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CONFIDENTIAL| © 2019CONFIDENTIAL| © 2019
Compass Therapeutics Jefferies 2019 Global Healthcare Conference
June 7th, 2019
1
CONFIDENTIAL| © 2019
Who We Are
2
• Therapeutic focus: immuno-oncology and autoimmunity
• Proprietary antibody discovery platform: First 40+ targets drugged
• Broad pipeline of novel therapeutic candidates targeting multiple targets of the immune system
• Growing biotech with lab/office/vivarium in Cambridge, MA
Key Milestones• Developed comprehensive and deep approach to antibody discovery: novel drug candidates and building
blocks for next-generation bispecific antibodies. StitchMabs™ HT screening platform.
• Nominated our first clinical candidate
• 2018 “Fierce 15” biotech company
• Completed $132 M in series A financing: OrbiMed, F-Prime, Cowen, Borealis, Thiel, Biomatics, Alexandria, BioMed
2019• Enroll Phase 1 Study: CTX-471 – novel CD137 agonist: https://clinicaltrials.gov/ct2/show/NCT03881488
• Begin IND enabling studies for our second candidate: first-in-class NKp30 bispecific
• Nominate a third clinical candidate: two new INDs in 2020
• Series B financing; IPO ready
CONFIDENTIAL| © 2019
Our Discovery Approach Bridges Innate & Adaptive Immunity
3
Tumor
Adaptive Immunity
Macrophage
Neutrophil
CD89
SIRPa
NKCD8+ CTL
MDSC
Treg
Innate ImmunityDC
Ag shedding
Her2BCMACD38CD200CD30
NKG2DCD226NKp30NKp46CD16a2B4
CD137NKG2DCD226CD2PD-1TIGITCD112RCD96
CD94CD2CD137TIGITCD112RCD96
CD89
SIRPa
PD-L1CD155CD112CD113CD47CD277
CD137TIGITTNFR2OX40GITR
PD-L1Gal-1Gal-3IL-6
CD40
VALIDATED ANTIBODY PANELS TO 40+ TARGETS FORM BUILDING BLOCKS FOR COMBINATION & BISPECIFIC SCREENING
OX40GITR
CONFIDENTIAL| © 2019
Compass Pipeline: June 2019
Discovery Phase I In Vitro In VivoIND Enabling
Studies
Mac
rop
hag
e T-
Cel
l N
K C
ell
AActivation
ACKPT Blockade
Phase II
CTX-471: Novel CD137 agonist
CTX-471 Combinations
CTX-8371: PD-1 x PD-L1 Bispecific
CTX-8573: BCMA x NKp30 Bispecific
NKp30 x TAA Platform
TGFβ x TIGIT Bispecific
Receptor x TAA Bispecifics
CTX-5861: SIRPα and Combinations
AActivation
ACKPT Blockade
AActivation
ACKPT Blockade TAA: Tumor associated antigen
CKPT: Checkpoint
CONFIDENTIAL| © 2019 5
T-Cells
ActivationCTX-471 - CD137 Agonist
Checkpoint blockadeCTX-8371 - PD1 x PDL1 Bispecific
CONFIDENTIAL| © 2019
CTX-471: Best in Class CD137 Agonist
6
NOVEL EPITOPE WITH DIFFERENTIATED ACTIVITY SUPPORTED BY EXTENSIVE PRECLINICAL DATA
CTX-471 Summary
Selection
▪ Panel of 70 antibodies
▪ 8 unique epitope bins
▪ Comprehensive in vitro characterization based on binding, signaling, activation, and drug-like properties
▪ 4 leads compared in vivo
Molecular Profile
▪ Fully human, IgG4 agonist
▪ Non-ligand competitive
▪ Differentiated epitope in CRD3/4
▪ Mouse/human/cyno cross-reactive
CTX-471 binds a unique, non-ligand competitive epitope in CRD3-4 of CD137
CD137L
CD137
Urelumab, 3H3
CTX-471
Utomilumab
CONFIDENTIAL| © 2019
Raising the Bar for Preclinical Efficacy - High Burden Tumor Models
7
Small CT26 tumor: ~75 mm3
➢ Typical size at which treatment begins in mouse efficacy studies
➢ Tumors this small are modestly sensitive to monotherapy with α-PD-1/L1, α-OX40, α-CTLA4, or α-CD137 (3H3)
➢ Small tumors can be eradicated by CTX-471 monotherapy
Large CT26 tumor: ~500 mm3
➢ Treating extremely large tumors of this size is generally considered futile
➢ Tumors this large are highly resistant to monotherapy α-PD-1/L1, α-OX40, α-CTLA4, or α-CD137 (3H3)
➢ Large tumors can also be eradicated by CTX-471 monotherapy
