a fully integrated cancer company. · a fully integrated cancer company. jefferies 2015 healthcare...

A Fully Integrated Cancer Company.

Jefferies 2015 Healthcare Conference

June 2, 2015

Robert Mulroy, President & CEO

Forward Looking Statements

2

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 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.

© Merrimack Pharmaceuticals, Inc. 2015

Integrated Medicine

Systems Foundation

Precision Diagnostics

Targeted TherapiesClinical

Translation

A Fully Integrated Cancer Company

© Merrimack Pharmaceuticals, Inc. 2015 3

Recent Progress/Highlights

4

•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

MM-398 NDA Filing

•Entered into a $970M Ex-US partnership for MM-398

•$250M near term funding expansion/commercial

•Development plan for 1L pancreatic and gastric

Baxter Partnership

•128 Ph2 BM+ patients w/ HRs between 0.26-0.37

•Registration path planned in breast and lung cancer

•Targeting >300,000 HRG+ BC & NSCLC patientsMM-121

•Launched Ph2 3L HER2+ breast cancer trial

•Designed for potential Accelerated Approval application

•Targeting ~8,000 US patients post T-DM1MM-302


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© Merrimack Pharmaceuticals, Inc. 2015

Systems-Driven Clinical Insights

Resistance Exposure Synergy

Network Dx uAnatomy Dx


Drugs Engineered to Specific Cancer Biology

PCMM-310

undisclosed

MM-131c-Met & EpCAM

DX-929Nano-imaging agent

Phase 1

MM-302

nano-doxorubicin

MM-151

EGFR

Phase 2MM-121

ErbB3

MM-141IGF1R-ErbB3

MM-111ErbB2-ErbB3

MM-302nano-doxorubicin

Phase 3

MM-398

irinotecan liposome injection


nanoliposomes antibody-targetednanoliposomes

mAb bi-specificantibodies

oligoclonal

MM-398 MM-302MM-310

MM-121 MM-141MM-131

MM-151

Systems Diagnostics

Network Inhibitors

Targeted Cytotoxics

MACK IM Regimens

Rational Development of Integrated Medicines

Network Activation:

Deposition:

398 302

310 312

121 111

151 141

FMX Dx929

Dx121 Dx111

Dx141 Dx151

131 161


9

Nano Target Payload

MM-398 Macrophages80,000 CPT-11;

locally activated SN-38

MM-302 HER230,000 Doxorubicin;

Internalized

MM-310TBA

Tumor AntigenTBA cytotoxic;

Locally activated

MM-398: 300-fold Increase in Exposure

Nanotherapeutics Designed for ProtectedDelivery and Prolonged Exposure

t1/2 (h) AUC∞(µg*h/ml)

CPT-11 .27 6

MM-398 10.7 2134


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


MM-398+5-FU/LV 6.1 (4.8-8.9)5-FU/LV 4.2 (3.3-5.3)

Unstratified HR: 0.67 (0.49-.092)p = 0.0122

Stratified HR: 0.57 (0.41-0.80)p = 0.0009

MM-398 Ph3 Results

Met clinical endpoints with MM-398 + 5-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


Ov

era

ll S

urv

iva

l P

ro

po

rti

on

Time from randomization (months)

0 3 6 9 12 15 180

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

# at risk:

119

117

68

97

34

51

11

20

6

8

1

0

Median OS, Months (95% CI)

Intent to Treat (ITT1) Population

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.

