ArQule April 2015 1
ArQule CorporateUpdate Safe Harbor This presentation and other statements by ArQule may contain forwardlooking 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 761and 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 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 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 oarq 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 Focus on tumor-enriched patient cohorts: tumors (pancreas, bladder) with high levels of NQ01, in partnership with UT Southwest 3
ArQule Financial Profile as of 2014 End o Cash balance Cash and marketable securities at year end 2014 Net use of cash guidance 2015 Cash and marketable securities 2015 end guidance o Stock data Shares outstanding Fully diluted shares outstanding o Key recent sources of funding Share offerings (Jan 2011 and Apr 2012) Partnership milestones Q4 2007-Q12014 $ 61 Mil $ 26-29 Mil $ 32-35 Mil ~63 Mil ~71 Mil $ 103 Mil $ 173 Mil 4
ArQule Clinical Stage Programs Product Target Indications Preclinical Phase 1b/2 Phase 3 Projected Phase 1 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 ARQ 751 FGFR FGFR NQ01 Next generation Cholangio carcinoma Solid tumors Solid tumors Proteus syndrome Solid Tumors Oncology and Rare diseases Ph 1 prep. Ph 1b Ph 1b Ph 2 preparation IND enabling Ph 2 PROPRIETARY PIPELINE 2016 5
Tivantinib Phase 3 HCC (Westw 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 **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. 6
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 7
METIV Based on Successful Randomized Phase 2 8
Tivantinib Successful NIH Ph 2* Prostate Cancer o STUDY DESIGN Randomized, double-blind, placebo controlled Phase 2 trial 78 patients randomized 2:1 to tivantinib vs. placebo Randomization stratified by previous abiraterone or sipulcel-t Primary endpoint progression-free survival (PFS) o CLINICAL OUTCOMES Trial met the end point of PFS, HR=0.53, (95% CI: 0.32 to 0.89), p=0.015 Safety data consistent with previous trials of tivantinib Data presented at ASCO GU, February 26, 2015, Abstract 146 *clinicaltrials.gov identifier NCT01519414 9
ArQule Program (ARQ 092 & ARQ 751) Product Target Indications Preclinical Phase 1 Phase1b/2 Phase 3 Approved 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 10
ARQ 092: Potential Best in Class Profile in Oncology o Phase 1a completed with 82 patients treated in three schedules o RP2Destablished 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 11
ARQ 092 Potent Pan- Inhibitor o ARQ 092 is an orally bioavailable, non-atp competitive allosteric inhibitor o Demonstrated inhibition of tumor cell lines with PI3K/ pathway alterations o Inhibition of tumor growth and downstream signaling in vivo in tumors with dysregulated PI3K/ pathway Analog Biochemical IC 50 (nm) 1 2 3 Pathway Inhibition in AN3CA Cells IC 50 (µm) @ 2hrs p- (S473) p- (T308) p- PRAS40 ARQ 092 2.7 14.4 8.1 0.06 0.04 0.31 ARQ 092 inhibits downstream pathway p- (T308) p- (S473) β-actin (µm) 0 0.012 ARQ 092 0.037 0.11 0.33 1.0 12
ARQ 092 Phase-1a: 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) PR -21% reduction in tumor burden -18% reduction in tumor burden Ongoing 0010 (NSCLC) 0025 (NSCLC) 0080 (NSCLC) 0012 (Ovarian) 0049 (Ovarian) 0028 (Head/Neck) 0081 (Colorectal) 0016 (Meningioma) Ongoing 4 months 0 10 20 30 40 50 60 70 PI3K/PI3K1 mutations 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 in Oncology Design &Objectives 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 & BTK responsive lymphomas 14
ARQ 092 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
NIH Phase 1 Trial with ARQ 092 in Proteus First ever attempt at systemic therapy in Proteus 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 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 Potent FGFR Inhibitor o o o o Potent inhibition against FGFR with demonstrated efficacy in FGFR2 amplified tumors Clean ADME profile, good oral bioavailability and drug-like properties Clinical responses observed in intrahepatic cholangiocarcinoma patients w FGFR2 fusions Phase 2 patient selection strategy defined and may provide rapid POC Biochemical IC 50 (µm) In Vitro PD (p-fgfr) EC 50 (µm) FGFR1* FGFR2* FGFR3* FGFR3 (K560E)* FGFR3 (K560M)* FGFR4* Kato-III SNU-16 0.004 0.002 0.004 0.009 0.011 0.034 0.062 0.067 K i (µm) FGFR1 FGFR2 0.0014 0.0006 ARQ 087 FGFR Inhibition Profile *Data generated using kinase assays at Carna Biosciences Experiments done using active forms of kinases 17
ARQ 087 Phase 1a Summary & Early Efficacy Signals o o Phase 1a completed, 60 patients treated, RP2D established as 300 mg daily 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 o Increased FGFR levels identified as a potential surrogate marker, evaluation of other biomarkers ongoing 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/bin intrahepatic cholangiocarcinoma patients with FGFR2 fusions; Phase 2 ongoing in cholangiocarcinoma 18
Cholangiocarcinoma Patient B (icca) PR Patient (ongoing in Cycle 5) with intrahepatic cholangiocarcinoma (FGFR2 BICC1 fusion) treatment-naive had a Partial Response: C3D1 35% after two cycles of treatment 19
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 20
ArQule Clinical Stage Programs Product Target Indications Preclinical Phase 1b/2 Phase 3 Projected Phase 1 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 ARQ 751 FGFR NQ01 FGFR Next generation Cholangio carcinoma Solid Tumors Solid tumors Solid tumors Proteus syndrome Oncology and Rare diseases Ph 2 preparation Ph 1b Ph 1b Ph 1 prep. IND enabling Ph 2 PROPRIETARY PIPELINE 2016 21