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From Bench to Clinic to MarketMay 2020

Table of Contents

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ResourcesWho we are

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Future DevelopmentsContract Development and

Manufacturing

Who we are

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Who are we?

LuinaBio is one of Australia’s most experienced

biopharmaceutical CDMO’s.

We offer two types of services:

• Strain and process development

• GMP manufacture of:

• Recombinant proteins & vaccines

• Live Biotherapeutics

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Why work with us?

• Over 20 years expertise in biopharmaceutical production from bacterial /

yeast cell lines

• Cell line development

• Process development

• GMP material for all clinical phases and market

• Experienced project management

• Highly cost competitive

• Extremely flexible with fast access and turnaround times

• Access R&D tax credit (43% upfront govt. rebate)

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Initial process flow

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Initial contact CDA RFP Proposal Evaluation Acceptance

Start of RM sourcing

Slot finalised

Invoicing

Project execution

Signature Evaluation Purchase Order Signature Evaluation MSA

Luina Bio Responsibility

Customer Responsibility

Continuing process flow

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Proposal Evaluation Acceptance

Signature Evaluation Purchase Order

Start of RM sourcing

Slot finalisedInvoicing

Project execution

Luina Bio Responsibility

Customer Responsibility

LuinaBio Experience

• Bacterial & Yeast Fermentation

• Live Biotherapeutics (Aerobic/Anaerobic; BSL1/BSL2)

• Recombinant proteins

• Carbohydrates and carbohydrate conjugates

• Vaccines and immunotherapies

• DNA/Gene therapies

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Track Record

LuinaBio provides services to global, multi-national and local

clients. Recent projects include:

• Recombinant protein from E.coli for a phase 3 trial in the US under IND

• Recombinant protein from E.coli conjugated to a carbohydrate for a

phase 2 in the US under IND and phase 2/3 trial in the EU;

• Over 10 strains strictly anaerobic LBP for phase 1 in the US under IND

• Whole cell killed vaccine for a phase 2 trial in the US and Australia

under IND.

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Cost comparison USA Australia

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100 72 44

USA

Australia

Australia ( with R&DTax)

Currency conversion rate AUD1 = USD 0.9Study By Frost and Sullivan 2016

Cost comparison for a standardized early phase trial conducted in Australia and USA

The savings for process development and manufacturing are comparable

Contract Manufacturing • Process Development

• Recombinant Proteins

• Live Biotherapeutics

• Vaccines

• Plasmid DNA

Process development

Luina Bio offers the following services to prepare your project for

successful cGMP Biomanufacturing

• Strain development

• Fermentation development

• Purification/recovery strategies

• Process validation

• QC assay development / validation

• GMP document preparation

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Case Study: Process development

• Luina Bio was approached to develop a method for the

manufacture of a recombinant protein for clinical use

Challenges

• Development of a suitably expressing E. coli strain. The host/vector

system is to be IP free.

• Development of fermentation conditions maximising yield resulted the

formation of inclusions bodies

• Development of a selective purification process minimising losses

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Luina Bio Solutions

• Selection of bacterial lines/plasmids that allows for ease of access,fermentation robustness and ease of mid-stream processing withfreedom to operate

• 5 plasmids trialled together with 2-3 host combinations

• Selection of induction system

• Selection of fermentation conditions adjusted to allow for the consistentand controlled expression of the native target protein into theperiplasmic space

• Purification was simplified following the presence of native protein inthe periplasmic space

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Case Study: Process Development

Outcome

• A new, rhamnose induced, highly performing plasmid/host

combination was created

• The optimal conditions for maximal native protein expression

were determined

• Purification efficiency was increased.

• The stage is set for simple and efficient cGMP biomanufacture

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Case Study: Process Development

Microbial Fermentation

Luina Bio offers the following services in microbial fermentation

for both bacterial and yeast strains:

• Master and working cell bank preparation, validation and storage

• Fermentation and subsequent downstream purification

• Downstream processing optimisation and development

• Up/downscale Fermentation

• Multiple feed strategies and media options

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Case Study: Novel recombinant protein

• Luina Bio was approached by a new client to manufacture a

recombinant protein designed in a novel expression system.

The client required the API for use in human clinical trials.

• Challenges

• A novel bacterial expression system not fitting within existing import or

OGTR licences.

