JMP Life Sciences Conference. June 2016

Transcription

1 JMP Life Sciences Conference June 2016

2 Forward Looking Statement This presentation includes certain estimates and other forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, including statements with respect to anticipated operating and financial performance, clinical results, potential partnerships, licensing opportunities and other statements of expectation. Words such as expects, anticipates, intends, plans, believes, assumes, seeks, estimates, should and variations of these words and similar expressions, are intended to identify these forward-looking statements. While we believe these statements are accurate, forward-looking statements are inherently uncertain and we cannot assure you that these expectations will occur and our actual results may be significantly different. These statements by the Company and its management are based on estimates, projections, beliefs and assumptions of management and are not guarantees of future performance. Important factors that could cause actual results to differ from those in the forward-looking statements include the factors described in the Company s filings with the U.S. Securities and Exchange Commission. The Company disclaims any obligation to update or revise any forward-looking statement based on the occurrence of future events, the receipt of new information, or otherwise. We have filed a shelf registration statement on Form S-3 (including a prospectus) with the SEC which was declared effective on April 1, Before you invest in the offering to which this communication relates, you should read the prospectus in that registration statement and the preliminary prospectus supplement related to this offering and the other documents the issuer has filed with the SEC for more complete information about the issuer and this offering. You may get these documents for free by visiting EDGAR on the SEC Web site at Alternatively, you may obtain a preliminary prospectus from Jefferies LLC by telephone at (877) or at Prospectus_Department@Jefferies.com. 2

3 Executive Summary Transitioning to Genomic Medicine Company Continued pipeline expansion based on CHOP / CAG collaboration Rich source of new opportunities Translational research continues to produce potential development targets Quality management and development capabilities NFC 1 Programs Advancing Rapidly mglurr+ ADHD Record response and recruitment to phenotype / genotype study Confirmation of mglur+ prevalence rate of 25% Enrollment initiating in June with data expected in 2H2016 US market opportunity of $2 3B 22q Deletion Syndrome Orphan program in collaboration with CHOP Enrollment initiating in Q3 with initial Open-Label data expected 2H2016 New Biologics Development Program with KHK in Severe Pediatric IBD 1st in class P2 ready biologic with minimal investment to POC Strong genetic thesis and significant unmet medical need High value commercial opportunity with first US launch anticipated in 2020 TARGT CNS Programs Viability of CNS approach demonstrated (ASGCT) POC in preclinical disease models expected in

4 Management Team Michael F. Cola Chief Executive Officer Garry A. Neil, M.D. Chief Scientific Officer Brian Piper Chief Financial Officer Michael C. Diem, M.D. SVP, Business & Corporate Development Sol Barer, Ph.D. Chairman of the Board 4

5 Development Pipeline NFC-1 Preclinical Phase 1 Phase 2 Phase 3 mglur+ ADHD (adolescent, age 12-17)* mglur+ ADHD (pediatric, age 6-12)** 22q Deletion Syndrome*** Anti-LIGHT Severe Pediatric Onset IBD TARGT CNS Preclinical POC * Phase 2/3 expected to initiate in June 2016 ** Initiate Phase 3, H *** Phase 1/2 expected to initiate in Q (pending CHOP approval) 5

6 Medgenics / CHOP Collaboration Exclusive option to the genomic discoveries in Rare and Orphan diseases made by Center for Applied Genomics (CAG) Genomically Validated Target Rational Search & Acquisition Genomically Guided Product Development Targeted Launch Medgenics Role: Match unique genetic discoveries with potential therapies Acquire the rights to programs that have been abandoned Ideal program: Correct MOA Excellent safety profile Prior failure in heterogeneous patient population Development and commercialization 6

7 CAG / CHOP Capabilities CAG s pediatric biobank contains a high percentage of rare genetic variants ~1.2M patient visits/year at CHOP 10% of all R/O disease patients in N. America are treated at CHOP Population is unique in that it represents the most severe forms of common diseases Global reach in many therapy areas Highly scalable infrastructure to support translational research Biobank (BB) Fully automated robotic biorepository Datasets (Genomics EMR) Over 75K pediatric and 150K related adult patients GWAS genotyped with associated longitudinal EMR since 2006 Data Analytics End to end internal Next- Gen sequencing capabilities Integrated bioinformatics Rapid identification of novel genetic biomarkers Consented Patients 85% of the BB patients are consented for longitudinal follow up and are eligible for call back for future studies In the last 9 years CAG has had over 450 peer reviewed publications focused on novel genetic discoveries 7

8 Genetic Influence in Pediatric Disorders Early Onset Disease: Distinct genetically driven Severe burden of illness Aggressive progression Less responsive to standard of care 8

