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CONFIDENTIAL| © 2019CONFIDENTIAL| © 2019

A Novel Class of NK-Cell Engagers Targeting NKp30

Monia Draghi, PhDCompass Therapeutics, Cambridge, MA-USA

1

CONFIDENTIAL| © 2019

Compass Therapeutics’ NK Cell Engager Platform

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§ Rapid, first responders§ Highly potent§ Versatile target killing ability§ Critical immune system mediators

Functions of NK cells

Green: live Multiple Myelomatumor cells

Compass’ lead NK cell engager demonstrates highly

efficient tumor cell killing

E:T ratio (2:1)

Effectors = primary NK cellsTargets = MM1R cells

Time 0


Components of Optimized NK Engagers

3

NK

Tumor

CD16

NK-RNK-R

LigandTAA

1

23

4

NK-R

TAA

IgG1

1. Specifically target 1 or more tumor associated antigens (TAA’s) to localize activity and reduce toxicity

2. Optimally engage CD16a through Fc to drive effective ADCC response

3. Trigger signaling of additional NK activating receptors to synergistically amplify CD16a response or maintain activity after CD16a downregulation

4. Inhibit checkpoint pathways to prevent NK cell suppression


Compass’ Novel Anti-NKp30 Bispecific Platform

4

Comprehensive antibody discovery

NK-R

BCMA

IgG1

Panel of StitchMabs™ and CLC bispecifics Ø Better activity than anti-BCMA monoclonal

Ø Activity does not require CD16a engagement

Anti-NKp30 bispecific identified as superior

Empirical Discovery of Optimal Bispecific NK Engagers

CTX-4419

BCMA [B cell maturation antigen]

§ Restricted expression in plasma cells

§ Expressed in malignant cells from untreated and relapsed

multiple myeloma (MM) patients

§ Despite several drugs have improved patient survival, MM

remains an unmet medical need

TAA

NK-R

CONFIDENTIAL| © 2019 5

NKp30 is a Potent Activating Receptor Expressed on NK cells and Other Effector Cells

Moretta A. et al., Ann Rev Immunol, 2011

• NKp30 is a potent activating receptor on NK cells

• Expressed on NK cells and subsets of effector T-cell populations such as γδ T cells

• Known roles in tumor control and pathogen clearance

Compass NK cells engagers activate CD16+ and CD16- NK cells

CD3

TCR gd

27%19%

FSC

NKp30

NKp30 is expressed on gd T cells in the bone marrow of MM patients

0 . 0 0 0 1 0 . 0 0 1 0 . 0 1 0 . 1 1 1 0

0

2 0

4 0

6 0

8 0

1 0 0

t a r g e t s : R P M I - 8 2 2 6

C o n c e n t r a t i o n ( n M )

% s

pe

cif

ic l

ys

is

C T X 4 4 1 9

B C M A - I g G 1 ( m A b )

H e r 2 - I g G 1

CD16neg NK cells (KHYG-1) tested towards BCMApos tumor cellsBCMA

NKp30

IgG1

IgG1

BCMA

NKp46 NKp30 NKp44

NKp30

CD16

A

NK cells from BM of MM patient


In vitro potency of CTX-4419

6

CTX-4419 Induces Potent NK Cell Killing of Target Cells%

mye

lom

a ce

ll ki

lling

N K p 3 0 N K G 2 D C D 1 6 A

0

2 0

4 0

6 0

8 0

1 0 0

% p

os

NK

ce

lls

H929 MM.1S RPMI-8226

<100,000 ~100-30,000 >30,000

n/a Targets: RPMI-8226

NK cells in bone marrow of MM patients

0 . 0 0 0 1 0 . 0 0 1 0 . 0 1 0 . 1 1 1 0 1 0 0

0

2 0 0

4 0 0

6 0 0

8 0 0

C o n c e n t r a t i o n ( n M )

IFN

g (

pg

/mL

)

C T X - 4 4 1 9

B C M A - I g G 1 m A b

I s o t y p e

CTX-4419 induces potent killing of autologous myeloma cells from

MM patients

§ Better potency than BCMA-IgG1 mAb§ Potent activity towards targets cells with high, medium

