(OTCQX: DYAI)

Producing Biologics with C1

BIO Conference 2017June 18, 2017

Safe Harbor Regarding Forward-Looking Statements

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Certain statements contained in this presentation are forward-looking statements within themeaning of the federal securities laws. These forward-looking statements involve risks,uncertainties and other factors that could cause Dyadic’s actual results, performance orachievements to be materially different from any future results, performance or achievementsexpressed or implied by such forward-looking statements. Any forward-looking statements speakonly as of the date of this presentation and, except as required by law, Dyadic expresslydisclaims any intent or obligation to update or revise any forward-looking statements to reflectactual results, any changes in expectations or any change in events. Factors that could causeresults to differ materially are discussed in Dyadic’s publicly available filings, includinginformation set forth under the caption “Risk Factors” in our December 31, 2016 Annual Reportfiled with OTC Markets on March 15, 2017. New risks and uncertainties arise from time to time,and it is impossible for us to predict these events or how they may affect us.

Dyadic Overview

Revolutionary protein expression technology “C1”: based on Myceliopthora thermophila fungus

Technology covered by over 20 patent families

Listed on the stock exchange (OTCQX: DYAI), liquidity of > 50m USD (1)

Experienced management & board– 20+ Years of Experience with Fungal Production Systems– 20+ Years in Pharmaceuticals

20+ Years of Commercial Enzyme Production with C1 technology

Hyper productive strain developed: >100 g/l with ~80% purity

Approved as safe (GRAS) by FDA for food and feed applications

Produced in up to 500,000l scale tanks

Biopharmaceuticals

Strategic focus since 2016 Powerful molecular toolbox enables

expression of complex proteins Successful Proof of Concept studies

mAbsVaccinesNon-

GlycosylatedProteins

Dyadic has demonstrated the power of C1 for the expression of biologics and is now looking to establish partnerships with biopharmaceutical companies

(1) As of March 31 , 2017, including ~ $7.4 million of restricted cash held in escrow until July 2017 from the DuPont transaction.

3DYADIC INFORMATION

C1 – The Most Productive Fungal Expression System for Biologics

4

A safe and reliable protein production platform, C1-derived vaccine showed no adverse clinical effects in mice5 Safety &

Reliability

Produces batches of proteins that are significantly purer than traditional production methods 12 Purity

Cuts preparation and production time in half compared to CHO3 Time Saving

Achieves much higher yields than traditional production systems in CHO, E. coli, S. cerevisiae, P. pastoris1 Yield

Grows under broader temperature & pH ranges and is easily scalable compared to CHO4 Robustness

C1 can minimize CapEx investments, production costs of biologics and overcome the limitations of traditional production systems

DYADIC INFORMATION

C1’s Unique Morphology Enables Non-Viscous Fungal Production

The low viscosity allows C1 to be used in established microbial production facilities,

requiring no additional CapEx investment

5

Visc

osity

(cP

)

Protein Yield

500

400

300

200

100

100

80

60

40

20

Pro

tein

(g/l)

Viscosity

Standard Fungal Line C1

Low Viscosity, High Yield

Filamentous fungi face challenges for their use in production due to high viscosity

C1 exhibits a unique morphology resulting in low viscosity

DYADIC INFORMATION

C1 Highly Robust Production Host

40ºC37ºC-32ºC25ºC

pH range

71 14

5 8C1 CHO

Rob

ustn

ess

1 After 2 Purification Steps, 2 No purification steps 3 Optimal range 32 - 37ºC. Source: Sellick, C. et al (2009) Optimizing CHO Cell Culture Conditions. Genetic Engineering and Biotechnology News Tutorial.

CH

O3

45ºC-

25ºC

C1

Operates under a wider temperature than CHO

Operates under a wider pH range than CHO

At scales ranging from laboratory shake flasksto 20,000l tanks and above

Using defined medium.

