SlideShare a Scribd company logo
1 of 49
Download to read offline
v.240216
► Hybrid business model since 2006
— Independent and founder owned
— CRO generating revenues
— Internal discovery projects (currently 2 oncology projects: NIK & BRD4)
► Proprietary discovery platform
— Unique expertise in protein structure determination
— Hit identification using proprietary WAC™ fragment screening
technology and crystallographic fragment screening (XFS)
► Delivered several hundreds of crystal structures to pharma,
biotech and academic clients worldwide
— Protein/small-molecule complexes
— Antibody/antigen complexes
— Industrial enzymes
► Experienced and skilled team of 28 (25 PhDs)
► Sales representatives in Boston & Japan
SARomics Biostructures at a glance
May 2023
Medicon Village
Broad spectrum of protein structure related services
Gene-to-structure Platform
Fragment-Based Hit Generation
Structure-Based Drug Design
FastLane™ Standard
FastLane™ Premium
Antibody-antigen Structures
NMR Services
Integrated Drug Discovery
Protein Shop
Industrial Enzymes
► Expression systems
— E. coli (in-house)
— BEVS (in-house)
— HEK293 & CHO (external 3rd–party collaborator)
► Protein purification & analysis
— ÄKTA systems
— SEC, IMAC, ion exchange etc.
— SDS-PAGE, Bradford
— Western blot
► Protein characterization
— DSF (thermofluor-based method, 96 wells)
— DLS (96 well format)
— Buffer screen (DLS+DSF)
— NMR, CD etc.
Protein Production Capabilities
State-of-the-art Crystallization Lab
SARomics Biostructures performs high-throughput low volume
crystallization using liquid handling, crystallization and imaging robotics
Crystallization robotics Microlitre robotics Plate hotel/imaging robotics
► Our lab is located 2 km away from the
world-leading MAX IV synchrotron
► Currently collecting data twice per month
at MAX IV (Lund), Diamond (Oxford), DESY
(Hamburg) or Soleil (Paris-Saclay)
Synchrotron Access
► The MAX IV Laboratory is the new Swedish national synchrotron facility
► SARomics is in a very advantageous position for access to MAX IV (no need to ship crystals)
► Access to one of the world’s most advanced synchrotron source substantially increases our
competitiveness and shortens turnaround times
► We benefit from a smaller, more coherent and more brilliant beam and are thereby able to
collect superior data on smaller crystals
Our Local Light Source
Our Local Light Source
FASTLANE™ PREMIUM
FastLane™ Library
FASTLANE™ STANDARD
Kinases:
BTK, CDK2, CDK5, CDK7, CK2, CLK3, DAPK3,
DYRK1A, EphA7, FGFR1, FRK, ITK, KIT, LATS2,
MAP2K4, NDR2, PFKFB3, PIM1, PIM3,
PIP4K2A, PLK1, PLK4, RET, RIPK3, RSK1,
RSK2, SRPK1, STK10, STK17A, STK17B,
TYK2, Vps34
Epigenetics targets:
ATAD2A, ATAD2B, KDM4C, SMARCA2B
FastLane™ Premium Structures
FastLane™ Premium Crystallization system up and running and ready
to be co-crystallized with customers compounds
(complexes delivered within 2 to 6 weeks)
Proteases:
USP7, USP8, USP21, Caspase-1, Cathepsin C, DPP4, Thrombin
Other:
Aldose reductase, BCAT2, Bfl-1, BlaC, BSSL, CD11b, cGAS,
CYP51A1, DHODH, DNA Gyrase B, eIF4E, Gal-1, Gal-3C, Gal-
8N, Gal-9N, Gal-9C, GART, GMPR2, HSA, Hsp90, IL-17A, K-
RasG12D, K-RasG12V, K-Ras3mut, LDHA, LeuT, NRP1, PDE4d,
PPARa, PPARg, PSD-95, PTP1B, RORg, S100A4, S100A9,
S100A12, SHP2, Tubulin, Ubiquitin
mAb targets:
CD28, CD47, CD137, GPVI, HER2, IL-4, IL-8, IL-13, IL-23, PD-1,
PD-L1, SARS CoV-2 RBD, TIM-3, Tissue factor, TNF⍺
Proteins in bold = not in the PDB
FastLane™ Premium Structures
Three novel kinase structures not in the PDB
LATS2
PIM3 NDR2
First crystal structure of CDK7-inhibitor complex
Small molecule CDK7 inhibitor LDC4297
Crystal structure of CDK7-LDC4297 complex (PDB code: 8P4Z)
determined by SARomics Biostructures (resolution 2.75 Å)
Unique IL-17A FastLane Premium crystallization system
applied to small molecule inhibitor discovery
Proprietary crystallization system for IL-17A
First IL-17A small-molecule complex crystal
structures published (without chaperone
Fab and HAP peptide).
Andrews et al., 2022, J Med Chem, 65, 8828.
Client project: LP0200 in complex with IL-17A
Collaboration with LEO Pharma, Ballerup, Denmark
PDB code: 7AMA
Proteins* ready to be expressed, purified
and crystallized according to existing verified
protocols (complexes delivered within 4 to 10
weeks)
FastLane™ Standard Structures
FastLane™ Standard
*Please see www.saromics.com for a complete list
► > 50 kinases
► > 30 phosphatases
► > 20 bromodomains
► > 20 other epigenetic targets
► > 25 other targets
Antibody-antigen complex structures
ANTIBODY-ANTIGEN
STRUCTURES
Use structural information for:
► Epitope definition to file stronger IP
► Understanding MoA
► Structure-based design
► Structural characterization of
protein drugs (HOS)
Fab-antigen Structures
Don’t work in the dark!
Access to structural information increases your understanding
and enables you to execute projects faster.
► Antibody engineering: affinity
maturation
► Antibody engineering: humanization
► Antibody engineering: ADC
MM-131 – Antigen Structures
Case Study
Client project: Bispecific anti-Met/EpCAM mAb MM-131 in complex with its antigens
Collaboration with Merrimack Pharmaceuticals, Cambridge, MA
Published in PNAS!
scFv-EpCAM Asymmetric Fc Fab-Met
Casaletto et al., 2019, PNAS, 116, 7533-7542.
Agonistic properties Low potency
Antagonistic with high potency
PDB codes: 6I07, 6HYG, 6I04
Structure-based engineering of a novel CD3ε-
targeting antibody for reduced polyreactivity
Client project: ADI-26906 Fab in complex with CD3ε N-terminal peptide
Collaboration with Adimab, Lebanon, NH
X-ray structure of ADI-26906 Fab in complex with
N-terminal peptide from CD3ε
Liu et al., 2023, MAbs, 15,
2189974-2189974.
• CD3 antibodies possessing cross-
reactivity with cynomolgus
monkey typically recognize a
highly electronegative linear
epitope at the extreme N-
terminus of CD3ε
• Using insights from the crystal
structure of anti-Hu/Cy CD3
antibody ADI-26906 in complex
with CD3ε and engineering, we
have derived high-affinity CD3
antibody variants with very low
polyreactivity and significantly
improved biophysical
developability.
PDB code: 8F0L
SARS-CoV-2 Fab complexes
Client project: 1D1 and 3D2 Fab’s in complex with SARS-CoV-2 RBD
Collaboration with Chulalongkorn University, Bangkok, Thailand
Crystal structures of two Fab fragment complexes.
Boonkrai et al., 2023, PLoS ONE,
18(5): e0284173.
PDB code: 8BSE, 8BSF
Davoceticept (ALPN-202) - An engineered
CD80 variant fusion therapeutic
Client project: ALPN-202 in complex with PD-L1
