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Une nouvelle technologie peptidique
pour la thérapie géniqueFrancois-Thomas Michaud / CEO 1
• Baccalauréat en Génie chimique - 2004
• Maîtrise en Sciences (M.Sc.) - 2006
• Doctorat (Ph.D.) en Génie chimique - 2009
• Fondation de l’entreprise Axonème - 2005
• Fondation de Feldan - 2007
• Co-Fondateur et CEO Feldan 2007 à aujourd’hui
Mon Parcours
3
EN BREF…
Use of Proteins as Biological Drugs
Biology 101: DNA → RNA → Protein
4
Use of Proteins as Biological Drugs
Druggable target space for biologics is restricted to
extracellular targets
Nb of human genes : 25 000
Nb of human proteins : 19 000 – 20 000
Nb of secreted/extracellular proteins : 8 000 – 9 000
10 000 – 12 000
intracellular targets
(~60% of proteome)
Intracellular delivery is still a challenge and slows therapy development
Miersch et al., 20165
WHAT IF YOU
COULD
EASILY DELIVER
PROTEINS
INSIDE CELLS ?
6
Solution : The Feldan Shuttle
→ A peptide that delivers protein & protein complexes into cells
nucleusendosome
NLS
Gene modulation/editing
CargoProtein
orprotein complexes
Peptide
+
7
Business Model and Corporate Strategy
Comment a-t-on fait ?
• Laissez-moi vous raconter une petite histoire…
9
2004 - Équipe laboratoire optimisation des bioprocédés
Alain Garnier, Université Laval
2005
Start-up Université Laval : Axoneme
Insert your company here !
2005 – 2006 Fondation Axoneme
Concours « On n’aura plus jamais besoin d’argent »
2007 – Fusion d’Axoneme et de Feldan
Spin out de l’Université Laval : Nos 1er « vrais bureaux »
2007
Les premiers labos de Feldan
Le deuxième « shipping center »
La vie de labo en 2009…
N. Messier2009 à aujourd’hui Développement
D. Guay2009 à aujourd’hui
Recherche
2010
Relocalisation : les seconds locaux de Feldan
2010
Les seconds locaux de Feldan
2010
Aménagement des labos
2011
Race against time - Too much noise
Research Proteins
Molecular Biology Products
Therapeutic Proteins
Life Science Services
3 internals R&D projects
4 products lines
3 offices and 4 sales agents
2 US distributors
Therapeutics: 5 projects in Middle East and South Asia
11 point of Sales Strategies
2013-Restructuration
F. Drouin2007-2015 : Co-fondateur
Recombinant Proteins
Life science industry
Ancillary proteins
Cell therapy industry
R&D : Shuttle Technology
2007 2013 2015
Shuttle - Therapies
2020
- Founded in 2007- Manufactures recombinant proteins- Expertise in hard-to-produce proteins- Developing of OEM relationships
- Innovative Shuttle technology- Entering genome editing space- Combining expertise and innovation- Producing proteins for medical appl.
- Entering the cell therapy space- Developing quality controls for cell therapy- Focusing on quality management- Producing growth factors and cytokines
Past & Looking Forward
Inception and expertise Focus on Cell therapy Development of Feldan Shuttle
Feldan Shuttle : Evolution of the Technology
Genome Editing (%)
Feldan
design
Genomic cleavage
products
Gene target
1st FS
generation
FS Predicted
(Algorithm)
Feldan shuttles : evolution & efficiency
16 13 43 21 68 71
Feldan Shuttle delivers CRISPR systems
Deal with Amgen
25
Feldan’s First Patent – August 22nd 2017
Deal with Green Cross
OBJECTIVES
1. Characterization of the Feldan Shuttle : delivery of therapeutic peptides
and intrabodies in cells
2. Determination of the In vivo applicability of the Feldan Shuttle :
CQDM will support Feldan in a 1.2M project
Alongside Dr. Frédéric Calon from Laval University, Feldan will test and enhance
the capacity of the Feldan Shuttle to deliver therapeutic proteins in cells.
CQDM’s support was made possible by the contribution of the Ministry of Economy Science and
Innovation, together with three CQDM industrial members: Sanofi, GlaxoSmithKline, and Janssen.
