ClinicalAc)vityofAdenosineA2AReceptor(A2aR)InhibitorCPI-444isAssociatedwithTumorExpressionofAdenosine

PathwayGenesandTumorImmuneModula)on

2 2

Drew Hotson1, John Powderly2, Leisha Emens3, Patrick Forde3, Matthew Hellmann4, Lawrence Fong5, Ben Markman6, Brett Hughes7, Jonathan Goldman8, Mario Sznol9, Daruka Mahadevan10, Shivaani Kummar11, Joshua Brody12, Philip Bonomi13, Jason Luke14, Matthew Riese15, Taofeek

Owonikoko16, Sherene Loi17, Amy Wiese18, Robert Doebele19, James Lee20, Chunyan Gu1, Stephen Willingham1, Ginna Laport1, Richard Miller1 and Ian McCaffery1

1Corvus Pharmaceuticals, Burlingame, CA; 2Carolina BioOncology Institute, Huntersville, NC; 3Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; 4Memorial Sloan Kettering Cancer Center, New York City, NY; 5University of California, San

Francisco, San Francisco, CA; 6Monash Medical Centre, Clayton, Australia; 7Royal Brisbane and Women’s Hospital, Herston, Australia; 8University of California, Los Angeles, Los Angeles, CA; 9Yale University School of Medicine, New Haven, CT; 10University of Arizona Cancer Center, Tucson, AZ; 11Stanford University School of Medicine, Stanford, CA; 12Icahn School of Medicine at Mount Sinai, New York City, NY;

13Rush University Medical Center, Chicago, IL; 14University of Chicago Medical Center, Chicago, IL; 15Medical College of Wisconsin, Milwaukee, WI; 16Emory University Hospital, Atlanta, GA; 17Peter MacCallum Cancer Centre, Melbourne, Australia; 18Karmanos Cancer Institute/Wayne

State University, Detroit, MI; 19University of Colorado Anschutz Medical Campus, Aurora, CO; 20University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA.

Capitalized title A2aR Disclosures

2

Consultancy 7 Hills, Actym, Amgen, Array, AstraZeneca, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, EMD Serono, Gilead, Janssen, Novartis, Merck

Clinical Trial Support to Institution

AbbVie, Boston Biomedical, Bristol-Myers Squibb, Celldex, Corvus, Delcath, Five Prime, Genentech, Immunocore, Incyte, Intensity, MedImmune, Macrogenics, Novartis, Pharmacyclics, Merck, Tesaro

Funding for CPI-444 clinical trial provided by Corvus

Background

•   An2-PD-(L)1an2bodiesareapprovedfortreatmentofseveralcancersbutasmallpropor2onofpa2entsbenefit

•   Mechanismsofan2-PD-(L)1resistancearenotwellunderstoodandnoagentsareapprovedtoovercomeresistance

•   Adenosinepathwaymediatestumorimmunosuppression;maybearesistancemechanismtoan2-PD-(L)1therapy

•   CPI-444isanoral,smallmoleculeinhibitorofA2ARthathasshownan2-tumorac2vityinan2-PD-(L)1resistant/refractory,andPDL-1nega2vepa2ents1

1Fong,ASCO2017; 2Beavisetal.,CanImmunRes2015;3Sharmaetal.,Cell2017

Adenosineinthetumormicroenvironment2,3

Adenosine

A2ARATPAMP

CD73

Tumor

TCell

CD39

TCell

PD-1PD-L1

An2-PD-1

CPI-444

Phase1/1bClinicalStudywithOralDrugCPI-444

DoseSelec@on

CohortExpansion100mgBID28days

DoseSelec@on

CohortExpansion100mgBID28days+840mgatezolizumab

Q2W

•  Prioran2-PD-(L)1allowed•  Resistant:SDorbeZer>3monthsof

treatment•  Refractory:progressionwithin3months

•  Musthaveprogressivediseaseonpriortherapy

•  Noselec2onforPD-L1expression

Eligibility

CPI-444Monotherapy

CPI-444withatezolizumab(an@-PD-L1)

