Professor Marilyn Anderson Chief Science Officer · Multi-Gene Expression Vehicles (MGEVs) C1 X C2...

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Annual General Meeting

23 November 2010

Professor Marilyn Anderson Chief Science Officer

Hexima Limited ©

Growth in world population

0�

2�

4�

6�

8�

10�

Year�

World Population�(billions)�

2000 BC� 2050 AD�0�

0.15 billion� 1.3 billion�

7.0 million�

9.0 billion�

2.5 billion�

2050 AD�

2010 AD�

1950 AD�

1860 AD�2000 BC�

World population has increased more than 5 times in 150 years

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Can we feed this growing population?

“Lifting a billion people out of poverty and feeding an extra 2.3 billion by 2050 will require an increase in cereal production by 70%.”

Lele, Science (2010),326, 1554,

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How do we feed everyone?

“We have about 40 years to radically transform agriculture, to work out how to grow more food without exacerbating environmental problems and to simultaneously cope with climate change”

-Godfray, Science 327, 812 (2010)

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Major projects

� Disease resistance - corn and soybean (Pioneer) - cotton - canola

� Insect resistance - Climate Ready grant

� MGEV-multigene expression vehicle - Research licences with Pioneer and Monsanto

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Hexima research

�  Hexima research is contracted to three groups based at The University of Melbourne and La Trobe University

�  Gene discovery – Professor Marilyn Anderson

�  Product development – Dr Robyn Heath

�  Pharmaceutical – Dr Mark Hulett

Mark, Robyn & Marilyn

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Disease resistance - corn

•  DuPont/Pioneer collaboration

•  Produce transgenic corn with sustainable resistance/tolerance to fungal diseases using genes encoding antifungal proteins (AFPs)

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Corn diseases

Yield losses from fungal diseases are in the range of 10-12% annually and cost about US $8 billion in North America. High disease regions can lose 25% of yield.

Gibberella stalk rot Diplodia ear rot

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Corn diseases

Some ear rot fungi produce mycotoxins that contaminate the grain and are hazardous to human and animal health.

Gibberella stalk rot

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Current management practices for fungal diseases

�   Fungicides - harsh chemical sprays

�   Breeding for resistance - only possible if resistance genes present in some cultivars

�   Management practices - crop rotation can be costly to farmers

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New approaches

How do plants normally protect themselves against disease?

� Plants are very efficient chemical factories. They produce natural defence molecules.

� Plant reproductive structures are an excellent source of natural defence molecules.

� We have isolated potent fungicides and insecticides from plants.

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Pipeline for new gene traits in crops plants

12 General industry timelines. Timelines will vary with crops and traits.

Discovery Phase 1 Phase 2 Phase 3 Phase 4

Identify genes for improved plant traits. Broad screens to identify multiple leads.

Proof of concept. Test genes in plants. Choose leads with best per-formance in glasshouse and limited field trials

Large scale transformation.Glasshouse & field testing. Choose commercial product candidates. Start regulatory process.

Trials of traits in elite germplasm. Regulatory process.

Commercial-isation, launch.

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Field trials etc

PHASE 1

TRAIT VALIDATION GENE DISCOVERY & OPTIMISATION

Gene discovery (AFP selection)

Gene optimisation

for corn

Corn transformation & proof of concept

in glasshouse

Milestones - DuPont/Pioneer collaboration

Transfer seed to Pioneer Applications

to other crops

Resistance to fungal disease in corn

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DISCOVERY PHASES 2-4

Phases may overlap

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Hexima corn disease program

�   Gene discovery – Dr. Nicole van der Weerden

Five teams located at La Trobe University and The University of Melbourne.

�   Gene constructs and plant analysis– Dr.Simon Poon

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Hexima corn disease program

�   Glasshouse -Mr.Bruce McGinness -Dr.Gianna Kalc

�   Corn transformation -Dr.Vijay Kaul

�   Disease bioassays -Mr.James McKenna

Five teams located at La Trobe University and The University of Melbourne.

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Disease project- achievements to date

� Disease resistance – corn �  Established skilled, specialist teams. �  Discovered several new AFPs with activity against corn

diseases (new patent application). �  Discovered new molecules that enhance the activity of the

AFPs (2 patent applications). �  New corn tissue culture facility and glasshouse

commissioned in Q1 2010 and fully operational. �  Established corn transformation. Produced transgenic

plants using several different genes. �  Started disease testing of transgenic plants (bioassays). �  Met all the milestones in the DuPont/Pioneer program �  Corn and soybean (Pioneer)

- looking for partners in other crops- wheat, canola, rice, cotton.

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Insect resistance

� Proteinase inhibitor technology to target caterpillar pests (major pests globally)

� Resistance to the Bt-toxins is beginning to emerge

� More urgent need for new insect control strategies

� Discovering genes that enhance the insecticidal properties of proteinase inhibitors

� Supported by Climate Ready Grant ($1.38 million from mid 2009-mid 2012)

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Multi-Gene Expression Vehicles (MGEVs)

C1

X

C2 T1

T1 C1 X

X Y

MGEV (circular) MGEV (linear)

� A tool for expressing and stacking small proteins

� Platform technology for the corn disease program. Allows production of multiple antifungal proteins from one gene

� Non-exclusive licence with Pioneer and Monsanto

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Number of Applications Lodged & Granted Patents (Cumulative)

19

0

20

40

60

80

100

120

2005/06 2006/07 2007/08 2008/09 2009/10

Applications Granted Patents

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Thank you to our scientific teams

�  Gene discovery – Prof.Marilyn Anderson

�  Product development – Dr.Robyn Heath

�  Pharmaceutical – Dr.Mark Hulett

�  Intellectual property – Dr.Susanna Herd

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Annual General Meeting

23 November 2010

Dr Robyn Heath Senior Vice President, Product Development

Hexima glasshouse facility at La Trobe University

Harvesting cobs & isolation of immature corn embryos

Transferring the antifungal gene & regenerating plants

New gene Plant cell

Infection & DNA insertion

Cell division

Plant regeneration in tissue culture

Transgenic corn plant

DNA construct in Agrobacterium tumefaciens

Transferring the antifungal gene & regenerating plants

GM corn plants