CONFIDENTIAL| © 2019
CTX-471 Induces Regression of ~500 mm3 Tumors
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Control CTX-471 CTX-471-AF-1 CTX-471-AF-2
Tu
mo
rV
olu
me
(m
m3
)
Days Post-Treatment Days Post-Treatment Days Post-Treatment Days Post-Treatment
0 20 40 600
500
1000
1500
2000
0 20 40 600
500
1000
1500
2000
0 20 40 600
500
1000
1500
2000
0 20 40 600
500
1000
1500
2000
0/6 4/6 6/6 4/6
✓ Tumors were allowed to grow to ~500 mm3 before treatment began✓ Therapeutic model, not a prevention model✓ Unprecedented Monotherapy activity for an I/O Antibody
CTX-471 AND CTX-471-AF CLONES WERE TESTED IN CT26 THERAPEUTIC IN VIVO MODEL
Low affinity Intermediate affinity High affinity
CONFIDENTIAL| © 2019
Generation of Long Term Immunological Response
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* P values from Log-rank test compared to control
P=0.008
P=0.01
P=0.0005
Survival Curve: Re-challenge
0 10 20 30 40
0
20
40
60
80
100
Days Post-Re-Challenge
Pe
rce
nt
surv
ival Isotype/ Naïve
CTX-471 CTX-471 –AF-1
CTX-471 –AF-2
Survival Curve: Monotherapy Treatment
POTENT AND FUNCTIONAL IMMUNOLOGICAL MEMORY – ALL CURED MICE REJECTED THE TUMOR
✓ Monotherapy treatment ✓ At > 8 x t1/2 all mice of Clone #1 and most mice of Parental survived ✓ All surviving mice re-challenged with CT-26 rejected the tumor
CONFIDENTIAL| © 2019 10
CTX-471-AF-1 Induces Comprehensive Reprogramming Within the Tumor Microenvironment
CD45
Sid
e sc
atte
r
18 ± 1 % 62 ± 25 %
Control CTX-471-AF-1
Increased Infiltration of Immune Cells in the TME
Protection/Reversion of T-cell Exhaustion
TIGIT
PD
-1
43 ± 5 % 8 ± 5 %
Control CTX-471-AF-1
31 ± 9 % 7 ± 3 %
Control CTX-471-AF-1
FOXP-3
CD
25
Treg Reduction in the TME
44 ± 4 % 24 ± 11 %
Control CTX-471-AF-1
CD11b
F4/8
0
Tumor Associated Macrophage Reduction in the TME
CONFIDENTIAL| © 2019
Combinations are Synergistically Effective In Vivo
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CT26HuHER2 ADOPTIVE TRANSFER MODEL – T-CELL MEDIATED ACTIVITY SHOWN FOR CTX-471
Control
Trastuzumab
Monotherapy
Combination
Combination (No T cells)
Days post-Treatment
Per
cen
t Su
rviv
al
40% survival @ D64
100% survival @ D64
0% survival @ D64
0 20 40 60 800
20
40
60
80
100
Control Her2 Mono CTX-471 MonoT
um
or
Vo
lum
e(m
m3
)
Note: Treatment initiated 6-days post tumor inoculation
0 20 40 600
500
1000
1500
2000
0 20 40 600
500
1000
1500
2000
0 20 40 600
500
1000
1500
2000
Days Post-Treatment Days Post-Treatment Days Post-Treatment
0/80/8 3/8
Parental Clone
Her2 + CTX-471Cocktail
(No T cells)
+
Parental Clone
Her2 + 471Cocktail
+
0 20 40 600
500
1000
1500
2000
0 20 40 600
500
1000
1500
2000
Days Post-Treatment Days Post-Treatment
8/8 0/8
CONFIDENTIAL| © 2019
CTX-471-AF causes Profound Tumor Necrosis of Very Large Tumors
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CONFIDENTIAL| © 2019
Tumor Rejection by CTX-471-AF is Associated with Increased Frequency and Penetration of CD8+ T Cells
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Co
ntr
ol
CTX
-47
1-A
F
Day 7 Day 10 Day 14
Anti-CD8 IHC
CONFIDENTIAL| © 2019
• Vision: a broad T-Cell and NK-cell activator that has efficacy after PD-1/PD-L1 blockade in the immune-sensitive tumors (‘hot tumors’) and activity in selected cold tumors– Widely expressed on T cells and NK cells
– Activation via CTX-471 leads to efficacy across a broad set of syngeneic tumors in mice
– Demonstrable activity in cold tumors such as colorectal cancer, pancreatic cancer, etc.