RCCNSCLCMelanomaTNBCOthers

Naive

Refra

ctory

Resis

tant

10

100

1000

CD

39 E

xpre

ssio

n

Naive

Refra

ctory

Resis

tant

10

100

1000

10000

CD

73 E

xpre

ssio

n

Naive

Refra

ctory

Resis

tant

10

100

1000

A2A

R E

xpre

ssio

n

PriorAn2-PD-(L)1TreatmentIncreasesA2AR,CD73andCD39Adenosinepathwayisapoten)almechanismofresistance

p=0.002

n=36 n=26 n=35

p=0.1

n=36 n=26

5

n=35 n=36 n=26 n=35

p=0.01

p=0.002

p=0.003

p=0.002

A2AR CD73 CD39 Exposuretoan2-PD-(L)1therapy(>3months)increasesA2AR,CD73,andCD39expression

RCC

NSCL

COt

her

10

100

1000

CD

39 E

xpre

ssio

n

RCC

NSCL

COt

her

10

100

1000

10000

CD

73 E

xpre

ssio

n

RCC

NSCL

COt

her

10

100

1000

A2A

R E

xpre

ssio

nAdenosinePathwayExpressionisHigherinRCCandNSCLCPre-TreatmentBiopsies

A2AR CD73

6 Other = bladder, colorectal, triple-negative breast, melanoma, prostate

p < 0.0001

p = 0.05

p = 0.03

p < 0.0001

CD39 p < 0.0001

p = 0.0002

n=19 n=33 n=49 n=19 n=33 n=49 n=19 n=33 n=49

RenalCellCohortsExpandedPa)entcharacteris)cs

RenalCellCancer(N=51)Prioran@-PD-(L)1exposureNaïveResistant/Refractory

16(31%)35(69%)

PD-L1Nega@ve(archival)* 91%

Median@mesinceIOagent,months(range) 1.6(1–71)

Histology 50(98%)Clearcell1(2%)Papillary

Medianage,years(range)No.ofpa@ents:singleagent/combina@onMediannumberpriortherapies(range)

64(44-70)25/263(1-5)

AdversePrognos@cFactors(%)VisceralmetastasesHepa@cmetastasesAnemiaElevatedLDH

88%20%45%21%

7 * PD-L1 status determined using FDA-approved assay (SP142, cutoff = 5%) Data cutoff 10/26/17

CPI-444An2-TumorAc2vityinRenalCellCancerResponseswithsingleagentandcombina)on

8

Single agent CPI-444 (atezolizumab-refractory)

Combination CPI-444 + atezolizumab

Partial Responses in RCC

ResistanttopriorIORefractorytopriorIONaïvetopriorIO

Single Agent Combination

Data cutoff 10/26/17

RenalCellCancerResponserateanddiseasecontrolrateinevaluablepa)ents

Treatment Objec@veResponseRate

DiseaseControlRate

CPI-444CPI-444+atezolizumab

2*/14(14%)2/16(13%)

4/14(29%)11/16(69%)

9 Drug Treatment (months)

CPI-444 + atezolizumab

% c

hang

e fro

m b

asel

ine

*1 unconfirmed

% c

hang

e fro

m b

asel

ine

CPI-444

Drug Treatment (months) Data cutoff 10/26/17

Treatment-RelatedAdverseEvents

10

AdverseEvents(Gr1/2)>5%Frequency(n=210)

CPI-444(%) CPI-444/Atezo(%)

Fa@gue 21 29

Nausea 12 14

Pruritus 11 10

Pyrexia 5 9

Decreasedappe@te 6 7

Diarrhea 7 5

Anemia 6 4

Vomi@ng 3 6

Rash 3 6

Grade > 3 Serious Adverse Events CPI-444 (n=1) •   Gr 3 nausea/vomiting/diarrhea CPI-444/Atezolizumab (n=5) •   Gr 3 immune related hepatitis, dermatitis,

mucositis, pneumonitis •   Gr 3 autoimmune hemolytic anemia •   Gr 3 increased ALT/AST •   Gr 3 thrombocytopenia/ Gr 4 encephalitis •   Gr 3 pneumonitis

