Corporate Overview. April 2016

Transcription

1 Corporate Overview April 2016

2 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, ARQ 751 and ARQ 531, 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

3 The ArQule Mission Our mission is to discover, develop and commercialize novel small molecule drugs in areas of high unmet need that will dramatically extend and improve the lives of our patients. Intrahepatic Cholangiocarcinoma/ FGFR translocated cancers ARQ 087 FGFR Inhibitor Proteus syndrome/ AKT mutant cancers ARQ 092 AKT Inhibitor Hepatocellular Carcinoma Tivantinib MET Inhibitor 3

4 The ArQule Strategy Our Strategy Precision Medicine All of our trials are biomarker driven targeting specific mutations which streamlines patient recruitment and enables more efficient go/no-go decisions Rare Diseases All of our trials target patient populations with either no approved therapy or inadequate therapies Patient Advocacy We are aligned with Patient Advocacy groups to help us better connect with the patient community 4

5 Pipeline of Products Tivantinib C-MET ARQ 087 FGFR ARQ 092 AKT ARQ 751 AKT ARQ 761 NQO1 ARQ 531 BTK Pre-Clinical Phase 1a/1b Phase 2 Phase 3 Collaborator METIV-HCC Trial (West) Fully Enrolled JET-HCC Trial (Japan) Intrahepatic Cholangiocarcinoma (icca) Solid Tumors Solid tumors/endometrial/ lymphoma cancer - Fully Enrolled Proteus syndrome Other Rare Diseases Cancer/ Rare Diseases Solid Tumors/Pancreatic Cancer Cancer Regulatory Designation SPA Orphan Drug Designation Orphan Drug Designation Orphan Drug Designation 5

6 Key Near Term Value Drivers ARQ 087 in Intrahepatic Cholangiocarcinoma (icca) Currently enrolling phase 2 portion of trial for icca in FGFR2 translocations Observed three partial responses in phase 1 portion of trial in patients with FGFR2 translocations Currently enrolling in phase 1b trial for other FGFR2 translocated cancers ARQ 092 in Proteus syndrome Our collaborator at the NIH is currently enrolling phase 1 Nature Scientific Reports publication on pre-clinical data confirm ARQ 092 was effective in suppressing AKT signaling ARQ 092 in cancers with AKT1 and PI3K mutations Enrollment completed in phase 1b trial Observed five partial responses in phase 1b thus far four with AKT mutations, one mutation unknown Tivantinib in Hepatocellular Carcinoma (HCC) Phase 3 METIV-HCC trial fully enrolled Planned interim analysis completed, trial to continue to completion Expect data by the end of Q3 16 Expect data by the end of Q3 16 Expect data by year-end 2016 Expect data by year-end

7 ARQ 087 FGFR Responses Trial Cancer Type FGFR Status # of Prior Therapies Treatment Duration Best Response/ Change in Tumor Size Phase 1a icca Not Tested 1 9 weeks SD/+16% Phase 1a icca FGFR2 KIAA weeks PR/-32% Phase 1a icca FGFR2 BICC weeks PR/-35% Phase 1a icca FGFR2 BICC1 2 8 weeks SD/+16%* Phase 1a icca FGFR2 TACC1 2 8 weeks SD/0%* Phase 1a icca FGFR2 CCDC weeks MR/-28% Phase 2 portion icca FISH positive 1 Ongoing MR/-18% Phase 1b Bladder FGFR2 Genetic Alteration 3 ongoing PR/-38% * Target lesion stable but new lesions detected PR = Partial Response defined as 30% shrinkage in tumor; MR = Minor Response defined as 15-30% shrinkage in tumor; SD = Stable disease Phase 2 for icca enrolling patients with FGFR alterations 7

