ArQule Jefferies Global Healthcare Conference June 2015 1
ArQule Corporate Update Safe Harbor This presentation and other statements by ArQule may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to clinical trials with the Company s product candidates, including tivantinib (ARQ 197), ARQ 092, ARQ 087, ARQ 761 and ARQ 751, competitive products, financial operations and results, corporate partnerships and other future business objectives, opportunities and strategies. Forward-looking statements are typically identified by words such as believe, expect, anticipate, intend, outlook, position and similar expressions, or future or conditional verbs such as will, should, would, and could. Forward-looking statements are subject to numerous assumptions, risks and uncertainties. Forward-looking statements speak only as of today, and ArQule assumes no obligation to update them. Actual results may differ materially from forward-looking statements or historical performance due to the factors discussed in this presentation and factors previously disclosed in ArQule s SEC reports. See discussion of Risk Factors in the Company s Annual Report on Form 10-K as filed with the SEC. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this presentation. ArQule s product candidates are in various stages of development and are not available for sale or use outside of approved clinical trials. ArQule and the ArQule logo are registered trademarks of ArQule, Inc. 2
ArQule Corporate Summary o Clinical development company with five drugs in Phase 3, 2, 1b of clinical development o Clinical development programs focused on biomarker defined oncology indications o Entering clinical development stage for treatment of Proteus Syndrome (orphan disease) in partnership with NHI o Sustainable flow of internally discovered molecules with one additional IND to be filed in 2015 o Continuing cost effective exploration of discovery platform in partnership with Beryllium o Experienced management and clinical development team 3
ArQule Financial Profile as of 2014 End o Cash balance Cash and marketable securities at March 31, 2015 Net use of cash guidance 2015 Cash and marketable securities 2015 end guidance o Stock data Shares outstanding Fully diluted shares outstanding $ 54 Mil $ 26-29 Mil $ 32-35 Mil ~63 Mil ~71 Mil 4
ArQule Clinical Programs Overview o Tivantinib, small molecule c-met inhibitor, in Phase 3 trials Pivotal Phase 3 clinical development program in 2 nd line hepatocellular carcinoma, c-met high patients only, with companion diagnostic o ARQ 087, small molecule FGFR inhibitor, in Phase 1b/2 trial Phase 2 in cholangiocarcinoma and Phase 1b in adrenocortical and other tumors harboring FGFR translocations, amplification/mutations o ARQ 092, small molecule inhibitor, in Phase 1b trial o Phase 1b in endometrial cancer, lymphoma and other tumors harboring either or PI3K mutations; Phase 1 in Proteus syndrome with NIH o ARQ 761, NQ01 inhibitor, preparing for Phase 2 trials Phase 2 in preparation in pancreas, bladder with high levels of NQ01. Partnership with UT Southwest. 5
ArQule Clinical Stage Programs Product Target Indications Preclinical Phase 1 Phase 1b/2 Phase 3 Projected data Tivantinib C-Met HCC Ph 3 METIV-HCC Trial (West) 2016 Tivantinib C-Met HCC Ph 3 JET-HCC Trial (Japan) ARQ 087 ARQ 087 ARQ 092 ARQ 092 ARQ 761 FGFR FGFR NQ01 Cholangio carcinoma Solid tumors Solid tumors Proteus syndrome Solid tumors Ph 1 prep. Ph 2 Ph 1b Ph 1b Ph 2 preparation PROPRIETARY PIPELINE 2016 ARQ 751 Next generation Oncology and Rare diseases IND enabling 6
