transforming the approach to vaccines and protein- based ... · transforming the approach to...
TRANSCRIPT
Transforming The Approach to Vaccines and Protein-
Based Therapeutics
Alain Doucet, Ph.D.
Manager, Process Development, Medicago2018-08-15
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Medicago Overview1
Novel Technologies2
Robust Pipeline3
© Medicago Inc.
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Success story
Canadian biopharmaceutical company with game-changing
technologies that offer potential advantages over current flu vaccines
(efficacy, cross-protection) and pandemic response capabilities
Focus Vaccines & therapeutic proteins
Manufacturing technology Transient expression in plants
Development technology Virus-like particles (VLPs)
Employees 300+ (expected to grow to 500+ by 2019)
OperationsQuebec City, Canada (HQ)
Research Triangle Park, Durham, North Carolina
Medicago Overview
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Research Lab
France
Research Lab
South Africa
• Head office in Quebec City
• 275+ employees
• R&D laboratory
• Pilot facility
• Research Triangle Park, Durham, NC
• 110+ employees
• Commercial cGMP facility
Canada
USA
Global Activities
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• Commercial
production of
Influenza
vaccines
• 44,000 m2 facility
on 90,000 m2 site
• Projected
capacity of 40-50
million doses
• Will consolidate
corporate
management,
R&D, testing labs,
pilot facility
New Proposed Facility in Quebec City
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Medicago Overview1
Novel Technologies2
Robust Pipeline3
© Medicago Inc.
All rights reserved.
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Starting material
• Gene(s) of interest
• Plants
Incubation (6-8 days)
• Infiltrated plant cells
producing & accumulating
recombinant products
Infiltration
• Getting the vector into
the leaf tissue
Purification
• Getting highly pure
product
Extraction
• Releasing the
recombinant products
into solution
VersatilityPlants are highly efficient at
expressing proteins of
varying complexity at high
yields.
1 2 3
54 6
VLP-based
vaccines
Transient Plant-Based Expression System
Monoclonal
antibodies
Vaccines in 5-6 weeks
Clinical-grade influenza
vaccines ready in 5-6
weeks after strain
identification
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Versatile Plant-Based Production Platform
Vaccines
Potential anti-viral vaccines for 20+ targets
Virus-like particles (VLP)
– Non-infectious
– Antigen presentation similar to natural virus
Enveloped viruses
o Influenza
Therapeutic proteins
Monoclonal antibodies against
– Ebola virus, collaboration with USA Biomedical Advanced Research and Development Agency
– Ebola virus, collaboration with the Public Health Agency of Canada
– Other targets
Influenza Norovirus
Non-enveloped viruses
oRotavirus (3 concentric layers + spike)
oNorovirus (1 layer)
Rotavirus
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*Egg-based vaccines *Cell-based vaccines *Plant- based vaccines
Recombinant
Vaccine
Flublok® (Protein
Sciences, acquired by
Sanofi Pasteur)
Virus-Like
Particules (VLPs)
Medicago’s
vaccine candidate
• Similar to a wild-type
virus; match sequence
• Lacking core genetic
material (non-
infectious)
• Highly efficient way to
present antigens to
immune system
• Good antibody and cell-
mediated immune
responses
• Safe: lacking core
genetic material
• Good antibody
response
• No cell-mediated
immune response
documented
VLPs: A Novel Approach to Influenza Virus Vaccines
Live
Attenuated
Flumist® (AZ)
• Mimics natural
infection
• Shown to be effective
in children only
• Risk: can revert
towards virulent form
• Difficult to produce in
scalable setting
1990s
Split
(Inactivated)
• Less reactogenic than
whole virus vaccines
• Good antibody
response
• No cell-mediated
immune response
• Long production
process
1960s
Subunit
Vaccine
Fluad™, Fluvirin®,
Flucelvax®
(Seqirus)
• Safe: lacking core
genetic material
• Long production
process
1980s 2013 2017 (Ph3)
Fluzone® (Sanofi
Pasteur), Fluarix®,
Flulaval® (GSK),
Afluria® (Seqirus)
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Influenza hemagglutinin proteins accumulate at the plasma membrane, forcing curvature of
the membrane and budding of virus-like particles containing host cell lipids and Influenza HA
proteins
Intact VLPs are extracted and purified to produce Influenza VLP candidate vaccines
Influenza VLP Production in Plants
From D’Aoust et al., Plant Biotechnology Journal, Volume 8: 607-619 (2010)
No need for NA:
No sialic acid in plants
In-planta
expression and
VLP assembly
Bioprocessing
Drug product
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• Clinical grade material in 5-6 weeks
• Rapid monovalent manufacturing
• 10 million doses in one month (with DARPA in 2012)
RAPID
• Ability to accurately match circulating strain
• No risk of mutation in plantsACCURATE
• No risk at scale-up vs. fermenters: one plant or 10,000 plants require the same growth conditions
• Capacity adjustable to market needs
• High yields
SCALABLE
• Co-expression of different proteins or subunits, from vaccines to antibodies
• Transient expression, no use of stable transgenic plant lines
VERSATILE
Competitive Advantages of the Plant-Based Platform
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0
20000
40000
60000
80000
100000
120000
140000
160000
180000
200000
Avril Mai Juin Juillet Août Septembre Octobre Novembre Décembre
Nu
mb
er
of
flu
ca
se
s w
orl
dw
ide
Identification of
strain A/H1N1
First wave
beginsSecond wave
begins
Vaccine supply gap
April May June July August September October November December
First Responder Capability During a Pandemic (H1N1)
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Medicago Overview1
Novel Technologies2
Robust Pipeline3
© Medicago Inc.
All rights reserved.
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Phase II Results
– 5 trials safely completed in 2,820 subjects (ages 18-64 & 65 and above)
– 30 µg per strain is the optimal dose that:
» Meets licensure criteria in healthy adults
» Offer the optimal antibody and cell-mediated responses
– The antibody response compares to that of licensed vaccines
– Cell-mediated responses are higher than a standard dose comparator vaccine
– VLP vaccine induces broader immune responses than licensed vaccines that can offer cross-protection in case of vaccine mismatch
– End of Phase II meeting with FDA: support Phase III trials in both adults and elderly (ages 65+)
Our Quadrivalent VLP Flu Vaccine Candidate
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Pivotal Phase III in 10,000 healthy adults in seven countries (18-64 years old) was recently
completed, data analysis is on-going
Phase 3 study in elderly (65+ years old, dose of 30 µg per strain) and in pediatric population
(7+ years old) planned
Phase 3 Efficacy Study in Healthy Adults
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Research Preclinical Phase I Phase II Phase IIIV
accin
es
Seasonal Flu
Pandemic
Rotavirus
Norovirus
An
tib
od
ies
Antibody 1
Antibody 2
Emergency
use
Current Pipeline
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Medicago plant-based system
– Production of virus-like particles for new vaccine development
• Non-infectious product
• Antigen presentation similar to natural viruses to maximize antibody and cell-based immune response
• Match sequence of natural viruses with potentially better efficacy
• Fast response by using transient expression system
– Expression and purification of high quality therapeutic proteins such as monoclonal antibodies
– High versatility for protein expression
Conclusions
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Thank you to all Medicago’s employees and collaborators over the years!