• Phase 1 will test the activity of CTX-471 in the relapsed patient population after PD-1 axis blockade– Immunological architecture is required for response: patients can not be refractory to PD-1 blockade
– Once efficacy has been established in the 2L, 3L, we will proceed to front line therapy
• Tumor types: all approved PD-1 and PD-L1 indications– Immunologically responsive based on at least 3 months of stable disease
– High unmet medical need due to limited response to CKPT blockers
– Second line NSCLC is a major commercial opportunity
• Execution– IND open as of 3/2019
– 6-8 Centers in the US: Dana Farber, MGH, Wash. U., Mary Crowley CC, Mt. Sinai, ITOR, Hackensack
– Currently screening patients
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CTX-471 Clinical Development Plan
PD-1 RefractoryCold tumors
Immune competent~50% of PD-1 population
CTX-471
CONFIDENTIAL| © 2019 15
NK-Cells
ActivationCTX-8573 – BCMA x NKp30 BispecificNKp30 Engager Platform
Checkpoint blockadeTIGIT x TGFβ Bispecific
CONFIDENTIAL| © 2019
Empirical Identification and Optimization of NK Bispecific Antibodies
16
Comprehensive antibody discovery
NK-R
BCMA
IgG1
Panel of BCMA-NKR StitchMabs™ and bispecificsexpressed and purified at 24 well scale
Primary ScreenPrimary NK cellsIgG1 Fc
Secondary screen – Effect of CD16a engagement
Combinatorial library
COMPASS SCREENING WORKFLOW FOR MULTISPECIFIC CONSTRUCTS
CONFIDENTIAL| © 2019 17
Next Generation NK Cell Bispecific Platform Targeting NKp30 Receptor
• First in class bispecific antibody targeting NKp30 activating receptor expressed by NK cells
• Overcomes CD16a deficiency
• Lowers the threshold of NK cell activation and induces NK cell-mediated killing of tumor cells expressing high, medium and low levels of TAAs with >100 fold increased potency compared to mAb
• Induces NK cell proliferation and cytokine release in the presence of target cells
• Wide therapeutic window with no activity in the absence of target antigen
• Leverages Compass common light chain and StitchMabs™
technologiesTumor cell
TAA
NK-Cell
CD16a
NKp30
CONFIDENTIAL| © 2019 18
NKp30 Bispecific Platform Significantly Enhances ADCC Potency of α-BCMA mAb SUPERIOR TUMOR CELL KILLING ACTIVITY MAINTAINED IN THE ABSENCE OF CD16A
NCI-H929 target cells4 hour incubation
BCMA
IgG1
NKp30
IgG1 Fc – CD16a Engagement
0 . 0 0 0 1 0 . 0 0 1 0 . 0 1 0 . 1 1 1 0
0
1 0
2 0
3 0
4 0
C o n c e n t r a t i o n ( n M )
% s
pe
cific
ly
sis
B C M A - N K p 3 0
B C M A m A b
H e r 2 m A b
Aglycosylated Fc – no CD16a
0 . 0 0 0 1 0 . 0 0 1 0 . 0 1 0 . 1 1 1 0
0
1 0
2 0
3 0
4 0
C o n c e n t r a t i o n ( n M )
% s
pe
cific
ly
sis
Target cell killing by primary NK cells
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 )
%
sp
ec
if
ic
ly
si
s
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
Target cell killing by CD16- KHYG-1 cell line
CONFIDENTIAL| © 2019 19
0. 0
00
1
0. 0
01
0. 0
1
0. 1 1
