Corporate Presentation. June 2015

Transcription

1 Corporate Presentation June 2015

2 Forward Looking Statement/Safe Harbor This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward-looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, statements about our ability to identify additional products or product candidates using our Extreme Genetics discovery platform; the initiation, timing, cost, progress and success of our research and development programs, preclinical studies and clinical trials; our ability to advance product candidates into, and successfully complete, clinical trials; our ability to receive milestone payments, royalties and sublicensing fees under our collaboration agreements, and the timing of such payments; our ability to develop and commercialize product candidates for orphan and niche indications independently; our ability to find families to support our Extreme Genetics discovery platform; our ability to discover genes and drug targets; our expectations regarding federal, state and foreign regulatory requirements; the therapeutic benefits, effectiveness and safety of our product candidates; the accuracy of our estimates of the size and characteristics of the markets that may be addressed by our products and product candidates; our and our collaborators ability to obtain and maintain regulatory approvals for our product candidates and the timing thereof; the plans, strategies and objectives of management for future operations; and any statements of assumptions underlying any of the items mentioned. These statements are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many factors, including but not limited to: our collaborations may not be successful or we may be unable to maintain our collaborations; clinical trials may not demonstrate the safety or efficacy of any of our product candidates or subsequent clinical trials may fail to replicate safety and efficacy data for a product candidate; any of our product candidates may fail in development, may not receive required regulatory approvals, or may not become commercially viable due to delays or other reasons; our and our collaborators competitors may successfully introduce competing products in the markets we target; we may be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our product candidates; and we may need additional funds to conduct research and development efforts. Except as required by law, we assume no obligation and do not intend to update these forwardlooking statements or to conform these statements to actual results or to changes in our expectations. 2

3 Deep Pipeline Provides Many Catalysts Anticipated 2015 Milestones Teva Collaboration Data from Phase 2b osteoarthritis trial Advance Phase 2b trial in post-herpetic neuralgia Genentech Collaboration Complete patient enrollment in GDC-0276 Phase 1 trial Discover novel pain genes in second discovery collaboration Proprietary Pipeline XEN801: file IND, complete Phase 1 and initiate Phase 2 acne trial Advance Dravet Syndrome Nav1.6 inhibitors into lead optimization Initiate next ion channel discovery program Discover novel genes in neurological disorders Corporate Potential for Glybera launch and royalty payments to Xenon 3

4 Extreme Genetics: Multiple Product Opportunities Single Gene Disorders Single Gene Disorders Lipid Targets Ion Channel Targets Cardiovascular LPL Nav1.7 Nav1.6 SCD1 Nav1.7 4

5 Diverse Pipeline Built on Extreme Genetics Product Indication Preclinical Phase 1 Phase 2 Phase 3 Approved Commercial Rights Glybera Lipoprotein Lipase Deficiency Osteoarthritis TV Postherpetic Neuralgia Xenon US Co- Promote Option Erythromelalgia GDC-0276 Pain Undisclosed Cardiovascular Target XEN801 Acne Nav1.6 Inhibitor Dravet Syndrome Extreme Genetics Pain Genetics 5

6 6 Glybera LPL S447X Gene Therapy

7 Glybera : First Approved Product From Xenon Platform Xenon and UBC identified LPL S447X Product Glybera is AAV- LPL S447X gene replacement product First approved gene therapy in EU Commercialization Treatment of LPLD with severe or multiple pancreatitis attacks despite dietary fat restrictions EU launch preparations ongoing by Chiesi Agreement with uniqure uniqure has exclusive worldwide rights; sublicensed to Chiesi for EU and 12+ other countries Xenon receives low twenties % royalty of what uniqure receives from Chiesi and low to mid single digit royalty on uniqure sales 7

8 Novel Candidates for Nociceptive & Neuropathic Pain Inhibitors of Nav1.7 Sodium Channel Blocker Topical for Peripheral Applications Selective Nav1.7 Blocker Oral for Systemic Applications 8

9 Increasing pain Nav1.7: Extreme Genetics Pain Target Erythromelalgia R1150W Genotype Congenital Indifference to Pain Increasing Nav 1.7 Activity 9

10 TV-45070: Strategic Alliance with Teva Teva is responsible for all development and commercialization and will complete three Phase 2 or later clinical trials Phase 2b trial in OA ongoing Phase 2b trial in PHN ongoing Upfront $41M Clinical Milestone $20M Regulatory Milestones up to $285M Sales-based Milestone $30M Royalties Low teens to low twenties Xenon has an option for U.S. co-promotion interest 10

11 Arm C Arm B Arm A TV in Osteoarthritis: Phase 2b Clinical Trial Ongoing 300 Patients at ~35 US Sites Randomized, double-blind, placebo-controlled study Placebo Primary Endpoint: Change from Baseline in Average Evening Pain Intensity using WOMAC 4% TV Weeks; Single Knee; Twice Daily Secondary Endpoints: Efficacy endpoints include 30% and 50% responder rates, Safety and PK 8% TV Analysis will include Stratification of Patients based on their R1150W Status Data Expected late Q2/early Q

12 Concentration (µm) TV-45070: Rationale for Osteoarthritis Genetic validation in patients with Nav1.7 loss of function and R1150W genotypes Pharmacological validation with sodium channel inhibitors TV penetrates knee joint at high concentrations POC in preclinical nociceptive pain models and Phase 2a dental trial Synovial Membrane Plasma 12 8% TV BID for 5 days in pigs