Collaboration with Alpine Immune Sciences, Seattle, WA
Published in Nature Communications!
X-ray structure of ALPN-202 CD80 vIgD in
complex with PD-L1
Maurer et al., 2022, Nat Comm, 13:1790.
The three mechanisms of action of ALPN-202:
• Blockade of PD-1–PD-L1 interaction
• PD-L1-dependent CD28 costimulation
• Blockade of CTLA-4–CD80/CD86 interactions.
PDB code: 7TPS
Structural basis of activation and antagonism of
receptor signaling mediated by interleukin-27
Client project: SRF388 Fab in complex IL-27
Collaboration with Surface Oncology, Cambridge, MA
X-ray structure of SRF388 Fab in complex with IL-27
Skladanowska et al., 2022, Cell Reports, 41, 111490.
• IL-27Ra interacts both with the p28 and EBI3
subunits of IL- 27
• SRF388 and IL-27Ra occupy mutually
exclusive binding sites on IL-27
• IL-27 mediates receptor assemblies distinct
from IL-12 and IL-23
PDB code: 7ZXK
Activin ligand trap
Client project: ActRIIB-Alk4-Fc in complex with activin A and anti-ActRIIB Fab
Collaboration with Acceleron Pharma, Cambridge, MA
PDB code: 7OLY
Structure of ActA/ActRIIB:
Alk4/anti-ActRIIB Fab complex
Goebel et al., 2022, iScience, 25, 103590.
Increased ligand specificity can be accomplished by using the
extracellular domains of both the type I and type II receptor to
mimic the naturally occurring signaling complex.
ATOR-1017 (evunzekibart), a 4-1BB agonist which activates
exhausted T cells in combination with anti-PD-1
Client project: ATOR-1017 in complex with 4-1BB (CD137)
Collaboration with Alligator Bioscience, Lund, Sweden
X-ray structure of ATOR-1017 in complex with 4-1BB (PDB code: 8OZ3)
Enell Smith et al., 2023, Cancer Immunol, Immunother.
• ATOR-1017 (evunzekibart), a second-
generation Fc-gamma receptor conditional
4-1BB agonist, was designed to overcome
the limitations of the first generation of 4-
1BB agonists, providing strong agonistic
effect while minimizing systemic immune
activation and risk of hepatoxicity.
• ATOR-1017 binds to a unique epitope on 4-
1BB enabling ATOR-1017 to activate T cells
• This translated into a tumor- directed and
potent anti-tumor therapeutic effect in vivo,
which was further enhanced with anti-PD-1
treatment
The bispecific 4-1BB x 5T4 agonist, ALG.APV-527, mediates
strong T cell activation and potent anti-tumor activity
Client project: ALG.APV-527 (Fab1618) in complex with 4-1BB (CD137)
Collaboration with Alligator Bioscience, Lund, Sweden
X-ray structure of Fab1618 in complex with 4-1BB
Nelson et al., 2022, Mol. Cancer Ther., 22-0395.
• ALG.APV-527 directs the stimulation of T
cells and NK cells to 5T4+ tumors and is
designed to minimize the toxicity observed
with other 4-1BB therapeutics
• Binding sites of ALG.APV-527 and the
4-1BBL on 4-1BB are distinct
PDB code: 7YXU
Targeting platelet GPVI with glenzocimab: a
novel mechanism for inhibition
Client project: Glenzocimab Fab in complex with platelet glycoprotein VI
Collaboration with Acticor Biotech, Paris, France
X-ray structure of glenzocimab in complex with GPVI
Billiald et al., 2022, Blood Adv., 007863R2.
• GPVI binding to vascular collagen initiates thrombus
formation and GPVI interactions with fibrin promote
the growth and stability of the thrombus.
• Crystal structure information enables the
elucidation of a novel mechanism for the powerful
anti thrombotic effect of glenzocimab, in which both
ligands are blocked through a combination of steric
hindrance and structural change.
PDB code: 7R58
Glenzocimab inhibits fibrin-
induced platelet aggregation
DutaFabs - engineered Fab’s that bind two
antigens simultaneously
Client project: DutaFab (Roche) in complex with its antigens PDGF and VEGFA
Published in Nature Communications!
X-ray structure of the DutaFab in complex
with PDGF-BB dimer and VEGFA dimer
Beckmann et al., 2021, Nat Comm, 12:708.
The DutaFab concept of
separating paratopes on a
single Fab
PDB code: 6T9E 6T9D
Dusquetide modulates innate immune
response through binding to p62
Client project: Dusquetide in complex with p62 (SQSTM1) ZZ domain
Collaboration with Soligenix, Princeton, NJ
X-ray structure of dusquetide in complex with p62ZZ
Zhang et al., 2022, Structure, 30, P1055.
• Next-generation IDR dusquetide penetrates
the cell membrane
• Dusquetide targets the ZZ domain of p62
• Treatment of cells with dusquetide, which
mimics arginylated ligands of p62ZZ, leads to
stabilization of the p62-RIP1 complex and an
increase in p38 phosphorylation and CEBP/B
expression
PDB code: 7R1O
NMR spectroscopy services
NMR SERVICES
► Protein structure determination in solution
► Peptide secondary structure assessment
► Protein-ligand and protein-protein complex structure
determination
► Fragment screening (19F, ligand or protein detected)
► Epitope mapping and dissociation constant (Kd)
determinations for compounds
► Higher Order Structure (HOS) validation of antibodies
► Expression and purification of 2H, 15N, and 13C-labelled
proteins in E. coli
NMR spectroscopy services
Broad range of custom protein NMR spectroscopy services
Ultra High Field NMR Instruments
900 MHz Bruker Avance III HD
► 4 RF channels
► Triple-axis pulsed field gradients
► TCI cryoprobe (1H/13C/15N, 3 mm)
Danish Center for Ultrahigh Field
NMR Spectroscopy (Århus)
► 950 MHz Bruker Avance III HD
► 4 RF channels
► TCI cryoprobe (1H/13C/15N, 5 mm)
► SampleJet
3x600 MHz Varian Inova/Bruker
► 3-4 RF channels
► Triple-axis pulsed field gradients
► Tripple resonance cryo-probe (1H/13C/15N)
► Triple resonance probe (1H/13C/X)
► 4 mm NANO probe
► Diffusion probe (1H/2H/19F)
Access to NMR instruments, automatic assignment, NUS sampling, fragment screening etc.
800 MHz Bruker Avance III HD
► 4 RF channels
► Triple-axis pulsed field gradients
► TXO cryoprobe (1H/13C/15N, 5 mm)
► Triple resonance probe, 8 mm
800 MHz Bruker Avance III HD
► 4 RF channels
► Triple-axis pulsed field gradients
► TCI cryoprobe (1H/13C/15N, 3 mm)
► SampleJet
700 MHz Bruker Avance III
► 4 RF channels
► Triple-axis pulsed field gradients
► QCI cryoprobe (1H/19F/13C/15N, 5 mm))
► SampleJet
NMR solution structure of a insulin receptor
activating peptide
Client project: NMR structure determination of IM459N21
Collaboration with Eli Lilly, Indianapolis, IN
NMR solution structure of the IM459N21 peptide
Kirk et al., 2022, Nat Commun., 13, 5695.
The findings illuminate unexplored
pathways for controlling the signaling of
the insulin receptor as well as
opportunities for development of insulin
mimetics.
PDB code: 8DI2
NMR solution structure of a stapled
anti-inflammatory peptide
Client project: NMR structure determination of sHVF18