• Expression only ever performed at small scale

• Atypical purification parameters

• Extremely low endotoxins specification on final API

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• Luina Bio Solutions

• Luina Bio was able to use internal skills to obtain necessary import and

OGTR licences.

• Luina Bio designed and implemented a successful scale-up program,

taking the final fermentation into our 600L fermenter.

• Luina Bio worked closely with the developers of the expression system

to refine and shorten the purification parameters, resulting in consistent

production.

• Luina Bio undertook an extensive risk assessment and process review

to eliminate the possibility of endotoxins contamination. A number of

facility enhancements were incorporated into the review.

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Case Study: Novel recombinant protein

• Outcome

• Luina Bio successfully introduced and upscaled the fermentation

process.

• Furthermore, increased refinement of the purification process resulted

in an approximately 50% increase in the overall product yield.

• The product was manufactured and released under cGMP.

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Case Study: Novel recombinant protein

Live Biotherapeutics

LuinaBio is highly experienced in working with aerobic to

strictly anaerobic strains:

• Aerobic/anaerobic cell bank preparation and qualification

• Aerobic/anaerobic fermentation up to 500L

• Aerobic/anaerobic mid stream and downstream processing

• Aerobic/anaerobic lyophilisation of live cultures

• Aerobic/anaerobic product packaging

• Entire process <100ppm O2 if needed

• BSL-1 /BSL-2

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Experience

• Bifidobacterium spp.

• Bacteroides spp.

• Dorea spp.

• Lactococcus spp.

• Eubacterium spp.

• Faecalibacterium spp.

• Bacillus spp.

• Odoribacter spp.

• Christianella spp

• Roseburia spp.

• Lactobacillus spp.

• Prevotella spp.

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Luina Bio has experience with the following bacterial genera:

Case Study: Live Biotherapeutic

Luina Bio was approached by a new client to manufacture a suite of

Live Biotherapeutic Products (LBPs) for use in a range of human

clinical trials.

Challenges

• New and novel bacteria not fitting within existing import permits

• Strict anaerobic control required to ensure organism viability

• Fermentation, harvesting, concentration and lyophilisation to be carried out

under strict anaerobic conditions

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Case Study: Live Biotherapeutic Luina Bio Solutions

• Use internal skills to obtain necessary import permits

• Installation of equipment to allow creation of anaerobic master cell banks

• Modification and requalification of large scale fermenters to create and

maintain strict anaerobic conditions

• Design and implementation of a cell concentration and harvest system that

could be sterilised in place and used while maintaining strict anaerobic

conditions

• Development and implementation of techniques to maintain strict

anaerobic conditions during lyophilisation and final dry product harvest and

sieving

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Outcome

Luina Bio successfully produced a suite of 10 lyophilised Live

Biotherapeutic Products that met or exceeded the clients’ viability

specifications.

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Case Study: Live Biotherapeutic

Vaccine Production

Luina Bio offers cGMP production of bacterial vaccines

• Production of recombinant vaccines

• Production of heat shock induced vaccines

• Production of live or killed bacterial vaccines

• Specialty in formalin killing and removal

• Human and animal health vaccines

• Documentation

• Support services

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Case Study: Vaccine Production

• Luina Bio was approached to produce vaccines effective

against meningococcal ACWY strains and Haemophilus

influenza, for use in human clinical trials

Challenges• Vaccine production potentially exposed manufacturing scientists to the infectious

agents that the vaccines are designed to protect against

• Complex mixtures of proteins are produced and ratios need to be maintained

during production

• Analytical techniques are required to identify and quantify the active components

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Luina Bio Solutions

• Luina Bio conducted an extensive risk assessment on the process and

implemented all recommendations to ensure operator safety, including

using operating procedures designed to provide higher than BSL2

protection within our PC2 Large Scale facility

• Fermentation and purification parameters were closely monitored to

ensure no deviations from the required process

• Luina Bio prepared and executed analytical validation protocols to

ensure analytical techniques were suitable

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Case Study: Vaccine Production

Outcome

• Luina Bio successfully manufactured the vaccines to meet client

specifications and timeline

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Case Study: Vaccine Production

Plasmid Production

Luina Bio offers cGMP production of plasmid DNA for transfection

of mammalian cells.