9 Program

10 NFC-1 Overview First program from the CHOP collaboration Phase 2/3 ready program via neurofix acquisition Program in mglur+ ADHD is highly de-risked Extensive safety database Strong Phase 1b efficacy signal in mglur+ ADHD (GREAT trial) Prevalence confirmed at approximately 25% Platform in place for rapid clinical development Potential accelerated path to approval in 22q DS Large orphan indication (75-150K US) Compelling genetic hypothesis and positive clinical signal Potential approval pathway with single pivotal trial Opportunity in additional mglur+ CNS / psych diseases 10

11 NFC-1: Strong Candidate for Repositioning NFC-1 previously tested in a large scale clinical trial in Vascular Dementia patients (Nippon Shinyaku) Patient cohorts not enriched for mglur+ mutations Failed on primary efficacy Excellent safety profile in >1,000 patients No addiction potential Excellent oral bioavailability and predictable PK Twice-daily dosing 11

12 NFC-1: First-in-class mglur Neuromodulator Dr. Hakonarson identified NFC-1 as a drug with potential to address mglur network disruptions caused by genetic mutations Small molecule, non-stimulant agonist of multiple mglurs: 1, 3, 5, 7, 8 Up-regulates GABA B receptors Positive effects seen in animal models Ameliorate cognitive impairment Reduce hyperactivity Enhance memory Antipsychotic activity 12

13 NFC-1 GREAT Study: Design and Execution Two-part Phase 1b trial, n=30 Part 1 Single Ascending Dose(SAD) / Pharmacokinetics(PK) SAD 24 hour PK mg Part 2 Ascending Dose Trial 1 week of placebo followed by 4 weeks active therapy Dose escalated: 50mg BID*-400mg BID* weekly (x4) Efficacy endpoints CGI, Vanderbilt, exploratory Single-blinded (to patients / families) Trial completed Q *Twice a day 13

14 Strong Efficacy Signal in Key Endpoints Treatment effect appeared more robust over time and at higher doses CGI-I: Proportion of Responders at Each Week for All Subjects Vanderbilt Scores: Proportion of Patients Improved from Pre-Study Baseline for All Patients Response rates for both scales (CGI-I and Vanderbilt Parent Rating Scale) approx 80% CGI-I, Clinical Global Impression of Symptom Improvement Responder Global rating of much or very much improved 14

15 mglur Network Mutation Classification: Genetic Tiers Genetic Tiers Defined by Proximity to mglur Network Tier 1 Mutations in genes in mglur receptors or that directly influence mglur signaling. n=17 Tier 1 79 Genes 10% of ADHD Tier 2 Mutations in genes that encode proteins that influence mglur. n=7 Tier Genes 20% of ADHD Tier 3 Mutations in genes that encode for proteins that interact with Tier 1 and 2 genes. n=6 Tier Genes 30% of ADHD Genetic tiers optimized for Tier 1 (not balanced) Prevalence of ADHD estimated 15

16 Core Mutations (Tier 1/2) Predict Higher Response CGI-I: Proportion of Responders at Week 5 by Genetic Tier (with 95% confidence intervals) Vanderbilt: Proportion of Responders at Week 5 by Genetic Tier (with 95% confidence intervals) Response rate appears to be correlated to the proximity to the core mglur genes Note: Data is for the subset of patients who titrated to the highest dose (N=18). Genetic tiers were not balanced. 16

17 Statistically Significant Improvement in Key Endpoints Improvement magnitude comparable to best in class drugs in complex, severe patients Average CGI - I score at the end of each week all patients Week 1 Week 2 Week 3 Week 4 Week 5 Mean P < Average Vanderbilt score at each week all patients Week 1 Week 2 Week 3 Week 4 Week 5 Mean P < Repeated Measures Analysis: mean scores by week CGI-I Scale: 1-7 Vanderbilt Scale (Questions 1-18):

18 NFC-1: GREAT Trial Study Summary Strong efficacy signal in multiple validated ADHD scales Improvement magnitude comparable to best in class drugs in complex, severe patients Improvement in multiple symptoms noted by caregivers Inattention, hyperactivity, anxiety, mood disorders Treatment effect more robust over time & at higher doses Genetic biomarker predictive of response to NFC-1 (Tier 1 & 2) Confirmation of PK profile Comparable to previous PK study; BID dosing Well tolerated, no treatment related serious adverse events Majority of patients enrolled in the long-term safety trial 18

