomarker-defined cancers 27

28 Financial Highlights $60.0M in cash, cash equivalents and marketable securities as of June 30, 2018 Two non-dilutive capital events following Q close: $18.0M milestone payment received from Shire $14.7M in net borrowings from July 2018 loan and security agreement with Hercules Capital These items combined are anticipated to fund planned operations into at least Q Eligible milestone payments related to 2017 asset sale (not included in cash runway): Shire Milestones Value Status Sale of ONIVYDE in two additional major European countries Sale of ONIVYDE in first major non-european, non-asian country First patient dosed in pivotal clinical trial in indication other than pancreatic cancer Total Ipsen Regulatory-Based Milestones* Value Status Approval by the FDA of ONIVYDE for the firstline treatment of metastatic adenocarcinoma of the pancreas, subject to certain conditions Approval by the FDA of ONIVYDE for the treatment of small cell lung cancer after failure of first-line chemotherapy Approval by the FDA of ONIVYDE for an additional, unrelated indication Total $18.0M $5.0M -- $10.0M -- $33.0M $225.0M -- $150.0M -- $75.0M -- $450.0M * To be passed through to stockholders, net of any taxes owed and subject to there being sufficient surplus at that time 28

29 Merrimack is Well-Capitalized to Deliver on Multiple Anticipated Data Readouts Management focused on prioritized pipeline and efficient use of cash Unencumbered pipeline H 2018: Top-line data from randomized Ph. 2 study of MM-121 in HRG+ non-small cell lung cancer 2H 2018: Safety data and maximum tolerated dose from MM-310 Ph. 1 study in solid tumors Continued advancement of preclinical pipeline Cash runway anticipated into at least the first quarter of

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