Turning DNA into Biologic Drugs quicker, cheaper and in larger quantities to improve the cost of protein therapeutics for the provider and patient

1. May 2012
The C1 Expression System Reinventing
Biologic Drug Production
(OTCQX: DYAI)

2. Safe harbor statement
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.
2

3. Dyadic overview
3
 Using synthetic biology, genomics and C1 molecular tools to glyco engineer and modify the
C1 Platform to reinvent the way biological drugs are developed & manufactured.
 Leverage two decades of C1 research & development, knowledge and commercial
experience gained from the ~ $100 million invested in Dyadic’s industrial biotech business.
 Future revenue through funded research and technology licensing, milestones & royalties
 Partners include Sanofi Pasteur and the ZAPI program
 Publically traded on the OTCQX exchange as DYAI
DYADIC AT A GLANCE

4. C1, in use by industry giants
4
Acquired by
C1 Platform, commercially proven

5.  With the proceeds from the DuPont transaction, along with anticipated industry and
governmental funding, Dyadic will have the necessary resources to accelerate the
further development and optimization of the C1 technology in the area of
biopharmaceuticals for many years.
– Programs we are currently engaged in; Sanofi Pasteur and the EU-funded ZAPI
program, are examples of the types of industry and governmental funded research
programs we will be pursuing.
 There is a growing and critical need to bring affordable generic versions of biological
drugs to the market and to patients sooner and at lower costs.
– Biosimilars Are Helping To Make Healthcare More Affordable
• Experts predict savings to the U.S. healthcare system could range from $44B to
$250B through 2025.1
 With C1’s unique growth and expression properties, coupled with its proven
programmability and scalability, C1 can be a game changer in developing &
manufacturing biological drugs faster, in larger quantities with both less CapEx and
OpEx, and potentially in some cases with even better performance.
5
The sale of Dyadic’s Industrial Biotech business to DuPont
for $75 million is a transformational event for Dyadic
1 Mulcahy AQ, Predmore Z, Mattke S. The cost savings potential of biosimilar drugs in the United States.
Available at: http://. Accessed July 29th, 2015. www.rand.org/content/dam/rand/pubs/perspectives/PE100/PE127/RAND_PE127.pdf
Dyadic – Dupont agreement

6. Biologics for
Pharmaceuticals

7.  Chemical drugs, like aspirin, are small molecules that are synthesized in a
laboratory. Because they are derived from chemicals with fixed structures,
they can be fully characterized by analytical techniques.
 In contrast, biologic drugs, or biologics, are large, complex molecules
designed to specifically interact with other protein molecules in the body. Due
to their complexity, biologics can only be manufactured in living cells, like
Dyadic’s hyper productive C1 living cells.
7
What is a Biologic?

8. Biologics currently account for 21% of total global spending on medicines
and are expected to grow at 10.1% CAGR until 2020 to $287m
8
Global pharmaceutical sales (US$ billion, list price, ex. rebates and discounts)
20142004
930
519
21%
79%
13%
87%
8%
Source: based on Alan Sheppard, IMS Health Thought Leadership, September 2015
Biologics are the fastest growing drug segment
The biologics market

9. Overview of the Global Biologic Drug Market
 In 2014, the global biological drugs market was worth US$161 Billion in 2014. With a 10.1% CAGR expected during
the forecast period of 2014 to 2020, the global biological drugs market is expected to reach a market value of
US$287 Billion by 2020. 1
 The “Global Biosimilar Market Outlook 2020”, reveals that the market, which was worth US$ 1.9 Billion in 2014, is
expected to reach US$25.5 Billion by 2020, growing at an impressive CAGR of 54.4%.
 The global biological drugs market is driven by factors such as:
– The growing prevalence of chronic conditions
– increasing geriatric population
– Accelerating regulatory compliance.
 This is due to increasing use of biological drugs in the treatment of diseases such as cancer, diabetes, and other
chronic diseases in the region. In addition, several clinics in the region are focusing on biological drugs for the
treatment of various diseases.
 The biological drugs market in Europe is growing due to increasing aging population in the region. For instance,
according to a UN report, elderly people accounted for 23.2% of the total population in Germany in 2000, and the
number is expected to reach 33.2% by 2025. Aging can lead to certain disorders such as age-related macular
degeneration and glaucoma, which require effective biological drugs for their treatment.
 The use of generics, including biosimilars is growing globally at an accelerated rate.
– Due to healthcare reform there is a big opportunity for biosimilars as doctors are incentivized to find and
prescribe lower cost treatments without negatively effecting patient care.
– Insurance companies, Medicare and Medicaid are forcing patients to try generics first and only pay for branded
drugs if the patients doctor can show it is necessary to attain the same health benefit.
1 Transparency Market Research - http://www.transparencymarketresearch.com/biological-drugs-market.html
Source: RNCOS - http://www.insightpharmareports.com/Affiliated-Reports/RNCOS/Global-Biosimilar-Market-Outlook-2020/
9

