NEXT-GENERATION IMMUNOMEDICINES - SEPTEMBER 2019
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NEXT-GENERATION IMMUNOMEDICINES
SEPTEMBER 2019
Forward-Looking Statements To the extent that statements contained in this presentation are not descriptions of historical facts, they may be deemed to be forward-looking statements under the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “anticipate,” “estimate,” “intend,” “next,” “near-term,” “future” and similar expressions, as well as other words and expressions referencing future events, conditions, or circumstances, are intended to identify forward-looking statements. Examples of forward-looking statements in this presentation may include, among others, statements regarding: (i) the timing, progress and results of our preclinical and clinical trials; (ii) the timing or likelihood of regulatory filings for our product candidates; (iii) our manufacturing capabilities and strategy; (iv) the potential benefits and activity of our product candidates; (v) our expectations regarding the nature of the biological pathways we are studying; (vi) our expectations regarding our FIND-IO platform; and (vii) the potential benefits of our relationships with Dr. Lieping Chen, Yale University and Eli Lilly and Company. Various factors could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: our limited operating history and no products approved for commercial sale; our history of significant losses; our need to obtain additional financing; risks related to clinical development, marketing approval and commercialization; and the unproven approach to the discovery and development of product candidates based on our FIND-IO platform. No forward-looking statement is a guarantee of future results or events, and one should avoid placing undue reliance on such statements. For further discussion of these and other factors that could affect the outcome of our forward-looking statements, see our filings with the Securities and Exchange Commission, including in "Risk Factors" and "Special Note Regarding Forward-Looking Statements" in our prospectus dated May 8, 2019. Except as otherwise indicated, this presentation speaks as of the date indicated herein. Except as required by law, we assume no obligation to update any forward-looking statements, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. The information in this presentation is not complete and may be changed. 2
NEXTCURE HIGHLIGHTS
Pipeline of • NC318: Phase 1/2 topline data in Q4 2019
• NC410 (LAIR-1): IND expected Q1 2020
Immuno-
• Additional research and development programs
medicines • Manufacturing: dedicated, state-of-the-art facility
Platform
• FIND-IO functional screening discovery engine
for Novel • Oncology partnership with Lilly: $40M upfront and equity
Target • Expanding into autoimmune diseases
Discovery
Proven • Experienced Management team
• Scientific founder Dr. Lieping Chen: discovered PD-L1 & other key targets
Abilities • Strong balance sheet to deliver on objectives
3
THE UNMET NEEDS OF CANCER PATIENTS ARE SIGNIFICANT