Collaboration with Lund University
Petruk et al., 2023, Nat Commun., 14, 6097.
Thrombin-derived C-terminal peptides (TCPs) are
endogenous anti-infective immunomodulators
interfering with CD14-mediated TLR-dependent
immune responses.
• Stapled version, sHVF18, displays a
conformationally stabilized, protease
resistant active innate fold
• Targets the LPS-binding groove of CD14
• Therapeutic efficacy in experimental models
of endotoxin shock in vivo
• Increases survival in mouse models of
systemic polymicrobial infection.
NMR solution structure of the sHVF18 peptide
PDB code: 8BWW
► 2D NMR spectroscopy can be used to study and compare HOS
of biologics using unlabeled proteins
► Proteins in formulation buffer can be studied with little need
for sample preparation
► Effects on HOS of oxidation or surfactant concentration can
be studied
► Time resolved processes can be followed using 2D spectra
with <1 h / spectra
► Applications:
— Batch-to-batch consistency
— Biosimilar/originator comparability
— Formulation optimization
NMR Higher Order Structure (HOS)
Computational chemistry
STRUCTURE-BASED
DRUG DESIGN
► Docking
► Pharmacophore and shape based modelling
► Virtual screening
► Library design
► Structure activity relationships
► Quantum chemical calculations
► State of the art computational software
technology
Computational Chemistry
Molecular modelling and data analysis capabilities
Accelerating Discovery
Through Structural Insight
FRAGMENT—BASED
HIT GENERATION
WAC™
• Primary screen
• Hit follow-up
Orthogonal
validation
• NMR & DSF
• Validation of
actives
Biochemical
assay
X-ray
• Analysis of
binding pose
Fragment
evolution
• SBDD support
• SAR by Catalog
• Synthesis
Fragment-Based
Hit Generation
Joint Fragment-Based Lead Discovery Platform
Fragment Screening
► Screening technologies
— WAC™
— NMR
— Thermal shift assay (DSF)
— In silico screening
— Biochemical screening (HCS)
— X-ray crystallography
► Fragments
— SBX/RGD library
— Client libraries
56 employees
• Medicinal chemistry
• Custom synthesis
• Peptide chemistry
• Analytical chemistry
(NMR & MS)
• In vitro ADME & phys chem
• In vitro biology
28 employees
• Structure-based
drug design
• X-ray crystallography
• Computational chemistry
• NMR screening
• Biophysics
• Protein chemistry
Fragment Screening & Validation of Hits
Suitable combinations of orthogonal techniques designed for each target
Protein-observed NMR
Ligand-observed NMR Thermal shift assay / DSF
Weak Affinity Chromatography
ΔTm at 62.5 μM
RG200001 7.3
RG200001 6.4
RG200002 10.4
RG200002 10.7
RG200003 -0.48
RG200003 -0.76
Primary screening technique
Follow-up techniques
X-ray crystallography X-ray – Fragment screening
Crystallization robotics MAX IV
Follow-up techniques
Hit validation techniques
Automatic soaking, data collection and analysis
Suitable for >50 fragments or more
► Internal library
— Collection of ~1100 fragments
— General purpose, (not target-directed) covering diverse
chemical space
— Focus on low-molecular weight fragments (<240)
— Experimental solubility (DMSO, water) on >25% of fragments
— Analytical data (LCMS, 1H-NMR) on all fragments
— MedChem friendly
► Privileged Library
— Diverse set of 230 fragments all with experimentally verified
solubility (>0.5 mM)
► >90% commercially available -> rapid SAR-by-catalogue
follow-up
SBX/RGD Fragment Library
Weak Affinity Chromatography (WAC™)
WAC™
► Immobilized target protein
► High throughput
► mM hits by
screening at 1-5 µM
► Made in Sweden
Principles of WAC™
Affinity LC/UV/MS Platform
Characteristics of WAC™
Affinity
• Immediate KD ranking from ~0.5 mM - 0.1 µM with isocratic elution
• Fragments are screened at low concentration (1-5 µM)
• Excess of protein sites enable detection of multiple binding fragments
Quality
• High precision and robustness
• Automatic quality control (MS or MS/MS detection)
• Low sensitivity to impurities
Throughput
• The use of fragment mixtures (< 100) gives high throughput
Consumption of Target
• Consumption of target is low (normal column: 5-7 mg; micro column: 2-5 mg)
• Protein immobilization using exposed lysines or AVI-tag for NeutrAvidin binding
• Long WAC column lifetime
Applied Biophysics for Drug Discovery, 2017
Eds. Donald Huddler, Edward R. Zartler
Chapter 7
Sten Ohlson and Minh-Dao Duong-Thi
Weak Affinity Chromatography (WAC)
Chapter 3
Björn Walse, Andrew P. Turnbull and Susan M. Boyd
Tailoring Hit Identification and Qualification Methods for Targeting
Protein–Protein Interactions
Working with WAC™ for 5 years
44
6
5
4
3 3 3
2 2 2
1 1 1 1 1 1 1 1 1 1
k
i
n
a
s
e
G
T
P
a
s
e
c
y
t
o
k
i
n
e
/
P
P
I
b
r
o
m
o
d
o
m
a
i
n
d
e
u
b
i
q
u
i
t
i
n
a
s
e
i
n
t
e
g
r
i
n
h
e
l
i
c
a
s
e
/
A
T
P
a
s
e
s
i
g
n
a
l
l
i
n
g
p
r
o
t
e
i
n
t
r
a
n
s
c
r
i
p
t
i
o
n
f
a
c
t
o
r
a
u
t
o
p
h
a
g
y
f
a
c
t
o
r
d
e
a
m
i
n
a
s
e
e
s
t
e
r
a
s
e
g
a
l
e
c
t
i
n
l
i
g
a
s
e
l
i
p
o
x
y
g
e
n
a
s
e
s
y
n
t
h
a
s
e
t
r
a
n
s
f
e
r
a
s
e
u
b
i
q
u
i
t
i
n
l
i
g
a
s
e
v
i
r
a
l
m
e
t
h
y
l
t
r
a
n
s
f
e
r
a
s
e
Target class occurrence Facts and learnings
• >50 FBLD projects over 5 years
• 20 distinct target classes
• WAC hit rates from 1% to 20% (avg 6%)
• Library quality and size matters
• Best follow-up: NMR, SPR, X-ray
Quirks, drawbacks
• Buffer with low ionic strength, less charge
shielding
• Ranking order can be disrupted by ionic
interactions
• Non-volatile additives not tolerated by MS
WAC™ offers
WAC™ Pilot
• Technique evaluation
• Protein and fragments
from client
• Screen of up to
50 fragments
Ligandability
• Evaluation of the target
ligandability, incl.
amenability for WAC™
• Limited screen of our
Privileged set of 230
fragments
WAC™ screen
• Two-step milestone
process
• Feasibility & setup
• Screen
• RGD/SBX collection
and/or client fragments
Ranking
• Rank fragment hits
obtained from other
fragment techniques
Follow-up studies
• NMR verification
• Co-crystallization
• Fragment evolution
• And more …
All results are owned by the client
FragMAX
A facility at MAX IV for high throughput fragment screening by X-ray Crystallography
In collaboration with
LP3
Accelerating Discovery
Through Structural Insight
INTEGRATED
DRUG DISCOVERY
Integrated project to Aqilion
Björn Walse
CEO
SARomics Biostructures AB
bjorn.walse@saromics.com
Tel: +46 46 26 10 470
www.saromics.com
Japanese distributor
Carna Biosciences. Inc.
BMA 3F • 1-5-5 Minatojima-Minamimachi • Chuo-ku
Kobe 650-0047 • Japan
Tel: +81 78 302 7091
Headquarters
Medicon Village • SE-223 81 Lund • Sweden
US branch
245 First Street • Cambridge MA 02142 • USA
Tel: +1 857 444 4570

