METRIC Study Key Eligibility Criteria

The METRIC Study METRIC Study Key Eligibility Criteria The pivotal METRIC Study is evaluating glembatumumab vedotin in patients with gpnmb overexpressing metastatic triple-negative breast cancer (TNBC). Approximately 300 gpnmb positive, metastatic TNBC patients will be enrolled in up to approximately 160 sites within the United States, Canada, Australia and Europe This is an open label, 2-to-1 randomized comparison of glembatumumab vedotin versus an active control, capecitabine (Xeloda ) Treatment Design Patients treated over 21-day cycles Randomized 2-to-1 to receive either: - Glembatumumab vedotin: an intravenous infusion of medication (1.88 mg/kg) on day 1 of each cycle, or - Capecitabine: oral medication (1250 mg/m 2 ) taken twice daily on days 1 through 14 of each cycle Treatment cycles continue as long as the cancer does not progress or until a study physician determines that the patient should stop receiving treatment in the study Tumor assessments conducted at 6-week intervals for 6 months and 9-week intervals thereafter, until documented progression Study Endpoints The primary endpoint for this study is progression free survival (PFS) Secondary endpoints include objective response rate, duration of response, overall survival, safety and pharmacokinetics Exploratory endpoints include quality of life and/or reduction in cancer-related pain, assessed through analgesic use To qualify for the METRIC study, a patient must: Be at least 18 years of age Have been diagnosed with metastatic TNBC with: - Minimal or no expression of estrogen and progesterone receptors (ER/PR); <10% of cells positive by immunohistochemistry - HER2 staining 0 or 1+ by IHC or copy number <4.0 signals/cell by ISH Have documented progression of disease based on radiographic, clinical or pathologic assessment during or subsequent to the last anticancer regimen received Have received 0-2 prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer Have prior chemotherapy treatment with a taxane and, if clinically indicated, an anthracycline No prior capecitabine Have ECOG performance status of 0-1 Have adequate bone marrow, liver and renal function No progression/recurrence during or within 3 months of completion of neoadjuvant or adjuvant therapy No ongoing neuropathy or other toxicities that are Grade 2 or worse in severity Breast cancer tumors must be confirmed to express gpnmb. This will be determined by submitting a tissue sample from the advanced (locally advanced/recurrent or metastatic) disease setting to a central laboratory for analysis prior to the study entry (~45% positivity rate). If you have patients who have been diagnosed with metastatic triple-negative breast cancer, we hope that you will consider the METRIC study. To learn more about this study, please contact the study investigator listed on the front of this brochure. Glembatumumab Vedotin (CDX-011) in Patients with Metastatic, gpnmb Overexpressing, Triple-Negative Breast Cancer HELP TAKE TRIPLE-NEGATIVE BREAST CANCER TREATMENT OPTIONS IN A NEW DIRECTION CONTACT A STUDY INVESTIGATOR clinicaltrials.gov/ct2/show/nct01997333