NON-RESPONDERS RAPID PROGRESSION LIMITED TREATMENTS
We Need New Solutions
4
COMMITTED TO DISCOVERING & DEVELOPING NOVEL,
FIRST-IN-CLASS IMMUNOMEDICINES TO IMPROVE LIVES
NEW POSITIVE IMPROVED
therapeutic options clinical responses quality of life
Focused on Cancer Patients Not Adequately Addressed Today
5
EXPANDING TARGETS BEYOND T CELLS
SUPPRESSIVE
MYELOID CELLS
New
NC318
Targets
NEUTROPHILS MACROPHAGES
T CELLS
New
Targets NATURAL DENDRITIC CELLS
KILLER CELLS NC410
New
Targets
6
EXPERIENCED TEAM WITH STRONG TRACK RECORD
HISTORY AND SUCCESS OF WORKING TOGETHER
Michael Richman
CEO
Steve Cobourn, CPA
CFO
Kevin N Heller, MD
CMO
Sol Langermann, PhD
CSO
Jim Bingham, PhD
CDO
Timothy Mayer, PhD
SVP, Corporate Development
Linda Liu, PhD
SVP, Research
Sebastien Maloveste, PhD
VP, Business Development
Dallas Flies, PhD
VP, Discovery Research
7
WORLD-RENOWNED SCIENTIFIC FOUNDER
AND KEY COLLABORATION
YALE COLLABORATION NATURE MEDICINE PUBLICATION
LIEPING CHEN, MD, PhD
Discovered multiple
key immune pathways,
including PD-L1
WORLD-RENOWNED
INSTITUTION
Sponsored research, clinical
samples, cell lines & models
TEAM OF COLLABORATORS
Roy Herbst, MD, PhD
David Rimm, MD, PhD
Mario Sznol, MD
8
NEXTCURE HAS DELIVERED ROBUST PRODUCT PIPELINE
IN LESS THAN 3 YEARS
NEXT WORLDWIDE
PROGRAMS CELLS DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONE RIGHTS
PRODUCT CANDIDATES
Phase 1
NC318 Tumors and
(S15) macrophages
ONCOLOGY complete in
Q4 2019
NC410 Dendritic IND filing in
(LAIR-1) & T cells
ONCOLOGY Q1 2020
DISCOVERY AND RESEARCH PROGRAMS
First IND
Multiple
Immune cells filing in
Programs
early 2021
First IND
FIND-IO Multiple
filing in
Platform cell types
late 2022
9
NC318
HUMANIZED
MONOCLONAL
ANTIBODY
Phase 1/2 Clinical Trial Initiated
October 2018
TARGET CELL TYPES MOA INDICATIONS
Tumors & Designed to block Advanced or
Siglec-15 (“S15”) metastatic solid
macrophages S15-induced
immunosuppression tumors, which could
include ovarian,
NSCLC, and head &
neck cancers
10S15 AS A TARGET
EXPRESSION NON-RESPONDERS FUNCTION
Tumors & Generally Non-Overlapping Potently Suppresses
Macrophages with PD-L1 Expression T Cell Function
Tumor
Cell Suppressed
T Cell
Tumors Tumors
M2 Express S15
OR Express PD-L1
Macrophage
S15
11S15 IS HIGHLY IMMUNOSUPPRESSIVE IN THE TME OF
MULTIPLE TUMOR TYPES
S15
S15
Tumor M2
cell macrophage
OR
Inactive
T cell
Myeloid
cell
Increase in
inflammatory
Distinct cytokines
Differentiation S15-induced
and survival myeloid cells
Immunosuppression
and tumor growth
12NC318 IS DESIGNED TO BLOCK
IMMUNOSUPPRESSIVE ACTIVITY INDUCED BY S15
S15
S15
Tumor M2
cell macrophage Dead tumor
NC318 cell
NC318
OR
Myeloid
Tumor
cell
killing
Promotes T cell
proliferation &
Decreases restores function
Differentiation inflammatory
and survival cytokines
13NC318: A POTENTIAL TREATMENT OPTION FOR
PD-1/PD-L1 NON-RESPONDERS
S15 AND PD-L1 EXPRESSION GENERALLY POTENTIAL NEW TREATMENT OPTIONS
DO NOT OVERLAP IN NSCLC TUMORS* FOR PD-1/PD-L1 NON-RESPONDERS
PD-L1+ PD-1/PD-L1 Treatment
S15 - of Cancer Patients
12000
12000
PD-L1 Tumor Signal
10000
10000 Responders Non-Responders
8000
