the$oral$selec+ve$inhibitor$of$nuclear$export$(sine ...*see poster: “selinexor-induced...
TRANSCRIPT
The$Oral$Selec+ve$Inhibitor$of$Nuclear$Export$(SINE)$Selinexor$(KPT=330)$Demonstrates$Broad$and$Durable$Clinical$Ac+vity$in$Relapsed$/$Refractory$Non$Hodgkin’s$
Lymphoma$$John$ Kuruvilla1,$ John% C.% Byrd2,% Joseph% Flynn2,% Ramiro% Garzon2,% Pierluigi% Porcu2,% Nina% Wagner?Johnston3,% Lynn%Savoie4,%Richard%Stone5,%Eric% Jacobsen5,%Morten%Mau?Sorensen6,%Peter%de%Nully%Brown6,%Rachid%Baz7,%Bijal%Shal7,% Ian%Flinn8,%Nashat%Gabrail9,%Vishal%KukreT1,%Rodger%Tiedemann1,%Yosef% Landesman10,% Boris% Klebanov10,% Eran% Shacham10,% Jean?Richard% Saint?MarTn10,% Tracey%Marshall10,% John% McCartney10,% Dilara% McCauley10,% Robert% Carlson10,% Sasha% Norori11,% Michael%Savona10,%Tami%Rashal10,%Mansoor%R%Mirza10,%Michael%Kauffman10,%Sharon%Shacham10%%
1"
(1)%Princess%Margaret%Cancer%Center,%Toronto,%Canada;%%(2)%The%Ohio%State%University,%James%Cancer%Hospital,%OH,%USA;%(3)%Washington%University%School%of%Medicine,%St.%Louis,%MO,%USA;%%(4)%University%of%Calgary%Division%of%Hematology,%Calgary,%Canada%%(5)%Dana?Farber%Cancer%InsTtute,%Boston,%MA,%USA;%%%(6)%Dept.%of%Oncology,%Rigshospitalet,%Copenhagen,%Denmark;%%(7)%H.%Lee%Moffid%Cancer%Center%&%Research%InsTtute%Inc.,%Tampa,%FL,%USA;%%(8)%Sarah%Cannon%Research%InsTtute,%Tennessee%Oncology,%Nashville,%TN,%USA;%%(9)%Gabrail%Cancer%Center,%Canton,%OH;%%(10)%Karyopharm%TherapeuTcs%Inc,%Newton,%MA,%USA;%(11)%Ozmosis%Research%Toronto,%Ontario,%Canada%%%
Presenter$Disclosures$
1"
Research$Support$ Leukemia%and%Lymphoma%Society%US,%Rasch%FoundaTon,%Celgene,%Hoffman%LaRoche,%Karyopharm,%NovarTs%
Consultant$ Hoffman%LaRoche%
Honoraria$ Amgen,%Celgene,%Gilead,%Hoffman%LaRoche,%Janssen,%Lundbeck,%Seadle%GeneTcs%
Scien+fic$Advisory$Board$ Lymphoma%Canada%(Chair)%
Major$Stockholder$ N/A%
Employee,$Speakers$Bureau$ N/A%
Oral$Selinexor$as$Novel$Therapy$for$NHL$
o ExporTn%1%(XPO1/Crm1)%is%the%major%nuclear%export%protein%with%>200%protein%and%a%few%RNA%cargos%
o XPO1%is%overexpressed%in%many%hematological%and%solid%tumor%cancers%and%correlates%with%poor%prognosis%or%resistance%to%chemotherapy%
1"
Poorer$prognosis$in$XPO1$overexpressing$MCL$(Yoshimura et al. (2014) Cancer Sci 105: 795)
XPO1$overexpression$in$DLBCL$cell$lines$and$primary$specimens$(Kuruvilla%et%al.%(2014)%EHA%19th%Annual%Congress)%
XPO1 Overexpression
XPO1 Normal Expression
XPO1 protein expression in 62 primary DLBCL samples
Selinexor:$First=in=Class,$Oral$Selec+ve$Inhibitor$of$Nuclear$Export$(SINE)$
1"
Selinexor
o Novel,%small%molecule%selecTve%inhibitor%of%XPO1%
o Oral%drug%given%1x,%2x,%or%3%Tmes%per%week%