8 ARQ 087 Potent FGFR Inhibitor Multi-kinase inhibitor that potently inhibits FGFR family with demonstrated activity in FGFR2 amplified tumors Clean ADME profile, good oral bioavailability and drug-like properties Clinical responses observed in intrahepatic cholangiocarcinoma (icca) patients with FGFR2 fusions in phase 1 trial Phase 2 patient selection strategy for icca that may provide rapid path to approval Biochemical IC 50 (µm) In Vitro PD (p-fgfr) EC 50 (µm) FGFR1* FGFR2* FGFR3* FGFR3 (K560E)* FGFR3 (K560M)* FGFR4* Kato-III SNU K i (µm) FGFR1 FGFR ARQ 087 FGFR Inhibition Profile *Data generated using kinase assays at Carna Biosciences Experiments done using active forms of kinases 8

9 About icca Intrahepatic cholangiocarcinoma (icca) is a rare disease icca is a type of bile duct cancer that impacts approximately 1.2 in 100,000 people in the U.S. with a rising incidence rate ~3,800 people* The incidence rate is believed to be higher in Europe and Asia There are few, if any symptoms, often leading to late diagnosis Current treatment options are surgery, chemotherapy and liver transplant Recurrence rate exceeds 60% icca has a diverse patient population with a need for precision medicine Multiple genetic mutations are believed to play a role in icca Estimate ~20% of the icca population has a translocation of the FGFR2 gene Other genetic mutations include AKT, IDH1, KRAS, TP53, and c-met The Cholangiocarcinoma Foundation recommends molecular testing for all patients * The Oncologist 2016;21:

10 ARQ 087 Phase 2 for icca Objectives Further explore positive responses observed in Intrahepatic Cholangiocarcinoma (icca) FGFR2 fusions and/or translocations in phase 1a trial and potential expedited path forward Determine Overall Response rate and response duration in icca with FGFR2 fusions Design A cohort of up to 20 (icca) patients with known fusions will be enrolled Secondary endpoints Tumor marker changes, safety and pharmacokinetics in this population Progression Free Survival FGFR-related markers Orphan drug designation granted by FDA 10

11 ARQ 092 and AKT1 Mutation The AKT1 mutation plays a role in oncology and Proteus syndrome ARQ 092 suppresses the AKT pathway via two modes of action 1) By binding to the inactive form of AKT, ARQ 092 prevents membrane localization and full AKT activation 2) ARQ 092 also directly inhibits the membrane associated active form of AKT Potential dual mechanism of action 11

12 Oncology PRs for ARQ 092 ARQ 092 Phase 1a Trial Disease Mutation Best ORR Dose Escalating Trial (n=82) ARQ 092 Phase 1b Trial (3 Expansion Cohorts) Lymphoma Cohort (n=8, fully enrolled) Lymphoma Cohort (n=8, fully enrolled) Endometrial Cohort (n=10, fully enrolled) AKT and PI3K Mutation Cohort (n=9 evaluable) Endometrial Cohort (n=10, fully enrolled) Small Lymphocytic Lymphoma PR = Partial Response defined as at least 30% shrinkage in tumor PIK3CA+PIK 3R1 Disease Mutation Best ORR Assessing dosing and durability Duration on trx (weeks) PR 32 Duration on trx (weeks) Follicular Lymphoma AKT1 E17K PR 17 Follicular Lymphoma Unknown PR 60+ Endometrial PIK3CA H1047R PR 30 Breast AKT1 E17K PR 12 Endometrial AKT1 E17K PR 8 12

13 ARQ 092 Oncology Phase 1b Three cohorts: Lymphoma (fully enrolled) Endometrial tumors (fully enrolled) AKT (AKT1 E17K) and PI3K (PIK3CA H1047R) activating mutations in solid tumors (fully enrolled) Dosing: 200 milligrams daily every other week for solid tumors and 600 milligrams once a week for lymphomas Preliminary signs of efficacy: Lymphoma: 2 PRs observed in heavily pretreated Follicular lymphoma (1 with AKT1 E17K mutation and one unknown) Endometrial: 2 PRs observed (1 with PIK3CA H1047R mutation and one AKT1 E17K mutation) AKT1 E17K mutation and PIK3CA H1047R: 1 PR in breast cancer and 1 MR in a parotid gland tumor Enrollment complete 13