10
10
0
0
2 0
4 0
6 0
8 0
1 0 0
A n t i b o d y C o n c e n t r a t i o n ( n M )
% S
pe
ci
fi
c
Ly
si
s
H929 MM.1S RPMI 8226 HL-60
Affinity Matured, Afucosylated BCMA x NKp30 Lead CTX-8573 Induces Highly Potent and Selective Lysis of BCMApos Tumor Cells Expressing Different Levels of Antigen
Ag expression level
BCMA negative tumor cells
Methods: Primary NK cells from one donor were cultured for 4 hours with tumor cells.E:T ratio 10:1
>500,000 ~100,000 <30,000
0. 0
00
01
0. 0
00
1
0. 0
01
0. 0
1
0. 1 1
10
10
0
0
2 0
4 0
6 0
8 0
1 0 0
A n t i b o d y C o n c e n t r a t i o n ( n M )
% S
pe
ci
fi
c
Ly
si
s
0. 0
00
01
0. 0
00
1
0. 0
01
0. 0
1
0. 1 1
10
10
0
0
2 0
4 0
6 0
8 0
1 0 0
A n t i b o d y C o n c e n t r a t i o n ( n M )
% S
pe
ci
fi
c
Ly
si
s
0. 0
00
01
0. 0
00
1
0. 0
01
0. 0
1
0. 1 1
10
10
0
0
2 0
4 0
6 0
8 0
1 0 0
A n t i b o d y C o n c e n t r a t i o n ( n M )
% S
pe
ci
fi
c
Ly
si
s
0. 0
00
01
0. 0
00
1
0. 0
01
0. 0
1
0. 1 1
10
10
0
0
2 0
4 0
6 0
8 0
1 0 0
A n t i b o d y C o n c e n t r a t i o n ( n M )
% S
pe
ci
fi
c
Ly
si
s
C T X - 8 5 7 3 [ N K p 3 0 x B C M A a f u c o s y l a t e d ]
C T X - 6 7 6 7 [ N K p 3 0 x B C M A ]
C T X - 7 9 8 6 [ N K p 3 0 x B C M A F c s i l e n t ]
C T X - 6 6 0 5 [ B C M A - I g G 1 m A b ]
I g G 1 i s o t y p e c o n t r o l
n o a n t i b o d y
BCMA copies per cell
8573 – BCMA x NKp30-afucosylated (NKp30/CD16a++)
6767 – BCMA x NKp30 (NKp30/CD16a)
7986 – BCMA x NKp30-aglycosylated (NKp30)
6605 – BCMA mAb (CD16a)
Isotype control
No antibody
CONFIDENTIAL| © 2019 20
Single Dose of 1st Generation BCMA x NKp30 Bispecific Depletes BM Plasma Cells & Expands BM NK-Cells in Cynomolgus Monkeys
Bone marrow plasma cell depletion (ELISpot)
Activation & expansion of bone marrow NK-cells
- 5 5 1 5 2 5 3 5 4 5 5 5
1
1 0
1 0 0
1 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
CT
X-4
41
9 (
nM
)
A K 7 4 9 J
B 6 0 1 6
IgG-like PK with 16 day β-phase half-life
30 mg/kg dose
COLLABORATION WITH DR. FRANCOIS VILLINGER AT NEW IBERIA RESEARCH CENTER
CONFIDENTIAL| © 2019
BCMA Targeting ProgramsMultiple myeloma and other cancers
Severe Autoimmune Indications driven by
pathological IgGsComments
Anti-BCMA (IgG1) + - Insufficient potency on low BCMA expressing cells
BCMA-ADCs + - Safety
CAR-T + - Safety & cost
BCMA x CD3 (‘BiTE’) + - Safety and product profile
NKp30 x BCMA + +Targets cells expressing high,
medium and low BCMA, PK/PD profile
21
Our NKp30xBCMA is Uniquely Suited to Target Severe Autoimmune Indications
NKp30
BCMA
IgG1
BCMA
IgG1
CONFIDENTIAL| © 2019 22
Indication Prevalence Limitations of Current Treatment Options
Light-chain amyloidosis1 ~40 cases per 1,000,000~12,000 pts in the U.S.
Up to 80% of pts are ineligible for ASCT, and plasma cell directed chemotherapy has been shown to fall short in addressing organ dysfunction caused by amyloid deposition
Myasthenia Gravis2 ~20 cases per 100,000.~60,000 pts in the U.S.
