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Page 1: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

August 10, 2016(OTCQX: DYAI)

Page 2: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

Certain statements contained in this presentation are forward-looking statements. These forward-looking

statements involve risks and uncertainties that could cause Dyadic’s actual results, performance or

achievements to be materially different from any future results, performance or achievements expressed or

implied by such forward-looking statements. Except as required by law, Dyadic expressly disclaims any intent

or obligation to update any forward-looking statements.

Safe Harbor Statement

2

Page 3: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

Strategic Opportunity: THE COMPANY

Dyadic (OTC: DYAI) is a global biotechnology company producing enzymes and proteins using a proprietary expression system based on the Myceliopthora thermophila fungus (“C1”)

Commercial use of the C1 platform technology in industrial biotechnology culminated in DuPont’s acquisition of Dyadic’s Industrial Biotech business for $75 million

Market capitalization: $54.6 million(1)

Net cash: $62.6 million(2)

– No debt Leadership team with a successful track record

(1) $ 1.44 per share (close of market on August 9, 2016) using the last publicly released March 31, 2016 share count of 37.9 million common shares

outstanding.. Please note the Company continued to buy back shares during Q2 2016, and thereafter which will be reported in our Q2 filing August 11th.

(2) As of March 31, 2016. Reflects $0 debt balance and excludes (i) ~$7.4 million held in escrow from DuPont Transaction with expected release in July

2017, and (ii) $2.1 million received 4/19/2016 from legal settlement.

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Strategic Opportunity (2): THE TECHNOLOGY

4

The C1 platform technology is a hyper-productive fungal expression system used to develop & manufacture large quantities of desired proteins at industrial scale more affordably

The C1 platform technology is proven and has been applied in the industrials sector by multiple market leaders: – DuPont– BASF– Abengoa– Codexis/Shell

Biopharmaceutical collaboration in EU ZAPI vaccine program

Excellent safety profile Dyadic retains exclusive sub-license rights to the C1

platform technology in biopharmaceutical indications

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Strategic Opportunity (3): THE OPPORTUNITY

5

Potential to remove a critical bottleneck inprotein development and manufacturingprocesses– Allows for rapid scaling

– Significantly lower CapEx and OpEx

Potential to improve therapeutic vaccine anddrug performance

Dyadic is seeking partnerships to sub-license,or partner its C1 platform technology in thevaccine, antibody and biosimilar industries

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Dyadic Target MarketsThe C1 platform technology has the potential to speed the development, decrease the CapEx & OpEx, improve therapeutic vaccine and drug performance, and lower the cost of manufacturing biologic vaccines and drugs

Global biological drug market to be $287B by

2020(3)

Global vaccine market to be $100B by 2025(1)

Biosimilar market to be $26B by 2020(4)

Global insulin market to be $42B by 2019(2)

Recombinant Vaccines

(Human and Veterinary)

Biosimilars / Biobetters (non-Gly)

Biosimilars / Biobetters (Gly)Novel Biologic

Products

(1) World Health Organization.(2) Human Insulin Market - Drugs Type, Brands, Delivery Devices, Applications - Forecasts to 2020.(3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020.(4) World Biosimilars Market (follow-on-biologics) Opportunities, and Forecast, 2014-2020. 6

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C1 Platform Technology

7

Page 8: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

Moscow State University

Scientific CollaborationsDyadic has a history of strong scientific collaborations

8

Enzyme Development

Genome Annotation

C1 Strain Development, Optimization

Development programs for gene expression, gene knock outs and gene discovery (low protease C1 strains and C1 molecular toolkit)

Performed annotation of the C1 genome, allowing identification of key metabolic functions that influence expression and glycosylation

Isolation, discovery and characterization of the enzymes expressed by the wild type and mutants of the C1 fungus

Fermentation, Process Development,

Optimization

Development, scale up and commercial scale production of enzymes and other proteins utilizing the C1 platform technology

Page 9: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

2016 - Develop C1 platform

technology as an expression host for:

‒ Vaccines‒ Biosimilars‒ New products

The 20-year Evolution of C1 Platform Technology

1992 Discovered C1

wild type strain which naturally produced neutral cellulaseenzymes

Wild type

1995 - 1996 Mutation led to

development of high cellulase C1 strain with unique morphology

Commercial launch of C1 enzymes for textile industry

1st

breakthrough1997 - 2007 Developed molecular

toolkit for optimizing C1-based recombinant protein production for commercialization

Produced variety of commercial products using the C1 strains

Successfully expressed human therapeutic proteins in C1

High throughput robotic screening developed and patented

Development

2005 - 2015 Sequenced and

annotated the C1 genome

Developed low cellulase C1 strain, enabling the commercial production of “purer enzymes

Hyper productivity reached 100 g/l with ~ 80% purity

2nd

breakthrough2009 - 2015 Developed

comprehensive enzyme library

Produced first commercial product using low cellulase C1

GRAS status acknowledged by FDA

Developed HC strains for biofuel enzyme production

Hyper productivity reached 100 g/l with ~ 80% purity

C1 for bio-industrial

2016 - 2018 Develop robust high C1

host strain for biopharmaceutical applications

Develop versatile easy to use construct library based on system biology

Develop glyco-engineered C1 strain to resemble human protein-glycosylation structure

Future development

C1 for biologic drugs and vaccines

9

1992 1995 1997 2005 2009 2016

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C1 Platform Technology - Commercially Proven C1 platform technology used by industry giants in areas such as ethanol and industrial enzyme production and vaccine development

10Note: Refer to pages 37 and 38 for additional details on commercial applications of C1.

Acquired by

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First Breakthrough: Morphology Change

Development lineage of low viscosity hyper-producing protein C1 strains

Propagules instead of hyphae results in hyper productivity and low viscosity

NG7C-19 HC

Viscosity Proteinyield

Visc

osity

(cP)

100

200

300

400

500

Prot

ein

(g/L

)

20

40

60

80

100

11

C1

UV13-6

HC

NG7C-19

UV mutagenesis

UV mutagenesis

NTG* mutagenesis

Wild-type

Cellulase over producer

De-repressed cellulase production

High cellulase, low viscosity mycelial fragmentation

Page 12: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

The Low Cellulase Strain for Protein ProductionDevelopment high productivity low protease activity of host strains for specific proteins productions

low cellulase prt- with specific protease disruption

Protease deficient strain

De-repressed cellulase production

12

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C1 White Strain 2.0

Expression of high levels of purer proteins

Second Breakthrough: High Purity

Dyadic’s C1 White Strains 2.0

successfully used in production of

single and multiple proteins derived

from fungal, bacteria, bacterial-

directed evolution, mammalian,

human and viral strains

Reduction of background proteins

that are not needed– Obtain purer protein– Higher levels of targeted protein

The C1 White Strain 2.0 is fermented

at large commercial scale

WT

LC

HC

C1 strain types

C1 “White Strains” 2.0 have very different protein background than the C1 Wild Type Strains

13

C1HC

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World Class Productivity and Purity

Synthetic biology start-ups – large and small –

struggle with the reality of scaling up microscopic

cellular factories into profitable business models

Dyadic’s patented and proprietary C1 platform

technology is being used to produce biological

products at very high yields, low cost and in large

commercial fermenters

Two serendipitous mutations led to the creation of the world class C1 platform technology

High yields, high purity, low cost at industry leading scale

Over 100 grams per liter protein

Up to 80% of target protein has been achieved

Commercially produced enzymes in a single 500,000 liter fermenter

100 g/L

80%purity

500,000 liter scale

14

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C1 strain non-toxic

Pathogenicity and toxigenicity data: strain is non-

infectious and no known toxins are produced

Peer-reviewed scientific literature have confirmed

— No known pathogencity

No mycotoxins found

C1 enzyme testing

In vivo feeding trials:– 14 day dose study in rats– 13 week subchronic rat study

Genotoxicity testing:– AMES bacterial mutagenesis– Chromosomal aberration test– Genetic mutation test

