Advanced Biologics and Biomanufacturing Program

Lynne LeSauteur (Interim Program Director)

Health-Canadian Ecosystem Total health expenditures in Canada was $242B in 2017: 11.5% of GDP.

The health care system faces important challenges: •  Demographics – the rise of chronic disease burden •  The cost of medicines which limits accessibility

Canada (and NRC) needs to: •  Invest in developing a pipeline of innovative medicines, •  Support acceleration of commercialization of new medicines and vaccines •  Establish effective public health ways to deliver new treatments to all Canadians.

SMEs do not have the wide-ranging expertise and expensive infrastructure needed for drug development. Instead, they rely on partnerships with translational organizations like NRC.

Biologics – The new generation of therapeutics Due to their high specificity, biologics offer effective treatments for diseases; adding to the arsenal of sophisticated targeted therapies. The biologics market share grew from 11% in 2008 to 24% in 2015. v  However, the design, manufacturing, and characterization of biologics is far more complex than for synthetic drugs and the production of

biologics remains a critical and expensive step in the development process.

Cell and gene therapies – The next generation of therapeutics Cell and gene therapies are emerging as the next generation of very promising therapies to address many unmet medical needs, with disease modifying outcomes such as tissue regeneration, immune cell reprograming, and gene replacements. v  However, technology advancements and innovative partnership models are needed to increase accessibility;

NRC can catalyze a national public health delivery model for new bed-side therapies.

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Some of the public health priorities •  Cancer will affect 1 in 2 Canadians and results in

an economic burden of $4B; •  Emerging and re-emerging infectious diseases

are a grave concern for vulnerable populations such as Indigenous peoples and have an estimated economic burden of $4.7B.

•  Neuropsychiatric conditions affects 3.6M Canadians; it has some of the highest direct costs to the healthcare system and an economic burden of $11,4B;

*Economic burden data are from PHAC’s Economic Burden of Illness in Canada custom report (2008)

Agenda

1.  NRC-Human Health Therapeutics

2.  Success of collaborations

3.  Advanced Biologics and

Biomanufacturing Program

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NRC organizational structure

Information and Communications

Technologies

Emerging Technologies

Aerospace

Automotive and Surface Transportation

Aquatic and Crop Resource Development

Human Health Therapeutics

Pacific Region

West Region

Engineering Life Sciences Industrial Research Assistance Program

NRC Herzberg Astronomy and Astrophysics

Security and Disruptive Technologies

Construction

Energy, Mining and Environment

Ocean, Coastal and River Engineering

Medical Devices Ontario Region

Quebec Region

Atlantic and Nunavut Region

National Office

Research Centers

DIVISIONS

Measurement Science and Standards

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NRC 2018-19 planned budget: $1B Total revenues 2017-18 $221M ∼3, 444 employees

340

65+ 25+

5experts

projects

Departments

candidates

3sites

$35Mannual invest

HHT Research Center

5 Departments: 1. Bioprocessing 2. DSP and A 3. Immunobiology 4. Translational Biosciences 5. Operations

Recognized leaders: •  Biologics and Vaccines product

process development •  Neurodegenerative disorders •  Immune and cancer related

diseases •  Emerging infections

One-stop shop from discovery to tech. transfer

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Omics Novel drug targets Molecular modeling and design Screening and functional assays Production platforms and Bioprocessing engineering In vitro and in vivo pharmacology, efficacy and safety models Biologics and Vaccines Analytical characterizaton Technology transfer

HHT enables Translation to regulatory studies

R&D environment activities

selected candidate

CMO’s Quality Management System NRC’s Quality Management System GMP environment

activities

tech transfer

IND / CTA package support

selected process

HHT CMO

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Canadian Biomanufacturing Opportunity

Ø  Sustained growth trends of biologics sales

Ø  Complexity of biomanufacturing → stickiness factor for local production

Ø  Major worldwide investment in mammalian cell biomanufacturing, yet shortage of CMO offer

Ø  Gap in mammalian cell biomanufacturing offer in Canada

Vaccine core technologies and pipeline

Adjuvants Mucosal pathogens and bio-threat Viral infections Glycoconjugate technologies Antibody engineering

CNS core technologies and pipeline

Blood-brain barrier carriers BBB-crossing therapeutics Difficult (CNS) targets Brain beyond Barriers (BBB) Carta BBB-CNS models

Biologics core technologies and pipeline Target discovery Anti-cancer antibodies and ADCs Lead optimization Biomanufacturing and characterization

Programs Strengths

HHT is a key player of business innovation Since 2012, HHT has grown its footprint in the Canadian biopharmaceutical sector by collaborating and assisting a wide array SMEs and organizations in the sector.