Glembatumumab Vedotin, an ADC targeting gpnmb in multiple cancers Glembatumumab vedotin (CDX-011) is an investigational, fully human monoclonal antibody-drug conjugate (ADC) designed to release monomethylauristatin E (MMAE) upon internalization into gpnmb-expressing tumor cells. MMAE binds to tubulin, inhibiting mitosis and leading to cell cycle arrest and apoptosis. The compound and its metabolites do not accumulate over time. gpnmb as a TNBC Therapy Target Triple-negative breast cancer (TNBC) represents a disease with substantial molecular heterogeneity.¹ Treatment with standard-of-care is associated with progressive resistance and short survival.² There is great interest in identifying molecular markers that can be targeted for therapeutic intervention.³ The transmembrane protein gpnmb is aberrantly expressed at high levels in a range of cancers including breast cancer. High tumor expression of gpnmb is: - Associated with invasion and metastasis 4 - Correlated with reduced time to progression and survival in breast cancer 3,4 - Implicated as a negative regulator of anti-tumor immune response Three Completed Clinical Studies Studied in more than 250 patients with heavily pre-treated breast cancer and melanoma Patients with TNBC derived greater clinical benefit from glembatumumab vedotin than from standard of care Phase 2 EMERGE study results published (Yardley, et al. J Clin Oncol. 2015) The EMERGE Study, a randomized Phase 2 study in patients with locally advanced or metastatic, gpnmb-positive breast cancer Study Design Examined whether the anti-cancer activity of glembatumumab vedotin is dependent upon gpnmb expression Randomized 124 patients (2-to-1) to glembatumumab vedotin (n=83) or to chemotherapy of the investigator s choice (IC) (n=41) Stratified by gpnmb expression pattern: highexpressing gpnmb in 40% of TNBC samples vs. 21% of all others Glembatumumab vedotin (1.88 mg/kg) was administered by IV infusion over 90 minutes once every three weeks. Up to two dose reductions (to 1.34 or 1.0 mg/kg) were allowed for toxicity. Investigator s choice (IC) consisted of single-agent chemotherapy, and dosing and supportive care were managed per standard practice. Study treatment continued until disease progression or intolerance, and after documented progression, IC-treated patients were permitted to receive glembatumumab vedotin in a crossover treatment phase. Efficacy The primary efficacy endpoint, objective response rate (ORR) of more than 10% for all patients, was not met; however, improvements in progression free (PFS) and overall survival (OS) were observed in TNBC patients with high gpnmb expression. Strong trends towards benefits were seen in all patients with high gpnmb expression, and in some cases were statistically significant. Patients receiving IC alone who crossed over to receive glembatumumab vedotin upon disease progression appeared to represent the better outcomes in the control arm, with a median survival of 12.5 months, as compared to those who did not cross over, with a median of 5.4 months. Similar outcomes observed for all patients on glembatumumab vedotin and IC, without selecting for gpnmb expression Efficacy Measures for Patients with TNBC and High gpnmb Expression Glembatumumab Vedotin Investigator s Choice Chemo Patients n=10 n=6 Overall Survival months Progression Free Survival months 10.0 5.5 HR=0.14, p=0.003 3.5 1.5 HR=0.11, p=0.0017 Objective Response Rate (ORR) n (%) 4 (40%) 0 Confirmed PR n (%) 1 (10%) 0 Stable Disease or Better n (%) 9 (90%) 1 (17%) ORR per RECIST 1.1, inclusive of response observed at a single time point Safety Adverse events were manageable and consistent with prior studies Rash, neutropenia, fatigue, nausea, vomiting, peripheral neuropathy and alopecia were more frequent in the glembatumumab vedotin arm Hematologic toxicity was less frequent than IC PFS and OS (but not ORR) were prolonged for patients who developed a rash in cycle 1 compared to those who did not; a similar association was observed in a Phase 1/2 melanoma study 5 Summary Patients with TNBC and tumor gpnmb overexpression may potentially derive the greatest benefit from glembatumumab vedotin The identified threshold for high gpnmb expression, 25% of malignant epithelial cells, includes 41% of the screened patients with TNBC (including archived samples) The ongoing pivotal METRIC study is enrolling patients in order to confirm these findings References 1. Cancer Genome Atlas Network. Nature. 2012; 490:61-70. 2. Crown, et al. Ann Oncol. 2012; 23:vi56-vi65. 3. Yardley, et al. J Clin Oncol. 2015; 33(14): 1609-19. 4. Rose, et al. Clin Cancer Res. 2010; 16(7):2147-56. 5. Ott, et al. J Clin Oncol. 2014; 32(32):3659-66. Xeloda is a registered trademark of Hoffmann-La Roche, Inc.

KEY INCLUSION CRITERIA Patients aged >18 years with mbc TNBC status (ER and PR < 10%; minimal or no expression of HER2) confirmed in advanced setting Documented PD during or subsequent to the last anticancer regimen Overexpression of gpnmb ( 25% of malignant epithelial cells expressing gpnmb, as determined by a central laboratory in at least one tumor obtained in the advanced setting) 0 to 2 prior chemotherapy containing regimens for advanced breast cancer Prior receipt of anthracycline containing chemotherapy in any setting, unless anthracycline therapy is not clinically indicated Prior receipt of taxane containing chemotherapy, in any setting ECOG Performance Status 0 to 1 Life expectancy of 3 months Measurable (target) disease by RECIST 1.1 criteria Resolution of all chemotherapy or radiationrelated toxicities to Grade 1 severity, except for alopecia Adequate bone marrow, liver and renal function See Protocol for Full List of Eligibility Criteria KEY EXCLUSION CRITERIA Progression/recurrence within 3 months of completion of neoadjuvant or adjuvant chemotherapy Baseline neuropathy > Grade 1 Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months prior to randomization Previously received capecitabine and discontinued due to progressive disease or intolerance Active systemic infection requiring treatment; Infection controlled by oral therapy will not be exclusionary Chronic use of systemic corticosteroids above the physiologic dose within 7 days of enrollment, except for premedication Significant cardiovascular disease Any underlying medical condition that, in the investigator s opinion, will make the trial inappropriate Other malignancy except for treated basal or squamous skin cancer, curatively treated in situ disease, or any other cancers free of disease for 5 years See Protocol for Full List of Eligibility Criteria