**Dose reduced from 240 mg tablet twice daily (BID) to 120 mg tablet BID following observation of higher incidence of neutropenia. DMC safety analysis of reduced dose cleared the trial to proceed. PK analysis of DMC-determined cohort demonstrated that 120 mg tablet BID has comparable exposure to 240 mg capsule as per the Phase 2 trial data. 7 Tivantinib Phase 3 HCC (West w Daiichi Sankyo) Tivantinib in HCC Second-Line, MET Diagnostic-High Phase 3 Pivotal Single Agent Trial With Companion Diagnostic Inoperable locally adv/metastatic disease Prior sorafenib treatment MET diagnostic-high (assessed by IHC) Companion diagnostic Tivantinib 120 mg tablet BID** ~200 pts Placebo ~100 pts Stratification Factors Vascular invasion Extra-hepatic spread AFP (< or > 200 ng/ml) Endpoints 1 o : OS 2 : PFS, safety 3 : ORR, DCR, TTP, PD, PK, biomarkers
Statistical Assumptions for METIV-HCC Trial Estimated Completion of Patient Accrual Q4 2015 o Primary endpoint OS o > 257 events required o Median OS assumption 7.7 months in treatment arm 5.0 months in placebo arm Hazard ratio = 0.65 o Interim analysis ~ 154 OS events (60 percent of OS events) Efficacy stop, no futility stop, minimal alpha spend 8
METIV Based on Successful Phase 2 Results Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study Volume 14, Issue 1, Pages 55-63, January 2013 Our trial provides new information regarding the likely role of MET in the biology of hepatocellular carcinoma, as a prognostic and predictive biomarker, and suggests that patients with METhigh tumours who have failed or are intolerant to sorafenib might benefit from a targeted MET inhibitor. Further study of tivantinib in a biomarker-selected patient population is warranted. MET-high patients o In the MET-high sub group, median time to progression was 2.7 months (95% CI 1.4 8.5) in the tivantinib group compared with 1.4 months (1.4 1.6) in the placebo group (HR 0.43, 95% CI 0.19 0.97; p=0.03 o Median overall survival was 7.2 months months (95% CI 3.9 14.6) for patients with MET-high tumours who received tivantinib versus 3.8 months (2.1 6.8) for MET-high patients who received placebo (HR 0.38, 95% CI 0.18 0.81; p=0.01 9
HCC a Significant Unmet Need o 5 th most common malignancy; 3 rd leading cause of cancer-related death worldwide [1] o Sorafenib is the only approved systemic agent for treatment of advanced 1 st Line HCC o No standard of care exists for 2 nd Line HCC o Several negative Phase 3 studies to date in both 1 st and 2 nd Line, NONE biomarker directed and NONE focused on selected patient population o Only one biomarker directed Phase 3 trial ongoing: METIV HCC testing tivantinib in 2 nd Line HCC o Great need for new, effective therapies but clinical and molecular diversity of HCC poses challenge for drug development [2] 1. Ferlay J, et al. Int J Cancer. 2010;127:2893-2917. 2. Llovet JM, et al. J Clin Oncol. 2013;31:3509-3516. 10
ArQule Program (ARQ 092 & ARQ 751) Product Target Indications Preclinical Phase 1 Phase1b/2 Phase 3 ARQ 092 Endometrial cancer Ph 1b ARQ 092 Lymphoma Ph 1b ONCOLOGY ARQ 092 Solid tumors Ph 1b ARQ 092 ARQ 092 ARQ 092 Proteus syndrome Cowden syndrome Cloves syndrome Ph 1 prep. Preclin. Preclin. DRIVEN ORPHAN DISEASES ARQ 751 Next generation Oncology and Rare diseases IND enable NEXT GENERATION 11
ARQ 092 Best in Class Profile o Phase 1a completed with 82 patients treated in three schedules o RP2D established for continuous (60 milligrams daily), intermittent (200 milligrams daily every other week) and weekly dosing (600 milligrams once a week) schedules o Well tolerated with hyperglycemia, rash, mild liver function impairment and stomatitis as adverse events o Safety profile differentiated from other inhibitors in the clinic; hyperglycemia precedes rash o Pharmacodynamics show correlation between blood sugar, insulin and drug levels o Target knockdown demonstrated in paired biopsies 12