Success of HHT collaborators

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•  Oncolytics, Reolysin, Phase II and III (NRC improved purification process) – 2013 •  Alethia, AB-16B5, Phase I trials in Canada and Russia (NRC’s antibody and cell line) – 2014 •  CanSino, Ebola vaccine (NRC’s cell line) – approved by Chinese FDA in 2018 •  PREVENT, Group A Streptococcus vaccine (NRC’s bioprocess) – 2016 •  Forbius, AVID100 IND approved by FDA (NRC co-developed) – 2017 •  Forbius AVID200 IND approved by FDA (HHT-discovered and co-developed) July 2018 •  VBI Vaccines, CMV vaccine in phase I (NRC’s cell line) – 2017 •  Zymeworks, ZW25, a Bi-Specific Antibody, for Cancer (NRC supported the overall development) – 2017 •  VBI Vaccines, VBI-1901, vaccine for Glioblastoma in Phase I/2a (NRC’s cell line) – 2018 •  HIA Vaccine licensing-2018 •  Kalgene, Anti-Alzheimer’s disease biologics (combines two of HHT’s technologies that were discovered at HHT,

licensed to Kalgene and co-developed ) – CTA anticipated in 2019 HHT is also licensing non-exclusively a number of core technologies, comprising its pTT vector platform, its CHO-BRI, 293-SF and BMAbE1(A549) cells; over the past five years over 150 licenses were signed.

IND application filed for FTIH clearance

from FDA

Co-development of an antibody-based drug candidate with a strategic partner

Selection of clones for 1L production

2016 2017 2018

Genetic Design of new drug candidates

Lead Selection

Development and transfer of Analytical methods

PK ELISA developed using

NRC antibodies to support clinical development

FTIH

Clone selection for 5 L production and USP data for tech transfer

DSP data available for tech transfer

Product Formulation

defined

NRC IND-enabling studies for Drug candidate

Post-tech transfer technical support

Multidisciplinary effort with more than 75 NRC members involved

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Merged Advancec Biologics and Biomanufacturing Program Goals

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Enable innovation in biologics and product process development to accelerate biologics development in Canada and address unmet needs

Need Strategic Partnerships; Assets, technologies, gaps

Leveraging Strengths and Interests

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BBB crossing CNS assets Difficult to access targets

Adjuvants Mucosal pathogens and bio-threat Viral infections

Anti-cancer Biologics Biomanufacturing and Characterization

Strengths Interests Novel immunomodulators Bites Checkpoint inhibitors Anti-cancer vaccines New ADCs Proprietary platforms Radiotherapeutics Keep existing focus based on needs Vaccines for unmet needs Difficult to access targets Personalized therapeutics Biosimilars Biobetters Improved Biomanufacturing and characterization: de-risking, faster, lower cost

NRC differentiators

1.  Integrated one-stop shop from lead identification to tech transfer

2.  NRC offers agility, transparency, track record and personalized collaboration

3.  Specific strength for different types of molecules (Ab, non-Ab, enzymes,

ADCs, vaccines, therapeutics that cross the BBB), pipeline of assets to co-

develop

4.  Availability of various expressions systems (eukaryotic, microbial)

5.  NRC proprietary cell lines

6.  Rapid identification and characterization of lead molecules

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Program partnerships

Over 50 targets with panels of antibodies 10 biotherapeutics in co-development Enabling technologies Gap filling

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EDNRB ADC for co-development

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Novel anti-EDNRB antibodies developed which perform as potent ADCs in melanoma xenograft model when conjugated DNA damaging agents (PNU-159682)

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Advance Biologics and Biomanufacturing Program:

BasicResearch

TargetSelec3onandValida3on

CandidateDesignandOp3miza3on

PreclinicalDevelopment

ClinicalPhaseI&II

ClinicalPhaseIII Market

NRC - HHT

Fill the pipeline Accelerate development Enable VC funding Minimize risk Transfer enabling technologies to industry Pre-IND package

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THANK YOU Lynne Le Sauteur• Director R&D, HHT NRC Tel: (514) 283-1012 • Lynne.lesauteur@cnrc-nrc.gc.ca www.nrc-cnrc.gc.ca