Cartherics Presentation Cell Gene Mesa Adapted for WEB 2 Oct … · 2019. 10. 23. · 2 Cartherics Pty Ltd §Founded 2015 §Laboratories and offices at Monash Health Translation Precinct,

Thefutureofcancertreatment.Combiningstemcellsandimmunotherapy.StrictlyconfidentialandproprietarytoCarthericsPtyLtd.

CARTHERICSTheFutureofCancerTreatment

October2019

Ourstrategy


CarthericsPtyLtd2

§ Founded2015

§ LaboratoriesandofficesatMonashHealthTranslationPrecinct,Melbourne,Australia

§ SeriesAfinancingAU$5Mcompletedlate2015§ SeriesBFinancingAU$5M(plusanoptionalAU$1.3M)§ FederalandStateGrantsAU$3.5M

§ CompanyoperationscommencedJanuary2016.


PreparingfortwoPhaseI/IIAutologousClinicalTrials3

1. CutaneousTCellLymphoma§ ProductCTH-001(anti-TAG-72CAR-Tcells)

2. RelapsedOvarianCancer§ ProductCTH-004

(anti-TAG-72;+genek/oCAR-Tcells)


Initialcancertarget:TAG-724

§ Glycoproteinfoundonthesurfaceofmanytypesofcancercells,includingbreast,colon,gastric,lung,pancreaticandovariancancers(+TCellLymphoma)

§ Humantissuedistributionstudieshaveshown>95%ofserousand>85%ofclearcellovariancancersareTAG-72positiveo Expressionlevelsincreaseinmalignantdisease.


KillinghumanovariancancerxenograftsinNSGmice:CTH-001(antiTAG-72)

5

TAG72 CAR-T cells kill ovarian cancer cells in vivo (NSG mice)

Tumorwt

Norm

alisedto

baseline

•  Ovcar3Tumorsgrownto100m3;•  TAG72CAR-Tcellsinjected3times,5daysapart;•  Controlmicegivennon-transducedTcells;•  Allcontrolshadtobeculledby40days;•  TAG72CAR-Tcellsshowedstrongreductionintumorsizeto70days

StrictlyConfidential

ControlTcells

ControlTcells CTH-001

CTH-001


KillinghumanovariancancerxenograftsinNSGmice:CTH-004(antiTAG-72+geneK/O)

6

-10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 1400

50

100

150

200

250

300

350

400

450

500

550

600

Days post CAR-T

Tum

ou

r M

ean

mm

3

NT

Seq3 TAG72

DGKaz KO

-10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 1400

50

100

150

200

250

300

350

400

450

500

550

600

Days post CAR-T

Tum

our

Mea

n m

m3

Cohort 10 OVCAR Seq3 TAG72 CRISPR CAR-T

NT

Seq3 TAG72 + 1 dose of DGKaz KO at day 85

Seq3 TAG72 + 1 dose of Seq3 TAG72 at day 85DGKaz KO

CTH-004

CTH-001

ControlTcells

CTH-004

CTH-004

CTH-001

ControlTcells


7 Histologyofhumantumoursandremnants

hCD3+CAR-Tcells TAG-72– brownstain

OVCAR3- CTH-004100days

OVCAR3- NonTransduced30days


TcelllymphomasexpresselevatedTAG-728

§ ThereisastrongprecedentfortreatmentoflymphomaswithCAR-Tcells

§ Asignificantproportion(>40%)ofpatientswithTcelllymphoma(TCL)showelevatedlevelsofcirculatingTAG-72+Tcellso Cartherics’CTH-001cellskilltheseTcells- seenextslide

§ Thereareveryfewtherapeuticoptionsavailableforthesepatients§ CarthericstostudyCarthericsCTH-001asanautologoustherapyforTCL.


Tag-72+CutaneousTCellLymphoma(CTCL)patients:CTH-0019

CTH-001 killing

CTH-001killing

CD4+/TA

G-72+

CD8+/TA

G-72+

0

10

20

30

40

50

Popu

latio

n fre

quen

cy(%

of C

D3+

)

TAG-72 expression on CD4 vs CD8 T cells

CTCL

HD

*p= 0.0259

n.s

H D(n = 1 5 )

C T C L(n = 4 9 )

0

1 0

2 0

3 0

4 0

5 0

Fre

qu

en

cy

of

CD

3+

/TA

G-7

2+

ce

lls

(% v

iab

le)

Me

an

± S

EM

* *

* *p < 0 .0 1

T ce lls

(no C

A R )

T A G-7

2 CA R (3

)0

5

1 0

1 5

D o n o r 1 C A R : C T C L P B M C s a s ta rg e ts

CD

3+

/TA

G-7

2+

ce

lls(%

via

ble

)

T ce lls

(no C

A R )

T A G-7

2 CA R (3

)0

2 0

4 0

6 0

D o n o r 1 C A R : J u rk a ts a s ta rg e ts

CD

3+

/TA

G-7

2+

ce

lls(%

via

ble

)

CAR-TkillingTAG-72+cells

CD4+ CD8+


Off-the-shelf– Allogeneiccancertherapy10

HLAhaplotypeiPSCs

UmbilicalCordBloodDonors


Carthericsisalsopreparingfor….11

§ ‘firstinhuman’PhaseI/IIAllogeneicCAR-NKcellclinicaltrial,ProductCTH-401;relapsedovariancancer,and

§ productdevelopedthroughFederalGovernmentCRC-PGrantofAU$3MilliontoCartherics,Mesoblast,CellTherapies,MonashUniversityandHudsonInstituteofMedicalResearch.


iPSCtoNKmethodofmanufacture12

Overview§ Totaltime:30days§ MethoddesignedonpatterningcelldevelopmentthatmimicsnaturalNKdevelopmentinthebody

§ Focusonxeno-free,scalable,molecularly-definedandclinicallytranslatablesystems

§ ~150,000iNK cellsperiPSC

iPSCHE iNK

progenitoriNK

mTesR1 Media BMedia A

Day0 Day8 Day22 Day30Day-1 Day3

Media C Media D

iPSC HE development iNK Progenitor iNK Maturation

Phase 1 Phase 2 Phase 3 Phase 4


iNK Cytotoxicfunctiononovariancancercellsinvitro13

10 20 30 40-2

0

2

4

6

8

10

Time from addition of effector cells (h)

Nor

mal

ised

cel

l ind

ex(A

vera

ge ±

SD

)

Target cells alone

CTH-403 (unsorted)

Non-transfected iNK

GFP iNK (unsorted)

Takehomemessage:

Howtoreadthegraphs?

Cancer growth/survival

Cancer killingcell

inde

x

Time

1. iPSC derived NK cells kill ovarian cancer in vitro

2. iPSC-NK cells function similar to normal NKS

3. TAG-72 CAR iNK increases killing of ovarian cancer

Ovarian cancer Ovarian cancerCancer aloneCancer alone in basal mediaCancer alone in NK mediaNK from healthy donorCord-derived NK

iPSC-derived NK (method#1)

iPSC-derived NK (method#2)

Legend

(TAG-72 CAR iNK)


Companyrelationships14

§ Mesoblast- CRCpartner§ CellTherapies(PeterMac)- CRCpartner,Manufacturingpartner

§ ToolGen- Partnershipforgeneediting§ PanCella - PartnershipforImmuno-cloakingandFail-safetechnology

§ BerryGenomics– Genomicspartnership.

Documents

Cartherics Presentation Cell Gene Mesa Adapted for WEB 2 Oct … · 2019. 10. 23. · 2 Cartherics Pty Ltd §Founded 2015 §Laboratories and offices at Monash Health Translation Precinct,