No adverse effects observed

No foreign DNA

Safety confirmed

C1 Has an Excellent Safety Profile

C1-cellulase accepted by FDA on September 29,

2009

GRAS notification letter is a public statement by

FDA acknowledging Dyadic’s safety

determination for the intended uses of C1

GRAS notification letters are broadly recognized

in the food and consumer products industries as

the safety standard

Generally Recognized as Safe (GRAS) status acknowledged by the FDA

15

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C1 Platform Technology Overview

16

Mature system for production of heterologous proteins

Excellent safety profile

Fully programmable, patented technology

C1 genome annotated

Platform

Low cost, commercially scalable fermentation at up to 500,000 liter scale

High purity and yield, 100+ grams per liter

No animal-derived ingredients used in media

Short development and fermentation times

Serves as both a research and production host

Production

Potential to generate improved immune response in vaccines

Favorable glycoprofile can be modified to become ‘human neutral’ to lessen immunogenicity

Potential to improve therapeutic vaccine and drug performance

Product

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Vaccine Applications

17

Page 18: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

$1.6B

$2.2B

$0.0

$0.5

$1.0

$1.5

$2.0

$2.5

$3.0

2011 2018

The Vaccines Market Opportunity

The vaccine market has increased from

$5B in 2000 to almost $32B in 2014– Influenza vaccine market: estimated to grow

from $2.9B in 2011 to $3.8B by 2018– Need for better patient immunization and

lower cost– US: $1.6B in 2011 to $2.2B in 2018

Global market projected to rise to $100B

by 2025

There are more than 120 new products in

the development pipeline

60 products are of importance for

developing countries– Vaccines are becoming an engine for both

the human and animal pharmaceutical industry

– Changing status of vaccines within the pharmaceutical industry

18

U.S. Vaccine Market

Global Vaccine Market

$32B

$100B

$0

$20

$40

$60

$80

$100

$120

2014 2025

Source: World Health Organization.

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Completion Of Sanofi Vaccine Collaboration

Sanofi Pasteur is one of the largest vaccine companies in the world

Entered into a Proof of Concept, Exclusive Option & Technology Transfer Agreement (March, 2011) to

evaluate Dyadic’s C1 technology to speed up the development & production of vaccines at a lower cost.– Research conducted on and off over 5 ½ years, partially funded by Sanofi

Project Results – Successfully demonstrated that the C1 technology is capable of producing vaccines at high levels, with the

potential to improve therapeutic vaccine performance. – Initial C1 produced antigen showed an equal or better immune response in mice trials than the existing antigen

Expected Project Benefits– We believe that the experience and knowledge obtained from the research is invaluable and expect it will

generate a greater interest in the C1 technology for developing and manufacturing biologic vaccines

Sanofi’s prior option rights to the C1 technology previously covered by the Agreement revert back to Dyadic.

Upon such reversion, Dyadic expects to leverage the knowledge gained, and the progress made from the

meaningful improvements to the C1 expression system across all biologic vaccine and drug indications.

R&D collaboration terminated by Sanofi, expected to end October 5, 2016

19

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ZAPI – New €22 Million Vaccine R&D Program

Program sponsored by the EU to develop a platform suitable for the rapid development and production of vaccines

and protocols to fast-track registration of developed products to combat epidemic Zoonotic diseases that have the

potential to effect the human population

Dyadic Nederland’s, B.V. is using C1 to express vaccines and neutralizing agents which if such research is

successful we anticipate the C1 platform technology may be chosen as a preferred platform within the ZAPI

research project– Two of the objectives we hope to attain through the ZAPI funded research project are as follows:

• Additional examples of vaccines and neutralizing reagents against emerging pathogens expressed from C1• C1 produced proteins regulatory pathway identified, and carried out at least in part, through collaborative

partnerships between human and veterinary medical institutions, governmental regulatory agencies, expert academic groups and industrial partners

ZAPI is a multi year project which full results may not be known for 3-4 years

20

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Additional Proof of Concept: Animal & Human Vaccines

• Leveraging the knowledge gained, and the progress made from the meaningful improvements to the C1 expression system from the Sanofi collaboration across a variety of biologic vaccine indications.