More Related Content

Similar to SARomics Biostructures 2024 Company Presentation

Hu cal platnimm alis adds
Hu cal platnimm alis addsHu cal platnimm alis adds
Hu cal platnimm alis addsBrandon Chackel
 
Data driven strategies and considerations for scalable purification of Plasmi...
Data driven strategies and considerations for scalable purification of Plasmi...Data driven strategies and considerations for scalable purification of Plasmi...
Data driven strategies and considerations for scalable purification of Plasmi...Merck Life Sciences
 
Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)
Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)
Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)Maki Ogawa
 
20161004 mapk dna_ref_standardslides
20161004 mapk dna_ref_standardslides20161004 mapk dna_ref_standardslides
20161004 mapk dna_ref_standardslidesMaki Ogawa
 
MRCT's Centre for Therapeutics Discovery
MRCT's Centre for Therapeutics DiscoveryMRCT's Centre for Therapeutics Discovery
MRCT's Centre for Therapeutics Discoverywarwick_amr
 
Pistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS Foundation
Pistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS FoundationPistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS Foundation
Pistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS FoundationPistoia Alliance
 
Summary of PROTAC And Other Targeted Protein Degradation Technologies.pdf
Summary of PROTAC And Other Targeted Protein Degradation Technologies.pdfSummary of PROTAC And Other Targeted Protein Degradation Technologies.pdf
Summary of PROTAC And Other Targeted Protein Degradation Technologies.pdfDoriaFang
 
BigDataEurope - Big Data & Health
BigDataEurope - Big Data & HealthBigDataEurope - Big Data & Health
BigDataEurope - Big Data & HealthBigData_Europe
 
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveVarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveGolden Helix
 
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveVarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveGolden Helix
 
Pistoia Alliance webinar on Antibody structures in the PDB
Pistoia Alliance webinar on Antibody structures in the PDBPistoia Alliance webinar on Antibody structures in the PDB
Pistoia Alliance webinar on Antibody structures in the PDBPistoia Alliance
 
Webinar: New RMC - Your lead_optimization Solution June082017
Webinar: New RMC - Your lead_optimization Solution June082017Webinar: New RMC - Your lead_optimization Solution June082017
Webinar: New RMC - Your lead_optimization Solution June082017Ann-Marie Roche
 
Peptide Tribulations in GtoPdb
Peptide Tribulations in GtoPdbPeptide Tribulations in GtoPdb
Peptide Tribulations in GtoPdbChris Southan
 
SOT short course on computational toxicology
SOT short course on computational toxicology SOT short course on computational toxicology
SOT short course on computational toxicology Sean Ekins
 
Pasteur Institute User Story - Cheminfo Stories 2020 Day 5
Pasteur Institute User Story - Cheminfo Stories 2020 Day 5Pasteur Institute User Story - Cheminfo Stories 2020 Day 5
Pasteur Institute User Story - Cheminfo Stories 2020 Day 5ChemAxon
 
Functional genomics
Functional genomicsFunctional genomics
Functional genomicsPawan Kumar
 
Expanding Your Research Capabilities Using Targeted NGS
Expanding Your Research Capabilities Using Targeted NGSExpanding Your Research Capabilities Using Targeted NGS
Expanding Your Research Capabilities Using Targeted NGSIntegrated DNA Technologies
 
Aug2014 abrf interlaboratory study plans
Aug2014 abrf interlaboratory study plansAug2014 abrf interlaboratory study plans
Aug2014 abrf interlaboratory study plansGenomeInABottle
 
LakePharma General Technical Overview
LakePharma General Technical OverviewLakePharma General Technical Overview
LakePharma General Technical OverviewJin Di, Ph.D.
 

Similar to SARomics Biostructures 2024 Company Presentation (20)

Hu cal platnimm alis adds
Hu cal platnimm alis addsHu cal platnimm alis adds
Hu cal platnimm alis adds
 
Data driven strategies and considerations for scalable purification of Plasmi...
Data driven strategies and considerations for scalable purification of Plasmi...Data driven strategies and considerations for scalable purification of Plasmi...
Data driven strategies and considerations for scalable purification of Plasmi...
 
Docking
DockingDocking
Docking
 
Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)
Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)
Reference Standards, gDNA, FFPE (MAPK, BRAF, EGFR, KRAS)
 
20161004 mapk dna_ref_standardslides
20161004 mapk dna_ref_standardslides20161004 mapk dna_ref_standardslides
20161004 mapk dna_ref_standardslides
 
MRCT's Centre for Therapeutics Discovery
MRCT's Centre for Therapeutics DiscoveryMRCT's Centre for Therapeutics Discovery
MRCT's Centre for Therapeutics Discovery
 
Pistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS Foundation
Pistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS FoundationPistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS Foundation
Pistoia Alliance European Conference 2015 - Nick Lynch / Open PHACTS Foundation
 
Summary of PROTAC And Other Targeted Protein Degradation Technologies.pdf
Summary of PROTAC And Other Targeted Protein Degradation Technologies.pdfSummary of PROTAC And Other Targeted Protein Degradation Technologies.pdf
Summary of PROTAC And Other Targeted Protein Degradation Technologies.pdf
 
BigDataEurope - Big Data & Health
BigDataEurope - Big Data & HealthBigDataEurope - Big Data & Health
BigDataEurope - Big Data & Health
 
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveVarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
 
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveVarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
 
Pistoia Alliance webinar on Antibody structures in the PDB
Pistoia Alliance webinar on Antibody structures in the PDBPistoia Alliance webinar on Antibody structures in the PDB
Pistoia Alliance webinar on Antibody structures in the PDB
 
Webinar: New RMC - Your lead_optimization Solution June082017
Webinar: New RMC - Your lead_optimization Solution June082017Webinar: New RMC - Your lead_optimization Solution June082017
Webinar: New RMC - Your lead_optimization Solution June082017
 
Peptide Tribulations in GtoPdb
Peptide Tribulations in GtoPdbPeptide Tribulations in GtoPdb
Peptide Tribulations in GtoPdb
 
SOT short course on computational toxicology
SOT short course on computational toxicology SOT short course on computational toxicology
SOT short course on computational toxicology
 
Pasteur Institute User Story - Cheminfo Stories 2020 Day 5
Pasteur Institute User Story - Cheminfo Stories 2020 Day 5Pasteur Institute User Story - Cheminfo Stories 2020 Day 5
Pasteur Institute User Story - Cheminfo Stories 2020 Day 5
 
Functional genomics
Functional genomicsFunctional genomics
Functional genomics
 
Expanding Your Research Capabilities Using Targeted NGS
Expanding Your Research Capabilities Using Targeted NGSExpanding Your Research Capabilities Using Targeted NGS
Expanding Your Research Capabilities Using Targeted NGS
 
Aug2014 abrf interlaboratory study plans
Aug2014 abrf interlaboratory study plansAug2014 abrf interlaboratory study plans
Aug2014 abrf interlaboratory study plans
 
LakePharma General Technical Overview
LakePharma General Technical OverviewLakePharma General Technical Overview
LakePharma General Technical Overview
 

