profile B6 company isfocusing onmetabolic diseases, including own pipelineoftherapeuticproducts. Currently the isusingtheLigand InDanio Trap system to buildits Homegrown pipeline comprehensively. and with thousandsofcompoundsscreened quickly screening outrobotically, steps canalsobecarried and fish. meansthatall The smallsize offishembryos shown similarpharmacological profiles inhumans alldrugstested sofarhave normally; to function tions required for thetransgenichumanNRproteins andcondi contain all cofactors they Importantly, are tiny, prolific, transparent anddrugabsorbent. specifically recruited protein ( cofactors together with active or metabolites as well as can then be isolated from these responding tissues, produce agreen fluorescent signal. NR The activated drugs, andactive cofactors thetransparent embryos tissuescontainingappropriatethe 48humanNRs. In to 48transgenic NRfish lines, eachexpressing oneof animal,” says Jens Tiefenbach, CSOofInDanio. inalltissuesofalive drugsandcofactors of active allows for and evaluation thesimultaneous detection identification of biologically SNuRMs. active “It InDanio’s Trap system drugs Selective resulted indwindlingnumbersofapproved drugs. tive nuclear- modulators (SNuRMs) have also NRs and the lack of suitable assays to identify selec physiological environments. Cross-reactivity between andpotential their cofactors ligandsin theirnormal screening platforms thatcanassessthereceptors, challenging recently becauseofthelackrobust drugshasbeen ofnovel NR-directed the discovery metabolic diseases, aswell asmostcancers. However, cardiovascular, neurodegenerative, reproductive and apeutic effects for conditions such as inflammatory, identifying novel naturalorsynthetic drugswithther Consequently, for NRsoffer opportunities enormous metabolism, development, growth andreproduction. roles incontrolling(NRs), which have important as nuclear receptorsof known transcription factors isthehighlydruggablefamily core area ofexpertise cost-effective, andfast. selective The company’s a live vertebrate, creating aplatform thatis highly favorable oftraditional aspects genic zebrafish ( Toronto-based usestrans BioscienceInc. InDanio and selectivity. targeting nuclear receptors and epigenetic regulators while allowing evaluation of , BioscienceInDanio Inc.’s unique Ligand Trap system provides for new discovery an open untapped fish oceanGreen www.indanio.com Bioscience Inc. InDanio Zebrafish are model, theidealvertebrate asthey NR of screening up out in a portfolio can be carried |March 2016 | nature.com/biopharmadealmakers nature.com/biopharmadealmakers Danio rerio Danio ) to combinethemost 1 isoptimized for the in vitro screening in Fig. 1 ). - - - - ing of both activator andrepressoring ofbothactivator NRs, aswell as throughput screening platform thatallows screen only commercially available space. InDanio’s Ligand Trap system isthe other companies in the NR- and cofactor-targeted Trap system as a source of competitive advantage for for eventual out-licensing, offers itsLigand InDanio additionto developing itsownIn pipelineofproducts capability discovery drug Unique families ofNRtargets. for FXR and ROR thehighlyattractive SNuRM activity and (2) several chemical new entities with potent (patent applicationnumberPCT/CA2014/000253); tial for repurposing asadrugfor liver diseases fatty to hasdetermined havethat InDanio strong poten forquinone originally marketed neurological diseases The company’s are leadproducts (1)idebenone, a peroxisome proliferator-activated receptors (PPARs). Xreceptorsecond onfarnesoid (FXR)andathird on focusing onRAR-related receptors orphan a (RORs), generative diseases;andinflammation. neurode non-alcoholic steatohepatitis; oncology; small molecules(L)orrecruited protein (P). cofactors (AP/MS) to identifydirectlybound spectrometry andmass purification tosubjected affinity specific responses. The responding NRcanbe screen showing differentcompound library tissue- cofactors. Above are possiblehitsofa two response ofthehumanNRto hostligand(s)and Ligand Trap transgenicfishshowing alimited The fishdenoted atthetop represents atypical Figure ofligandtrap 1:Overview fishuses. brain InDanio hasthree leadprograms: early-stage InDanio one SNuRM 1 Sma L T Fish screen l l mol e cu AP/MS -L compound Response toendogenous hormone andcofactors l e Bound in vivo in vivo SNuRM 2 , vertebrate, high- heart cofactors AP/MS -P Bound , high-content for compounds l iv e r

- - - ADVERTISER RETAINS FORCONTENTADVERTISER SOLERESPONSIBILITY types ofcollaborationstypes tion ofpreviously identifiedNR-targeted compounds andevaluation. drugdiscovery NR-directed it the mostligands comprehensive makes solution for to and alsoidentifydirectly boundcofactors ability (e.g., HDAC1 andHDAC8). The Ligand Trap system’s a suite linesfor ofcofactor epigeneticdrugdiscovery of48NRlines,available notonlyaportfolio butalso thefuture, willhaveepigenetic cofactors. In InDanio 1. opportunities,” says AnneCheung, CEOofInDanio. lines,NR orcofactor aswell asourpipelineproduct of of collaborations surrounding our portfolio types programs.discovery We are opento establishingall the successofNR-targeted andepigeneticsdrug are confidentourLigand Trap system willenhance integrated withtheexistingLigand Trap system. “We laborations entailingcustom assay development target-validation or broader research services, col models:screening contracts,ness partnership throughbe arranged anumberofdifferent busi assays.RNA injection usingtransient activities various and characterizing such asdeveloping assays for proteins of interest compound libraries, aswell asfor custom services usingcustomer-supplied orin-housediscovery The company isalsoavailable for using InDanio’sselectivity large of NR lines. portfolio for toxicity, bioavailability, and NR tissue selectivity surrounding ourportfolio “ Drug discovery services includethecharacteriza services Drug discovery Access to InDanio’s platform can drugdiscovery

contact Tiefenbach, J. Email: Email: Tel: +1-416-899-2889 Toronto, Ontario, Canada InDanio Bioscience Inc. Jens Tiefenbach, CSO CEO Cheung, Anne [email protected] We are opento establishing all [email protected] et al. PLoS ONE

5 , e9797(2010). Anne Cheung, CEO ADVERTISEMENT FEATUREADVERTISEMENT de novo or NRdrug - - -