19 NFC-1: ADHD Program Phase 2/3 mglur+ ADHD, Adolescents N=90, Ages ADHD Phenotype / Genotype Pediatrics, Adolescents N=1,000+ Design: Non-interventional Multi-center (25) Genotype 1,000+ ADHD subjects, age 6-17, identifying patients who are mglur+ Objectives: Confirm prevalence of mglur+ Expedite enrollment in Phase 2/3 interventional trials Timing: Ongoing Phase 3 mglur+ ADHD, Pediatrics N= TBD, Ages 6-12 Phase 3 mglur+/- ADHD, Ages 6-17 N=TBD 19

20 Phase 2/3 Study in Adolescents with mglur+ ADHD Objective: Optimize dose in adolescents, confirm Phase 1b results Endpoints: ADHD-RS, CGI-I FPFV June 2016 H2 2016: Topline Data Phenotype / Genotype Multi-center: 25 sites ~150 mglur+ ADHD subjects: age Phase 2/3 mglur+, N=90 Placebo controlled 1:1 Randomization Same sites as Phen / Geno FPFV: June 2016 NFC-1 6 weeks 1 week follow-up Placebo 6 weeks 1 week follow-up 20

21 ADHD: Background and Rationale for Genomic Medicine Approach Most prevalent neurodevelopmental disorder in children Highly heritable* (70%); Heterogeneous, suggesting multiple causes Early studies, focused on individual genes, failed to identify an underlying cause Based upon network biology and genotyping, CAG described genetic mutations identifying a novel subset of inherited ADHD** Network mutations mimics Mendelian inheritance and account for ~25% of ADHD ADHD Inattention Hyperactivity Impulsivity * Farone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit / hyperactivity disorder. Biol Psychiatry 2005; 57: **Nature Genetics 44, (2012). 21

22 Potential for Superior Product Profile Current treatment paradigm exposes children to multiple stimulants in a fail first approach NFC-1 clinical profile in mglur+ ADHD patients Effective non-stimulant Non-scheduled Excellent safety profile in >1,000 patients No evidence of growth retardation, addiction, sleep disturbance No evidence of cardiovascular risk No expectation for black box warning Potential to address co-morbid symptoms (e.g., anxiety, conduct, mood) Eliminates need for drug holidays Potential for increased compliance and adherence 22

23 mglur+ ADHD: Market Opportunity Overall US ADHD Market 2015 Sales in excess of $10B* ~6M pediatric / adolescent patients** Stimulants dominate market: 90+% of total prescriptions mglur+ ADHD Market, ages M patients (~25% mglur+) $2-3B market opportunity based upon current pricing and compliance / adherence Potential upside for premium pricing with superior product profile *IBIS World.com ** Trends in the Parent-Report of Health Care Provider-Diagnosed and Medicated Attention-Deficit / Hyperactivity Disorder: United States, , Journal of the American Academy of Child & Adolescent Psychiatry, Volume 53, Issue 1, January 2014, Pages e2 23

24 Program

25 NFC-1 in 22q Deletion Syndrome Prevalence estimates range from 1/2,000 to 1/4,000 Physical Symptoms Heart defects Cleft palate Gastrointestinal problems Poor wound healing Skeletal abnormalities Surgical / Medical Therapies Mortality <4% after CV surgery (excluding critically ill infants) Psychiatric Symptoms* No Effective Therapy Approx. 40% progress to schizophrenia *Jonas et al Biol Pyschiatry 2015;75:

26 22q Patients in GREAT Study Two 22q patients in the trial; one deletion and one duplication Parents reported significant symptom improvement in both Marked improvement in CGI-I and Vanderbilt Both families elected to enroll in long-term safety trial to maintain access to NFC-1 26

27 Phase 1/2 Study in 22q Deletion Syndrome Objective: Explore symptoms from three neuropsychiatric disorders: ADHD, Anxiety, and Autism Spectrum Disorders (ASD) Endpoints: CGI-I, ADHD-RS, PARS, CARS-2 FPFV Q (pending final CHOP approval) H2 2016: Responder rate data from open-label phase Open-label Phase N=30, age weeks dose optimization FPFV: Q Single center: CHOP Responders Randomized Non Responders NFC-1 Fixed dose 7 weeks Placebo 7 weeks Exit Study 27

28 Program

29 Overview First-in-Class Biologic from Kyowa Hakko Kirin Initial Development in Severe Pediatric Onset IBD Phase 2 Ready Antibody (Sanofi) Strong Regulatory Exclusivity and Robust Intellectual Property Portfolio High Value Commercial Opportunity with Potential for Indication Expansion World Class Partners Kyowa Hakko Kirin The Children s Hospital of Philadelphia Rapid and Capital Efficient Global Development Pathway Minimal investment to POC Single Pivotal Trial for registration 29