o No%known%drug?drug%interacTons%through%CYP450s%
o Potent%anT?lymphoma%effects%in%vitro%and%in%vivo%in%NHL%models%%
o AnT?tumor%acTvity%in%ongoing%Phase%I%and%II%studies%in%advanced%hematologic%and%solid%tumors%
o Selinexor$interferes$with$ac+vity$of$proteins$known$to$play$cri+cal$roles$in$NHL$
o Reduces$expression$of$the$proto=oncogene$proteins$c=myc,$Bcl=2,$Bcl=6,$Mdm2,$BTK,$Cyclin$D$and$survivin$for$which$overexpression$correlates$with$poor$prognosis$
o Blocks$NF=κB$ac+va+on,$which$is$required$for$ABC$DLBCL$cell$survival$$
o Reac+vates$p53,$for$which$muta+on$is$associated$with$poor$prognosis$
o Selinexor$shows$robust$an+=cancer$ac+vity$in$mul+ple$preclinical$models$of$NHL,$including$canines$with$spontaneous$lymphoma,$largely$independent$of$genotype$
Selinexor$is$a$Ra+onal$Therapy$for$NHL$
1"
Selinexor$Phase$1$Study$Design$(NCT01607892)$
1"
Relapsed/Refractory$B=Cell$
MM/WM,$$NHL$$,$CLL$
Relapsed/Refractory$B=Cell$
AML$
MM/WM,$$DLBCL$35$mg/m2$and$60$mg/m2$$
Dose$Escala+on$Cohorts$ Dose$Expansion$Cohorts$
Acute$Myeloblas+c$Leukemia$
T=Cell$Lymphoma$
$Arm$1$
Arm$2$
Arm$3$
ALL$(B=$or$T=Cell)$Arm$4$
Arm$5$CML$(Accelerated/Blast)$
Arm$6$MM$+$Dexamethasone$
DLBCL$(+$375$mg/m2$Rituximab)$Arm$7$
Selinexor$Phase$1$Study$Design$• ObjecTves%(modified%3+3%design)%
– Primary:%Safety,%tolerability%and%Recommended%Phase%2%Dose%(RP2D)%of%KPT?330;%%
– Secondary:%PharmacokineTcs%(PK),%pharmacodynamics%(PDn),%anT?tumor%response;%confirmaTon%of%RP2D%of%selinexor%
• Selinexor%dosing%– 10%doses/cycle%(2?3%doses/week)%or%8%doses/cycle%(twice%weekly)%or%4%doses/
cycle%(once%weekly)%– Doses%3%mg/m2%–%80%mg/m2%
%• Major%eligibility%criteria:%%
– PaTents%(ECOG%≤1)%with%relapsed/refractory%hematologic%tumors%with%no%available%standard%treatments;%No%acTve%CNS%disease%%%
– Documented%progression%at%study%entry%– ANC%>1000/µL,%Platelets%>30,000/µL%
1"
Selinexor$Phase$1:$DLT$Criteria$
• ≥%3%missed%doses%in%28%days%at%target%dose%%• DisconTnuaTon%of%a%paTent%due%to%a%toxicity%in%Cycle%1%• Non$Hematologic:%%
– Grade%≥3%%nausea/vomiTng,%dehydraTon%or%diarrhea%while%taking%opTmal%supporTve%medicaTons%
– Grade%3%faTgue%≥5%days%while%taking%supporTve%care%%– Grade%3%AST%or%ALT%elevaTon%lasTng%longer%than%7%days%%
• Hematologic:%%– Grade%4%neutropenia%≥7%days%– Febrile%neutropenia%%– Grade%≥3%thrombocytopenia%associated%with%bleeding%%%%
1"
Selinexor$Phase$1$Study:$Pa+ent$Characteris+cs$
Characteris+cs$ N*$=$71$
Mean%Age%(Range)% 63%(23%–%79)%
Male%to%Female% 43%:%28%
Mean%Prior%Treatment%Regiments%(Range)% 3%(1–12)%%
ECOG%Performance%Status%(0:1:2)% 24%:%45%:%02%
Non$Hodgkin's$Lymphoma$(NHL)$