• Biodistribution (in different organs)
• Immunogenecity
• Toxicity
• Efficiency
Shuttle - Therapies
Looking Forward
29
Aujoud’hui…
What if Delivery Was Not An Issue?
SAFETY
EFFICIENCY
- Minimum alteration of host cells
- No insertion risk
- Efficient Ex vivo & In vivo
- Easy scale-up
- Broad applicability
Ideal
Delivery
Method :
nucleusendosome
NLS
Gene modulation/editing
CargoProtein
orprotein complexes
Peptide
+
The Feldan Shuttle
CRISPR nucleases
Antibodies
Transcription factors
Peptides
Cell penetration Availability in cytoplasm
Mécanisme d’action du Shuttle…
FeldanShuttle
C’est quoi dans la boîte ?
Shuttle Intracellular Delivery Mechanism
gather
Extraction
NK cells
+/ CRISPR
nuclease
Gene knock-out Transplantation
Cancer patient
Hyperactive
NK cells
Tumor
cells
NK cell-based immunotherapy
Cytotoxicity
Killing of
tumor cells
Influence of tumor
microenvironment
Optimization of
genome editing in
NK cell model
Validating KO
impact in primary
NK cells
In vivo
cytotoxicity
testing
Preclinical
Studies
Timeline
Partners / Collaborators
Q12018
Q32018
Cancer Immunotherapy: Adoptive NK Cell Therapy
IND
Filing
Phase I/II
Clinical Trial
Q42019
Q12020
NK amplification strategy
NK clinical trial experience
NK amplification strategy
Access to primary NKs Canada immunotherapy leader
Funding
Canada – Korea Collaborative Industrial Research
& Development Program
TOTAL FUNDING : CAD $1.4M TOTAL PROJECT VALUE : CAD $2.8M
In vivo Therapeutic Pipeline Modalities
Intravitreal injection
Other types of
direct injections
InstillationLUNGS
EYES
Intracellular
protein
replacement
REPEAT
INJECTIONS
PERMANENT
In vivo gene
editing-CRISPR nuclease-
THERAPEUTIC STRATEGY IN VIVO ADMINISTRATION ROUTE
Marker
alone
Marker
+
Deliver of protein markers (GFP or luciferase) to mouse lungs using the Feldan Shuttle
Delivery POC : Lungs
The Shuttle can deliver proteins to the lungs via intranasal instillation
10x
10x 20x
20x
20x
Intranasal
instillation
InstillationLUNGSIntracellular
protein
replacement
REPEAT
INJECTIONS
THERAPEUTIC STRATEGY IN VIVO ADMINISTRATION ROUTE
Rhizomelic Chondrodysplasia Punctata (RCDP)
- Ultra rare genetic disease (1:500 000 birth)
- RCDP patients have several physical afflictions (bones, neurons, eyes, lungs)
- Most patients die from respiratory failure
GOAL : Deliver recombinant protein in lungs
to reverse pulmonary symptoms
Rhizomelic Chondrodysplasia Punctata (RCDP)
Discovery phase package
10x
Delivery in lungs (in vivo)
GFP +
Peroxisome targeting Overexpression of Pex7 in RCDP cells (ex vivo)
RCDP cells Pex7 in RCDP cells
Deliver
recombinant
protein
ex vivo
On-going work
Pre-clinical phase
Instillation of Shuttle/Therapeutic protein in RCDP mice
Motley et al., 2002 (Am J Hum Genet)
InstillationLUNGS
PERMANENT
In vivo gene
editing-CRISPR nuclease-
THERAPEUTIC STRATEGY IN VIVO ADMINISTRATION ROUTE
- Rare genetic disease : 30 000 patients in the US, 4 000 in Canada
- CF patients mainly suffer from mucus accumulation and sever lung infections that can cause death
- Some patients do not respond to drugs
GOAL : Deliver CRISPR nuclease to correct
the mutated gene
Cystic Fibrosis (CF)
Cystic Fibrosis (CF)
Discovery phase package
10x
Delivery in mouse lungs
GFP +
On-going work : Instillation of Shuttle/CRISPR nucleases in CF animal models
Delivery in primary human cells
10x 100x
Delivery in humantracheal explants
Gene editingof human cells
(ex vivo)
GFP + GFP +
