mcsaf sas global overview · 2020-04-07 · •antibody-drug conjugates •linker technologies...
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McSAF SASGLOBAL OVERVIEW
Labs: Faculté de pharmacie, Université de Tours31 avenue Monge, 37200 Tours, FR
HeadQuarters: 1 rue Claude Thion, 37000 Tours, FR
Location and partners
PROPRIETARY TECHNOLOGY
• Antibody-Drug Conjugates• Linker technologies• Site-specific technology & DAR control
R&D DIVERSIFICATION
• Bioconjugates
• Next Generation ADCs
• New Applications
R&D societyBio-Organic & Bioconjugate Chemistry
Spin-Off from “Molecular & Therapeutic Innovation” Team in France (University of Tours)
Founded in Dec 2015
ONE EXPERTISE“Chemical Tools for Bioconjugation & Biodrugs”
A DEDICATED TEAMHighly qualified & wide range of expertise (biochemists and chemists with high level background in heterocyclic chemistry, medicinal chemistry and bioconjugate chemistry)
A NETWORKExperts, KOLs & strategic partners aiming to support your development & needs
A SPECIFIC & GLOBAL APPROACHAnswer specific needs by providing customized solutions with high quality standards.
SERVICES
• Custom Synthesis & Process Optimization
• Chemical Modification of Biomolecules
• Tools, Intermediates & Reference Molecules
mAbsBispecific AbsNanobodies
ProteinsPeptides
Etc.BIOCONJUGATES
INDICATIONS ★ Oncology★ Immunology
OthersE.g. Fertility A
PPLICATIONS ★ Therapeutic
★ Diagnostic
OthersE.g. Green Chemistry
Overview
09-12 2015Preliminary study/market
08 2016Exclusive license agreement, WW
07 2013ADC Patent filing
12 2015McSAF SAS
Q1 2016RecruitmentsDir R&D, Dir Op
06-07 2016Nomination iLAB
www.McSAF.fr
10 2016JEI
status
Q2 2017BPI Financial support
Q4 2017Recruitments R&D + BD
Scientific committee06 2015
Winner of BPI Emergence
competition
Q1 2017R&D team
reinforcement
Q3 2017Région Financial support ANR Prog agreement
Q4 2018BPI Financial support
Our proprietary technology
In vitro potency of McSAF ADC-Head 02:
Cell lines: BT-474 (HER2+) / MCF-7 (HER2-)
IC50McSAF-ADC HEAD 02-MMAE MMAE T-DM1
BT-474 0,57 nM 0,29 nM 45,78 nM
Patent WO2015004400A1:New antibody-drug conjugates & uses in therapy.
Joubert N.; Viaud-Massuard MC.; Respaud R.
Filed in 07.2014 WW exclusive license from the University of
Tours (08.2016)
✓ Homogeneity Site-Specific & DAR Control Technologies
leading to more homogeneous ADC species
✓ Stability Great stability of the coupling, minimizing
undesired release of payload in plasma
Technology:• Head 01: Next Generation Maleimide
Technology• Head 02 & 03: New Heterocyclic Technology
Reduction Rebridging
✓ Reproducibility From µg to 10 mg scales with the same
DAR profile
✓ Simplicity No prior re-engineering of the mAb &
retention of native structure & functionalities
Main advantages:
0
20
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120
0,001 0,01 0,1 1 10 100 1000
Via
bili
ty (
%)
Concentration (nM)
BT-474 (HER2+)
0
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60
80
100
120
0,001 0,01 0,1 1 10 100 1000
Via
bili
ty (
%)
Concentration (nM)
MCF-7 (HER2-)
No impact on the binding Similar activity to T-DM1Study carried out by Xentech.
