Investor Presentation. January 2017

Transcription

1 Investor Presentation January 2017

2 Forward Looking Statement This presentation incudes certain estimates and other forward-ooking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, incuding statements with respect to anticipated operating and financia performance, cinica resuts, potentia partnerships, icensing opportunities and other statements of expectation. Words such as expects, anticipates, intends, pans, beieves, assumes, seeks, estimates, shoud and variations of these words and simiar expressions, are intended to identify these forward-ooking statements. Whie we beieve these statements are accurate, forward-ooking statements are inherenty uncertain and we cannot assure you that these expectations wi occur and our actua resuts may be significanty different. These statements by the Company and its management are based on estimates, projections, beiefs and assumptions of management and are not guarantees of future performance. Important factors that coud cause actua resuts to differ from those in the forward-ooking statements incude the factors described in the Company s fiings with the U.S. Securities and Exchange Commission. The Company discaims any obigation to update or revise any forward-ooking statement based on the occurrence of future events, the receipt of new information, or otherwise. 2

3 Executive Summary AEVI-001 (NFC 1) SAGA Phase 2/3 cinica tria in mgur+ ADHD Enroment compete; top-ine data Q mgur+ prevaence rate of ~25% confirmed US market opportunity of $2B $3B Phase 1/2 cinica tria in 22q Deetion Syndrome Study initiated at CHOP Initia data expected in H AEVI-002 Anti-LIGHT mab Program Successfuy transferred IND FDA Type B meeting competed Initiating signa finding study Initia data expected in H Pipeine Deveopment GNMX/CAG transationa research continues to produce potentia deveopment targets 3

4 Management Team Michae F. Coa Chief Executive Officer Garry A. Nei, M.D. Chief Scientific Officer Brian Piper Chief Financia Officer Michae C. Diem, M.D. SVP, Business & Corporate Deveopment So Barer, Ph.D. Chairman 4

5 Genomic Medicine Approach

6 GNMX/CHOP - Genetic Discoveries to Drugs Excusive option to the genomic discoveries in Rare and Orphan diseases made by Center for Appied Genomics (CAG) Identification of disease causing genetic mutations aows for repurposing drug deveopment programs Genomicay Vaidated Target Rationa Search & Acquisition Aevi Genomics Roe: Genomicay Guided Product Deveopment Match unique genetic discoveries with potentia therapies Acquire the rights to programs that have been abandoned Idea program: Correct MOA Exceent safety profie Inadequate efficacy in heterogeneous patient popuations Lead deveopment and commerciaization Targeted Launch 5-7 years of deveopment time and of miions of doars can be saved with this approach. Programs de-risked by genomic biomarker. 6

7 Center for Appied Genomics (CAG) at CHOP CAG s pediatric biobank contains a high percentage of rare genetic variants ~1.2M patient visits / year 10% of a R/O disease patients in N. America are treated at CHOP Popuation is unique in that it represents the most severe forms of common diseases Goba reach in many therapy areas Highy scaabe infrastructure to support transationa research Biobank (BB) Fuy automated robotic biorepository Datasets (Genomics EMR) Over 75K pediatric and 150K reated adut patients GWAS genotyped with associated ongitudina EMR since 2006 Data Anaytics End to end interna Next- Gen sequencing capabiities Integrated bioinformatics Rapid identification of nove genetic biomarkers Consented Patients 85% of the BB patients are consented for ongitudina foow up and are eigibe for ca back for future studies In the ast 9 years CAG has had over 600 peer reviewed pubications focused on nove genetic discoveries 7

8 Benefits of Genomic Guided Drug Deveopment Genomic biomarkers improve overa program outcomes Smaer, faster, cinica trias Increased probabiity of reguatory success Targeted aunch Improved response rates Higher Vaue Medicines Potentia abe expansion in adjacent genetic diseases 8

9 AEVI-001 Program Update

10 ADHD: Rationae for Genomic Medicine Approach Most prevaent neurodeveopmenta disorder in chidren (5-11%) Highy heritabe* (70%); Heterogeneous, suggesting mutipe causes Eary studies focused on individua genes faied to identify causa associations Nove discovery from CAG, based on network bioogy, identified an underying cause of disease in a subset (2225%) of ADHD patients** ADHD Inattention Hyperactivity Impusivity * Farone SV, Peris RH, Doye AE, et a. Moecuar genetics of attention-deficit / hyperactivity disorder. Bio Psychiatry 2005; 57: **Nature Genetics 44, (2012). 10