Ov

era

ll S

urv

iva

l P

rop

ort

ion

Time from randomization (months)

0 3 6 9 12 15 180

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

# at risk:

71

66

52

63

25

38

10

16

6

6

1

0

Per Protocol (PP2) Population

MM-398+5-FU/LV 8.9 (6.4-10.5)5-FU/LV 5.1 (4.0-7.2)

Stratified HR: 0.47 (0.29-0.77)p = 0.0018

Median OS, Months (95% CI)

US EU28 JP

Diagnosed Incidence

45 76 30

First-line 4.2 7.0 1.0

Second-line 10.5 14.1 5.0

Third-line + 4.0 4.7 2.3

Total Eligible 18.7 25.8 8.3

Post-Gemcitabine PanC Opportunity

Positive Post-Gemcitabine Metastatic Patient Dynamics

• Patients receive gemcitabine in all lines of therapy

• Differentiated from “second-line” therapy

• ~19,000 eligible patients in US

• Post-gemcitabine treatment rates growing

Significant Worldwide Opportunity Annually (000’s)

B

A

C


13

New Standard of Care Opportunity

Oncologists View of MM-398

60%37%

3%0%

20%

40%

60%

80%

Superior toSome or All

Equivalent SlightlyInferior

% P

olle

d O

nc

olo

gis

ts*

*Source: Clarion TPP Analysis, July, 2014

MM-398 regimen viewed more favorably than FOLFOX across dimensions of efficacy, safety and dosing*

13

0%

20%

40%

60%

80%

100%

Current 2L Practice

8% Gem/Tarceva®

20% Gem Mono

20% Gem/Abraxane®

20% Capecitabine

20% FOLFOX

10% FOLFIRINOX

% S

ha

re*

2% Other


MM-398 Diagnostic Approach with Ferumoxytol*

14

Be

st C

han

ge in

Tu

mo

r Le

sio

n S

ize

Presented at ICSB 2014 and AACR 2014

Pre FMX MRI 24 hours post FMX MRI

• 9 patients• 31 lesions• 6 indications

More FMX uptake

grow

stable

shrink

*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.


MM-398 Path Forward & Next Steps

15

• Rolling NDA submission completed in April

• Received Fast Track and Orphan Drug designations; have requested Priority Review

Regulatory

• 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

Commercial

• Planning trial initiations in front-line pancreatic and HER2-negative gastric

• ISTs in glioma and Ewing’s sarcoma

• Deposition diagnostic development

Expansion


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 cardiotoxicityof doxorubicin


Significant Need for Improved Treatment Options in Late-line HER2+ MBC

1st Line 2nd Line3rd, 4th Line or

greater

Number of Patients (per year in US)*

8,800 7,500 8,500

Standard of Care Therapy

Pertuzumab + trastuzumab +

taxaneT-DM1 No clear SOC

Median PFS 18 months1 10 months2 3.3 months3

Clinical Outcome

• ~30% progress in 12 months

• ~20% don’t respond

• ~30% progress in <6 months


• Rapid progression


1CLEOPATRA, Baselga, et al 2012 2EMELIA, Verma, et al 2012 3TH3RESA, Krop, et al 2014

*Taken from Decision Resources, 2014 report17© Merrimack Pharmaceuticals, Inc. 2015

MM-302 Shows Promising Ph1 Activity

• 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 2015


MM-302 Phase 1 Efficacy(MM-302 alone, with trastuzumab and with trastuzumab and

cyclophosphamide)

MM-302 HERMIONE Trial:Potential Registration Path in HER2+ MBC

• 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 0.625 (8 mo experimental arm vs. 5 mo control arm )

Patient population

•HER2-positive MBC

•Anthracycline-naive

•Prior exposure to pertuzumab and T-DM1

Primary end-point:

Progression-Free

Survival

Ran

do

miz

atio

n 1

:1

(25

0 p

atie

nts

)

Experimental Arm

• MM-302 (Q3W)• Herceptin (Q3W)

Control Arm

• Chemo of Physician’s Choice• Herceptin (Q3W)


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

20

MM-121 Designed to Target Biomarker Positive (BM+) patients

# p

atie

nts

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

Unmet need


MM-121 PFS Data in Biomarker-Selected Population

Study Biomarker Positive Population

N HR Prevalence P-value

Breast 34 0.26 45% 0.003

Ovarian 57 0.37 38% 0.007

Lung 37 0.35 54% 0.008

21

0.00

0.25

0.50

0.75

1.00

0 2 4 6 8 10

0.00

0.25

0.50

0.75

1.00

0 2 4 6 8 10

Time (months) Time (months) Time (months)

paclitaxel

MM-121 +paclitaxel

exemestane

MM-121 +exemestane

erlotinib

MM-121 +erlotinib

HRGHIGH *(Archived tissue)