Data cutoff 10/26/17

ScreeningA2ARandCD73AssociatedwithResponseDoubleposi)veA2AR,CD73maybepredic)ve

11

Pro

gres

sion

R

egre

ssio

n

A2AR

low

A2AR

high

-100

-50

0

50

100

150T

um

or

Resonse (

Best %

Change)

A2AR

Neg Pos

Tum

or R

espo

nse

(Bes

t % C

hang

e) p=0.01

n = 35 n = 32

Partial Responses✝

✝Tissue not available for all PRs

CRC (MSI-H) NSCLC RCC RCC

CD73

low

CD73

high

-100

-50

0

50

100

150

Tum

or

Resonse (

Best %

Change)

CD73

p=0.09

n = 16 n = 51

Neg Pos Neg Double Positive

A2AR+/CD73+

p=0.0006

n = 49 n = 24

ScreeningA2AR,CD73AssociatedwithDiseaseControlRateDoubleposi)veA2AR,CD73maybepredic)ve

Nega@ve Posi@ve

A2AR 4/39(10%) 10/34(29%)

CD73 2/22(9%) 12/51(24%)

A2AR+CD73(DoublePosi@ve) 4/49(8%) 10/24(42%)*

*p=0.0007

DiseaseControlRate(allindica@ons;biomarkerassessable)

CD73Q1/Q2to4

Q1 Q2toQ4

0.0 0.5 1.0

JITTER

0.0 0.5 1.0

JITTER

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

log2FOLD

CD8infiltrationIHC

single-agentfoldCD73Q1vs

Q2to4

CD73Q1/Q2to4

Q1 Q2toQ4

0.0 0.5 1.0

JITTER

0.0 0.5 1.0

JITTER

-3

-2

-1

0

1

2

3

4

5

6

Delta

PD-L1IHCsingle-agent

deltaCD73Q1vsQ2to

4Gene/CD73Q1/Q2to4

CXCL9

Q1 Q2toQ4

CXCL10

Q1 Q2toQ4

GZMA

Q1 Q2toQ4

GZMB

Q1 Q2toQ4

IDO1

Q1 Q2toQ4

LAG3

Q1 Q2toQ4

0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0 0.0 1.0

-3

-2

-1

0

1

2

log2FOLD

Sheet3

InCD73+Tumors,SingleAgentCPI-444InducesExpressionofTcellAc2va2onMarkersinPost-DoseBiopsies

Infiltration IFNγ Induction Effector Checkpoints

Neg Pos Neg Pos Neg Pos Neg Pos Neg Pos Neg Pos Neg Pos Neg Pos

z

CXCL9 p=0.02

CXCL10 p=0.07

GZMA p=0.07

GZMB p=0.04

IDO1 p=0.01

LAG3 p=0.16

CD73 Expression (in Screening Biopsies)

Log 2

Fol

d C

hang

e (P

ost/P

re B

x)

Gen

e E

xpre

ssio

n

CD

8 Lo

g 2 F

old

Cha

nge

(Pos

t/Pre

Bx)

CD73 Expression (in Screening Biopsies)

Inflammation

PD

-L1

Cha

nge

(Pos

t-Pre

Bx)

CD8 (IHC) p = 0.005

PD-L1 (IHC) p = 0.15

Summary

16 16 14

•   TumorexpressionofA2AR,CD73andCD39areincreasedinpa2entsthatareresistanttopriortreatmentwithan2-PD-(L)1

•   RCCandNSCLChavehightumorexpressionofadenosinepathwaygenesA2AR,CD73andCD39

•   CPI-444hasan2-tumorac2vityinRCC–   Reponsesseeninan2-PD-(L)1resistant/refractorypa2ents–   A2ARandCD73expressioninscreeningbiopsiesisassociatedwithresponseto

therapy

•   CPI-444increasesCD8+infiltra2onintumorsandinducesexpressionofIFNγ-dependentgenesandTh1ac2va2on

•   Thisstudycon2nuestoenrollpa2entswithRCCandNSCLCinexpansioncohorts

Acknowledgements

Patients and their Families Clinical Investigators and their staff Colleagues at Corvus