• Master and working cell bank preparation, validation and storage

• Fermentation and subsequent downstream purification

• Downstream processing optimisation and development

• Up/downscale Fermentation

• Multiple feed strategies and media options

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Case Study: Plasmid Production

Luina Bio was approached to produce Plasmid DNA in GMP by

an Australian biotechnology company

Challenges

• Complexity of growing the transformed bacterial cell line

• Challenging purification procedures had to be transferred and

perfected to ensure a useable product was obtained

• Analytical transfer and management of analytical suppliers

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Luina Bio Solutions

• A process was developed for maximal expression of the plasmid

• Fermentation and purification parameters were closely monitored to

ensure no deviations from the required process

• Purification processes were developed to ensure repeatability of

process

• Luina Bio prepared and executed analytical validation protocols to

ensure analytical techniques were suitable

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Case Study: Plasmid Production

Outcome

• Luina Bio successfully manufactured the plasmid to meet client

budget, specifications and timeline

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Case Study: Plasmid Production

ResourcesFacilities

Equipment

Licenses

Quality

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Facilities

LuinaBio's 1,200m2 facility is located in Brisbane,

Australia

• It comprises of a series of modular clean room laboratories with

ISO 8 fermentation suites and support areas.

• Purification and final product isolation suites are ISO 7 clean

rooms.

• The laboratory area is supported by a range of raw material, in-

process and finished product storage areas ranging from -80°C to

controlled ambient.

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Layout

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Processes and Equipment

• Fermentation at 5L, 30L, 75L and 500L scale

• Fed batch capabilities

• Cell recovery

• discrete centrifugation

• continuous centrifugation

• ultrafiltration

• Microfluidics and Niro Soavi high pressure homogenizers for cell rupture

• Final product filtration

• Lyophilisation

• bulk (up to 40L)

• vials

• stoppering

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• Chromatography

• AKTA 100 system (100mL/min)

• AKTA Biopilot (800mL/min)

• AKTA Bioprocess skid (2,000mL/min)

• AKTA Ready single-use Bioprocess skid (6,000mL/min)

• Chromatography columns 2L to 200L

• Independent Cell Culture Suites

• State-of-the-Art Testing Laboratories – with a full array of testing capabilities

• cGMP Compliant Warehousing – for raw materials and formulated bulk product

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Processes and Equipment

Facility Licenses

LuinaBio has the following operating licenses:

• TGA (Australian FDA equivalent) license for the

manufacture of human therapeutic API's from

biological and synthetic sources

• APVMA (Veterinary equivalent of the TGA) license for

manufacture of sterile immunobiological products

• OGTR license for the production of products from

genetically modified organisms

• DAF (formerly AQIS) facility license for import and use

of biologic materials

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Quality Management

LuinaBio invests heavily in Quality Management• We operate under and comply with the PIC/S GMP code

• Audited and certified by the TGA in November 2018

• Audited by clients including the Pfizer and Zoetis global audit teams

• Audited to USFDA requirements by independent consultants

• We expect and welcome your audit

• More information on our quality systems is available

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Future developmentProcess Development Aseptic Fill Finish

Microbiome production

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Process Development

Luina Bio will enhance its process development capability by creating a new

laboratory in Brisbane.

• The first phase of the laboratory expansion is currently operational and

allows our scientists to work on early upstream and downstream

development, scale up and analytical work.

• The second phase will start soon and will allow us to expand our parallel

fermentation capability and bring our scale up capacity to 500L.

This will allow us to be faster and more responsive to our customers

development needs.

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Aseptic Fill Finish

Luina Bio has started work on building an aseptic fill finish plant in Darra, QLD.

The plant will be able to aseptically fill bottles, vials and syringes (0.5 to10ml) in cGMP with

runs up to 5,000 units. The plant will be entirely based on single use materials to ensure

compliance and rapid access

The core of the work in this facility is expected to come from companies looking for Phase 1

and 2 aseptic fill-finish independently from the nature of their API.

Expect start date Q4 2021

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GMP Manufacturing

Luina Bio has started planning for the establishment of a greenfield site commercial live

microbial biotherapeutic product manufacturing plant for the pharmaceutical industry.

This plant will have a number of medium to large scale fermenters in parallel each with its

own dedicated purification and freeze drying train. All trains will be able to work in strictly

anaerobic conditions if needed.

This will allow our customers to have faster production of multiple strains as a number of

strains will be fermented concurrently.

Expected Start date Q4 2021

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Thank youMax Rossetto, General Manager, Business Development

E: Max.Rossetto@luinabio.com.au T: +61 400 987 334

Supporting you

From Bench to Clinic to Market