?Aggressive%B?Lymphoma%(DLBCL,%Follicular%Grade%3b,%Transformed)%%
DLBCL%N=31,%Trans%N=11,%Follicular%Grade%3b%N=1%%%
?Follicular%Lymphoma%&%Other%Indolent% 10%PaTents%
?Mantle%Cell% 4%PaTents%
?T%Cell%Lymphoma% 5%PaTents%
?Burkid’s%Lymphoma% 1%PaTent%
?Richter’s%TransformaTon$ 8%PaTents%
1"
*%As%of%1?December?2014%
Selinexor$Phase$1$Study:$Doses,$DLT$and$MTD$
*All%paTents%in%Arm%1%(NHL,%CLL,%MM%and%WM)%were%included%for%DLT%evaluaTon%
1"
! 10$Cohorts$Evaluated:$! $Doses%Ranging%from%3%–%80%mg/m2%%
%! 3$DLTs*$Have$Been$Seen$(Only$in$10$doses/cycle$schedule):%
! Dose%Level:%%16.8%mg/m2;%MM%pt%with%Grade%4%thrombocytopenia%%! Dose%Level:%%23%mg/m2;%FL%pt%with%Grade%4%thrombocytopenia%%! Dose%Level:%%30%mg/m2;%CLL%pt%with%Grade%2%faTgue,%pt%missed%3%doses%
! Expansion$Cohort$1%%! 35%mg/m2;%DLBCL%–%MM%–%WM%paTents%%%%
! Expansion$Cohort$2$$! 60%mg/m2;%DLBCL%paTents%
Selinexor$Phase$1$Study:$Drug$Related$AEs$
1"
0 10 20 30 40 50 60
LeukopeniaNeutropenia
AnemiaThrombocytopenia
Hyponatremia
Blurred vision
DehydrationSensory neuropathy
ProteinuriaSyncope
DyspepsiaConfusion
Muscle weaknessConstipation
DizzinessWeight lossDysgeusia
DiarrheaVomitingAnorexia
FatigueNausea
AE incidence (% of pts)
Grade 1Grade 2Grade 3Grade 4
N=67
AEs for ≥ 5% of pts
Selinexor$Phase$1$Study:$Common$AEs$By$Cycle$
1"
0 10 20 30 40 50 60 70 80
AnemiaProteinuria
LeukopeniaNeutropenia
Thrombocytopenia
Creatinine increased
Blurred vision
Sensory neuropathyHyperhidrosis
PruitusDyspepsia
Muscle weaknessDizziness
DysgeusiaWeight loss
AnorexiaVomiting
FatigueDiarrheaNausea
AE incidence (% of pts)
Grade 1Grade 2Grade 3Grade 4
N=25
CYCLE 1
0 10 20 30 40 50 60 70 80
AnemiaProteinuria
LeukopeniaNeutropenia
Thrombocytopenia
Creatinine increased
Blurred vision
Sensory neuropathyHyperhidrosis
PruitusDyspepsia
Muscle weaknessDizziness
DysgeusiaWeight loss
AnorexiaVomiting
FatigueDiarrheaNausea
AE incidence (% of pts)
Grade 1Grade 2Grade 3Grade 4
N=25
CYCLE 2
• Possibly%or%probably%drug?related%AEs%in%the%25%NHL%that%made%it%through%at%least%Cycle%2%• AEs%(other%than%hematological)%are%substanTally%reduced%ater%Cycle%1%%
0 10 20 30 40 50 60 70 80 90-100
-80
-60
-40
-20
0
20
40
60
Time (days after first selinexor dose)
Plat
elet
cou
nt
(% c
hang
e fro
m b
asel
ine)
Effect of Selinexor On platelet counts
N=31 NHL pts
0 100 200 300 400-100
-80
-60
-40
-20
0
Baseline platelet count
Plat
elet
cou
nt a
fter o
ne c
ycle
(% c
hang
e fro
m b
asel
ine)
Selinexor-induced change inplatelet count vs baseline count
N=15 NHL pts
AverageChange
Data from pts maintained at a set dose from the start (3-80 mg/m2, QOD x2-3/wk), over the period of platelet count measurement.