13 Arm C Arm B Arm A TV in PHN: Phase 2b Clinical Trial Ongoing 330 Patients Randomized, double-blind, placebo-controlled study Placebo Primary Endpoint: Change from Baseline in Numeric Rating Scale to week 4 4% TV Weeks; Twice Daily Secondary Endpoints: Efficacy endpoints include 30% and 50% responder rates, QoL and Safety 8% TV Analysis will include Stratification of Patients based on their R1150W Status 13

14 TV-45070: Rationale for PHN Phase 2b PHN trial Ongoing Proportion of responders % Proportion of responders % Genetic validation: Nav1.7 up-regulated in PHN Pharmacological validation with sodium channel inhibitors POC in preclinical neuropathic pain models and Phase 2a PHN trial TV Placebo % % Improved > 30% p=0.049 Improved > 50% p= R1150W Carriers Non-Carriers 14 Similar reduction in mean daily pain score for both TV and placebo (primary endpoint)

15 Novel Candidates for Nociceptive & Neuropathic Pain Inhibitors of Nav1.7 Pan Sodium Channel Blocker Topical for Peripheral Applications Selective Nav1.7 Blocker Oral for Systemic Applications 15

16 Strategic Alliance with Genentech Collaboration for oral, selective Nav1.7 inhibitors Genentech responsible for all development and commercialization Upfront $10M Development Candidate $5M Approval of CTA $8M Pre-clinical & Clinical Milestones Up to $45.5M Regulatory Milestones Up to $387.5M Sales-based Milestones Up to $180M Royalties Mid single digit to 10% 16

17 Relative Fold Potency Number of pain events over 30 minutes GDC-0276: Oral, Nav1.7 Inhibitor in Phase Collaboration Development Candidate Phase Selective Nav1.7 Inhibitor Preclinical Efficacy p < hnav1.7 CNS CNS Cardiac CNS 0 Vehicle GDC

18 18 Proprietary Pipeline

19 Extreme Genetics: Multiple Product Opportunities Single Gene Disorders Single Gene Disorders Lipid Targets Ion Channel Targets Cardiovascular LPL Nav1.7 Nav1.6 SCD1 Nav1.7 19

20 Dravet Syndrome: Nav1.6 Inhibition Indication Orphan disease of severe childhood epilepsy 10% premature death by age 12 High unmet need; 7,500 to 15,000 U.S. patients Mechanism Discovered Nav1.1 genetic link to epilepsy ~80% of Dravet is caused by Nav1.1 loss of function Other epilepsies caused by gain of function of Nav1.6 Stage of Development Potent, selective Nav1.6 inhibitors identified Preclinical POC in animal seizure model IND expected in

21 Nav1.6: Differentiated Approach to Epilepsy Nav 1.6 Pyramidal Excitatory Nav 1.1 Interneuron Inhibitory 21

22 Nav1.6: Differentiated Approach to Epilepsy Nav 1.1 Haploinsufficiency Nav 1.6 Inhibitor Nav 1.1 Reduced Negative Regulation Increased Nav 1.6 Activity Selective Nav 1.6 Inhibitor Treat Dravet 22

23 XEN801: Differentiated Treatment of Acne Indication 11M moderate; 1.2M severe acne patients in US Significant medical need Mechanism SCD1 knockout mice show sebaceous gland atrophy, lowered sebum lipids & increased retinoic signaling SCD1 is expressed in human sebaceous glands Mechanism in common with isotretinoin Stage of Development XEN801 formulated in a light gel IND-enabling studies ongoing 2015 milestones: IND filing, Phase 1 trial and initiate Phase 2 trial 23

24 XEN801: Dual Action on Sebum & Retinoic Acid SFA SCD1 Sebocyte Apoptosis MUFA Sebum Lipids Retinoic Acid NGAL 24

25 Size of sebaceous glandular units (mm 2 ) Concentration (ng/g or ml) XEN801: Reduces Size & Number of Sebaceous Glands Efficacy in multiple animal models Local high skin concentrations & low systemic exposure p = p = Vehicle 0.5% XEN % XEN801 1 Dermis Plasma 1% XEN days in pigs 25

26 XEN801: Phase 1 and Phase 2 Clinical Plan Phase 1 Cohort 1 Cohort 2 Screening Dosing Dosing 2 wks 2 wks 2 cohorts of 12 patients to assess safety and PK Screening Phase 2 Dosing F/up 12 wks ~100 patients with moderate to severe acne to assess efficacy, safety, PK Primary efficacy endpoint: change from baseline in total lesion count 26

27 Xenon Extreme Genetics: Future Drug Targets Single Gene Disorders Single Gene Disorders Novel pain genetics in collaboration with Genentech Proprietary genetics in neurological conditions 27

28 28 Financials & Near Term Milestones

29 Financials and Capital Efficiency $150M+ in non-equity partner funding to date Up to $32.5M in potential milestone payments over next 24 months $75.4M cash*(3/31/15); IPO completed November 2014 US$ Cash* $60.2M (12/31) $49.3M (12/31) $84.0M (12/31) Revenue $14.3M $27.4M $28.4M Expenses $17.5M $17.6M $17.3M Net Profit (Loss) ($4.3M) $12.0M $11.1M 29 * Cash, cash equivalents and marketable securities

30 Deep Pipeline Provides Many Catalysts Anticipated 2015 Milestones Teva Collaboration Data from Phase 2b osteoarthritis trial Advance Phase 2b trial in post-herpetic neuralgia Genentech Collaboration Complete patient enrollment in GDC-0276 Phase 1 trial Discover novel pain genes in second discovery collaboration Proprietary Pipeline XEN801: file IND, complete Phase 1 and initiate Phase 2 acne trial Advance Dravet Syndrome Nav1.6 inhibitors into lead optimization Initiate next ion channel discovery program Discover novel genes in neurological disorders Corporate Potential for Glybera launch and royalty payments to Xenon 30