Gene editingof mouse lungs (in vivo)
Neg.CTL
+CRISPR
Pre-clinical phase
Red signal : in vivo gene editing
Bronchus
Delivery POC : Eyes
6 weeks post-deliveryIntrastromal injection of
Shuttle + Cas9
Opacity of the cornea of Gusb mice- After intrastromal injection of CRISPR -
Lig
ht
sca
tte
rin
g
FS+Cas9 +gRNA
Negative CTL
Normal level of corneal opacity
The Shuttle can deliver active cargos to the eyes
Intra-stromal injectionSubretinal injection
RPE
RETINA
GFP injection under the retina(24h)
Intra-vitreal injection
Direct injection of GFP in the eye(24h)
Lung (intranasal instillation)
Intramuscular injection
Brain(Intracranial injection)
Subcutaneous injection
Heart(Langendorff perfusion)
Eye(Subretinal injection)
Liver(Portal vein injection)
Eye(Intravitreal injection)
Delivery POC : In vivo results
Partnered : Intracellular Antibodies
Target engagement of
antibodies delivered(ex : α-NUP98 antibody)
Delivering antibodies in the cytoplasm
influences targeted cellular pathway(ex : α-Cas3 antibody)
NEXT STEPS : - Work on Amgen intracellular targets- Develop the I.V. potential of the Shuttle:
encapsulation, PEGylation or complexation
Antibodies against perinuclear protein
Cell Nucleus
Apoptosis
activation
+ unspecific IgG
+ α-Caspase 3 IgG
10 20 30 40 50 60 70 80
Increase of apoptosis (% vs resting cells)
Resting
Cells
(-CTL)
nucleus
Binding of
intracellular or
transmembrane
targets
Feldan Shuttle
antibody
Release in cytoplasm
Modulation of intracellular using
antibodies delivered by the Shuttle
Leadership
Advisors
Elie Haddad, MD, PhDHead of the Immuno-Allergy, Sainte-Justine Hospital
Paul McCray, MD
Roy J. Carver Chair University of Iowa
Denis-Claude Roy, MD, FRCPC
Director CRHMR, Dana Farber (Harvard)
Hooshmand Sheshbaradaran, PhD
Roche, Pharmacia (Pfizer), Zeneus (Cephalon)
Nicolas Noiseux, MD, MSc, FRCSC
Heart surgeon, CHUM, Full professor, UdM
Board of DirectorsBenoit Cyr, MSc, EngExecutive Chairman Feldan, Ex-CEO Biogénie
Francois-Thomas Michaud, PhD, EngCo-founder & CEO Feldan
Jean De Serres, MD, MSc, MBAEx-CEO Hema-Quebec, CMO Palladin
Xavier Harland, CFAEx-CFO Acasti Pharma
Peter Morand, PhDEx-CEO NSERC
Jean-Luc Sansregret, MScEx-VP Biogénie
Andy SheldonCEO of Medicago
Leadership
Francois-Thomas Michaud, PhD, Eng.CEO and Co-founder
Meriem Benchabane, PhDMarket Intelligence and B.D. Director
Vincent Menard, PhD, MBAStrategic development Director
David Guay, PhDResearch Director
Pierre-Alain Moisset, PhD, MBAOperations Director
Nancy Messier, PhDDevelopment Director
45The best people like to work on multidisciplinary teams where they can bring their
expertise to problems and projects much bigger than themselves.
OWNERSHIP
TEAMWORK
FUN
We are owners of Feldan’s future. We stake our reputation
on the excellence of our work and accept accountability to
meet our business needs, improve our systems and help
others improve their effectiveness. We are Feldan.
We mobilize our resources in order to promote optimal
efficiency and performance in all our business activities.
We take pride in having a highly diverse team withcomplementary backgrounds, the union of which
makes us a unique, disruptive and innovative
company.
We believe having fun and enjoying our work is
essential to achieve our mission, we celebrate
successes and we have fun working together.
Our Values
Francois-Thomas Michaud:
Cell: +1.418.953.3048
For Further Information
Contact us:
48
