NOVOZYMES BIOPHARMA - · PDF fileVELTIS® Enzymes for Biocatalysis Novozymes Drug Discovery Drug ... human FcRn in mouse albumin background 11 ... •Amylolytic enzymes

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NOVOZYMES BIOPHARMA - PRODUCTS, TECHNOLOGIES AND MARKETS

Rose A. Lance, Novozymes Biopharma

Jefferies Healthcare Conference, June 2-5, 2014, 2014

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Safe Harbor Statement

This presentation and its related comments contain forward-looking statements, including financial expectations. Forward-looking statements are by their very nature associated with risks and uncertainties that may cause actual results to differ materially from expectations. The uncertainties may include unexpected developments in the international currency exchange and securities markets, market-driven price decreases for Novozymes’ products, and the introduction of competing products in Novozymes’ core areas.

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Novozymes – The World Leader in Bioinnovation

Household Care

Food & Beverages

Bioenergy Agriculture

& Feed Technical &

Pharma

Who are we?

*A+B shares Apr, 2014

Founded 1925

Listed 2000

Ticker NZYM B

Exchange Copenhagen

Market Cap* US$ 15bn

Long-term targets: > 10% organic sales growth from 2015 > 24% EBIT margin > 22% ROIC

Global: +6,000 employees, 700 products in 140 countries

R&D intensive: ~7,000 patents, 13-14% of sales spent on R&D

Profitable: $2.1bn/€1.5bn in sales and 24.7% EBIT margin in 2013

Majority owner Novo A/S controls 25.9% of the capital and 70.5% of the votes

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Bioenergy

• Corn ethanol • Cellulosic biofuels

• Unique biotech-focused business with a strong legacy of delivering growth, earnings, and cash flow

• ~13-14% of annual sales invested in R&D

• Global provider of enzymes to all market segments creates global market leader position

• Leveraging competencies across segments accelerates pace of innovation, reduces competition and creates

high barriers to entry

Uniquely Diversified Group - Creates Synergies and New Opportunities

Household Care

• Laundry & Dishwasher detergents

• Cleaning products

Food & Beverages

• Baking • Starch to syrups • Brewing & Alcohol • Healthy concepts

Agriculture & Feed

• Animal feed • BioAgriculture

Technical & Pharma

• Textile & Leather • Pulp & Paper • Wastewater • Pharma ingredients

16% 36% 27% 14% 7%

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Strong Macro Trends Expected to Drive Need for Improved Drug Development and Treatments

More wealthy populations:

End result: • Growing demand for biologics • Patent expiries driving new potential • Overall Healthcare Cost pressure • Regulatory framework is still very new

Aging populations:

Pressure to innovate and reduce cost:

• Diabetes

• Cancer

• Obesity

• …

• Osteoarthritis

• Cataract

• Dermal fillers

• …

• Need for well

defined ingredients

• Need for extended

dosing

• Need for stable

liquid formulations

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Novozymes provides solutions to: Stabilize drugs

Improve formulation

Improve dosing regime

Increase patient compliance

Reduce manufacturing cost

Novozymes Focuses on Supporting Drug Development

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Novozymes’ Products and Technologies Support Pharma Companies in Their Development

Bacillus-derived hyaluronic acid offering superior safety, consistency and performance offers cost savings and minimized risk

• Used as an ingredient in medical devices and pharmaceutical products

• Next generation albumin-based technology to create longer-lasting drugs through albumin fusion or chemical conjugation

• Improved dosing regimes for increased patient compliance

• High quality and animal-free recombinant albumins developed to provide customers with a safe and consistent, regulatory compliant product

• Used as an ingredient to stabilise drug and vaccine products and in medical devices

• Comprehensive biocatalysis enzyme portfolios including lipases, proteases, esterases, oxido-reductases and amylolytic enzymes

• Improved yields, simplified processes and fewer byproducts in API manufacturing

Hyaluronic Acid Recombinant Albumin USP-NF*

VELTIS® Enzymes for Biocatalysis

Novozymes

Drug Discovery Drug

Development Manufacturing Distribution

Sales and Marketing

The classic pharma value chain

*Meets National Formulary (NF) standards as published by United States Pharmacopeia (USP).