10. The C1 technology will be further developed to enable its
use in the development & manufacturing of biologic drugs
10
• Biosimilar market
$25.53 billion by
2020 (projection)
• Global biological
drug market will
reach $287 billion
by 2020 (projection)
• Global insulin
market $42 billion
by 2019
(projection)
• Vaccine market
approx. $35 billion
in 2014
Recombinant
Vaccines
(Human and
veterinary)
Biosimilars /
Biobetters
(non-Gly)
Biosimilars /
Biobetters
(Gly)
New
products
21
4 3
Dyadic market projection

11. 11
Vaccines
C1 Vaccine have
to go through pre-
clinical
Vaccine must be
proven through
clinical trials
Non-
glycosylated
Biosimilars
Regulatory
pathways still
developing
Most leading
biologics coming
off patent are
glycosylated
Development requires
deep expertise in
biologics development
and manufacturing
scale-up
Glycosylated
Biosimilars /
Biobetters
C1 requires
additional
research and
development to
enable:
• glycoprotein
production with
uniform Mannose
structures
• glycoprotein
production with
humanization of
N-glycan
structures
New drug
development
Regulatory
approval
Glyco-
engineering
development
Vast screening
development
Dyadic challenges

12. WHY RECOMBINANT
VACCINES?
AND WHY NOW?

13.  Global market projected to rise to $ 100 B by 2025
 There are more than 120 new products in the development
pipeline
 60 products are of importance for developing countries.
 Vaccines: becoming an engine for both the human and animal
pharmaceutical industry
 Changing status of vaccines within the pharmaceutical industry.
13
 The vaccine market quadrupled in value from
$ 5B in 2000 to almost $ 24 B in 2013.
 Influenza vaccine market: estimated at $2.9 B in 2011
to $3.8 B by 2018.
 US : $1.6 B in 2011 to $2.2 B in 2018
13
The vaccines market opportunity

14. CURRENT DYADIC VACCINE
PROGRAMS
14

15. R&D collaboration to utilize C1 expression
system for vaccine applications
 Sanofi Pasteur is one of the largest vaccine
companies in the world
 Goal is to speed up the development &
production of new vaccines at a lower cost
C1 produced vaccine showed an equal or
better immune response in mice trials than
the existing vaccine
15
Sanofi partnership in drug development

16.  Dyadic recently delivered what we believe to be sufficient quantities
of a second vaccine produced using C1 for Sanofi to test in mice
trials.
– Objective of this mice trial is to see if the same encouraging
results that were obtained in the first mice trial reported in a
Press Release on October, 7 2015, will be reproduced with this
second C1 produced vaccine.
• “C1 produced vaccine showed an equal or better immune
response in mice trials than the existing vaccine”
 We are working on expressing and producing sufficient quantities of
additional vaccine variants in the Sanofi research project for further
evaluation by Sanofi.
Reproducing encouraging results
16
 Expect a Go / No Go decision from Sanofi sometime in the later
half of 2016.