Recently uploaded

Traction part 2 - EOS Model JAX Bridges.
Traction part 2 - EOS Model JAX Bridges.Traction part 2 - EOS Model JAX Bridges.
Traction part 2 - EOS Model JAX Bridges.Anamaria Contreras
 
Fordham -How effective decision-making is within the IT department - Analysis...
Fordham -How effective decision-making is within the IT department - Analysis...Fordham -How effective decision-making is within the IT department - Analysis...
Fordham -How effective decision-making is within the IT department - Analysis...Peter Ward
 
20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf
20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf
20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdfChris Skinner
 
WSMM Media and Entertainment Feb_March_Final.pdf
WSMM Media and Entertainment Feb_March_Final.pdfWSMM Media and Entertainment Feb_March_Final.pdf
WSMM Media and Entertainment Feb_March_Final.pdfJamesConcepcion7
 
The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...
The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...
The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...Operational Excellence Consulting
 
Cyber Security Training in Office Environment
Cyber Security Training in Office EnvironmentCyber Security Training in Office Environment
Cyber Security Training in Office Environmentelijahj01012
 
Church Building Grants To Assist With New Construction, Additions, And Restor...
Church Building Grants To Assist With New Construction, Additions, And Restor...Church Building Grants To Assist With New Construction, Additions, And Restor...
Church Building Grants To Assist With New Construction, Additions, And Restor...Americas Got Grants
 
20200128 Ethical by Design - Whitepaper.pdf
20200128 Ethical by Design - Whitepaper.pdf20200128 Ethical by Design - Whitepaper.pdf
20200128 Ethical by Design - Whitepaper.pdfChris Skinner
 
8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR
8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR
8447779800, Low rate Call girls in New Ashok Nagar Delhi NCRashishs7044
 
Entrepreneurship lessons in Philippines
Entrepreneurship lessons in  PhilippinesEntrepreneurship lessons in  Philippines
Entrepreneurship lessons in PhilippinesDavidSamuel525586
 
Guide Complete Set of Residential Architectural Drawings PDF
Guide Complete Set of Residential Architectural Drawings PDFGuide Complete Set of Residential Architectural Drawings PDF
Guide Complete Set of Residential Architectural Drawings PDFChandresh Chudasama
 
Darshan Hiranandani [News About Next CEO].pdf
Darshan Hiranandani [News About Next CEO].pdfDarshan Hiranandani [News About Next CEO].pdf
Darshan Hiranandani [News About Next CEO].pdfShashank Mehta
 
Technical Leaders - Working with the Management Team
Technical Leaders - Working with the Management TeamTechnical Leaders - Working with the Management Team
Technical Leaders - Working with the Management TeamArik Fletcher
 
1911 Gold Corporate Presentation Apr 2024.pdf
1911 Gold Corporate Presentation Apr 2024.pdf1911 Gold Corporate Presentation Apr 2024.pdf
1911 Gold Corporate Presentation Apr 2024.pdfShaun Heinrichs
 
8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR
8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR
8447779800, Low rate Call girls in Shivaji Enclave Delhi NCRashishs7044
 
EUDR Info Meeting Ethiopian coffee exporters
EUDR Info Meeting Ethiopian coffee exportersEUDR Info Meeting Ethiopian coffee exporters
EUDR Info Meeting Ethiopian coffee exportersPeter Horsten
 
Chapter 9 PPT 4th edition.pdf internal audit
Chapter 9 PPT 4th edition.pdf internal auditChapter 9 PPT 4th edition.pdf internal audit
Chapter 9 PPT 4th edition.pdf internal auditNhtLNguyn9
 
Kenya Coconut Production Presentation by Dr. Lalith Perera
Kenya Coconut Production Presentation by Dr. Lalith PereraKenya Coconut Production Presentation by Dr. Lalith Perera
Kenya Coconut Production Presentation by Dr. Lalith Pereraictsugar
 
WSMM Technology February.March Newsletter_vF.pdf
WSMM Technology February.March Newsletter_vF.pdfWSMM Technology February.March Newsletter_vF.pdf
WSMM Technology February.March Newsletter_vF.pdfJamesConcepcion7
 
Healthcare Feb. & Mar. Healthcare Newsletter
Healthcare Feb. & Mar. Healthcare NewsletterHealthcare Feb. & Mar. Healthcare Newsletter
Healthcare Feb. & Mar. Healthcare NewsletterJamesConcepcion7
 

Recently uploaded (20)

Traction part 2 - EOS Model JAX Bridges.
Traction part 2 - EOS Model JAX Bridges.Traction part 2 - EOS Model JAX Bridges.
Traction part 2 - EOS Model JAX Bridges.
 
Fordham -How effective decision-making is within the IT department - Analysis...
Fordham -How effective decision-making is within the IT department - Analysis...Fordham -How effective decision-making is within the IT department - Analysis...
Fordham -How effective decision-making is within the IT department - Analysis...
 
20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf
20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf
20220816-EthicsGrade_Scorecard-JP_Morgan_Chase-Q2-63_57.pdf
 
WSMM Media and Entertainment Feb_March_Final.pdf
WSMM Media and Entertainment Feb_March_Final.pdfWSMM Media and Entertainment Feb_March_Final.pdf
WSMM Media and Entertainment Feb_March_Final.pdf
 
The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...
The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...
The McKinsey 7S Framework: A Holistic Approach to Harmonizing All Parts of th...
 
Cyber Security Training in Office Environment
Cyber Security Training in Office EnvironmentCyber Security Training in Office Environment
Cyber Security Training in Office Environment
 
Church Building Grants To Assist With New Construction, Additions, And Restor...
Church Building Grants To Assist With New Construction, Additions, And Restor...Church Building Grants To Assist With New Construction, Additions, And Restor...
Church Building Grants To Assist With New Construction, Additions, And Restor...
 
20200128 Ethical by Design - Whitepaper.pdf
20200128 Ethical by Design - Whitepaper.pdf20200128 Ethical by Design - Whitepaper.pdf
20200128 Ethical by Design - Whitepaper.pdf
 
8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR
8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR
8447779800, Low rate Call girls in New Ashok Nagar Delhi NCR
 
Entrepreneurship lessons in Philippines
Entrepreneurship lessons in  PhilippinesEntrepreneurship lessons in  Philippines
Entrepreneurship lessons in Philippines
 
Guide Complete Set of Residential Architectural Drawings PDF
Guide Complete Set of Residential Architectural Drawings PDFGuide Complete Set of Residential Architectural Drawings PDF
Guide Complete Set of Residential Architectural Drawings PDF
 
Darshan Hiranandani [News About Next CEO].pdf
Darshan Hiranandani [News About Next CEO].pdfDarshan Hiranandani [News About Next CEO].pdf
Darshan Hiranandani [News About Next CEO].pdf
 
Technical Leaders - Working with the Management Team
Technical Leaders - Working with the Management TeamTechnical Leaders - Working with the Management Team
Technical Leaders - Working with the Management Team
 
1911 Gold Corporate Presentation Apr 2024.pdf
1911 Gold Corporate Presentation Apr 2024.pdf1911 Gold Corporate Presentation Apr 2024.pdf
1911 Gold Corporate Presentation Apr 2024.pdf
 
8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR
8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR
8447779800, Low rate Call girls in Shivaji Enclave Delhi NCR
 
EUDR Info Meeting Ethiopian coffee exporters
EUDR Info Meeting Ethiopian coffee exportersEUDR Info Meeting Ethiopian coffee exporters
EUDR Info Meeting Ethiopian coffee exporters
 
