2016 Year-End Results and Conference Call. March 14, 2017

Transcription

1 2016 Year-End Results and Conference Call March 14, 2017

2 Forward Looking Statement This communication contains "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of All statements other than statements of historical fact are statements that could be forward-looking statements. You can identify these forward-looking statements through our use of words such as may, will, can, anticipate, assume, should, indicate, would, believe, contemplate, expect, seek, estimate, continue, plan, point to, project, predict, could, intend, target, potential and other similar words and expressions of the future. These forward-looking statements are subject to risks and uncertainties that may cause actual future experience and results to differ materially from those discussed in these forward-looking statements. Important factors that might cause such a difference include, but are not limited to, the timing, cost and uncertainty of obtaining regulatory approvals for product candidates; our ability to develop and commercialize products before competitors that are superior to the alternatives developed by such competitors; the validity of our patents and our ability to avoid intellectual property litigation, which can be costly and divert management time and attention; and the other factors listed under Risk Factors in our filings with the SEC, including Forms 10-K, 10-Q and 8-K. Celldex does not undertake any obligation to release publicly any revisions to such forward-looking statement to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. 2

3 Pipeline, Celldex Sponsored Studies Drug Candidate and Indication Target Preclinical Phase 1 Phase 2 Phase 3 Glembatumumab vedotin Triple negative breast cancer gpnmb METRIC (registrational study) Glembatumumab vedotin Metastatic melanoma Varlilumab Head and neck, ovarian, colorectal and renal cell carcinomas, and GBM CDX-0158 Gastrointestinal stromal tumors (GIST) and other KIT-positive tumors CDX-3379 Multiple solid tumors gpnmb CD27 KIT ErbB3 (3 arms: monotherapy complete; + varli & + checkpoint inhibitor ongoing) + nivolumab (BMS collaboration) monotherapy ongoing; combo planned in combo regimens CDX-014 Renal cell carcinoma TIM-1 monotherapy ongoing; combo planned 3

4 Pipeline, Third-Party Sponsored Studies* Drug Candidate and Indication Target Preclinical Phase 1 Phase 2 Phase 3 Glembatumumab vedotin Uveal melanoma Sponsor: NCI (CRADA) Glembatumumab vedotin Squamous cell lung cancer Sponsor: PrECOG, LLC CDX-1401 / CDX-301 Multiple solid tumors Sponsor: CITN gpnmb gpnmb NY-ESO-1 Flt3L * In addition to the studies listed above, Celldex also has an Investigator Initiated Research (IIR) program with seven studies ongoing with our investigational agents and additional studies currently under consideration. 4

5 Preclinical Programs CDX-1140 TAM Program Bispecific Antibodies Fully human antibody targeted to CD40 Data at SITC, ASH 2016 Potent agonist activity and a safety profile that allows systemic dosing at levels that provide good tissue and tumor penetration in preclinical models IND planned in 2017 Comprised of the targets Tyro3, AXL and MerTK Potential applications in oncology, inflammation, and infectious disease Developing antibodies and assays to select drug candidates for development Developing a bispecific antibody program that combines different immune targeting antibodies Update later in

6 Glembatumumab Vedotin: ADC Targeting gpnmb in Multiple Indications gpnmb is aberrantly expressed at high levels in a range of cancers Predominantly intracellular in normal cells; may localize to the cell surface in cancer Associated with the ability of cancer cells to invade and metastasize; correlated with reduced time to progression and survival in breast cancer Glemba is designed to release the potent cytotoxin MMAE upon internalization into gpnmb-expressing tumor cells Target Population 2016 Projected Incidence* Est. % Patients gpnmb Positive Est. # Patients gpnmb Positive All Breast Cancers (invasive) 249,000 Metastatic Triple Negative Breast Cancer 20,000 ~20% ( 25% expression) ~40% ( 25% expression) 50,000 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 6 *Estimated patient numbers are calculated based on American Cancer Society incidence projections for 2016