30 CAG / CHOP Discovery: Genetic Link to Pediatric Onset IBD Key Points Established importance of the DcR3 gene in pediatric IBD Loss of function of DcR3 correlates with severity Prevalence between 10-15% Nature Genetics VOLUME 40 NUMBER 10 OCTOBER

31 Rationale for Anti-LIGHT Approach DcR3 is strongly linked to Severe Pediatric Onset IBD 1 Initial strategy to augment DcR3 Very short half life Toxicity reported with previous DcR3 analog Rational Search based on biological pathway LIGHT overexpressed in IBD DcR3 LOF increases LIGHT 2 Decoy Receptor 3 DcR3 Immune Cell LIGHT HVEM LTbR Our Approach: Therapeutic antibody which mimics DcR3 regulation by binding LIGHT 1 Hakonarson, et al Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nature Genetics 40 (10): Mauri DN, et al LIGHT, a new member of the TNF superf amily, and lymphotoxin alpha are ligands for herpesvirus entry mediator.immunity 8 (1):

32 Human Biomarker Study Supports Role of LIGHT in IBD Single center non-interventional biomarker study* Normal (n=26) Ulcerative Colitis (n=27) Crohn's Disease (n=28) LIGHT mrna Fold Increase vs Normal *Data on file 32

33 Severe Pediatric Onset IBD: Top Down Treatment Paradigm Step-up approach Top-down approach to more aggressive disease Treatment Objectives: Induce remission with anti-tnfα immediately so patients can develop normally Avoid steroids and IMs Manage utilization of anti-tnf alphas to extend time before resistance develops Opportunity: 30% of patients do not respond to anti-tnfα Up to 50% of patients who initially respond, resistance will develop within 3 years 1 Creates significant opportunity for new Therapies / MOAs, that can treat anti-tnf alpha failures 1 Altwegg & Vincent (2014) TNF Blocking Therapies and Immunomonitoring in Patients with Inflammatory Bowel Disease. Mediators of Inflammation. doi: /2014/

34 Rapid Development Pathway to Approval Severe Pediatric Onset IBD POC Trial Single Phase 3 Pivotal Registration Trial Anticipated Phase 1b design: Single center (CHOP) N = up to 12 patients Duration 8 12 weeks Ascending dose Endpoints: Endoscopic Evaluation, Pediatric Crohn s Disease Activity Index (PCDAI), Safety Estimated Cost: ~$2M Long Term Safety Trial 34

35 Severe Pediatric Onset IBD: Anti-LIGHT Opportunity (US Pop.) Initial Target: anti-tnfα failure with DcR3 Loss of Function 2,000 3,000 IBD patients in US $300-$400M opportunity (based conservative pricing) Pediatric IBD Prevalence: 71/100,000 1 (52,000) Anti-TNF Usage 35-55% 2 (24,500) Potential Upside Pediatric anti-tnfα failures: 15,000 16,000 IBD Patients in US Pediatric indications with DcR3 LOF (juvenile idiopathic arthritis, psoriasis, etc.) Responders (70%) 3 (17,000) Resistance to anti- TNF s (50%) 4 (8,500) Non-responders (30%) 3 (7,350) DcR3 LOF (15%) (1,100) DcR3 LOF (15%) 1 Kappleman et al. (2007) Clin Gastro Hepat 2 Oliva-Hemker (2015) J Pedtr 3 Remicade Monograph 4 Altwegg-Vincent (2014) Mediators of Inflamm (1,275) 35

36 TARGT CNS Goal: sustained autologous large molecule production in central nervous system (CNS) Future disease targets: Metastatic and primary brain tumors Lysosomal storage diseases with CNS involvement Preclinical and IND-enabling work ongoing ASGTC: Preclinical POC presented in 2 species with TARGT CNS for adalimumab and epo Potential IND filing in

37 Corporate & Financial

38 Financial Summary ~$43.9M cash balance (cash and cash equivalents) at 3/31/16 Current resources estimated to fund operations into Q ~33.2M shares outstanding at 3/31/16 ~9.6M options and ~5M warrants outstanding with a weighted average exercise price of $6.03 and $6.67, respectively, at April

39 Upcoming Milestones R&D Programs Timing NFC-1 Complete enrollment in phenotype / genotype study Q2 16 Initiate enrollment in Phase 2/3 mglur+ ADHD Adolescent Trial Q2 16 Top line data H2 16 Initiate enrollment in Phase 1/2 22q Deletion Syndrome Trial* Q3 16 Initial open-label responder data H2 16 Initiate Signal Finding Study Q4 16 Initial open-label responder data H1 17 TARGT CNS Preclinical POC H2 16 *Pending final CHOP approval 39