Glembatumumab Vedotin 1

Glembatumumab Vedotin: gpnmb is an Attractive Target gpnmb is aberrantly expressed at high levels in a range of cancers Predominantly intracellular in normal cells May become localized to the cell surface in cancer Associated with the ability of the cancer cell to invade and metastasize Correlated with reduced time to progression and survival in breast cancer TARGET POPULATION 2016 Projected Incidence* Est. % Patients gpnmb Positive Est. # Patients gpnmb Positive All Breast Cancers (invasive) 249,000 ~20% ( 25% expression) 50,000 Metastatic Triple Negative Breast Cancer 20,000 ~40% ( 25% expression) 8,000 Metastatic Melanoma (Stage III/IV unresectable) 20,600 >80% 16,500 Squamous Cell Lung Cancer 54,000 >85% 45,900 Osteosarcoma 800 >60% 500 Head and Neck Cancer 62,000 >40% 25,000 Pancreatic Cancer 53,000 >55% 29,000 Glioblastoma 12,000 >66% 7,900 *Estimated patient numbers are calculated based on American Cancer Society incidence projections for 2016 2

Glembatumumab Vedotin: ADC Targeting gpnmb in Multiple Indications Antibody drug conjugate designed to release the potent cytotoxin MMAE upon internalization into gpnmbexpressing tumor cells Celldex proprietary target and antibody Fully human IgG2 anti-gpnmb monoclonal antibody Toxin and linker licensed from Seattle Genetics; same technology as Adcetris (brentuximab vedotin) MMAE binds to tubulin, inhibiting mitosis and leading to cell cycle arrest and apoptosis Companion diagnostic to detect gpnmb in development 3 Adcetris is a registered trademark of Seattle Genetics, Inc.

Glembatumumab Vedotin: Summary of Clinical Experience (completed trials) Three completed clinical studies (n=283, including control; patients treated with glembatumumab vedotin=255) Phase 1/2 unresectable stage III or stage IV melanoma (n=117) 1 Phase 1/2 advanced, heavily pre-treated breast cancers (n=42) 2 Phase 2 EMERGE study in advanced, heavily pre-treated breast cancers (n=124) 3 MTD (Phase 2 dose) was established as 1.88 mg/kg q3w in melanoma study; more frequent dosing regimens (q2/3w and qw) were associated with increased toxicity In these early studies, ORR and PFS at the Phase 2 dose have been favorable for the heavily-pretreated populations studied (advanced melanoma and breast cancer) Although sample sizes are small, patients with tumors expressing higher levels of gpnmb consistently appear to derive greater clinical benefit from glembatumumab vedotin as compared to the entire population of treated patients In both breast cancer studies, the subset of patient with triple negative breast cancer, where treatment options are limited, also appeared to derive greater clinical benefit from glembatumumab vedotin 1. Ott, et al. J Clin Oncol. 2014; (32)32: 3659-66. 2. Bendell, et al. J Clin Oncol. 2014; 32(32):3619-3. 25. Yardley, et al. J Clin Oncol. 2015; 33(14): 1609-19. 4