14 PI3K/AKT/mTOR in Rare Diseases CLOVES/PROS PI3K Cowden syndrome PHTS PTEN Shp2 deficient (PTPN11 Y297C ) AKT Proteus syndrome LEOPARD syndrome mtor AKT plays a role in multiple rare over-growth diseases 14

15 About Proteus Syndrome According to the patient advocacy and support group, the Proteus Syndrome Foundation ( the condition was named for Proteus, the Greek god who could transform his shape Patients experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth (overgrowth) of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body which may appear normal 15

16 Proteus Syndrome Patients Proteus syndrome is a rare disorder and an orphan disease (incidence <1 in 1 million people worldwide) Only a few hundred individuals have been reported in medical literature Approximately 50 patients are being actively followed by the NIH in a longitudinal study with the total patient population estimated to be 100 to 200 in the U.S. Patient registries are available in some European countries where advocacy groups are also active Although patients may have minimal or no manifestations at birth, the disease develops and becomes apparent in early childhood (6-18 months) and rapidly progresses with intense growth in the first 10 years of life Very few patients reach adulthood Causes of death for Proteus syndrome patients are bullous lung degeneration, deep vein thrombosis, pulmonary embolism and more rarely cancer Currently the only available therapeutic intervention for Proteus syndrome is surgery, which is problematic and characterized by poor wound healing; symptomatic removal of lesions does not arrest continued overgrowth 16

17 ARQ 092 Proteus Trial Design On-going NIH sponsored Phase 1 study A 3+3 Phase 1 dose escalation design Continuous dosing based on preclinical and oncology clinical data Safety and percent inhibition of p-akt 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-akt inhibition and ARQ 092 concentration Change in Proteus syndrome symptoms Imaging Photography Quality of life and patient reported physical functioning Phase 1 trial enrolling Orphan drug designation granted by FDA 17

18 Proteus Trial First Cohort Data Demographics Three adult males dosed Dosing All three patients dosed with ARQ 092 at lowest dose as determined by the protocol Dosing continues at lowest dose Data Protocol defined pre-specified decrease of at least 50% in AKT signaling was achieved in all three patients on biopsies at days 15 and 75 Pharmacokinetic profile similar to ARQ 092 in oncology Safety profile acceptable Next Steps: NIH to enroll second cohort with patients ages 12 to 18 AKT knockdown achieved in first cohort 18

19 ARQ Next-Generation AKT ARQ 751 is an orally available small molecule, next generation AKT inhibitor Diversified portfolio of AKT inhibitors might provide us the opportunity to best address oncology and rare disease Plan to begin a biomarker-driven clinical trial in first half of 2016 in cancers with AKT mutations Pre-clinical profile for ARQ 751 defines a highly potent and highly selective molecule 19

20 ARQ 761 NQO1 Inhibitor ARQ 761 is an NQO1 inhibitor with the potential to enhance the effect of chemotherapy and other cancer therapies NQO1 is over-expressed in many cancers ~90% of pancreatic and NSCLC cancers: fold ~60% of breast, prostate and colon cancers: 5-20 fold NQO1 as a key target in rapid, selective tumor cell death More than 50+ peer-reviewed publications supporting all aspects of mechanism NQO1 over-expression within the tumor drives rapid H ² O ² production via bioamplification Normal detoxification function of NQO1 is hijacked into futile redox cycle, amplifying drug concentration 100x in 2 minutes Normal cells unaffected due to little NQO1 expression are protected by high catalase levels, which scavenge H ² O ² 20

21 ARQ 761 Clinical Trials Collaboration with the University of Texas Southwestern Medical Center where trials are funded by our partner ARQ 761 is an intravenously administered prodrug of β-lapachone Activity has been demonstrated in vitro and vivo testing against a wide range of tumors Phase 1a testing with ARQ 761 identified anti-cancer activity as measured by tumor responses occurring exclusively in a portion of the patient population with high levels of NQO1 Phase 1b cohorts are focusing on patients with high levels of NQO1 in solid tumors Currently recruiting in a Phase 1/2 trial in pancreatic cancer in combination with chemotherapy first cohort is fully enrolled 21