11 CAG Breakthrough Discovery Research by Dr. Hakonarson indicated approximatey 20% of ADHD patients have an underying mgur network mutations 10 fod increased frequency of copy number variations (CNV) in the mgur gene network detected in ADHD popuation vs. norma contros Dr. Hakonarson found these mutations in severa reated neuropsychiatric diseases Eia, Gessner et a. Nature Genetics,

12 mgur Mutations Highy Predictive of ADHD In a binded study of 155 mgur+ patients assessed in CHOP psychiatry >98% were diagnosed with ADHD H. Hakonarson, data presented at 63rd Annua American Academy of Chid and Adoescent Psychiatry in Oct

13 AEVI-001: First-in-cass mgur Neuromoduator Dr. Hakonarson identified AEVI-001 as a drug with potentia to address mgur network disruptions caused by genetic mutations Sma moecue, non-stimuant agonist of mutipe mgurs: 1, 3, 5, 7, 8 Up-reguates GABA B receptors Positive effects seen in anima modes Ameiorate cognitive impairment Reduce hyperactivity Enhance memory Antipsychotic activity 13

14 AEVI-001 GREAT Study: Design and Execution Two-part Phase 1b tria, n=30 mgur+ patients identified at CHOP Part 1 Singe Ascending Dose(SAD) / Pharmacokinetics(PK) SAD 24 hour PK mg Part 2 Ascending Dose Tria 1 week of pacebo foowed by 4 weeks active therapy Dose escaated: mg BID weeky for 4 weeks Efficacy endpoints CGI, Vanderbit, exporatory Singe-binded (patients/famiies) 14

15 Strong Efficacy Signa in Key Endpoints Treatment effect more robust over time and at higher doses CGI-I: Proportion of Responders at Each Week for A Subjects Vanderbit Scores: Proportion of Patients Improved from Pre-Study Baseine for A Patients Response rates for both scaes (CGI-I and Vanderbit Parent Rating Scae) approx 80% CGI-I, Cinica Goba Impression of Symptom Improvement Responder Goba rating of much or very much improved 15

16 Geneticay Tiered mgur Network Mutations Tier 1 Mutations in genes in mgur receptors or that directy infuence mgur signaing. n=17 Tier 1 79 Genes 10% of ADHD Tier 2 Mutations in genes that encode proteins that infuence mgur. n=7 Tier 3 Mutations in genes that encode for proteins that interact with Tier 1 and 2 genes. n=6 Genetic tiers optimized for Tier 1 (not baanced) Prevaence of ADHD estimated Tier Genes 20% of ADHD Tier Genes 30% of ADHD 16

17 Tier 1 & 2 Mutations Predict Higher Response CGI-I: Proportion of Responders at Week 5 by Genetic Tier (with 95% confidence intervas) Vanderbit: Proportion of Responders at Week 5 by Genetic Tier (with 95% confidence intervas) Response rate appears to be correated to the proximity to the core mgur genes Note: Data is for the subset of patients who titrated to the highest dose (N=18). Genetic tiers were not baanced. 17

18 Statisticay Significant Improvement in Key Endpoints Magnitude of response is comparabe to best in cass drugs in compex, severe patients Average CGI - I score at the end of each week a patients Week 1 Week 2 Week 3 Week 4 Week 5 Mean P < Average Vanderbit score at each week a patients Week 1 Week 2 Week 3 Week 4 Week 5 Mean P < Repeated Measures Anaysis: mean scores by week CGI-I Scae: 1-7 Vanderbit Scae (Questions 1-18):

19 AEVI-001: GREAT Tria Study Summary Strong efficacy signa in mutipe vaidated ADHD scaes Magnitude of improvement is comparabe to best in cass drugs in compex, severe patients Improvement in mutipe symptoms noted by caregivers Inattention, hyperactivity, anxiety, mood disorders Treatment effect more robust over time & at higher doses Genetic biomarker predictive of response to AEVI-001 (Tier 1 & 2) Confirmation of PK profie Comparabe to previous PK study; BID dosing We toerated; no treatment reated serious adverse events Majority of patients enroed in the ong-term safety tria 19