Phase 2 EMERGE Study in Metastatic Breast Cancer: Efficacy Measures (ITT) All Patients Triple Negative High gpnmb Expression Triple Negative and High gpnmb Expression Glemba (n=83) IC (n=41) Glemba (n=28) IC (n=11) Glemba (n=23) IC (n=11) Glemba (n=10) IC (n=6) Overall Survival Progression Free Survival Partial Response (PR) [n (%)] Confirmed PR [n (%)] Stable Disease or Better [n (%)] 7.5 7.4 6.9 6.5 10.0 5.7 10.0 5.5 HR=1.37, p=0.20 HR=0.65, p=0.30 HR=0.67, p=0.31 HR=0.14, p=0.003 2.3 2.0 2.8 1.6 2.8 1.5 3.5 1.5 HR=1.19, p=0.42 HR=0.69, p=0.38 HR=0.63, p=0.18 HR=0.11, p=0.0017 10 (12%) 5 (12%) 5 (18%) 0 7 (30%) 1 (9%) 4 (40%) 0 5 (6%) 3 (7%) 2 (7%) 0 3 (13%) 1 (9%) 1 (10%) 0 41 (49%) 19 (46%) 17 (61%) 3 (27%) 15 (65%) 3 (27%) 9 (90%) 1 (17%) Responses per RECIST 1.1 Yardley, et al. J Clin Oncol. 2015; 33(14): 1609-19. 5 On target effect clearly demonstrated in targeted patient populations

EMERGE: High Tumor gpnmb Expression Correlates with Response Glembatumumab Vedotin Treated Patients Investigator Choice Treated Patients Thresholds of 10% and 25% gpnmb-positive tumor epithelial cells both show significant enrichment of responders The more conservative choice of 25% gpnmb expression was chosen for entry into METRIC Yardley, et al. J Clin Oncol. 2015; 33(14): 1609-19. 6

Glembatumumab Vedotin Safety Profile In breast cancer and melanoma patients, the most frequent ( 20% of patients) treatment-related toxicities were: Rash/alopecia Skin-related AEs were more common/severe in melanoma Rash associated with greater PFS and ORR in melanoma and prolonged PFS/OS in EMERGE breast cancer study Neutropenia Fatigue/anorexia Nausea/vomiting Diarrhea Peripheral neuropathy Glembatumumab vedotin safety profile is consistent with the class of drugs using the same linker and MMAE, including the approved drug Adcetris Glembatumumab vedotin hematologic toxicity may be less frequent/severe Glembatumumab vedotin rash (mild to moderate severity) may be more frequent (compared with agents recently approved for refractory breast cancer 2,3 ) 1. Younes, et al. N Engl J Med. 2010; 363(19): 1812-21. 2. Perez, et al. J Clin Oncol. 25(23):3407-14. 3. Cortes, et al. Lancet. 2011; 377(9769):914-23. Adcetris is a registered trademark of Seattle Genetics. 7

RANDOMIZE (2:1) Registration Study Design in gpnmb Over-expressing TNBC (METRIC) Patients with metastatic TNBC overexpressing gpnmb ( 25% tumor cells by IHC) n=300 glembatumumab vedotin 1.88 mg/kg IV Day 1 of 21-day cycles capecitabine (Xeloda ) 1250 mg/m 2 BID Days 1-14 of 21-day cycles Primary: PFS Secondary: ORR DOR OS Stratification: Line of chemotherapy for advanced disease 0-1 vs. 2 PFS after receipt of taxane therapy 6 months vs. PFS > 6 months Prior anthracycline therapy YES / NO Study initiated Dec 2013 Tumor assessments (6 week intervals x 6 months; 9 week intervals thereafter) until documented progression Survival follow-up (12 week intervals) Clinicaltrials.gov Identifier NCT01997333 Xeloda is a registered trademark of Genentech. 8

METRIC Key Inclusion Criteria Patients with advanced carcinoma of the breast (histologically or cytologically confirmed) gpnmb over-expression ( 25% of tumor epithelial cells positive by IHC) on samples obtained in the setting of advanced disease confirmed/determined at a central laboratory (Clarient) ER and PR negativity defined as ER/PR: <10% of cells positive by IHC HER2 negativity defined according to 2013 ASCO/CAP guidelines Prior receipt of taxane-containing chemotherapy in any setting Prior receipt of anthracycline containing chemotherapy in any setting, unless anthracycline therapy is not clinically indicated in the opinion of the treating investigator 0-2 lines of chemotherapy for advanced disease ECOG performance status 0 to 1 Life expectancy 3 months 9

METRIC Key Exclusion Criteria Subjects unable to provide informed consent and/or unable to comply with the study procedures Investigational therapy within 4 weeks before planned start of study treatment Persistent neuropathy > NCI-CTCAE v 4.0 Grade 1 at Randomization Known active brain metastases unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months prior to randomization Significant cardiovascular disease 10