ARQ 092 Phase 1a Trial Summary Selected Patients with Tumor Types Who Stayed on Treatment with ARQ 092 for More Than 16 Weeks Baseline 0036 (Lymphoma CLL) 0039 (Endometrial) 0007 (Endometrial) 0018 (Endometrial) 0047 (Pancreatic neutroendocrine) 0019 (Neuroendocrine) 0008 (neuroendocrine) 0060 (Pancreatic neuroendocrine) 0009 (Pancreatic neutroendocrine) 0010 (NSCLC) 0025 (NSCLC) 0080 (NSCLC) 0012 (Ovarian) 0049 (Ovarian) 0028 (Head/Neck) 0081 (Colorectal) 0016 (Meningioma) PR -21% reduction in tumor burden -18% reduction in tumor burden Ongoing Ongoing 4 months PI3K/PI3K1 mutations 0 10 20 30 40 50 60 70 Weeks 70-year-old White male with chronic lymphocytic leukemia /small lymphocytic lymphoma diagnosed in 2002, received 5 lines of prior therapies 13
ARQ 092 Phase 1b Oncology Design o Objectives Identify a molecularly defined population where ARQ 092 demonstrates evidence of clinical activity o Based on dose escalation patients, preclinical data and literature, three additional cohorts are enrolling (1 E17K) and PI3K (1047R) activating mutations Endometrial tumors with PI3K and activating mutations Lymphomas with PI3K and BTK responsive lymphomas 14
ARQ 092 First in Class in Proteus Syndrome o Proteus syndrome is a rare disorder (incidence <1 in 1 Million people worldwide) characterized by non-cancerous overgrowth of skeleton, skin, adipose tissue and central nervous system o Approximately 100 patients are being actively followed clinically in the US and ~200 in West 15
ARQ 092 NIH Phase 1 Trial in Proteus Syndrome First ever attempt to systemic therapy in Proteus Syndrome o Proposed study A standard 3+3 Phase 1 dose escalation design Continuous dosing based on preclinical and oncology clinical data Safety and percent inhibition of p will be analyzed after completion of each dose level prior to determining the need for a dose escalation to the next dose level o Objectives Safety and tolerability Tissue p inhibition and ARQ 092 concentration Change in Proteus syndrome manifestations Imaging Photography Quality of life and patient reported physical functioning 16
ARQ 087 Phase 1a Trial Summary o Phase 1a completed, 60 patients treated, RP2D established as 300 mg daily o Safety profile differentiated from other FGFR inhibitors, no renal toxicities so far o Preliminary single agent activity: confirmed stable disease > 16 weeks in 10 of 57 subjects in dose expansion cohorts, including two adrenocortical tumors o Increased FGFR levels identified as a potential surrogate marker, evaluation of other biomarkers ongoing o Phase 1b patient selection strategy defined to provide rapid POC currently focusing in adrenocortical tumors and those with FGFR translocations, amplification and mutations o CHOLANGIOCARCINOMA Responses observed in Phase 1a/b in intrahepatic cholangiocarcinoma patients with FGFR2 fusions; Phase 2 ongoing in cholangiocarcinoma 17
ARQ 087 Cholangiocarcinoma Patient B PR Patient (ongoing in Cycle 5) with intrahepatic cholangiocarcinoma (icca) (FGFR2 BICC1 fusion) treatment-naive had a Partial Response: C3D1 35% after two cycles of treatment 18
ARQ 087 Phase 2 Trial in Cholangiocarcinoma o Objectives Determine Overall Response rate and response duration in Intrahepatic Cholangiocarcinoma (ICC) with FGFR2 fusions o Design A cohort of up to 20 ICC patients with known fusions will be enrolled Secondary endpoints Tumor marker changes, safety and pharmacokinetics in this population Progression Free Survival FGFR-related markers 19
ArQule Clinical Stage Programs Product Target Indications Preclinical Phase 1 Phase 1b/2 Phase 3 Projected data Tivantinib C-Met HCC Ph 3 METIV-HCC Trial (West) 2016 Tivantinib C-Met HCC Ph 3 JET-HCC Trial (Japan) ARQ 087 ARQ 761 ARQ 092 ARQ 087 ARQ 092 FGFR NQ01 FGFR Cholangio carcinoma Solid Tumors Solid tumors Solid tumors Proteus syndrome Ph 2 preparation Ph 1b Ph 1b Ph 1 prep. Ph 2 PROPRIETARY PIPELINE 2016 ARQ 751 Next generation Oncology and Rare diseases IND enabling 20