& low BCMA

CT

X- 4

41

9

BC

MA

- I gG

1 m

Ab

CT

X- 4

41

9

BC

MA

- I gG

1 m

Ab

CT

X- 4

41

9

BC

MA

- I gG

1 m

Ab

- 1 0 0

0

1 0 0

2 0 0

3 0 0

4 0 0

EC

50

(p

M)

CONFIDENTIAL| © 2019 7

CTX-4419 Does Not Activate NK Cells in the Absence of BCMA Expressing Target Cells

Primary NK cells, H929 target cells, 10 nM antibody

NK

+ H

92

9

NK

al o

ne

0

1 5 0

3 0 0

4 5 0

6 0 0

7 5 0

9 0 0

IFN

g (

pg

/mL

)

C T X 4 4 1 9

B C M A - I g G 1 ( m A b )

0. 0

00

1

0. 0

01

0. 0

10

. 1 11

0

0

1 0

2 0

3 0

4 0

5 0

6 0

C o n c e n t r a t i o n o f C T X 4 4 1 9 ( n M )

% p

os

itiv

e N

K c

ell

s

C D 1 3 7

C D 6 9

N K + H 9 2 9

N K i n t h e a b s e n c e

o f t u m o r

0. 0

00

00

1

0. 0

00

1

0. 0

1 11

00

0

1 0

2 0

3 0

4 0

5 0

A n t i b o d y C o n c e n t r a t i o n ( n M )

tu

mo

r l

ys

is (

%)

Targets: JeKo-1~5,000 BCMA copies/cell

Targets: HL-60BCMA negative

Opportunity for Better Safety Profile Compared to Other Cell Engagers


Single Dose of CTX-4419 Potently Depletes Immunoglobulin-Secreting Cells in Bone Marrow of Cynomolgus Monkeys and Decreases Serum IgM levels

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- 1 6 1 3 2 0 2 7 3 4 4 1 4 8 5 5

0

2 0

4 0

6 0

8 0

1 0 0

1 2 0

1 4 0

1 6 0

D a y s

Se

ru

m I

gM

(%

)

A K 7 4 9 J

B 6 0 1 6

0 1 0 2 0 3 0 4 0

0

2 5 0

5 0 0

7 5 0

1 0 0 0

5 0 0 0

1 0 0 0 0

D a y s p o s t t r e a t m e n t

Ig

s

ec

re

tin

g

ce

lls

pe

r

1

mil

lio

n

to

ta

l c

ell

s T o t a l I g

I g G

I g M

I g A

0 1 0 2 0 3 0 4 0

0

2 5 0

5 0 0

7 5 0

1 0 0 0

5 0 0 0

1 0 0 0 0

D a y s p o s t t r e a t m e n t

Ig s

ec

re

tin

g c

ell

s

pe

r 1

mil

lio

n t

ota

l c

ell

s

CTX-4419 displays IgG-like PK in cynomolgus monkey

Animal #AK749J Animal #B6016


Compass’ NK Engager Platform Summary

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Ø Key properties of CTX-4419, a first-in-class NKp30xBCMA bispecific§ Potent - Enhances ADCC, cytokine production, and NK-cell proliferation compared to monoclonal antibodies§ Large therapeutic window - Active against target cells with wide range of antigen expression, but no activity in the

absence of target§ Resistant to CD16a downregulation - Activates NK cells in the absence of CD16a engagement § Highly manufacturable - Monoclonal-like drug-like properties and pharmacokinetics§ Flexible format – Common-LC format amenable to multi-TAA or multi-NKR targeting§ Potential to target additional effector cell types

Ø CTX-4419 induces potent depletion of plasma cells in cynomolgus monkeys

Ø Compass’ highly modular platform has the potential to tailor TAA and NK cell receptors to target multiple indications


Acknowledgments

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William McConaughyBeata BobrowiczSujan LamaNiharika KuraDalton Markrush

Jason E. GoetzmannKenneth RogersFrancois Villinger

Thank you !

Immunology-Immunopharmacology

Allison NelsonJamie SchaferNaomi MaymanRobert Tighe

Antibody Discovery & Engineering-Protein Sciences

Jennifer Watkins-YoonSara HaserlatAmanda OliphantJason LajoieMichael SchmidtPiotr Bobrowicz

Poster # 1010- Monday -March 25, 2019

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