Chapter 9 PPT 4th edition.pdf internal audit
Chapter 9 PPT 4th edition.pdf internal auditChapter 9 PPT 4th edition.pdf internal audit
Chapter 9 PPT 4th edition.pdf internal audit
 
Kenya Coconut Production Presentation by Dr. Lalith Perera
Kenya Coconut Production Presentation by Dr. Lalith PereraKenya Coconut Production Presentation by Dr. Lalith Perera
Kenya Coconut Production Presentation by Dr. Lalith Perera
 
WSMM Technology February.March Newsletter_vF.pdf
WSMM Technology February.March Newsletter_vF.pdfWSMM Technology February.March Newsletter_vF.pdf
WSMM Technology February.March Newsletter_vF.pdf
 
Healthcare Feb. & Mar. Healthcare Newsletter
Healthcare Feb. & Mar. Healthcare NewsletterHealthcare Feb. & Mar. Healthcare Newsletter
Healthcare Feb. & Mar. Healthcare Newsletter
 

SARomics Biostructures 2024 Company Presentation

  • 2. ► Hybrid business model since 2006 — Independent and founder owned — CRO generating revenues — Internal discovery projects (currently 2 oncology projects: NIK & BRD4) ► Proprietary discovery platform — Unique expertise in protein structure determination — Hit identification using proprietary WAC™ fragment screening technology and crystallographic fragment screening (XFS) ► Delivered several hundreds of crystal structures to pharma, biotech and academic clients worldwide — Protein/small-molecule complexes — Antibody/antigen complexes — Industrial enzymes ► Experienced and skilled team of 28 (25 PhDs) ► Sales representatives in Boston & Japan SARomics Biostructures at a glance May 2023 Medicon Village
  • 3. Broad spectrum of protein structure related services Gene-to-structure Platform Fragment-Based Hit Generation Structure-Based Drug Design FastLane™ Standard FastLane™ Premium Antibody-antigen Structures NMR Services Integrated Drug Discovery Protein Shop Industrial Enzymes
  • 4. ► Expression systems — E. coli (in-house) — BEVS (in-house) — HEK293 & CHO (external 3rd–party collaborator) ► Protein purification & analysis — ÄKTA systems — SEC, IMAC, ion exchange etc. — SDS-PAGE, Bradford — Western blot ► Protein characterization — DSF (thermofluor-based method, 96 wells) — DLS (96 well format) — Buffer screen (DLS+DSF) — NMR, CD etc. Protein Production Capabilities
  • 5. State-of-the-art Crystallization Lab SARomics Biostructures performs high-throughput low volume crystallization using liquid handling, crystallization and imaging robotics Crystallization robotics Microlitre robotics Plate hotel/imaging robotics
  • 6. ► Our lab is located 2 km away from the world-leading MAX IV synchrotron ► Currently collecting data twice per month at MAX IV (Lund), Diamond (Oxford), DESY (Hamburg) or Soleil (Paris-Saclay) Synchrotron Access
  • 7. ► The MAX IV Laboratory is the new Swedish national synchrotron facility ► SARomics is in a very advantageous position for access to MAX IV (no need to ship crystals) ► Access to one of the world’s most advanced synchrotron source substantially increases our competitiveness and shortens turnaround times ► We benefit from a smaller, more coherent and more brilliant beam and are thereby able to collect superior data on smaller crystals Our Local Light Source
  • 10. Kinases: BTK, CDK2, CDK5, CDK7, CK2, CLK3, DAPK3, DYRK1A, EphA7, FGFR1, FRK, ITK, KIT, LATS2, MAP2K4, NDR2, PFKFB3, PIM1, PIM3, PIP4K2A, PLK1, PLK4, RET, RIPK3, RSK1, RSK2, SRPK1, STK10, STK17A, STK17B, TYK2, Vps34 Epigenetics targets: ATAD2A, ATAD2B, KDM4C, SMARCA2B FastLane™ Premium Structures FastLane™ Premium Crystallization system up and running and ready to be co-crystallized with customers compounds (complexes delivered within 2 to 6 weeks) Proteases: USP7, USP8, USP21, Caspase-1, Cathepsin C, DPP4, Thrombin Other: Aldose reductase, BCAT2, Bfl-1, BlaC, BSSL, CD11b, cGAS, CYP51A1, DHODH, DNA Gyrase B, eIF4E, Gal-1, Gal-3C, Gal- 8N, Gal-9N, Gal-9C, GART, GMPR2, HSA, Hsp90, IL-17A, K- RasG12D, K-RasG12V, K-Ras3mut, LDHA, LeuT, NRP1, PDE4d, PPARa, PPARg, PSD-95, PTP1B, RORg, S100A4, S100A9, S100A12, SHP2, Tubulin, Ubiquitin mAb targets: CD28, CD47, CD137, GPVI, HER2, IL-4, IL-8, IL-13, IL-23, PD-1, PD-L1, SARS CoV-2 RBD, TIM-3, Tissue factor, TNF⍺ Proteins in bold = not in the PDB
  • 11. FastLane™ Premium Structures Three novel kinase structures not in the PDB LATS2 PIM3 NDR2
  • 12. First crystal structure of CDK7-inhibitor complex Small molecule CDK7 inhibitor LDC4297 Crystal structure of CDK7-LDC4297 complex (PDB code: 8P4Z) determined by SARomics Biostructures (resolution 2.75 Å)
  • 13. Unique IL-17A FastLane Premium crystallization system applied to small molecule inhibitor discovery Proprietary crystallization system for IL-17A First IL-17A small-molecule complex crystal structures published (without chaperone Fab and HAP peptide). Andrews et al., 2022, J Med Chem, 65, 8828. Client project: LP0200 in complex with IL-17A Collaboration with LEO Pharma, Ballerup, Denmark PDB code: 7AMA
  • 14. Proteins* ready to be expressed, purified and crystallized according to existing verified protocols (complexes delivered within 4 to 10 weeks) FastLane™ Standard Structures FastLane™ Standard *Please see www.saromics.com for a complete list ► > 50 kinases ► > 30 phosphatases ► > 20 bromodomains ► > 20 other epigenetic targets ► > 25 other targets
  • 16. Use structural information for: ► Epitope definition to file stronger IP ► Understanding MoA ► Structure-based design ► Structural characterization of protein drugs (HOS) Fab-antigen Structures Don’t work in the dark! Access to structural information increases your understanding and enables you to execute projects faster. ► Antibody engineering: affinity maturation ► Antibody engineering: humanization ► Antibody engineering: ADC
  • 17. MM-131 – Antigen Structures Case Study Client project: Bispecific anti-Met/EpCAM mAb MM-131 in complex with its antigens Collaboration with Merrimack Pharmaceuticals, Cambridge, MA Published in PNAS! scFv-EpCAM Asymmetric Fc Fab-Met Casaletto et al., 2019, PNAS, 116, 7533-7542. Agonistic properties Low potency Antagonistic with high potency PDB codes: 6I07, 6HYG, 6I04
  • 18. Structure-based engineering of a novel CD3ε- targeting antibody for reduced polyreactivity Client project: ADI-26906 Fab in complex with CD3ε N-terminal peptide Collaboration with Adimab, Lebanon, NH X-ray structure of ADI-26906 Fab in complex with N-terminal peptide from CD3ε Liu et al., 2023, MAbs, 15, 2189974-2189974. • CD3 antibodies possessing cross- reactivity with cynomolgus monkey typically recognize a highly electronegative linear epitope at the extreme N- terminus of CD3ε • Using insights from the crystal structure of anti-Hu/Cy CD3 antibody ADI-26906 in complex with CD3ε and engineering, we have derived high-affinity CD3 antibody variants with very low polyreactivity and significantly improved biophysical developability. PDB code: 8F0L