Presented by:
Selinexor$Phase$1$Study:$Effects$on$Platelet$Count$
1"
• Selinexor%induced%~50%%decrease%in%platelet%count%over%the%first%cycle,%without%further%significant%loss%over%subsequent%cycles%
• Platelet%loss%is%due%to%inhibiTon%of%megakaryocyte%progenitor%maturaTon*%• Platelet%loss%percentage%was%independent%of%baseline%platelet%count%• TPO%agonist%or%IL?11%treatment%can%be%effecTve%at%increasing%platelet%count%
*See Poster: “Selinexor-Induced Thrombocytopenia Results from the Inhibition of Megakaryocyte …” Abstract No. 1458, ASH 2014
Cycle 1-Dose 7
840 21
N=4/pt
Cycle 2-Dose 7
4 300 21
N=2/pt
Averageinduction
Cycle 3-Dose 7
4 300 21
N=2/pt
Time (hr post dose)
Schedule 2 (QoD, 10 doses/cycle)
0
2
4
6
8
10
12
XPO
1 ex
pres
sion
in le
ukoc
ytes
(F
old
pred
ose
leve
l)
Cycle 1-Dose 1
10
5
6
9
8
5
8 241 42 48
N/pt as indicated
0
1
2
3
4
5
XPO
1 ex
pres
sion
in le
ukoc
ytes
(F
old
pred
ose
leve
l)
Cycle 1-Dose 1
15
12
12
97
8 2440 48
N/pt as indicated
Cycle 1-Dose 5
8
N=2/pt
40
Averageinduction
Time (hr post dose)
Schedule 3 (QoD, 8 doses/cycle)Cycle 1-Dose 6
8
N=2/pt
40
Selinexor$Phase$1$Study:$XPO1$expression$in$PBMCs$
1"
• Selinexor%induces%XPO1%gene%expression%in%circulaTng%leukocytes%that%reaches%a%maximal%effect%4%hr%ater%the%first%dose.%
• Leukocyte%XPO1%inducTon%is%maintained%by%10%QoD%doses/cycle,%but%is%not%maintained%with%8%QoD%doses/cycle%
• Provides%pharmacodynamic%basis%for%parTal%recovery/beder%tolerability%with%less%intensive%8%QoD%doses/cycle%%
Presented by:
1"
• Immunohistochemical%assessment%of%DLBCL%tumor%specimens%from%a%paTent%with%a%parTal%response%to%selinexor%%
%• Increased%apoptosis%(Apoptag/
Cleaved%Casp3)%%%• ReducTon%in%expression%of%%
NF?κB%and%variety%of%oncoproteins%(BTK,%p?STAT?3,%p?JAK3)%relevant%to%NHL%
Selinexor$Phase$1$Study:$Primary$Tumor$IHC$
KI67%
Follicular)Lymphoma)0401096)PR)49mg/m2)
BCL2%
NF,κB%
BTK%
Cleav.%Casp3
%
STAT
3%(P,S727)%
JAK3
%(P,Y785)%
Predose) Selinexor)314)weeks)
Predose) Selinexor)314)weeks)
DLBCL 040-402 PR 60mg/m2
Apo
ptag
X
PO
1
BTK
STA
T3 (P
-S72
7)
JAK
3 (P
-Y78
5)
STA
T3 (P
-S72
7)
Predose Selinexor 3-4 weeks Predose Selinexor 3-4 weeks
NF-κB
C
leav
. Cas
p3
Presented by:
1"
• Immunohistochemical%assessment%of%DLBCL%tumor%specimens%from%a%paTent%with%a%parTal%response%to%selinexor%%
%
• Increased%apoptosis%(Apoptag/Cleaved%Casp3)%%
%
• ReducTon%in%expression%of%%
NF?κB%and%variety%of%oncoproteins%(BTK,%p?STAT?3,%p?JAK3)%relevant%to%NHL%
Selinexor$Phase$1$Study:$Primary$Tumor$IHC$
Selinexor$Phase$1$Study:$Responses$in$Heavily$Pretreated$Pa+ents$with$NHL$$
ORR=Overall%Response%Rate,%CR=Complete%Response,%PR=ParTal%Response,%SD=Stable%Disease,%PD=Progressive%Disease%%1%paTent%is%pending%response;%15%paTents%were%not%evaluable%for%response%(Responses%as%of%1?December?2014)%