Purit

y

C1 White Strain 2.0 2

C1 1st

Generation2E. Coli 1 C1 delivers Higher levels

of the target protein (100 g/L)

Significantly higher purity(80% purity

CHO 2

WT

LC

HC

6DYADIC INFORMATION

C1 Fermentation Process

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Seed Tank

200L – 500m3

FERMENTER

Harvest Tank

Seed flask

Inoculum

Defined medium

NH4OH for pH control

Glucose feeding

Processing & Recovery

Packaging Assembly Filling Formulation Purification

Fed-Batch technology

Fed-batch technology, simple defined media and scalable process with commercial success

DYADIC INFORMATION

Reproduction rate of cell 2x higher than for CHO Protein production rate at least 1.5 fold Higher purity of protein achieved may decrease recovery time

C1 Enables Shorter Production Cycles in Comparison to CHO

1

1

2

2

3

3

0 1 2 3 4 5

CHO

C1

Duration of Steps in Production

*Note: Protein Recovery may be faster due to higher purity of C1 production

Week 1 Week 2 Week 3 Week 4

Batch Cycle time is reduced by >50% in comparison to CHO, freeing up capacity

Production time reduced by >14 days

1: Biomass Expansion 2: Protein Production 3: Protein Recovery*

8DYADIC INFORMATION

Protein Production by C1Fermentation profile of total protein production by HC strain Vs. single proteins production by LC strain

9DYADIC INFORMATION

C1 Production strain = HC strainC1 White strain = LC strain

LC strain expressing Indigenous enzyme by licensee partner

LC strain expressing heterologous enzyme for licensee partner

(1)

(2)

(1)

(2)

0

5

10

15

20

25

30

35

40

Per.C6 CHO C1 ComplexBiologics Yield

3

10

30

9

15

< 60

0

10

20

30

40

50

60

S. cerevisiae P. pastoris C1Industrial/Simple

Protein Yield

C1 Has the Potential to Produce Significantly More Protein

Simple/Non-Glycosylated Proteins Complex Proteins, e.g. mAbs

Yiel

d in

g/l

>3 times higher yield 2 to 10 times

higher yield

Sources: 1 Boehringer Ingelheim, BioXcellence production: www.bioxcellence.com. & Shane Cox Gad (2007) Handbook of Pharmaceutical Biotechnology. Wiley Interscience, New Jersey. 2 Non-GMP conditions, non purified. 3 Susan Gotensparre (2007) Crucell. InPharmaTechnologist.com. 4 Non-GMP conditions, not purified, expected based on small scale production experience

High cell density attainable More protein produced Protein is secreted Both for small and large scale production Codon optimization established For heterologous proteins of both bacterial and mammalian origin

High productivity of C1 proven

10

1

2

34

2 3

20

KeyHighest yield claimedRealistic estimate

1

40

15

20

11

C1 for Biologics

Production of heavy & light chain successful MS/MS data reveals correct structure Binding to target confirmed via ELISA

Heavy chain

Light chain

Case Study 1: Humira Production of Fab successful The structure was confirmed by MS analysis Specificity of binding confirmed via ELISA

72h 96h

Case Study 2: Lucentis

C1 has produced biologically-active monoclonal antibodies Protease deficient strains with no mAb degradation successfully generated

Successful Initial Engineering of C1 for mAb Production

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C1 Expresses mAbs: Generic Humira and Lucentis

Prod

uctiv

ity

0 20 40 60 80 100 120 140 160

Time (h)

Ranibizumab level

DYADIC INFORMATION

Proteases Deletion for Stabilizing Humira

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0 4 8 24Single deletion

0 4 8 24Triple deletion

Hrs:

ΔproA ΔproA, ΔproB, ΔproC

First stage - Three proteases deletions enabled the development of a strain in which In vitro stability of heavy chain against C1. fermentation culture filtrates could be obtained

0 F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 buffer

Humira spiking

HC

LC

DYADIC INFORMATION

Successful expression of new mAbs for third party

The expression was done in the new developed C1 strain with lowproteins background

This protease deficient strain expresses stable mAbs.