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Benefits • Proven clinical performance • Long patent life • Flexible and scalable manufacturing by fusion or conjugation in a variety of expression hosts • Patient-friendly dosing and low risk of adverse events • Provided by technology developer with strong heritage and track record in albumin supply

Novozymes’ Half-Life Extenstion Platform: VELTIS®

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Short Half-Life Reduces Therapeutic Effect

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Improved pharmacokinetics to reduce dose/side effects

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Has a naturally long plasma half-life of ~19 days for well understood reasons:

• Size - retained by kidney/glomerulus

• FcRn (neonatal Fc receptor) binding: pH-dependent recycling “rescues” albumin from degradation and prolongs half-life

1

10

100

1000

10000

100000

1000000

0 100 200 300 400

Mean

± S

EM

seru

m c

on

c.

(n

g/

mL)

Time (hr)

Albumin +FcRn recycling

Albumin -FcRn recycling 60%

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Albumin is the Ideal Vehicle for Half Life Extension

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• Veltis variants show similar trends across species with increased and decreased FcRn binding relating directly to decreased and increased half-life

• More than 2X increase in half life with albumin variants compared to native albumin

• Pharmacokinetics of albumins evaluated in a number of in vivo models • WT Mouse • Transgenic mouse* • Non human primate

NT – Not tested

*Transgenic mouse – human FcRn in mouse albumin background

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Increased receptor affinity >2X albumin half-life in a range of models

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• In silico studies

• EpiMatrix Protein score

• -29.9 to -32.0

• In vitro Class II HLA binding and ex vivo T-cell assays

• No significant HLA binding

No Significant Immunogenicity Predicted From a Range of Screening Tools

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Thrombopoietin

Erythropoietin

IgA

Fibrinogen-Gamma

Albumin

IgG FC Region

GMCSF

Follitropin - Beta

Fibrinogen-Alpha

Beta-2-Microglobulin

Interferon-Beta

GHRH

Tetanus Toxin

Influenza-HA

EpiMatrix Scores

“Considering our global and regional analysis as a whole, we find the risk that these proteins will create or contribute to anti-therapeutic immune response to be minimal”

Veltis albumin variants

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Veltis® Offers a Potential Route to Once-Monthly Dosing

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Optimise your protein or peptide for: Control of dosing

intervals and size Reduced toxicity Improved efficacy

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Company Deal Drug Target Pre-clin

PI PII PIII MAA stage

Fusion + expression

Several molecules (G-CSF, BNP, …)

Bio- betters

X X X

Fusion Blood coagulation factors

FIX, FVIIa, + others

X X X

Fusion + expression

Kunitz Domain proteins and antibody fragment

Several X

Publicly available information on companies using Novozymes’ VELTIS® technology:

A Number of VELTIS® Candidates are in Clinical Development

Albiglutide® (GLP-1 albumin fusion) for diabetes type II, approved in both the EU and the US in 1H 2014

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http://www.gsk.com/index.htm

http://www.cslbehring.com/s1/cs/enco/1151443990667/content/1151443991017/home.htm

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• Lipases

• Proteases

• Esterases

• Oxido-reductases:

• laccases,

• peroxidases,

• Chloroperoxidase

• Amylolytic enzymes

Advantages of enzyme manufacturing

Improved productivity

Shortened synthesis route

Replaces costly chiral resolving agents

Significant reduction in waste streams

Stereo-, regio-, and chemo-selectivity

Simplified processing and purification

Fewer by-products, reducing impurities

Mild reaction conditions

Sustainable process

• Novozymes has a comprehensive enzyme portfolio for biocatalysis

• New focus as an important tool for cost effective and sustainable manufacturing of Fine Chemicals and Pharma

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Enzymes for Biocatalysis: Manufacturing APIs with Enzymes

http://www.google.com/url?sa=i&source=images&cd=&cad=rja&docid=-91gohf8yXJE8M&tbnid=nY4jzOty1jSCBM:&ved=0CAgQjRwwAA&url=http://images.businessweek.com/ss/05/12/bestproducts/index_01.htm&ei=eRllUeaaEMiRtAbliICIBQ&psig=AFQjCNFeNPLqreBNPNOET1ZLeDjUlQNiFw&ust=1365666553304724