Corticosteroids and immunosuppressants are associated with a number of significant side effects. Use of Soliris only blocks the activity of complement recruited by the pathogenic IgGs directed against the ACh receptor. It does not address the blocking of the Ach receptor by pathogenic IgGs, nor the receptor cross-linking and internalization by these IgGs.
Pemphigus Vulgaris3 ~1-10 cases per 1,000,000~300-3,000 pts in the U.S.
Patients who do not respond to corticosteroids and immunosuppressants are treated with IVIg or Rituxan. Even with IVIg and Rituxan, complete remission may take several months, and some patients do not respond.
Immune Thrombocytopenia1 ~9.5 cases per 100,000~30,000 pts in the U.S.
Treatment for ITP is focused on either reducing the autoimmune destruction of the platelets, or directly stimulating platelet production with specific growth factors. Use of IVIg and plasmapheresis can lead to serious complications, and while thrombopoietin receptor agonists lead to increases in blood platelet counts, they do not address the underlying destruction of the platelets.
Sources: 1National Organization for Rare Disorders, 2Myasthenia Gravis Foundation, 3International Pemphigus & Pemphigoid Foundation
Potential Indications for a BCMA-Directed Cell Depletion Agent
CONFIDENTIAL| © 2019 23
NKp30 x BCMA effect on serum IgM in a Monkey is similar to 6 courses of Plasmapheresis in humansTARGETING PATHOGENIC ANTIBODIES IN AUTOIMMUNE DISEASE
D a y 0 D a y 4 8
0
2 5
5 0
7 5
1 0 0
Se
ru
m I
gM
(
%)
Guptill, Autoimmunity, 2016Animal #1, Drop of IgM level in serum
CONFIDENTIAL| © 2019 24
NKp30 x BCMA effect on serum IgM in a Monkey is similar to Fc/FcRnblockade in humansTARGETING PATHOGENIC ANTIBODIES IN AUTOIMMUNE DISEASE
D a y 0 D a y 4 8
0
2 5
5 0
7 5
1 0 0
Se
ru
m I
gM
(
%)
Ulrichts, 2017 (ARGX-113)Animal #1, Drop of IgM level in serum
CONFIDENTIAL| © 2019
• NKp30 identified as optimal bispecific partner for targeting and activating NK cells through unbiased screen leveraging Compass discovery platform
• Key properties of NKp30 bispecifics– Potent - Enhance 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 - Activate 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
• BCMA x NKp30 program– Robust killing of target cells with high, medium, & low BCMA
– Potent depletion of plasma cells in cynomolgus monkey
– Cell line development & additional primate studies underway with potential IND’s in multiple myeloma or autoimmune disease in 1H2020
• Her2 x NKp30– Bispecifics identified against multiple epitopes of Her2 with improved ADCC potency compared to trastuzumab
– Lead clone CTX-7144 entering affinity maturation
• Multiple campaigns in progress for additional targets in hematological and solid tumors with preliminary lead ID in 2019
25
NKp30 Bispecific Engager Platform Summary
CONFIDENTIAL| © 2019CONFIDENTIAL| © 2019
I
Our Pipeline
Effective Modulation of the Immune System
26
CONFIDENTIAL| © 2019
Compass Therapeutics: 2019 and Beyond
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BUILDING A FULLY INTEGRATED BIOPHARMACEUTICAL COMPANY
-
-
Val
ue
Cre
atio
n
2015-2016
2017
2018
2019
2020
• CTX-471 Efficacy Data
• BCMA x NKp30 Phase 1
• TAA#2 x NKp30 IND
• Next-Gen checkpoint
blocking bispecific
• Clinical stage company
• 2nd clinical candidate at IND-
enabling studies
• 3rd clinical candidate
announced
• Several prospects for
candidates 4th, 5th and 6th
• Pharma collaboration
• Clinical candidate
• 2nd lead: NKp30 x BCMA
• Candidates for IND3, IND4
• Multiple CLC mAbs
• Bispecifics with unique activity
• Several I&I programs
advancing in parallel
• Clinical lead CTX-471
• CLC antibodies
• StitchMabs™
• 30 discovery campaigns
complete
• Infrastructure
• In vitro and in vivo
platforms
• Bispecific from published
seq.
• Proprietary mAbs
CONFIDENTIAL| © 2019CONFIDENTIAL| © 2019
Compass Therapeutics Jefferies 2019 Global Healthcare Conference
June 7th, 2019
28
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