Fermentation process optimization is underway to increase theproductivity further

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C1 Expresses mAb: More Success in mAb Expressions by C1

SDS-PAGE Western Blot

Con

trol

s

C1+

mAb

4

LC

HC

LC

HCm

Ab4

Mar

ker

C1

PS

C1+

mAb

4

DYADIC INFORMATION

Further Improvement of C1 Production Platform for BiologicsDyadic has experience with each of the molecular tools necessary to optimize the strain for high productivity and functionality for the targeted protein class

Genetic manipulation

Computational biology

Man9 G0 G2F

Genome sequence

Extensive genetic tools

Changing the cellular

regulatory circuit

+

Libraries of efficient strong

promoters

+/-

Libraries of TF and signal

peptides and / or carrier proteins

+/-

Libraries of protease

deletion strains

+/-

Glycoengineering to form mammalian-like

glycan structures in progress

Juststarted

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Gene 1Pr Carrier

DYADIC INFORMATION

C1 Strains DevelopmentSteps in developing better C1 strain for therapeutic protein production

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HCproduction strain

LC 0production strain

LC 1production strain

LC 103production strain

LC 104production strain

Basic therapeutic protein Productivity:

Proteolytic Activity:

0 g/L 20 g/L

High Low

Proteolytic Activity:

0 g/L 20 g/L

High Low

Proteolytic Activity:

0 g/L 20 g/L

High Low

Proteolytic Activity:

0g/L 20 g/L

High Low

Proteolytic Activity:

0 g/L 20 g/L

High Low

Basic therapeutic protein Productivity:

Basic therapeutic protein Productivity:

Basic therapeutic protein Productivity:

Basic therapeutic protein Productivity:

DYADIC INFORMATION

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C1 for Vaccines

C1 for Vaccine Production – Lower Costs & Higher Efficacy

Easy scale up, lower production costs due to higher yield (in comparison to CHO/yeast/ E. coli)

C1 produced antigen generated an equal, or better, immune response in mice than the industry standard antigen

International collaboration ongoing in vaccine development

Key Advantages

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The C1 technology platform:

A leap in technology that shows the potentialto change the way in which both Human andAnimal Health Biopharmaceutical companiesbring their biologic vaccines and drugs tomarket faster, in greater volumes, at lowercost, and with newer beneficial properties.

DYADIC INFORMATION

ZAPI, is a research and development program sponsored by the EU withthe goal of developing a platform suitable for the rapid development andproduction of vaccines and protocols to fast-track registration ofdeveloped products to combat epidemic Zoonotic diseases that have thepotential to effect the human population.

ZAPI Project goal

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ZAPI Project

Western blot

Δ Δ

72 h 96 h

WTWT Three different antigens each one for different virus were expressed by C1 and secreted to the medium

A specific protease that was responsible for cleaving one antigen was identified and knocked out

C1 antigen passed the first animal test – with more animal tests expected to be performed

An optimized fermentation process is now being developed

DYADIC INFORMATION

C1 Advantages as Production Host for Biologics

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High productivity

Low viscidity

High purity protein secretion

Defined media based on Glc

Fed batch technology no need for perfusion

5-7 days fermentation

C1 culture

Advance genetic tool box

Site specific integration Vs. random integration

DYADIC INFORMATION

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Human vaccine

Animal health

mAbs

FC-Fusions

Mimic mAbs

Hormones

(*)

(***)

(*)

(**)

(**)

(**)(*) Successful expression by C1 system(**) C1 expression in progress(***) Future plan

C1 culture

C1 – Potential Products

DYADIC INFORMATION

Summary - Key Advantages of C1

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Dyadic is looking for partners in the biopharmaceutical space to exploit the potential of C1.

For further inquiry, please contactmjones@dyadic.com

Further benefits: Unique properties that can be

engineered for the desired product profile

A toolbox for strain engineering to optimize production of different biologics (vaccines, simple proteins, antibodies)

Short production

cycles

2

High purity of produced

protein Robust and reliable

manufacturing

3

4

First product shown to be safe in animal studies

5

Highprotein yields

1

Thank You

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