60
29
2
49
0
11
032 0 1
10
66
22
0 0 00
20
40
60
80
100
DAR 0 DAR 1 DAR 2 DAR 3 DAR 4 DAR 5 DAR 6 DAR 7 DAR 8
% D
AR
FGM conjugate (ex:Adcetris®)
BTX - ADC head 02
Our proprietary technology
Highly homogeneous ADCs:
On Trastuzumab (IgG1)
On Nivolumab(IgG4)
First assay on Brentuximab
(IgG1)Work in progress…
TTZ : TrastuzumabBTX : BrentuximabNVM : Nivolumab
4
1116
2217
149
612 0 2 3
88
50 0 0
0
20
40
60
80
100
DAR 0 DAR 1 DAR 2 DAR 3 DAR 4 DAR 5 DAR 6 DAR 7 DAR 8
% D
AR
Lysine conjugate (ex:Mylotarg®)
NVM - ADC head 02
4
1116
2217
149
613
0 1
11
72
13
0 0 00
20
40
60
80
100
DAR 0 DAR 1 DAR 2 DAR 3 DAR 4 DAR 5 DAR 6 DAR 7 DAR 8
% D
AR
Lysine conjugate (ex:T-DM1, Kadcyla®)
TTZ - ADC head 02
FGM = First GenerationMaleimide
0
20
40
60
80
100
0 5 10 15
% o
f m
on
om
er
Time (weeks)
Size Exclusion Chromatography (SEC)
Hydrophobic Interaction Chromatography (HIC)
0,0
1,0
2,0
3,0
4,0
5,0
6,0
7,0
8,0
0 5 10 15
Ave
rage
DA
R
Time (weeks)
Our proprietary technology
Storage stability:
0
20
40
60
80
100
0 5 10 15
% D
AR
4
Time (weeks)
Conditions: 4 °C / PBS buffer / pH 7,4
Conclusion: In storage conditions, McSAF’s technology provides highly stable ADCs:- No diminution of average DAR- No diminution of the DAR 4 species- No aggregation
0
20
40
60
80
DAR 0 DAR 1 DAR 2 DAR 3 DAR 4 DAR 5
% D
AR
200 µL500 µL1 mL
Reproducibility:
Process (n=14, 1 mg scale) Laboratory scale-up
0
20
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60
80
DAR 0 DAR 1 DAR 2 DAR 3 DAR 4 DAR 5
% D
AR
1 mg2,5 mg5 mg
0
2
4
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10
12
0 12 24 36 48 60 72 84 96
Co
nce
ntr
atio
n (
ng/
mL)
Time (h)
Conclusion: In human plasma, ADCs produced with McSAF’s technologyare more stable
0
100
200
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500
600
700
800
0 12 24 36 48 60 72 84 96
Co
nce
ntr
atio
n (
%)
Time (h)
Our proprietary technology
Plasma stability:
TTZ – FGM -ValCit-PAB-MMAE
Human plasma (37 °C)
Masse Spectrometry quantification of free MMAE released by ADCs
Study carried out by Eurofins.
TTZ – FGM -ValCit-PAB-MMAE
TTZ – ADC head 02 -ValCit-PAB-MMAE
TTZ – ADC head 02 -ValCit-PAB-MMAE
ACRONYM MabCHEM
TITLEImpact of BioDrug modifications on their effects in vitro & invivo
FUNDINGCentre - Loire Valley Region (ARD2020 Fund onBioTherapies)
PROGRAM
DURATION3 years, 2017 - 2020
SCIENTIFIC
PROJECT
Taking a global overview exploring new concepts for bothmAb and ADC optimization, this program aims to:- develop specific knowledge and technologies for mAb
stability enhancement toward enzymatic cleavage- develop new generations of ADCs with an original
controlled release of the drug.
ACRONYM ADC-AgroMed
TITLEConjugation between an allosteric modulator and an anti-
RFSH nanobody for medical and veterinary applications
FUNDING Centre - Loire Valley Region
PROGRAM
DURATION2 years, 2016 - 2019
SCIENTIFIC
PROJECT
Today, in order to stimulate follicular growth, recombinant
or extractive hormone agonists of the FSH receptor are
intensively used. The side effects and unsatisfactory
outcomes resulting from these treatments give us the
opportunity to find an alternative. This project aims to
build a nanobody, a small antibody fragment against the
FSH receptor, which will be covalently linked to a drug able
to stimulate the reproduction mechanism for veterinary
and medical use.
