transforming the approach to vaccines and protein- based ... · transforming the approach to...

Transforming The Approach to Vaccines and Protein-

Based Therapeutics

Alain Doucet, Ph.D.

Manager, Process Development, Medicago2018-08-15

© Medicago Inc.

All rights reserved.

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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

© Medicago Inc.


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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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© Medicago Inc.


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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

© Medicago Inc.


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Medicago Overview1

Novel Technologies2

Robust Pipeline3

© Medicago Inc.


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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

© Medicago Inc.


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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

© Medicago Inc.


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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)

© Medicago Inc.


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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

© Medicago Inc.


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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

© Medicago Inc.


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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)

© Medicago Inc.


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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

© Medicago Inc.


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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

© Medicago Inc.


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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

© Medicago Inc.


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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

transforming the approach to vaccines and protein- based ... · transforming the approach to...

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