oral small molecule glp-1 receptor (glp-1r) agonists for
TRANSCRIPT
Oral Small Molecule GLP-1 Receptor (GLP-1R) Agonists for Type 2 Diabetes
(T2DM) with Negligible Nausea and Vomiting
vTv Identified the First Oral Small Molecule (allosteric) Agonists of the GLP-1 Receptor in 2004
April2016 vTvTherapeu1cs,LLC 2
2004 Start of vTv’s Oral GLP-1R Agonist Research Program
2005 Byetta Approved in the US
2008 vTv’s First Generation,
TTP054, FIM Study
2012 vTv’s Second Generation,
TTP273, FIM Study
vTv’s GLP-1R Agonists Program Genesis
q Coordinatedu1liza1onofdatafromcellEC50assays,livermicrosomestability,andpharmacokine1csledtopotentleadserieswhichresultedin2clinicalcandidates
April2016 vTvTherapeu1cs,LLC 3
TTP-595(TTProbe™)EC5045µM
TTP054EC5040nM
(ClinicalPOC)
TTP273EC505nM
(ClinicalPOM)Phase2ongoing
FirstGenera1onSeries
SecondGenera1onSeries
vTv's Oral GLP-1R Agonists q Novel,small,orallybioavailablemoleculesthatac1vatethehumanGLP-1R
q Stand-aloneallostericGLP-1receptoragonists
q SpecificfortheGLP-1receptorØ Func1onalbiasforG-proteinsignaling
q TypicalGLP1PharmacologyinanimalsandhumansØ Enhancesinsulinsecre1oninresponsetoglucoseØ DecreasesglucoseØ Decreasesfoodintakeandbodyweight
April2016 vTvTherapeu1cs,LLC 4(Rodent:EC5034nM;34%ac1va1on)
Oral Small Molecule GLP-1 Receptor (GLP-1R) Agonists with Negligible Nausea and Vomiting
April2016 vTvTherapeu1cs,LLC 5
Nausea Vomi:ngPlacebo(n=21) 0 1200QD(n=11) 1 1400QD(n=9) 1 1200BID(n=10) 0 0400BID(n=4) 0 0
TTP054-108Phase1bT2DonMeBormin4w
Nausea Vomi:ng
Placebo(n=50) 3 2200QD(n=27) 1 0400QD(n=51) 0 0800QD(n=56) 4 3
TTP054-201Phase2T2DonMeBormin12w
TTP273-102Phase1bT2DonMeBormin2w
q TTP054andTTP273aresafeandwelltoleratedatalldosestestedØ NegligibleNauseaandVomi1ngØ NoevidenceofHypoglycemia
Nausea Vomi:ngPlacebo(n=29) 0 025QD(n=9) 1 050QD(n=9) 0 025BID(n=9) 0 075QD(n=8) 1 075QPM(n=7) 0 0100QD(n=9) 0 1*150QD(n=9) 0 075BID(n=8) 1 0150BID(n=8) 1 0450QD(n=7) 0 0
*unrelatedtostudydrug
TTP273 Shows Greater Improvement in Glycemic Control than TTP054 in a Phase 1b Trial
April2016 vTvTherapeu1cs,LLC 6
q TTP273ismoreefficaciousthanTTP054inphase1batthesamedosesdespiteshorterstudydura1on
TTP273 Seems to Have a Better Effect on Body Weight Loss than TTP054 in a Phase 1b Trial
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q Noweightlosswasseeninphase1bTTP054trialcomparedtoplaceboq TTP273phase1btrialshowedatrendinweightlosswiththeBIDdoseregimentsdespiteshorterstudydura1onandisocaloricdiet
q Ina3monthphase2studywithTTP054,significantbodyweightloss(1Kg)observedinthetargetpopula1on(A1c8-11%)atthehighdosegroup(800mgQD)
Proof of Concept
April2016 vTvTherapeu1cs,LLC 8
Phase2:TTP054-201
Ina3monthphase2study,TTP054showedsignificantreduc:oninA1c
• 3month,randomized,double-blind,placebo-controlled,parallelgrouptrialin184type2diabe1csonstabledosesofmecormin
• 7-11.5%baselineHbA1c• Arms:Placebo;TTP054200mg,400mgand800mgQD• Primaryendpoint:ChangefrombaselineinHbA1cat3
months
vTv Oral GLP1r Agonists: a Better Alternative to the GLP-1 Analogue therapy
EffectsObservedinPa:ents vTvGLP1rAgonists GLP-1
Analogues
SafetyNosignificantgastrointes1nalsideeffects
ü X
Convenience
Oral ü XIdealforco-formula1onwithexis1ngOADs ü XNoneedformedicaldevice ü X
Efficacy
Lowersbloodglucose ü ü DecreasesHbA1clevels ü ü Weightloss ü ü
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q With a superior safety and convenience profile, TTP273 could provide an alternative to current GLP-1r therapies and expand the use of this therapeutic class
Acknowledgements
April2016 vTvTherapeu1cs,LLC 10
q vTvDiscoveryanddevelopmentteams
q PatriciaMcDonald’slabatTheScrippsResearchIns1tute,Florida