  • 19. SARS-CoV-2 Fab complexes Client project: 1D1 and 3D2 Fab’s in complex with SARS-CoV-2 RBD Collaboration with Chulalongkorn University, Bangkok, Thailand Crystal structures of two Fab fragment complexes. Boonkrai et al., 2023, PLoS ONE, 18(5): e0284173. PDB code: 8BSE, 8BSF
  • 20. Davoceticept (ALPN-202) - An engineered CD80 variant fusion therapeutic Client project: ALPN-202 in complex with PD-L1 Collaboration with Alpine Immune Sciences, Seattle, WA Published in Nature Communications! X-ray structure of ALPN-202 CD80 vIgD in complex with PD-L1 Maurer et al., 2022, Nat Comm, 13:1790. The three mechanisms of action of ALPN-202: • Blockade of PD-1–PD-L1 interaction • PD-L1-dependent CD28 costimulation • Blockade of CTLA-4–CD80/CD86 interactions. PDB code: 7TPS
  • 21. Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27 Client project: SRF388 Fab in complex IL-27 Collaboration with Surface Oncology, Cambridge, MA X-ray structure of SRF388 Fab in complex with IL-27 Skladanowska et al., 2022, Cell Reports, 41, 111490. • IL-27Ra interacts both with the p28 and EBI3 subunits of IL- 27 • SRF388 and IL-27Ra occupy mutually exclusive binding sites on IL-27 • IL-27 mediates receptor assemblies distinct from IL-12 and IL-23 PDB code: 7ZXK
  • 22. Activin ligand trap Client project: ActRIIB-Alk4-Fc in complex with activin A and anti-ActRIIB Fab Collaboration with Acceleron Pharma, Cambridge, MA PDB code: 7OLY Structure of ActA/ActRIIB: Alk4/anti-ActRIIB Fab complex Goebel et al., 2022, iScience, 25, 103590. Increased ligand specificity can be accomplished by using the extracellular domains of both the type I and type II receptor to mimic the naturally occurring signaling complex.
  • 23. ATOR-1017 (evunzekibart), a 4-1BB agonist which activates exhausted T cells in combination with anti-PD-1 Client project: ATOR-1017 in complex with 4-1BB (CD137) Collaboration with Alligator Bioscience, Lund, Sweden X-ray structure of ATOR-1017 in complex with 4-1BB (PDB code: 8OZ3) Enell Smith et al., 2023, Cancer Immunol, Immunother. • ATOR-1017 (evunzekibart), a second- generation Fc-gamma receptor conditional 4-1BB agonist, was designed to overcome the limitations of the first generation of 4- 1BB agonists, providing strong agonistic effect while minimizing systemic immune activation and risk of hepatoxicity. • ATOR-1017 binds to a unique epitope on 4- 1BB enabling ATOR-1017 to activate T cells • This translated into a tumor- directed and potent anti-tumor therapeutic effect in vivo, which was further enhanced with anti-PD-1 treatment
  • 24. The bispecific 4-1BB x 5T4 agonist, ALG.APV-527, mediates strong T cell activation and potent anti-tumor activity Client project: ALG.APV-527 (Fab1618) in complex with 4-1BB (CD137) Collaboration with Alligator Bioscience, Lund, Sweden X-ray structure of Fab1618 in complex with 4-1BB Nelson et al., 2022, Mol. Cancer Ther., 22-0395. • ALG.APV-527 directs the stimulation of T cells and NK cells to 5T4+ tumors and is designed to minimize the toxicity observed with other 4-1BB therapeutics • Binding sites of ALG.APV-527 and the 4-1BBL on 4-1BB are distinct PDB code: 7YXU
  • 25. Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition Client project: Glenzocimab Fab in complex with platelet glycoprotein VI Collaboration with Acticor Biotech, Paris, France X-ray structure of glenzocimab in complex with GPVI Billiald et al., 2022, Blood Adv., 007863R2. • GPVI binding to vascular collagen initiates thrombus formation and GPVI interactions with fibrin promote the growth and stability of the thrombus. • Crystal structure information enables the elucidation of a novel mechanism for the powerful anti thrombotic effect of glenzocimab, in which both ligands are blocked through a combination of steric hindrance and structural change. PDB code: 7R58 Glenzocimab inhibits fibrin- induced platelet aggregation
  • 26. DutaFabs - engineered Fab’s that bind two antigens simultaneously Client project: DutaFab (Roche) in complex with its antigens PDGF and VEGFA Published in Nature Communications! X-ray structure of the DutaFab in complex with PDGF-BB dimer and VEGFA dimer Beckmann et al., 2021, Nat Comm, 12:708. The DutaFab concept of separating paratopes on a single Fab PDB code: 6T9E 6T9D
  • 27. Dusquetide modulates innate immune response through binding to p62 Client project: Dusquetide in complex with p62 (SQSTM1) ZZ domain Collaboration with Soligenix, Princeton, NJ X-ray structure of dusquetide in complex with p62ZZ Zhang et al., 2022, Structure, 30, P1055. • Next-generation IDR dusquetide penetrates the cell membrane • Dusquetide targets the ZZ domain of p62 • Treatment of cells with dusquetide, which mimics arginylated ligands of p62ZZ, leads to stabilization of the p62-RIP1 complex and an increase in p38 phosphorylation and CEBP/B expression PDB code: 7R1O
  • 29. ► Protein structure determination in solution ► Peptide secondary structure assessment ► Protein-ligand and protein-protein complex structure determination ► Fragment screening (19F, ligand or protein detected) ► Epitope mapping and dissociation constant (Kd) determinations for compounds ► Higher Order Structure (HOS) validation of antibodies ► Expression and purification of 2H, 15N, and 13C-labelled proteins in E. coli NMR spectroscopy services Broad range of custom protein NMR spectroscopy services
  • 30. Ultra High Field NMR Instruments 900 MHz Bruker Avance III HD ► 4 RF channels ► Triple-axis pulsed field gradients ► TCI cryoprobe (1H/13C/15N, 3 mm) Danish Center for Ultrahigh Field NMR Spectroscopy (Århus) ► 950 MHz Bruker Avance III HD ► 4 RF channels ► TCI cryoprobe (1H/13C/15N, 5 mm) ► SampleJet 3x600 MHz Varian Inova/Bruker ► 3-4 RF channels ► Triple-axis pulsed field gradients ► Tripple resonance cryo-probe (1H/13C/15N) ► Triple resonance probe (1H/13C/X) ► 4 mm NANO probe ► Diffusion probe (1H/2H/19F) Access to NMR instruments, automatic assignment, NUS sampling, fragment screening etc. 800 MHz Bruker Avance III HD ► 4 RF channels ► Triple-axis pulsed field gradients ► TXO cryoprobe (1H/13C/15N, 5 mm) ► Triple resonance probe, 8 mm 800 MHz Bruker Avance III HD ► 4 RF channels ► Triple-axis pulsed field gradients ► TCI cryoprobe (1H/13C/15N, 3 mm) ► SampleJet 700 MHz Bruker Avance III ► 4 RF channels ► Triple-axis pulsed field gradients ► QCI cryoprobe (1H/19F/13C/15N, 5 mm)) ► SampleJet
  • 31. NMR solution structure of a insulin receptor activating peptide Client project: NMR structure determination of IM459N21 Collaboration with Eli Lilly, Indianapolis, IN NMR solution structure of the IM459N21 peptide Kirk et al., 2022, Nat Commun., 13, 5695. The findings illuminate unexplored pathways for controlling the signaling of the insulin receptor as well as opportunities for development of insulin mimetics. PDB code: 8DI2