• Further demonstrate high level productivity, with the potential to improve therapeutic vaccine performance for both animal & human vaccines.• Seek additional funding from industry and government • Potentially initiate internally funded research & development programmes

21

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Biologics Applications

22

Presenter
Presentation Notes
.
Page 23: August 10, 2016 (OTCQX: DYAI) - Dyadic …...2016/08/10  · (3) Global Market Study on Biological Drugs: North America to Witness Highest Growth By 2020. (4) World Biosimilars Market

Biologics Market Summary

In 2014, biologics accounted for 21% of total global

spending on medicines– Biologic spending are expected to grow at 10.1%

CAGR until 2020 to $287B

The global biosimilar market is growing due to the

need for lower cost biologics– $1.9B market in 2014 is expected to reach $25.5B by

2020, growing at an impressive CAGR of 54.4% – Increasingly greater drug pricing pressures along with

competition for biosimilars is expected to reduce drug pricing by 45% or more

Biologics are the fastest growing drug segment

Source: Global Biosimilar Market Outlook 2020. 23

New technologies like C1 provide the pharmaceutical industry with a way to insure patient access and affordability

to biologic drugs while helping the industry maintain profitability

C1 has the potential to:– Lower the costs of biologics– Help bring new and improved biologics to market– Help to overcome protein expression challenges of potential biologics stuck in R&D

Global pharmaceutical sales (US$ billion, list price, ex. rebates and discounts)

20142004

930

519

21%

79%13%

87%

8%

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Case Study: Glycosylated Proteins Generic HumiraDyadic produced biologically-active monoclonal antibodies in C1

Heavy chain

Light chain

Source: Peter Punt, TNO.

Expression was achieved of both heavy and light chains

Heterodimeric antibody molecules were formed efficiently, allowing simple purification of the protein from the

culture fluid using Protein A

Cell-based bio-assays performed revealed almost complete bioactivity

Production levels of 2 g/L reached after 4 days in fermenter

24

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Case Study: Generic Humira (Cont.)

Protease deficient strains were developed to improve

the stability of expressed heterologous proteins

State of the art molecular engineering methods based

on computational biology will enable us to eliminate

specific proteases to stabilize biologic proteins

Low Cellulase with Low Protease Activity

Protease

C1(wt)

0

10

20

30

40

0 20 40 60 80 100

time (h)

pept

ide b

onds

(mm

ol)

C1 WT UV18-25#100f

0

10

20

30

40

0 20 40 60 80 100

time (h)

pept

ide b

onds

(mm

ol)

C1 Δ proteases

25

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Case Study: Generic Humira (Cont.)

In vitro stability of heavy chain against C1 fermentation culture filtrates

26

0 4 8 24Single deletion

0 4 8 24Triple deletion

Hrs:

ΔproA ΔproA, ΔproB, ΔproC

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Case Study: Non Glycosylated Proteins

• Recently initiated internally-funded R&D programmes to demonstrate

• The production of insulin• Global insulin market to be $42B by

2019(1)

• The production of ranibizumab, a generic version of Lucentis• Global Lucentis market was $3.5B

in 2015 (2)

27(1) Human Insulin Market - Drugs Type, Brands, Delivery Devices, Applications - Forecasts to 2020(2) Global Lucentis Market – FierceBiotech August 8, 2016

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C1 Platform Technology Advantages

Grows and expresses proteins over a wide range of pH levels and temperatures– Allows gene expression under conditions optimal for the activity and stability of a wide range of targets

Integrated gene expression system increases the likelihood of successful expression