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Key Advantages of Biocatalytic Route

Chemical Synthesis Biocatalytic Route

Low protein loading (0.8%) Resolution at first stage - wrong

isomer can be recycled High throughput All reactions conducted in water E-factor improved from 86 to 17

Starting material reduction by 800 Mt (cumulative)

Drastic reduction in solvent usage Mandelic acid usage - 500Mt

eliminated (cumulative) Energy usage reduced by 83%

Improvements due to replacing chemical process with chemoenzymatic reaction

Inefficient Resolution at racemic

Pregabalin stage

Pregabalin Biocatalytic Route

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Source: Organic Process Research & Development 2008, 12, 392-398

http://www.google.co.in/url?sa=i&source=images&cd=&docid=PD87nA7DH_4XnM&tbnid=dnGTgX7xRzzdPM:&ved=0CAgQjRwwAA&url=http://www.jvbien.com/?p=5064&ei=saa5UcHBJJDyrQfQyYCwCQ&psig=AFQjCNHdxrWsAi0vneK8Bauq39WoMI-vHQ&ust=1371207729727833

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In Summary

• Novozymes’ products and technologies aim at supporting the healthcare industry develop better, safer and more economical treatments.

• Novozymes is the world leader in recombinant Albumin, half-life extension technologies based on albumin and recombinant hyaluronic acid.

• Novozymes’ range of recombinant enzymes enables optimization of manufacturing of a range of small molecules via biocatalytic processing

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Recombinant Albumin USP-NF*

Half-life Extension

Recombinant hyaluronic acid

• Recombumin® Prime • Recombumin® Alpha • AlbIX

• Veltis®

• Hyasis® • Hyasis® Link

Pharmaceutical Enzymes

• Proteases and lipases • rTrypsin for • Novel proprietary

enzymes being explored

Novozymes Biopharma: Knowledge-based solutions driving the development of innovative, safer, and more consistent medical devices and pharmaceutical products

For more information visit www.novozymes.com/investor or www.biopharma.novozymes.com

Rose A. Lance, Novozymes Biopharma [email protected], +01 203-878-4436

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Hyaluronic Acid – Hyasis®

Novozymes Hyasis® is the next generation of high-quality hyaluronic acid offering superior safety, consistency and performance. Achievements: • Established as a strategic supplier for several

multinational players as well as smaller companies promoting novel Hyaluronic acid technologies

Key advantages: No animal-derived raw materials (Bacillus-

derived) No production of endotoxins or exotoxins No organic solvents Targeted molecular weight High batch-to-batch consistency in

production Fewer manufacturing deviations 5 x faster dissolving time Superior heat stability for more efficient

sterilization process Hyasis® Link – versatile and proven

crosslinking technology

With Novozymes Hyasis® you get: • New standard for purity and cGMP level • Significant cost savings in production

• Minimized business risk with a reliable

supplier

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Recombinant Albumin - Recombumin

Novozymes Recombumin® products are ideal products for a range of applications including the manufacture of medical devices, drug delivery and drug stabilisation Key advantages: Excellent stabiliser for peptides, proteins

and vaccines

Allows development of liquid presentations for patient convenience and compliance

Assured sourcing from a global leader in industrial biotechnology means robust supply chain

High purity, cGMP, animal-free materials designed for use in biomanufacturing

No need for warnings on final drug labels regarding risk of disease transmission

With Novozymes rAlbumins you get: • Quicker route to market with established

regulatory package

• Reduced risk with animal free sourcing

• Reduced quality associated costs

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In 2014 we are focusing on a range of areas within Novozymes Biopharma

• Continued new data proving the novel half life extension platform

• More Feasibility studies with large pharma and biotech companies on the novel half life extension platform

• Growth in sales of enzymes for biocatalysis

• Solidify Hyasis and Recombumin platforms for future growth

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Documents

NOVOZYMES BIOPHARMA - · PDF fileVELTIS® Enzymes for Biocatalysis Novozymes Drug Discovery Drug ... human FcRn in mouse albumin background 11 ... •Amylolytic enzymes