  • 32. NMR solution structure of a stapled anti-inflammatory peptide Client project: NMR structure determination of sHVF18 Collaboration with Lund University Petruk et al., 2023, Nat Commun., 14, 6097. Thrombin-derived C-terminal peptides (TCPs) are endogenous anti-infective immunomodulators interfering with CD14-mediated TLR-dependent immune responses. • Stapled version, sHVF18, displays a conformationally stabilized, protease resistant active innate fold • Targets the LPS-binding groove of CD14 • Therapeutic efficacy in experimental models of endotoxin shock in vivo • Increases survival in mouse models of systemic polymicrobial infection. NMR solution structure of the sHVF18 peptide PDB code: 8BWW
  • 33. ► 2D NMR spectroscopy can be used to study and compare HOS of biologics using unlabeled proteins ► Proteins in formulation buffer can be studied with little need for sample preparation ► Effects on HOS of oxidation or surfactant concentration can be studied ► Time resolved processes can be followed using 2D spectra with <1 h / spectra ► Applications: — Batch-to-batch consistency — Biosimilar/originator comparability — Formulation optimization NMR Higher Order Structure (HOS)
  • 35. ► Docking ► Pharmacophore and shape based modelling ► Virtual screening ► Library design ► Structure activity relationships ► Quantum chemical calculations ► State of the art computational software technology Computational Chemistry Molecular modelling and data analysis capabilities
  • 36. Accelerating Discovery Through Structural Insight FRAGMENT—BASED HIT GENERATION
  • 37. WAC™ • Primary screen • Hit follow-up Orthogonal validation • NMR & DSF • Validation of actives Biochemical assay X-ray • Analysis of binding pose Fragment evolution • SBDD support • SAR by Catalog • Synthesis Fragment-Based Hit Generation
  • 38. Joint Fragment-Based Lead Discovery Platform Fragment Screening ► Screening technologies — WAC™ — NMR — Thermal shift assay (DSF) — In silico screening — Biochemical screening (HCS) — X-ray crystallography ► Fragments — SBX/RGD library — Client libraries 56 employees • Medicinal chemistry • Custom synthesis • Peptide chemistry • Analytical chemistry (NMR & MS) • In vitro ADME & phys chem • In vitro biology 28 employees • Structure-based drug design • X-ray crystallography • Computational chemistry • NMR screening • Biophysics • Protein chemistry
  • 39. Fragment Screening & Validation of Hits Suitable combinations of orthogonal techniques designed for each target Protein-observed NMR Ligand-observed NMR Thermal shift assay / DSF Weak Affinity Chromatography ΔTm at 62.5 μM RG200001 7.3 RG200001 6.4 RG200002 10.4 RG200002 10.7 RG200003 -0.48 RG200003 -0.76 Primary screening technique Follow-up techniques X-ray crystallography X-ray – Fragment screening Crystallization robotics MAX IV Follow-up techniques Hit validation techniques Automatic soaking, data collection and analysis Suitable for >50 fragments or more
  • 40. ► Internal library — Collection of ~1100 fragments — General purpose, (not target-directed) covering diverse chemical space — Focus on low-molecular weight fragments (<240) — Experimental solubility (DMSO, water) on >25% of fragments — Analytical data (LCMS, 1H-NMR) on all fragments — MedChem friendly ► Privileged Library — Diverse set of 230 fragments all with experimentally verified solubility (>0.5 mM) ► >90% commercially available -> rapid SAR-by-catalogue follow-up SBX/RGD Fragment Library
  • 41. Weak Affinity Chromatography (WAC™) WAC™
  • 42. ► Immobilized target protein ► High throughput ► mM hits by screening at 1-5 µM ► Made in Sweden Principles of WAC™ Affinity LC/UV/MS Platform
  • 43. Characteristics of WAC™ Affinity • Immediate KD ranking from ~0.5 mM - 0.1 µM with isocratic elution • Fragments are screened at low concentration (1-5 µM) • Excess of protein sites enable detection of multiple binding fragments Quality • High precision and robustness • Automatic quality control (MS or MS/MS detection) • Low sensitivity to impurities Throughput • The use of fragment mixtures (< 100) gives high throughput Consumption of Target • Consumption of target is low (normal column: 5-7 mg; micro column: 2-5 mg) • Protein immobilization using exposed lysines or AVI-tag for NeutrAvidin binding • Long WAC column lifetime Applied Biophysics for Drug Discovery, 2017 Eds. Donald Huddler, Edward R. Zartler Chapter 7 Sten Ohlson and Minh-Dao Duong-Thi Weak Affinity Chromatography (WAC) Chapter 3 Björn Walse, Andrew P. Turnbull and Susan M. Boyd Tailoring Hit Identification and Qualification Methods for Targeting Protein–Protein Interactions
  • 44. Working with WAC™ for 5 years 44 6 5 4 3 3 3 2 2 2 1 1 1 1 1 1 1 1 1 1 k i n a s e G T P a s e c y t o k i n e / P P I b r o m o d o m a i n d e u b i q u i t i n a s e i n t e g r i n h e l i c a s e / A T P a s e s i g n a l l i n g p r o t e i n t r a n s c r i p t i o n f a c t o r a u t o p h a g y f a c t o r d e a m i n a s e e s t e r a s e g a l e c t i n l i g a s e l i p o x y g e n a s e s y n t h a s e t r a n s f e r a s e u b i q u i t i n l i g a s e v i r a l m e t h y l t r a n s f e r a s e Target class occurrence Facts and learnings • >50 FBLD projects over 5 years • 20 distinct target classes • WAC hit rates from 1% to 20% (avg 6%) • Library quality and size matters • Best follow-up: NMR, SPR, X-ray Quirks, drawbacks • Buffer with low ionic strength, less charge shielding • Ranking order can be disrupted by ionic interactions • Non-volatile additives not tolerated by MS
  • 45. WAC™ offers WAC™ Pilot • Technique evaluation • Protein and fragments from client • Screen of up to 50 fragments Ligandability • Evaluation of the target ligandability, incl. amenability for WAC™ • Limited screen of our Privileged set of 230 fragments WAC™ screen • Two-step milestone process • Feasibility & setup • Screen • RGD/SBX collection and/or client fragments Ranking • Rank fragment hits obtained from other fragment techniques Follow-up studies • NMR verification • Co-crystallization • Fragment evolution • And more … All results are owned by the client
  • 46. FragMAX A facility at MAX IV for high throughput fragment screening by X-ray Crystallography In collaboration with LP3
  • 47. Accelerating Discovery Through Structural Insight INTEGRATED DRUG DISCOVERY
  • 49. Björn Walse CEO SARomics Biostructures AB bjorn.walse@saromics.com Tel: +46 46 26 10 470 www.saromics.com Japanese distributor Carna Biosciences. Inc. BMA 3F • 1-5-5 Minatojima-Minamimachi • Chuo-ku Kobe 650-0047 • Japan Tel: +81 78 302 7091 Headquarters Medicon Village • SE-223 81 Lund • Sweden US branch 245 First Street • Cambridge MA 02142 • USA Tel: +1 857 444 4570