22 Pre-Clinical BTK Inhibitor ARQ 531 BTK Inhibitor Overview As seen with other kinase inhibitors, such as Gleevec, primary and secondary resistance to ibrutinib in B-cell malignancies is emerging in patients BTK-C481S mutation is a major secondary resistance mechanism for ibrutinib, contributing to more than 80% of such cases in CLL and MCL In pre-clinical studies, ARQ 531 potently inhibits the BTK-C481S mutant as well as the wild-type BTK Next Steps Plan to complete pre-clinical studies in 2016 and file for IND approval in

23 Tivantinib in HCC Snapshot Tivantinib is a class leading investigational oral inhibitor of the MET receptor tyrosine kinase currently in phase 3 clinical development in two biomarkerdefined trials for second-line treatment of hepatocellular carcinoma (HCC) in a MET-high population METIV-HCC trial being conducted in the West (U.S., Europe, South America, and rest of world), partnered with and co-funded with Daiichi Sankyo¹; this trial is fully accrued JET-HCC trial being conducted in Asia (Japan and select Asian countries), partnered with and funded by Kyowa Hakko² Previous studies support drug activity in MET-high patients In NSCLC (non-small cell lung cancer) a pre-defined sub-analysis from phase 3 trial, MARQUEE In HCC (hepatocellular carcinoma) a successful randomized double blind phase 2 trial In CRC (colorectal cancer) Stage 1 data from a phase 2 investigator-initiated trial Granted Orphan Drug Status for HCC by the FDA and EMA Composition of Matter patent protection through 2030 (U.S.) ¹ Development and Commercialization partnership with Daiichi Sankyo for U.S., Europe, South America, and rest of world. ² Development and Commercialization partnership with Kyowa Hakko for Japan, and select Asian countries. 23

24 HCC High Unmet Need Limited Treatment Options for HCC Current treatment options¹ Surgery Tumor ablation Embolization therapy Radiation treatment Targeted therapy 1 st line therapy - sorafenib is the only approved systemic agent Need for 2 nd line therapy No standard of care exists at this time for 2 nd line therapy Several phase 3 studies in 2 nd line HCC failed brivanib, everolimus, and ramucirumab Tivantinib is the only drug in a biomarker-driven phase 3 trial for HCC ¹ American Cancer Society. Liver Cancer Overview. 24

25 Tivantinib Phase 3 Trial Design METIV-HCC (West)¹ (NCT ) MET-high patients receiving tivantinib in advanced HCC Patients with MET-high (assessed by IHC) inoperable locally advanced metastatic HCC treated with 1 prior systemic therapy (sorafenib) Companion diagnostic Conducted under FDA SPA Stratification Factors Vascular invasion Extra-hepatic spread AFP (< or > 200 ng/ml) Endpoints 1 o : OS Tivantinib 120 mg tablet BID* 2 : PFS, safety ~200 pts Placebo ~100 pts 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. R A N D O M I Z E D ¹ Development and Commercialization partnership with Daiichi Sankyo for U.S., Europe, South America, and rest of world. 25

26 2016 Goals PROPRIETARY PIPELINE ARQ 092 AKT Inhibitor Complete phase 1b trial in oncology make decisions on next steps Analyze preliminary phase 1 data in Proteus syndrome make decisions on next steps Explore opportunities in other rare over-growth diseases ARQ 087 FGFR Inhibitor Complete phase 2 trial in intrahepatic cholangiocarcinoma make decisions on next steps Complete phase 1b in oncology make decisions on next steps ARQ 751 next-generation AKT Inhibitor Initiate phase 1 trial in oncology with AKT1 and PI3K mutations PARTNERED PIPELINE Tivantinib Compete METIV-HCC planned interim analysis to occur by early Q2 16 Completed 3/16 Study to continue to the final analysis 26

27 Financial Profile Cash Balance Cash and marketable securities at March 31, 2016 $47.6 Mil 2016 Guidance Net use of cash Projected cash balance end of 2016 $23-25 Mil $29-31 Mil Shares Outstanding* ~71 Mil * Includes Registered Direct Offering announced on February 29,