8000
6000
6000
PD-L1+ and S15- PD-L1- and S15+ PD-L1- and S15-
4000
4000
2000
2000
00
0 2000 4000 6000 8000 10000 12000 14000 16000
Potential
2000 4000 6000 8000 10000 12000 14000 16000
Likely to patient
S15 Tumor Signal Opportunities
respond to population for
for FIND-IO
anti-PD-1 / NC318
PD-L1- S15+ platform
PD-L1 therapy monotherapy
S15 - PD-L1 -
treatment
*>200 NSCLC samples in preclinical research
Wang et al., Nat Med 2019 Mar 4
Toki et al., AACR Poster 3151 2019
14S15 IS CLINICALLY
AND FUNCTIONALLY RELEVANT
S15
IN TUMORS
Clinical • Increased expression on tumor cells and
immunosuppressive macrophages in
Relevance multiple cancer types
• Minimal expression in normal tissues
S15
KNOCK-OUT • S15-deficient mice showed
MODEL
Functional – Enhanced antigen-specific T cell
responses in vivo
Relevance – Delayed tumor progression
– Increase in survival
15NC318 RESTORED IMMUNE FUNCTION IN VITRO
Myeloid Cell Survival
)
1.5
1 .5
n m
and Differentiation
INHIBITED
C e ll V ia b ilit y
0 4 5
Blocked survival of
Cell Viability
1.0
1 .0
Myeloid Cell NC318
( A b s o rb a n c e
N C 3 1 8
Control
C o n tro l
Differentiation 0.5
0 .5
No S15 Protein
N o S 1 5 P r o t e in A d d e d
myeloid cells
and Survival 0
0 .0
5
5
5
.5
1
2
4
8
6
2
2
2
.2
1
3
0
6
.1
0
.0
mAb (g/mL)
0
0
m A b ( g /m L )
IL-1 IL-6 TNF-
IL -1 IL -6 T N F -
DECREASED 250
2 5 0 1500
1 5 0 0 3000
3 0 0 0
200
2 0 0
p g /pg/mL
p g pg/mL
p g pg/mL
/m L
/m L
m L
Pro-Inflammatory and 150
1 5 0
1000
1 0 0 0 2000
2 0 0 0
Decreased IL-1β,
TNF-α
IL-1β
IL-6
100
1 0 0
500 1000
IL-6 & TNF-α
5 0 0
Pro-Tumorigenic
1 0 0 0
50
5 0
00 0 00
Cytokines
0
Control 5G12 NC318 Control 5G12 NC318 Control 5G12 NC318
mAb mAb mAb
6 0 60
2000
D iv id e d C e lls
+ S 1 5 P r o te in
PROMOTED Increased T cell
% Divided Cells
40 1500
IFN-g pg/mL
4 0
Tumor-Specific 2 0 20
1000
proliferation &
500
T Cell Function IFN-g production
%
0 0 0
in b 8 Control
te Control
A
3
NC318
1 5G12 NC318
ro m
P o
l mAbN C mAb
l tr
o n
tr o
n
o C
C
16NC318* HAS SHOWN MONOTHERAPY ACTIVITY
IN A NUMBER OF ANIMAL MODELS
800
Tumor Volume (mm3)
Control
600
5G12
REDUCED 400
p≤0.0001
CT26 tumor model
Tumor Growth 200
0
0 5 10 15 20 First 2 doses at 20 mg/kg followed by 10
Days Post Tumor Inoculation mg/kg, Q4D, 7 doses
100
80
Percent Survival
Control
Control
INCREASED 60
5G12
5G12
CT26 tumor model
40 p≤0.001
Survival 20
0
0 10 20 30 40
Days Post Tumor Inoculation
p≤0.01
p = 0 .0 0 5 4
20
2 0
n o d u le s
LungNodules
15
1 5
Nodules
DELAYED 10
1 0
MC38 tumor model
Lung Metastasis
Lung
L u n g
55
00
Control
C o n tro l 5G12
5 G 1 2
30 mg/kg, Q7D, 4 doses
*Murine surrogate is 5G12
17NC318 MONOTHERAPY TRIAL UNDERWAY
DESIGNED FOR RAPID PROOF-OF-CONCEPT
PHASE 1 PHASE 2
• Opened in 4Q 2018; Complete in 4Q 2019 • Open in 1Q 2020; Complete in 4Q 2020
• Dose-escalation1 • Efficacy assessment
• Safety, tolerability, and biomarker • Tumor types shown to have elevated
readouts S15 expression, including NSCLC,
• Advanced or metastatic solid tumors ovarian, and head & neck
Biopsy (S15 & PD-L1 expression) Biopsy Biopsy2
NC318
Q2W
dosing
Screen On treatment Off study
