profile B22 to the urgent needfor . new environmentthe regulatory hasevolved inresponse on thebasisofdata submitted in2008. Sincethen, Administration (FDA) declinedto approve iclaprim 82% andlinezolid, 85%). The USFood andDrug at test of cure (pooledclinical cure rate: iclaprim, and iclaprim forbetween clinical cure rates infections, which showed similar safety and efficacy structure andskin in patientswithcomplicated skin phase 3studies(ASSIST-1 and-2)were conducted waslicensedto anddevelopedaprim by Arpida. Two Originally discovered by F. Hoffman-LaRoche, icl clinical program Late-stage propensity for ofresistance induction of linezolid or2.0 compared with1.0 tested strainsof requiredconcentration oficlaprim 90%of to kill 2014), including (2012– patients withABSSSIandHABPworldwide from collected a rangeofGram-positive bacteria alone potent thantrimethoprim is 16 timesmore2015 has also shown thaticlaprim against Gram-positive pathogens. plus sulfamethoxazoleas potent as does. thantrimethoprim the DHFRbindingsite ofbacteria for shows amuchhigheraffinity iclaprim methoprim, replication pathway, role DNA inbacterial whichhasakey targets thefolatemechanism ofaction synthesis tive dihydrofolate (DHFR)inhibitors. reductase Its belongsto theunderutilizedIclaprim classofselec activity bactericidal Rapid as methicillin-resistant including infections caused by such resistant bacteria pneumonia(HABP), and hospital-acquired bacterial infections structure (ABSSSIs) andskin skin bacterial infections, bacterial mon and serious such as acute being developed for thetreatment ofthemostcom leadproduct candidate, is iclaprim, Its tant bacteria. life-threatening infections caused by multidrug-resis pany and antibioticsagainstserious developing new ate treatment withthebestavailable . and life-threatening infections thatrequire immedi pital setting, where succumbto patientsoften serious resistant infections isincreasingly urgent inthehos The needfor antibioticsto new combatmultidrug- infections. structure testingand skin clinical for skin acuteand is bacterial in late-stage Motif Bio’s iclaprim shows andlow of resistance propensity for rapid activity induction bactericidal infections bacterial life-threatening and serious for antibiotic Potent late-stage www.motifbio.com BioSciences,Motif Inc. Iclaprim is rapidly bactericidal ( is rapidlyIclaprim bactericidal from in JMILaboratories An independentreport com Bioisaclinical-stagebiopharmaceutical Motif |June2016 | In vitro 1 . Designed to overcome resistance to tri data show that iclaprim alone is at least aloneisatleast datashow thaticlaprim

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MIC after 2–3passages.MIC after Additionally, causednomutationsindihydrofolate iclaprim reductasegenes. 22repeat after passages, inducedlarge andrifampin changesin whereasconcentration (MIC) trimethoprim for arepresentative clinical strainof in vitro Figure andlow resistance activity profile. 1:Iclaprimbactericidal selected patients,selected becauseofitslow renal toxicity may be an appropriateIclaprim initialantibiotic for New frontline treatment option is plannedfor late 2016. inpatientswithHABP of 2017.Apivotal phase3trial als are anticipated to becompleted inthesecondhalf patient wasannouncedinMarch 2016,andbothtri while minimizingsafety events. ofthefirst Dosing parameters efficacy associated withantibacterial hours), whichoptimizes thepharmacodynamic of intravenous infusionin500 be clinicalcure at1–2weeks theendoftreatment. after dose of treatment. endpoint will secondary The key inlesionsizereduction thefirst at48–72hoursafter 75 cm ized withABSSSIsandhave alesion-size area ofatleast -2 willeachenroll 600adultpatientswhoare hospital resulting savings. and inpharmacoeconomic REVIVE-1 potentially reducing thelengthofhospitalstay and profile,eliciting amuchfaster bactericidal thereby to oficlaprim show noninferiority while Iclaprim Vancomycin Treatment) aimto clinicaltrials FDA andEuropean Evaluation Board. Medicines foriclaprim thetreatment ofABSSSI,withinputfrom the approval formarketing anintravenous formulation of ing. The pivotalaimto new obtain phase3clinicaltrials program clinicaltest to andreturned late-stage iclaprim experience, it has improved the original development 2014and, inDecember buildingonprevious iclaprim colony-forming units. ( 99.9%ofMRSAwithin4–6hoursdrugexposure, versus killed 8–10hoursforIclaprim vancomycin. CFU, a 2

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2×MIC . Iclaprim induced only a small change in minimum inhibitory inducedonlyasmallchangeinminimuminhibitory . Iclaprim r e 9 s e r mg mg v 10 e d - - - . Staphylococcus. aureus ATCC 25923(trimethoprimsensitive).* Induction ofresistancewithiclaprim b ADVERTISER RETAINS FORCONTENTADVERTISER SOLERESPONSIBILITY MIC (mg/ml) 1. Lumsden, Bio. CEOofMotif now,”engaging with strategic partners said Graham in the second half of 2017, we are to begin keen side thecountry. to expected complete trials “With out partners the United States seeking andisactively ready for commercialization in2018. inEurope.expected approved, If couldbe iclaprim drug approval. Ten years isalso ofdataexclusivity exclusivity from10 years thedate ofmarket ofnew designation for ABSSSIandHABP, iteligible for making tion and a qualified infectious diseases product (QIDP) onset ofinfection.” wrong—it choicefrom hasto betheright theinitial patients, you cannotafford to gettheinitial antibiotic Huang, Bio. chiefmedicalofficeratMotif these “In treatmentthat may make more complex,” saidDavid ties, such as diabetes, and renal obesity impairment threatening MRSA infection with specific comorbidi a hospitalized andlife- patientwhohasaserious resistance. patientwillbe believe theiclaprim “We profile andlow for propensity thedevelopment of 100 120 140 20 40 60 80 0 Motif Bio is planning to commercializeMotif in iclaprim The FDA hasgranted afast-track iclaprim designa 0 Morgan, A. contact *Similar resultswereobtainedwithatrimethoprim-resistant(F98Y)S.aureus Email: [email protected] +1-936-577-5770 Tel: USA York, New York, New Motif BioSciences, Inc. Officer Medical Chief Huang, David et al 5 ( a ) Iclaprim is rapidly bactericidal israpidlybactericidal ) Iclaprim . Future Microbiol. Trimethoprim Staphylococcus aureus 10 Passage in vitro andtrimethoprim: Iclaprim number ADVERTISEMENT FEATUREADVERTISEMENT

4 , 131–143(2009). . Serial passage study passagestudy . Serial 15 Rifampin 20 (MRSA). (MRSA). . 25 - - -