20 AEVI-001: ADHD Program Phase 2/3 (SAGA) mgur+ ADHD, Adoescents N=90, Ages ADHD Phenotype / Genotype Pediatrics, Adoescents N=1,000+ Objectives: Design: Non-interventiona Muti-center (25) Confirm prevaence of mgur+ Characterize mgur+ phenotype Expedite enroment in Phase 2/3 interventiona trias Genotype 1,000+ ADHD subjects, age 6-17, identifying patients who are mgur+ Phase 3 mgur+ ADHD, Pediatrics N= TBD, Ages 6-12 Phase 3 mgur+ ADHD, Chidren N=TBD, Ages

21 SAGA: Phase 2/3 Study in Adoescents with mgur+ ADHD Objective: Optimize dose in adoescents, confirm Phase 1b resuts Endpoints: ADHD-RS, CGI-I Enroment compete Top-ine Data: Q Phenotype / Genotype Muti-center: 25 sites mgur+ ADHD subjects: age Phase 2/3 mgur+, N=90 Pacebo controed 1:1 Randomization Same sites as Pheno / Geno AEVI weeks 1 week foow-up Pacebo 6 weeks 1 week foow-up 21

22 ADHD Phenotype/Genotype Study Design: 25 ADHD Investigationa Sites Across the U.S. 1,800+ ADHD patients ages 6-17 years Non-interventiona Muti-center (25) Objectives: Confirm prevaence of mgur+ Phenotypic differences in mgur+/- Expedite enroment in Phase 2/3 interventiona trias Timing: Ongoing Saiva Coection Study site obtains saiva sampe and sends to CAG for DNA extraction Consented Patients 95% of the study subjects have agreed to be contacted for future studies CHOP/CAG Biobank DNA extraction Genetic sequencing BioBanking of DNA Aevi Genomics Database Evauation of genotype and phenotype data Identification of subjects for future trias 22

23 Mutation Prevaence Confirmed in Phenotype/Genotype Study Age Group mgur+ (n) Tota (n) % Pediatrics (ages 6-12) % Adoescents (ages 13-17) 271 1,274 21% Addressabe pediatric/adoescent patient popuation: 1.2M - 1.5M Data presented at 63 rd Annua American Academy of Chid and Adoescent Psychiatry Meetings (AACAP) in Oct

24 mgur+ ADHD Patients: Higher Prevaence of Negative Symptoms (n=1013) In mgur+ patients*: Symptoms associated with emotiona dysreguation most prominent: disruptive behavior, anger contro Emotiona dysreguation often has significant ife consequences** Majority of symptoms more prevaent *Data presented at 63 rd Annua American Academy of Chid and Adoescent Psychiatry Meetings (AACAP) in Oct 2016 **Shaw, et a, Emotion Dysreguation in Attention Deficit Hyperactivity Disorder American Journa of Psychiatry, Voume 171, Issue 3, March 2014, pp

25 AEVI-001: Potentia for Superior Product Profie Aevi-001 cinica profie in mgur+ ADHD patients Effective non-stimuant (non-schedued) Exceent safety profie in >1,000 patients No evidence of growth retardation, addiction, seep disturbance No evidence of cardiovascuar risk No expectation for back box warning Potentia to address co-morbid symptoms (e.g., emotiona dysreguation) Potentia for increased compiance and adherence Average time to discontinuation of current medication is 4 months; fuy compiant for ony 2 months* 25

26 mgur+ ADHD: Market Opportunity Overa US ADHD Market 2015 Saes in excess of $10B* ~6M pediatric / adoescent patients** Stimuants dominate market: 90+% of tota prescriptions mgur+ ADHD Market, ages M - 1.5M patients (~25% mgur+) $2B - $3B market opportunity based upon current pricing and compiance / adherence Potentia upside for premium pricing with superior product profie 26

27 AEVI-001: 22q11.2 Deetion Syndrome Overview

28 Orphan Opportunity - 22q11.2 DS Prevaence estimates range from 1/2,000 to 1/4,000 Physica Symptoms Heart defects Ceft paate Gastrointestina probems Poor wound heaing Skeeta abnormaities Surgica / medica therapies mortaity <4% after CV surgery (excuding criticay i infants) Psychiatric Symptoms* No effective therapy Approx. 40% progress to schizophrenia *Jonas et a Bio Pyschiatry 2015;75:

29 Phase 1/2 Study in 22q Deetion Syndrome Objective: Expore symptoms from three neuropsychiatric disorders: ADHD, Anxiety, and Autism Spectrum Disorders (ASD) Endpoints: CGI-I, ADHD-RS, PARS, CARS-2 FPFV June 2016 (pending fina CHOP approva) H2 2016: Responder rate data from open-abe phase Open-abe Phase N=30, age weeks dose optimization FPFV: June 2016 Singe center: CHOP Responders Randomized Non Responders Aevi-001 Fixed dose 7 weeks Pacebo 7 weeks Exit Study 29

30 AEVI-002: Anti-LIGHT mab Program

31 AEVI-002: Anti-LIGHT mab Program First-in-Cass Bioogic from Kyowa Hakko Kirin Initia deveopment in Severe Pediatric Onset IBD Phase 2 ready antibody Strong reguatory excusivity and robust inteectua property portfoio High vaue commercia opportunity with potentia for indication expansion Rapid and capita-efficient goba deveopment pathway Minima investment to POC Singe pivota tria for registration Program Update Successfuy transferred IND FDA Type B meeting competed Agreement on pan to requaify tria suppy Agreement on design of first POC tria in patients 8 weeks active treatment 31

32 Rationae for Anti-LIGHT Approach DcR3 is strongy inked to Severe Pediatric Onset IBD 1 Initia strategy to augment DcR3 Very short haf ife Toxicity reported with previous DcR3 anaog Rationa Search based on bioogica pathway LIGHT overexpressed in IBD DcR3 LOF increases LIGHT 2 Decoy Receptor 3 DcR3 Immune Ce HVEM LIGHT LTbR Our Approach: Therapeutic antibody which mimics DcR3 reguation by binding LIGHT 1 Hakonarson, et a Loci on 20q13 and 21q22 are associated with pediatric-onset infammatory bowe disease. Nature Genetics 40 (10): Mauri DN, et a LIGHT, a new member of the TNF superf amiy, and ymphotoxin apha are igands for herpesvirus entry mediator.immunity 8 (1):

33 Rapid Deveopment Pathway to Approva Severe Pediatric Onset IBD POC Tria Singe Phase 3 Pivota Registration Tria Anticipated Phase 1b design: Singe center (CHOP) N = up to 12 patients Duration 8 weeks Ascending dose Long Term Safety Tria Endpoints: Endoscopic Evauation, Crohn s Disease Activity Index (CDAI), Safety Estimated Cost: ~$2M 33

34 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 immediatey so patients can deveop normay Avoid steroids and IMs Manage utiization of anti-tnf aphas to extend time before resistance deveops Opportunity: 30% of patients do not respond to anti-tnfα Up to 50% of patients who initiay respond, resistance wi deveop within 3 years 1 Creates significant opportunity for new Therapies / MOAs, that can treat anti-tnf apha faiures 34

35 Severe Pediatric Onset IBD: Anti-LIGHT Opportunity (US Pop.) Initia Target: anti-tnfα faiure with DcR3 Loss of Function 2,000 3,000 IBD patients in US $300-$400M opportunity (based conservative pricing) Pediatric IBD Prevaence: 71/100,000 1 (52,000) Anti-TNF Usage 35-55% 2 (24,500) Potentia Upside Pediatric anti-tnfα faiures: 15,000 16,000 IBD Patients in US Pediatric indications with DcR3 LOF (juvenie 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) 1 Kappeman et a. (2007) Cin Gastro Hepat 2 Oiva-Hemker (2015) J Pedtr 3 Remicade Monograph 4 Atwegg-Vincent (2014) Mediators of Infamm DcR3 LOF (15%) (1,275) 35

36 Financias & Miestones

37 Financia Update $47M cash baance (cash and cash equivaents) at 9/30/16 Current resources estimated to fund operations through Q ~37.1M shares outstanding at 10/31/16 37

38 Upcoming Miestones R&D Programs Timing AEVI-001 Compete enroment in Phenotype / Genotype study Compete enroment in SAGA: Phase 2/3 mgur+ ADHD Adoescent Tria Top-ine data Q1 17 Initiate enroment in Phase 1/2 22q Deetion Syndrome Tria Q1 17 Initia open-abe responder data H1 17 AEVI-002: Anti-LIGHT mab Initiate Signa Finding Study Initia open-abe responder data H

39 Thank You