7 Registration Study Design in gpnmb Over-expressing TNBC (METRIC) Patients with metastatic TNBC overexpressing gpnmb ( 25% tumor cells by IHC) n=300 RANDOMIZE (2:1) 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 Treat until unacceptable toxicity or disease progression Tumor assessments (6 week intervals x 6 months; 9 week intervals thereafter) until documented progression Survival follow-up (12 week intervals) Primary endpoint PFS, secondary endpoint OS 300 patients; randomized 2:1 glembatumumab vedotin to capecitabine ~139 sites open across U.S., EU, Canada and Australia; actively accruing PFS on Xeloda monotherapy: ~ months 1,2 1. Kotsori, et al. Oncology. 2010; 79(5-6): Rugo, et al. Cancer Res. 2009;69(2 Suppl):Abstract nr Xeloda is a registered trademark of Genentech 7

8 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 [months] Progression Free Survival [months] Partial Response (PR) [n (%)] Confirmed PR [n (%)] Stable Disease or Better [n (%)] HR=1.37, p=0.20 HR=0.65, p=0.30 HR=0.67, p=0.31 HR=0.14, p= HR=1.19, p=0.42 HR=0.69, p=0.38 HR=0.63, p=0.18 HR=0.11, p= (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%) On target effect clearly demonstrated in targeted patient populations Yardley, et al. J Clin Oncol. 2015; 33(14): Responses per RECIST 1.1 8

9 METRIC Enrollment Improves Over Past 6 Months; Positive Data from Metastatic Melanoma Study Broad education initiatives increase awareness of glembatumumab vedotin and METRIC among physicians; expansion into Europe METRIC study calls for 203 events to evaluate the primary endpoint, PFS Single-agent glembatumumab vedotin in Phase 2 Stage IV metastatic melanoma study had an 11% response rate, 52% disease control rate and a median duration of response of 6 months in patients who had failed a checkpoint inhibitor and BRAF/MEK targeted therapy, if appropriate New combination cohorts added to metastatic melanoma study Combination with varlilumab Combination with either Opdivo or Keytruda Third-party collaborations ongoing in squamous cell lung cancer and uveal melanoma 9

10 Varlilumab: Immune Modulating mab Targeting CD27 Induces activation and proliferation of human T cells when combined with T-cell receptor stimulation 1,2 Varlilumab 1. Ramakrishna, et al. J Immunother Cancer. 2015; 3: Thomas, et al. OncoImmunology 3, e27255;

11 Varlilumab Clinical Development Greatest opportunity is in combination with other agents Studied as a single-agent to establish a safety profile and assess immunologic and clinical activity in patients with cancer Conducted a broad Phase 1 combination program across multiple indications to look at safety and dosing Generated very little toxicity despite showing clear immunologic activation Focus of Phase 2 Clinical Development Combination with glembatumumab vedotin in metastatic melanoma Collaborative study with BMS with Opdivo 11

12 Phase 2 Study of Varlilumab + Nivolumab with BMS Renal Cell Carcinoma n = 25 Multiple Dosing Schedules Colorectal Cancer n = 18 Glioblastoma n = 20 Varlilumab + Nivolumab n = 171 Ovarian Cancer n = 54 Head and Neck Squamous Cell Carcinoma n = 54 12

13 CDX-0158, a Potent Inhibitor of KIT in Phase 1 Humanized monoclonal antibody that prevents KIT activation in tumor cells and mast cells KIT is important in the oncogenesis of many tumor types including GIST, sarcomas, small cell lung cancer, melanoma, AML and mast cell leukemia Acquired resistance to Gleevec, Sutent and Stivarga develops via KIT mutations; high unmet need for new, effective therapies CDX-0158 designed to block receptor dimerization and ligand binding Has shown activity in preclinical models of common KIT resistance mutations Phase 1 dose-escalation study to determine the maximum tolerated dose, a recommended Phase 2 dose, and the safety profile of CDX-0158 in patients with advanced, refractory GIST and other KIT-positive tumors; initiated in December 2015; enrolling ~36 patients Gleevec is a registered trademark of Novartis AG. Sutent is a registered trademark of Pfizer, Inc. Stivarga is a registered trademark of Bayer AG. 13