Fertility
Impact of biodrug
modifications
GLOBAL COLLABORATIVE R&D PIPELINE
ACRONYM ADC NEW PAYLOADS
TITLE New Immunoconjugates for HER2+ breast cancers
FUNDING Centre - Loire Valley Region (APR IR 2017)
PROGRAM
DURATION3 years, 2018 - 2021
SCIENTIFIC
PROJECT
The project aims to design and evaluate new ADCs made by
the combination of an anti-HER2 antibody (specifically
targeting the tumour), and a new generation of payloads,
distinct from the usual cytotoxic drugs commonly developed
in the field of ADCs.
GLOBAL COLLABORATIVE R&D PIPELINE
ACRONYM DBAb-Tol
TITLE
Design and development of new bispecific antibodyconjugates with immunosuppressive drugs for inducing ®ulating the immune tolerance
FUNDING ANR (French National Research Agency)
PROGRAM
DURATION3 years, 2017 - 2020
SCIENTIFIC
PROJECT
The limitations of the cell therapy using dendritic cells, keycells in the immune response, have been clearlydemonstrated by the number of clinical trails showing nopatient benefit.Our ambition is to develop in-situ DC subset targetingentities, using a bispecific antibody linked toimmunosuppressive drugs to induce a tolerant status inhumans.
IS drugbsAb
Immune tolerance
Breastcancer
… to be continued…
Cardiovascular diseaseOther Cancers
ImageryDiagnostic
ACRONYM CITMER
TITLETherapeutic targeting of Merkel Cell carcinoma
(CIblage Thérapeutique du carcinome de MERkel)
FUNDINGFrench Society of Dermatology (Société Française de
Dermatologie SFD)PROGRAM
DURATION2 years, 2018 - 2020
SCIENTIFIC
PROJECT
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a
5-year survival estimated at 40%. Until recently, treatment of
inoperable metastatic patients was based on platinum-based
poly-chemotherapy, with no benefit to survival. The use of
immunotherapy targeting PD-L1 (Avelumab) provided an
objective response in 30% of inoperable patients who failed
conventional chemotherapy. However, the high proportion of
non-responders to Avelumab encourages the development of
new treatments. The project aims to compare, in vitro and in
vivo, a novel therapeutic antibody and its ADC form targeting
MCC cells and to propose this new therapeutic solution in
clinical trials.
Dermato -oncology
GLOBAL COLLABORATIVE R&D PIPELINE
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- Notes
Spin-off from the “Molecular & Therapeutic Innovation” Team in France (GICC,University of Tours), McSAF is a young innovative company, founded inDecember 2015. McSAF is specialised in bio-organic and bioconjugatechemistry, with a specific focus on developing and providing Best-In-ClassTechnologies and R&D services to BIO Industries, with the aim of supportingtheir current developments in biomolecules of interest.
Our core expertise covers therapeutic peptides, proteins and antibodies, butalso drug conjugates, especially antibody-drug conjugates (ADCs), for which wehave acquired a worldwide exclusive licence from the University of Tours, anddeveloped a specific know-how regarding new linker technologies.Our team, led by our two co-founders, the CEO and the scientific director, iscomposed of a scientific department with 4 researchers and a Ph.D. student,and is completed by one person in charge of the business development.
We are engaged in 3 main activities:
• Technology Provider: new linker technologies specific to ADC development,which aim to answer actual needs in terms of site-specific and DAR controltechnologies
• Innovation: we are engaged in several internal and external R&D programsrelating to both bioconjugates in general, and next generation ADCs fornovel applications.
• Service Provider: from custom synthesis of small molecule to biomoleculemodification and optimization especially to allow them to be bioconjugated.
www.mcsaf.frContact:AUDREY DESGRANGES, Business Developer,
[email protected]+33 (0)2 47 24 12 54