C1 platform technology offers many advantages over current expression systems

Bacterial Fungal Mammalian E.coli Saccharomyces Pichia C1 CHO

Cost low low low low high

Growth rate high high high high low

Culture media and conditions simple simple simple simple complex

Post-translational modifications no some some some yes

28

In the same amount of time, Dyadic’s C1 platform technology is expected to produce up to 20 times the g/L compared to CHO cells(1)

~CHO Cell Yield 2-10 g/L(2)

C1 Industrial Yield (Actual)

C1 Biopharmaceutical Yield (Expected in 2-3 years)

12-15 days

10-20 g/L 20-40 g/L

80 g/L 160 g/L

5-7 days

5-7 days

(1) C1 has a single cycle fermentation time of approximately 5-7 days compared to CHO single cycle fermentation time of 12-15 days.(2) Range based on approximate yield of Lonza and ThermoFisher CHO cell line expression systems.

5-7 days

5-7 days

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Indicative Savings for Biosimilars with C1C1 productivity provides the potential to dramatically lower CapEx

29

C1CHO

(1) Represents lower range of yield. Refer to page 15 for additional details.

500

100

0

50

100

150

200

250

300

350

400

450

500

2-10 G/L 20-40 G/L

DE

VE

LOP

ME

NT

CO

STS

($ M

ILLI

ON

S)

YIELD (1)

10,000L fermenter reduced to a 1,000L fermenter

Capital investment required to build launch capacity

Factory with launch capacity must be built 24 months before FDA approval,

or very costly CMO

FDA license easier for small factory

Additional costs beyond factory investment related to

clinical trials ($300mm), regulatory ($10mm), and initial

marketing ($20mm) would still be required to complete

the full product development

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Conclusion: Commercially Proven

30

Validated by industry giants

Excellent safety profile

Utilizing the same cell line saves time as well as

increases the probability of cultivating a successful

commercial process

Potential to produce up to 20 times the g/L per day

compared to CHO

Significant capital and operating expense savings

Potential to improve therapeutic vaccine and

drug performance

Toolkit already developed to allow for sophisticated genetic modifications to

C1 strains

Experienced management team

Dyadic’s C1 platform technology, a hyper productive cell line, programmable and

commercially scalable

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Dyadic Legal Proceedings

On April 14, 2009, Dyadic filed a lawsuit against its former outside legal counsel alleging breach of fiduciary duty and professional negligence.

Dyadic has now settled with three of the original defendants– These settlements allow the Company to focus on its pharmaceutical business and continue to vigorously pursue our

claims in this litigation against the primary defendant, Greenberg Traurig Summary of settlements paid to the Company

– August 8, 2012 settlement agreement whereby Jenkens & Gilchrist paid the Company $525,000 on behalf of itself and Mr. Schwimmer

– July 31, 2015 settlement agreement whereby the Company received a net payment of $2,170,000 from Moscowitz & Moscowitz, PA, Norman Moscowitz and Jane Moscowitz

– April 5, 2016 Settlement Agreement whereby the Company received a net payment of $2,100,000 from Bilzin SumbergBaena Price & Axelrod LLP

Status of ongoing litigation– On March 2, 2016, the lawsuit was scheduled for a six-week jury trial commencing Friday, January 6, 2017 for Dyadic’s

case against Greenberg Traurig, P.A. and the Estate of Robert I. Schwimmer(1), who previously represented the Company while an attorney at Greenberg Traurig

– On July 8, 2016, the Court heard oral argument on Greenberg Traurig’s Renewed Motion for Summary Judgment as to its judgmental immunity affirmative defense. It is expected that the Court will enter an Order on the Renewed Motion in August 2016.

– The trial remains set to begin January 6, 2017

• (1) Greenberg Traurig has agreed to assume the liability for the estate of Robert I Schwimmer, and accordingly a motion has been filed with the court.

31

Trial against former outside legal counsel remains set for January 6, 2017

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Thank you. Q&A:

32