Peripheral Blood for: Cytokine Analysis, Immune Phenotyping, Immune Function, TCR Clonal Analysis
(1) Dose escalation evaluates 6 dose cohorts (8 mg – 800 mg or approximately 0.1 - 10 mg/kg) administered every 2 weeks
(2) In Phase 2 portion of trial
18NC318 PHASE 1 TRIAL STATUS AS OF MARCH 31, 2019
ENROLLMENT SAFETY RESPONSES
• 21 subjects dosed • No dose limiting • Evaluations every 8
• 4th dose cohort open toxicities or drug-related weeks
SAEs • 1 confirmed partial
• 10 different tumor types
• 1 transient elevation of response
• Recruitment on schedule
amylase (grade 3) and • 6 stable disease
lipase (grade 4) that was
• 6 progressive disease
deemed probably
• 8 subjects not yet
related to NC318(1)
evaluated
• Possibly NC318-related
AEs limited to transient
asymptomatic lab
findings or grade 1
events
• Angeles Clinic • MSKCC • Next Oncology • NYU • Yale University
(1) The patient was asymptomatic and both elevations resolved without any interventions within 72 hours
19NC318
DESIGNED TO RESTORE
IMMUNE FUNCTION IN A
HIGHLY SUPPRESSIVE TUMOR
MICROENVIRONMENT
MOA / Preclinical studies complete
• Relieved S15-mediated inhibition of T cells
• Increased IFN-γ production
• Decreased inflammatory cytokines
First-in-Human trial initiated in
October 2018
□ Complete Phase 1 and report topline
data in Q4 2019
□ Complete Phase 2 in Q4 2020
20NC410
DECOY HUMAN FUSION PROTEIN
TARGETING THE TME
IND Filing Expected Q1 2020
TARGET CELL TYPES MOA INDICATIONS
Leukocyte- Dendritic cells Promotes T cell Advanced or
Associated and T cells function and metastatic solid
Immunoglobulin- dendritic cell activity tumors
like Receptor-1
(LAIR-1)
21LAIR-1 & LAIR-2 FUNCTIONAL RELATIONSHIP
LAIR & LIGANDS LAIR-1 LAIR-2
LAIR-1 and LAIR-2 bind Ligands are expressed in response to LAIR-2 modulates LAIR-1 mediated
collagen and C1q inflammation & inhibit immune function inhibition
Tissue Tissue
LAIR-1 LAIR-2 Damage Damage
Membrane Soluble Decoy
Bound (Binds with higher affinity
than LAIR-1)
Inhibited
T cell
Activated
T cells
LAIR LIGANDS Inhibited Activated
Dendritic Dendritic
Cells Cells
Collagen C1q
22NC410 IS DESIGNED TO PREVENT IMMUNE
SUPPRESSION CAUSED BY LAIR-1
NC410 is a Fusion Protein of LAIR-2 and a Decoy for LAIR-1
Activated Dead
T Cell Tumor LAIR-1
Cell
LAIR-2
Collagen
C1q
Activated
Dendritic NC410
Cell
NC410 Promotes T Cell Function and Dendritic Cell Activation
23NC410 ENHANCED T CELL EXPANSION
AND RELIEVED IMMUNOSUPPRESSION
p≤0.05
11 xx 10 6 6
1 0
*
) (c o u n ts /m L
C e l l s (counts/mL)
11 xx 10
1 0
5 5
BLOCKED Human CD8+ T cell
CD8+ TT Cells
Suppression 11 xx 10
1 0
4 4 expansion in vivo
+
C D 8
3
1 03
11 xx 10
Control
C o n tr o l 0.1
0 . 1 mg/kg
m g /k g 0.3 mmg/kg
0 .3 g /k g 1 mmg/kg
1 g /k g
NC410
400
4 0 0
Control
C o n tro l
0.1 mg/kg NC410
)
0 .1 m g / k g N C 4 1 0
Tumor Volume (mm3)3
(m m
300
3 0 0 0.3 mg/kg NC410
0 .3 m g / k g N C 4 1 0
1 mg/kg NC410
1 m g / k g N C 4 1 0
Human PBMCs in mice:
DECREASED
T u m o r V o lu m e
p≤0.01
200 **
CD8+ T cell activity
2 0 0
Tumor Volume
100
1 0 0 decreased tumor volume
00
Day1 10
D a y 0 Day1 13
