Dyadic Inc.How the C1 Platform Will Change the

Production Approach for Recombinant Vaccines

(OTCQX: DYAI)

Influenza and Zoonotic DiseasesAugust 21-22, Birmingham, UK

Ronen Tchelet & Matthew Jones

Safe Harbor Regarding Forward-Looking Statements

2

Certain statements contained in this presentation are forward-looking statementswithin the meaning of the federal securities laws. These forward-looking statementsinvolve risks, uncertainties and other factors that could cause Dyadic’s actualresults, performance or achievements to be materially different from any futureresults, performance or achievements expressed or implied by such forward-lookingstatements. Any forward-looking statements speak only as of the date of thispresentation and, except as required by law, Dyadic expressly disclaims any intentor obligation to update or revise any forward-looking statements to reflect actualresults, any changes in expectations or any change in events. Factors that couldcause results to differ materially are discussed in Dyadic’s publicly available filings,including information set forth under the caption “Risk Factors” in our December 31,2016 Annual Report filed with OTC Markets on March 15, 2017. New risks anduncertainties arise from time to time, and it is impossible for us to predict theseevents 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 June 30, 2017 including ~ $7.4 million of cash received on July 6, 2017 from the escrow due to the DuPont Transaction

3DYADIC 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

4

Visc

osity

(cP)

Protein Yield

500

400

300

200

100

100

80

60

40

20

Prot

ein

(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

5DYADIC INFORMATION

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

6DYADIC 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)

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

8

C1 for Biologics

The expression of recombinant HAs by C1

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Expression and performance of 5 different HA’s

Influenza strain Expression Functional HANew Caledonia, A (H1N1) Yes YesTexas, A (H1N1) Yes YesPuerto Rico A (H1N1) Yes YesCalifornia, A (H1N1) Yes YesFlorida B Yes Yes

Agglutination test

DYADIC INFORMATION

Immunogenicity Study of HA/New Caledonia Produced by C1

Products: 3-Fold Escalating doses of C1-HA: 1 - 3.33 - 10 - 30 μg (8 mice/group=32 mice) Negative control groups

o PBS (5 mice)o C1 mock preparation 1(The fractions before the fractions where HA normally

eluted off the column): 30 μg (5 mice) o C1 mock preparation 2 (The fractions where the HA normally elutes off the

column) : 30 μg (2 mice)

10

D28

IM immunizations

D0 D49D27

Mice study was conducted by Sanofi-Pasteur

DYADIC INFORMATION

Immunogenicity Evaluation of C1 HA/New Caledonia

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1.0 μg 3.33 μg 10 μg 30 μg

Dose (μg HA)

Dose Response D493.0

2.5

2.0

1.5

1.0

00

0

0

++

+

+

+

0

0

0

+

+

+

0+

0

0+

+

+

0+

+

0

0

0

+

+

+

+

Antibody response measured by Hemaglutination Inhibition response after 2 Intra Muscular injections in Mice:

DYADIC INFORMATION

HA

titer

–D

49 (l

og10

)

830

453

104108

HA - C1

1 3.33 10 30

HI t

itera

gain

stIn

fluen

za v

irus

1000

100

10

530 30 0

C1Mock1

C1Mock1 PBS

Negative control

μg HA μg HA

HA-C1 Excellent Immunogenic Properties

1μg 3.33μl 10μg 30μg

50% (4/8 )

57.1% (4/7 )

100% (8/8 )

100% (8/8

C1 HA Dose Groups

Immunogenicity Study of HA/NC produced by C1

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The full length recombinant HA produced in C1 did not induce any negativeclinical signs in mice. No weight loss. No negative clinical signs during the experiment (visual observations taken each day).

The full length of HA/New Caledonia produced in C1 showed excellentimmunogenic properties in mice.

C1 can easily produce levels of 1 g/L of HAs and other antigens in 5 daysfermentation therefore:

In seasonal Influenza Vaccine—total doses distributed = 146M/year Each 0.5 mL dose is formulated to contain: 15 µg of HA for each strain. Thus, 3 X 1000L scale fermentation runs will be able to supply the annual global

HA/strain needs against Influenza of 2,175 g.

HA/New Caledonia

DYADIC INFORMATION

ZAPI, is a research and development program sponsored by the EU with the goal ofdeveloping a platform suitable for the rapid development and production of vaccinesand protocols to fast-track registration of developed products to combat epidemicZoonotic diseases that have the potential to effect the human population.

ZAPI Project goal

Three different antigens each one for different virus wereexpressed by C1 and secreted to the medium.

In the lead antigen the specific protease responsible for cleavagewas identified and knocked out and generated the production ofstable antigen.

One of the C1 expressed antigens was tested in a very smallmice test within the ZAPI project. Preliminary resultsindicated that the C1 produced antigen generated animmune response in mice that protected the mice, and didnot have negative effects on the health of the mice

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ZAPI Project

DYADIC INFORMATION

Nano-particleExpression molecule

BRUNE KD et al., Bioconjug Chem. 2017

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

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

We developed low proteases strain with low proteins background.

The mAbs are being secreted into the medium and form the correct structure.

C1 expresses several mAbs in a mid digit g/L in 6 days fermentation.

So far we reach 100% success in expressing different mAbs with the sameproductivity level.

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C1 Expresses mAbs

DYADIC INFORMATION

A) SDS-PAGE B) Western Blot

Con

trol

s

C1+

mAb

4

LC

HC

LC

HC

mAb

4

Mar

ker

C1

PS

C1+

mAb

4

mAb

4

(1) (2)

Preparation of Proteases Deletions Strains

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Identified Proteases

Class 1 3 proteases

Class 2 4 proteases

Class 3 1 protease

Class 4 1 protease

Class 5 no protease identified

Class 6 no protease identified

Class 7 no protease identified Fermentation broth fractions

are run on PAGE gel POI solution is covered the gel Identified white bands are

being extracted and theproteases are being identifiedby MS analysis

A CB

F1 F2 F3 F4 F5

Genome analysis and Blast Identification of C1 proteases Constructing single protease

deletion libraries

Creating POI-specific proteases deletion strain

Creating set of single protease deletion strains

A. Specific approach B. General approach

DYADIC INFORMATION

C1 Glycoengineering

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Glycoengineering of C1 strain will provide the formation of various glycan structures to evaluate immunogenicity

C1 typical Glycan structure

Man3Man6Man9 Man8 Man7 Man5

High mannose Core 5 – 25%

Glycoformstypes Genotype

Aglyco any

Man3 STT3, ΔEndoT, ΔALG3, (ΔALG6 or Gls2 or Endo-mannosidase)

Man5 STT3, Man’aseI, ΔEndoT

Hex6 STT3, ΔEndoT, ΔALG3

G0 Man3; GNTI, GNTII

G0F G0; GMD/FX (fucose synthesis pathway), FucT (fucosyltransferase)

G2 G0; GalT (galactosyltransferase)

DYADIC INFORMATION

Current heterologous glycoforms types

Defined glycoforms types

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 110production strain

LC 120production 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

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

bi-specific antibodies

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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