HRGHIGH, HER2LOW

(Pre-Rx biopsy)HRGHIGH *

(Pre-Rx biopsy)

Breast cancer Ovarian cancer Lung cancer

N=16

N=18

N=38

N=19

N=23

N=14

Comparison of MM-121+SOC vs. SOC for biomarker positive patients

* HER2 was low in the majority of breast and NSCLC samples, so HER2 measurements were not needed.


Blocking Heregulin is a Large Opportunity in Oncology

ER/PR+, HER2-

Breast

45%

Bladder

39%

Liver

48%

Pancreatic

33%

ER-/PR-/HER2+

Breast

Cervical

Lung, Adeno

Prostate

35%

59%

59%

45%

Triple Negative

Breast

Colorectal

Lung, Squamous

Melanoma

49%

28%

87%

34%

ER/PR+, HER2+

Breast

53%

Head & Neck

97%

Ovarian

Uterine

33%

21%

Data from TCGA, based on the observed prevalence of heregulin in ER/PR+, HER2- breast cancer


MM-121: Targeted Indications Represent 326K Patients Annually

Breast cancerMM-121 + paclitaxel

HRG+(~45%)ER+, HER2-

mBCHRG-

paclitaxel

MM-121 + chemotherapyHRG+(~49%)

TNBC

HRG-

chemotherapy

Lung cancerMM-121 + docetaxel/pemetrexed

HRG+(~54%)EGFR w.t.

NSCLCHRG-

docetaxel/pemetrexed

HRG+

36K

HRG+

6K

HRG+

284K

MM-121 Eligible Patients


G7 2013

MM-121 NSCLC Trial Initiated

• Initiated a Ph2 biomarker-selected clinical trial in patients with heregulinpositive non-small cell lung cancer (NSCLC)

– Merrimack’s first study to prospectively select patients based on heregulinstatus

– 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


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

MM-141 Ph2 Pancreatic Study Design

Front-line Metastatic

Pancreatic Cancer

Placebo +

nab-paclitaxel and gemcitabine

(73)

R

1:1

MM-141 +

nab-paclitaxel and gemcitabine

(73)

Screening

High Free IGF-

1 (158)

Low Free

IGF-1 (~104)

Observational

Group*

Interventional

Group**

Safety Run-in

(6-12)

*OS data

collection

• Patients to receive: • MM-141 (2.8 grams IV ) or placebo q2w

• Nab-paclitaxel (125 mg/m2 IV) and gemcitabine (1000 mg/m2 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

**Mandatory tissue

sample for HRG

analysis26© Merrimack Pharmaceuticals, Inc. 2015

Upcoming Milestones

• MM-398– NDA filing acceptance

– 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


* None of our product candidates are approved for any indication by the FDA or any other regulatory agency.

Candidate* Design TargetInvestigational

Disease State(s)Preclinical Phase 1 Phase 2 Phase 3

MM-398Irinotecan

liposome injectionTopo I/DNA replication

Currently under FDA review

MM-302HER2-targetednanoliposomal

doxorubicin

Topo II/DNA replication

Breast

MM-121Monoclonal

antibodyErbB3 NSCLC, Breast

MM-111 Bispecific antibody ErbB3 and ErbB2 Gastric

MM-141Bispecific

tetravalent antibody

IGF-1R and ErbB3 Pancreatic

MM-151Oligoclonal

antibodyEGFR Colorectal

MM-310Targeted

nanoliposomeUndisclosed Cancer

MM-131 Bispecific antibodyHGF-R (c-Met) and

EpCAMCancer

Oncology Pipeline

AntibodiesNanoliposomes


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