D a y 3 Day1 15
D a y 5
24NC410 PROMOTED IMMUNE CELL ACTIVATION
IN THE PRESENCE OF COLLAGEN AND C1Q
REVERSED COLLAGEN REVERSED C1Q SUPPRESSION OF
SUPPRESSION OF HUMAN PBMCS HUMAN MYELOID CELLS
1200
1 2 0 0
800
8 0 0
Immune Cell Activation (TNF- pg/mL)
Collagen peptide 20 g/mL C1q 10 g/mL
Myeloid Cell Activation (IL-6 pg/mL)
p g /m L )
p g /m L )
1000
1 0 0 0
600
6 0 0
(T N F -
(IL -6
800
C e ll A c t iv a t io n
8 0 0
A c tiv a tio n
400
4 0 0
600
6 0 0
C e ll
M y e lo id
200
2 0 0
Im m u n e
400
4 0 0
00
00 g/mL
g / m L 1 0 g/mL
10 g / m L 1 0 0 g/mL
100 g / m L 00 g/mL
g / m L 2.5 g/mL
2 .5 g / m L
10 g/mL
1 0 g / m L
NC410 NC410
25NC410 SUMMARY
Based on normal immune regulatory mechanism
Promoted T cell function and dendritic cell activity in
preclinical studies
Designed to alleviate tumor-mediated immunosuppression
IND-enabling tox studies in progress
cGMP manufacturing
IND filing expected Q1 2020
26FINDING SOLUTIONS
WITH A POWERFUL
DISCOVERY ENGINE
Functional, Integrated, NextCure Discovery in Immuno-Oncology
FUNCTIONAL READOUTS
• T cell activation • Apoptosis
• Cytokine release • Effector function
• Proliferation • Pathway reporters
TARGET LIBRARIES CELL TYPES
• Primary
• Membrane proteins • Cell lines
• Soluble proteins • Lymphoid
• Small molecules • Myeloid
• Soluble factors • Tumor
27FIND-IO SCREENING METHODOLOGY
CELL TYPES
Immune Host Cell +
TARGET LIBRARY Cell Target Gene
HOST CELL
TRANSFECT
One Gene Per Well BI-DIRECTIONAL READOUTS
(+) or (-) interaction
Plasma Membrane Proteins increases or decreases red
Secreted Proteins or green intensity
FUNCTIONAL READOUTS
28JURKAT “T CELL LINE” SCREENING
AND VALIDATING FIND-IO HITS
Identified Novel T Cell
Stimulators and Inhibitors
Vector Control
45
B7-2 Stimulators
40
B7-1 Positive Controls
35 Gene Library
Jurkat-NF-kB-GFP
FasL Negative Controls
Vector controls
Parameter 1
30 Transfection Control
Gene Library
25 Stimulatory B7-2
Parameter 1 Control
20 Parameter 2 Control
15
10
5
Inhibitors TRAIL
0 Inhibitory TRAIL
0 50 100 150 200 250 300 350
Parameter 2
293T-CD3-NF-kB-RFP
REPRODUCIBILITY ROBUSTNESS RELEVANCY
29LILLY – NEXTCURE PARTNERSHIP
TO VALIDATE PLATFORM AND APPROACH
Synergies
Overview
Structure
• Each party has options to
™ exclusively license certain
FIND-IO antibodies
Targets Human mAbs
Terms
• Upfront: $25M
• Equity investment: $15M
DISCOVERY • R&D support
COLLABORATION • Option payments
• Development & sales milestones
• Royalties
ONCOLOGY
30DIVERSIFICATION BEYOND ONCOLOGY
TODAY TOMORROW FUTURE
FIND-IO FIND-AI
Oncology Autoimmunity Neuro-Inflammation
Gene Libraries
Immune Cells
Functional Screening
31ANTICIPATED NEAR-TERM MILESTONES
• Complete Phase 1 and report topline
NC318 data in Q4 2019
• Complete Phase 2 in Q4 2020
• Complete IND-enabling tox studies
NC410
• File IND in Q1 2020
• Identify novel targets and initiate
™ DISCOVERY
FIND-IO validation
32Committed to Addressing the Unmet Needs of Cancer Patients
With New Solutions
FOCUSED PROVEN INNOVATIVE EXPERIENCED FUTURE
Approach Momentum Platform Team Deliverables
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