1"
Cancer$Type$ Selinexor$Dose$$(mg/m2)$ N*$ $ORR$(%)$ CR$(%)$ PR$(%)$ SD$(%)$ PD$(%)$
Aggressive$B=NHL$(DLBCL,$FLgrd3b,$Transformed)$
≤$20$ 4$ 1$(25%)$ ==$ 1$(25%)$ 1$(25%)$ 2$(50%)$
20$–$50$ 19$ 7$(37%)$ 4$(21%)$ 3$(16%)$ 5$(26%)$ 7$(37%)$
≥$60$ 10$ 4$(40%)$ ==$ 4$(40%)$ 4$(40%)$ 2$(20%)$
Follicular$&$Other$Indolent$NHL$$
$≤$30$ 4$ ==$ ==$ ==$ 4$(100%)$ ==$
≥$35$ 4$ 2$(50%)$ ==$ 2$(50%)$ 1$(25%)$ 1$(25%)$
Burkim’s$Lymphoma$ ≥$60$ 1$ ==$ ==$ ==$ ==$ 1$(100%)$
Mantle$Cell$Lymphoma$
≤$30$ 2$ 1$(50%)$ ==$ 1$(50%)$ 1$(50%)$ ==$
≥$35$ 1$ ==$ ==$ ==$ ==$ 1$(100%)$
T=Cell$Lymphoma$≤$30$ 2$ 1$(50%)$ ==$ 1$(50%)$ 1$(50%)$ ==$
≥$35$ 1$ 1$(100%)$ 1$(100%)$ ==$ ==$ ==$
Richter’s$Transforma+on$
≤$30$ 3$ 1$(33%)$ ==$ 1$(33%)$ 2$(67%)$ ==$
≥$35$ 1$ 1$(100%)$ ==$ 1$(100%)$ ==$ ==$
TOTAL$ 52$ 19$(37%)$ 5$(10%)$ 14$(27%)$ 19$(37%)$ 14$(27%)$
-100
-80
-60
-40
-20
0
20
40
60
80130140
Tum
or v
ol. (
max
% c
hang
e fr
om b
asel
ine)
Aggressive LymphomaFollicular LymphomaMantle Cell LymphomaRichter'sTransformationT-cell Lymphoma
-100
-80
-60
-40
-20
0
20
40
60
80130140
Tum
or v
ol. (
max
% c
hang
e fr
om b
asel
ine)
Aggressive LymphomaFollicular LymphomaMantle Cell LymphomaRichter'sTransformationT-cell Lymphoma
Selinexor$Phase$1$Study:$Evaluable$Pa+ents*$Maximal$%$Change$in$Lymph$Node$from$Baseline$
1"
Progressive$Disease$
Par+al$Response$
%%Denotes%paTents%with%PET/CT%confirmed%Complete%Response%%*Excludes%paTents%who%clinically%progressed%(N=11),%withdrew%consent%(N=9),%did%not%have%a%post%treatment%scan%(N=4),%no%disease%quanTficaTon%(N=3),%%or%pending%(N=1)%As%of%1?December?2014%%
N=40$
0 2 4 6 8 10 12 14 20 24
-100
-80
-60
-40
-20
0
Cycle
Tum
or v
olum
e(%
cha
nge
from
bas
elin
e)
Duration of ResponseMedian DOR = ~ 7 Months (N=19)
(CR by PET SCAN)
PRCR
+
+
++
+
+ remainson study
0 1 2 3 4-60
-40
-20
0
20
40
60
80
100
120
250
270
Cycle
Tum
or v
olum
e(%
cha
nge
from
bas
elin
e)
SD Duration(N=15)
SD
Selinexor$Phase$1$Study:$Dura+on$of$Disease$Control
1"
Selinexor$Phase$1$Study:$Responses$Across$Subtypes$of$Relapsed$/$Refractory$DLBCL$
Responses$in$Diffuse$Large$B=Cell$Pa+ents$as$of$1=December=2014$
Type$ N$ DCR$(%)$ ORR$(%)$ CR$(%)$ PR$(%)$ SD$(%)$ PD$(%)$
GCB% 11% 9%(82%)% 4%(36%)% 1%(9%)% 3%(27%)% 5%(45%)% 2%(18%)%
Non%GCB% 5% 4%(80%)% 2%(40%)% 1%(20%)% 1%(20%)% 2%(40%)% 1%(20%)%
Pa+ents$with$“Double$Hit”$DLBCL$as$of$1=December=2014$
Pa+ent$ID$ Best$Response$ %$Reduc+on$in$Lymph$Nodes$ Days$on$Study$ Prior$Therapies$
046% CR$ 73%%(PET%NegaTve)% 429+% CHOP=R,$RICE$
058% PD$ ??% 57% CHOP=R,$RICE$%
072% PR$ ?65%% 214% R=CHOP,$Benda,$RICE,$DHAP=R,$BEAM$
086% SD$ ?45%% 104% CHOP=R,$GDP,$Ibru+nib+Lenalidomide$