14 CDX-3379, a Unique ErbB3 Inhibitor is Phase 2 Ready Human monoclonal antibody designed to block the activity of ErbB3 (HER3) ErbB3, a member of the EGFR family, is believed to be an important receptor regulating cancer cell growth and survival and is expressed in many cancers, including head and neck, thyroid, breast, lung, gastric and melanoma Differentiated from other ErbB3 inhibitors in development; may play an important role in overcoming resistance to therapy CDX-3379 binds to a unique epitope in ErbB3 and locks the receptor in its inactive state 1 Mechanism of action suggests CDX-3379 can block both ligandindependent and ligand-dependent ErbB3 signaling Very favorable pharmacologic profile, including a longer half-life than other anti-erbb3 drug candidates Potential best-in-class ErbB3 inhibitor 1. Lee, et al. PNAS. 2015;112(43):

15 Phase 1 Study of CDX-3379 as Single Agent and in Combination CDX Erbitux (n=16) Head & Neck, Colorectal CDX-3379 Dose Escalation In patients with refractory, advanced tumors 5, 10, 20 mg/kg (n=14) and 15 mg/kg or 1200 mg (n=7), every 3 weeks Safety PK, PD, MTD CDX Tarceva (n=8) NSCLC CDX Zelboraf (n=4) BRAF-mutant tumors CDX Herceptin (n=10) HER2+ BC, Esophageal 15 or 20 mg/kg CDX-3379, every 3 weeks No MTD identified; no dose limiting toxicities (DLTs) observed as single agent; most common AEs (predominantly grade 1-2) were rash, diarrhea, dry mouth In combinations, DLTs in 5 of 38 patients (13%), resolved with medical therapy/dose interruptions; toxicity consistent with profile of partner drugs* Trial Identifier: NCT *Data as of 31-Mar-2016 Erbitux is a registered trademark of Eli Lilly & Co. Tarceva is a registered trademark of Astellas. Zelboraf and Herceptin are registered trademarks of Genentech.

16 CDX-014: ADC Directed to a Novel Renal Cell Carcinoma and Ovarian Target Fully human anti-tim-1 IgG1 antibody covalently linked to a potent cytotoxin, monomethyl auristatin E (MMAE) TIM-1 (T-cell Immunoglobulin Mucin-1) expression upregulated in several human cancers, most notably renal cell and ovarian carcinomas; has very restricted expression in healthy tissues 1 Ovarian Cancer Model CDX-014 Phase 1/2 study in advanced renal cell carcinoma (clear cell and papillary) initiated July 2016 Phase 1 dose-escalation study to assess safety and MTD CDX-014 exhibits potent in vitro cytotoxic activity against TIM-1 expressing cell lines and in vivo anti-tumor activity in xenograft models 2 1. Lin, et al. Am J Surg Pathol. 2007; 31(3): Thomas, et al. AACR Poster #

17 Fourth Quarter and Year-End 2016 Financial Results Year Ended Dec. 31, Quarter Ended Dec. 31, Net Loss (128.5) (127.2) (32.3) (32.7) Net Loss Per Share (1.27) (1.31) (0.30) (0.33) R&D Expense G&A Expense Cash, Cash Equivalents & Marketable Securities Shares Outstanding In millions (U.S. Dollars), except per share amounts 17

18 Milestones Program Timeframe Accomplishment Glembatumumab vedotin Triple negative breast cancer Sept Complete METRIC enrollment Metastatic melanoma Fall 2017 YE 2017 Present data from varlilumab cohort Complete enrollment to Opdivo/Keytruda cohort Varlilumab Multiple solid tumors (with Opdivo) May/June 2017 Q Data from Phase 1 dose-escalation Complete enrollment in Phase 2 study CDX-0158 GIST & other KIT-positive tumors YE 2017 Report data from Phase 1 dose-escalation study CDX-3379 Multiple solid tumors 2017 Advance into Phase 2 study CDX-014 Renal cell carcinoma 2017 Complete enrollment in Phase 1 dose-escalation 18

19 2016 Year-End Results and Conference Call March 14, 2017