DCR=Disease%Control%Rate%(CR+PR+SD),%ORR=Overall%Response%Rate%(CR+PR),%CR=Complete%Response,%PR=ParTal%Response,%SD=Stable%Disease,%PD=Progressive%Disease%(+%paTent%remains%on%study)%
1"
Subtyping%was%available%for%16%evaluable%paTents%
Selinexor$Phase$1$Study:$Rituximab$Combo
1"
! ARM$7:%PaTents%receive%a%combinaTon%of%selinexor%with%rituximab%%! Dosing%Scheme%Below:%%%
! Three%paTents%have%been%enrolled%on%ARM$7%thus%far%%%
! Cohort%1:%45%mg/m2%selinexor%+%375%mg/m2%rituximab%has%cleared%DLT%evaluaTon%%! Responses%include%1%ParTal%Response%(55%%ReducTon)%and%2%Progressive%Disease%%
! Cohort%2:%60%mg/m2%selinexor%+%375%mg/m2%rituximab%is%currently%enrolling%%
Case$Study:$Pa+ent$040=050:$Refractory$DLBCL$:$Complete$Response$
! 51%year%old%female%–%DLBCL%
! March%2006%–%Stage%IV%DLBCL%R?CHOPX6%
! Jan%2010%–%Relapse%Stage%IV%DLBCL%GDPX2%and%Autologous%SCT%–%Maintenance%Rituximab%(NCIC%CTG%LY12%RCT)%
! April%2011%–%Relapse%in%Neck%–%RadiaTon%
! Jan%2012%–%Relapse%in%Neck%–%steroids%
! Feb%2012%–%PD%in%Neck%–%Panabinostat%X6%cycles%RPh2%
! Jul%2013%–%Relapse%–%steroids%%
Selinexor$Treatment$
! October%7,%2013,%iniTates%Selinexor%35%mg/m2%%
! MRI:%74%%reducTon%in%cycles%1%&%2%
! PET%CT%negaTve%Cycle%12,%:%CR%
%
1"
Baseline Cycle 12
Rel/Ref$DLBCL$040=050:$PET$Confirmed$Complete$Response$
1"
Baseline Cycle 14 Baseline Cycle 14
Conclusions$
" Novel,%oral%SINE%selinexor%(KPT?330)%can%safely%be%given%as%monotherapy%to%paTents%with%heavily%pretreated%NHL%
" Main%toxiciTes:%anorexia,%nausea,%faTgue,%thrombocytopenia%" Phase%2/3%Recommended%Dose%is%60%mg/m2%BIW%%
" Selinexor%has%favorable%PK%and%PD%characterisTcs%" Single?agent%anT?tumor%acTvity%across%all%NHL%types%with%durable%cancer%control%
>9%months;%median%DOR%~%7%months%" Marked%acTvity%across%GCB,%nonGCB,%and%Double?Hit%DLBCL%" Further%evaluaTon%of%selinexor%in%NHL%is%currently%enrolling%in%two%separate%Phase%
2%Studies:%%" DLBCL%–%SADAL:%randomized%study%of%%selinexor%+%low%dose%dexamethasone%
(NCT02227251)$$" Richter’s%TransformaTon%–%SIRRT:%open%label%study%with%selinexor%monotherapy%
(NCT02138786)$$%
1"
Acknowledgments$%%%%%%%%%%We%would%like%to%thank:%%– PaTents%and%their%families%%
– InvesTgators,%co?invesTgators%and%the%study%teams%at%each%parTcipaTng%center%%
• Hackensack%University%Hospital,%NJ%%• Princess%Margaret%Cancer%Centre,%Toronto%%• Rigshospitalet,%Copenhagen,%Denmark%%• Moffid%Cancer%Centre,%Tampa%• Dana%Farber%Cancer%InsTtute,%Boston%
%
The$study$was$sponsored$by$Karyopharm$Therapeu+cs$Inc.$
1"
• Gabrail%Cancer%Center%Research,%Ohio%• Sarah%Cannon%Research%InsTtute,%TN%• The%Ohio%State%University%%• Tom%Baker%Cancer%Centre,%Calgary%%• Washington%University;%St%Louis,%MO%• Weill%Cornell%University;%New%York%
TM