17. 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.
Select Commercial Parties Select Academic Institutions
ZAPI – New €22 Million Vaccine R&D Program
17

18.  Dyadic Nederland's, BV. is using C1 to express vaccines and neutralizing
agents which if such research is successful we anticipate the C1 platform
will 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.
ZAPI regulatory pathway guidance
18

19. WHY BIOSIMILARS?
AND WHY NOW?

20. Biosimilars Are Helping To Make Healthcare More
Affordable
 Today, the healthcare landscape is rapidly evolving. One key factor driving this change is the increasing
use of biologic medications. Biologic medicines offer important treatment options for disabling and life-
threatening diseases.
 Unfortunately, the cost of biologic drugs can be prohibitively expensive. With more patients now
shouldering out-of-pocket expenses for medications, there is an urgent need to provide expanded access
to affordable biologics. Biosimilars offer the exciting possibility of providing patients lower cost alternatives
to branded biologic products.
20
Biosimilars

21.  As the aging population grows in developed and undeveloped
countries there is a growing need to deliver more medicines
and therapies to more people around the world faster, in
greater volumes and at lower cost
 Investment into biosimilars is at an all-time high, with over 70
biosimlar mAbs under development with over a dozen in Phase
I, Phase II and Phase III clinical trials
 First biosimilar, Zarxio (filgrastim-sndz), was approved by the
U.S. FDA in March 2015
 Drug companies continue to invest heavily into making
incremental changes to their existing drugs, and manufacturing
processes, such as developing and producing drugs using Cho
cells
 “Global Biosimilar Market Outlook 2020”, the biosimilar
market, was worth US$ 1.89 Billion (2014), expected to reach
US$25.53 Billion (2020), growing at a CAGR of 54.4%.3
 There is little sign yet of any disruptive improvement in the
efficiency of drug research translating into cheaper medicines.
The health systems and insurers have little choice but to pay
the drug companies whatever they are ask for.
21
Growing Demand For Lower Cost Biologic Drugs
Biosimilar market growing
at a CAGR of 54.4%, to
reach $25 billion by 2020

22. Source: http://lab.express-scripts.com/insights/drug-options/infographic-two-biosimilars-to-save-227-billion
Avastin® – (bevacizumab)
Epogen® – (epoetin alfa)
Herceptin® – (trastuzumab)
Humira® – (adalimumab)
Intron A® – (interferon alfa-2a)
Neulasta® – pegfilgrustin
Neupogen® – filgrastin
Pegnitron® – peginterferon alfa-2a
Prochit® – epoetin alfa
Remicade® – infliximab
Rituxan® – rituximab
00
20
40
60
80
100
120
140
2014 2016 2018 2020 2022 2024
$140B
$120B
$100B
$80B
$60B
$40B
$20B
$0
Cost without
Biosimilars
Cost with
Biosimilars
 FDA panel recommends first biosimilar approval, Zarxio a Novartis cancer drug as a biosimilar
alternative to Amgen's Neupogen
 The approval of Zarxio could save patients and payers as much as $5.7 billion over the next decade
$
250B
Potential saving
22
$250 billion could be saved in next decade with 11 new biosimilars
Biosimilars saving

23. 23
SepAugJulyJunMarJan
Market trends
Regulatory
Market trends
Regulatory
Omnitrope sole
subsidied somatropin
from Jan 2015 in NZ
Granix close to
20%
penetration
USA
Australia to recommend
pharmacy-level substitution of
biosimilars
Novartis launches
Zarxio in US at
15-percent
discount to
Neupogen
Enbrel approval in
South Korea
Hospira launches first
BS mAbs inflectra in
major European
markets
Biosimilar 15%
share of Spanish
infliximab market
(June only)
Samsung submits
infliximab Biosimilar
application to EMA
Biosimilar 90%
share of danish
infliximab market
(July only)
Finland stands
behind
interchangeability of
biosimilars
Lilly/BI launch
lantus BS in UK
(15% discount)
FDA approves
first biosimilar
Zarxio
Samsung submits
Enbrel Biosimilar
application to EMA
Source: Alan Sheppard, IMS Health Thought Leadership, September 2015
2015 – Biosimilars continue to make steady progress
Biosimilars progress in 2015

24. Where Are Biosimilars Currently Available?
 Biosimilars are already available worldwide through biosimilar approval pathways implemented in
countries across the globe.
 The European Union has been approving biosimilars since 2006. Other highly regulated markets
such as Japan, Australia, and Canada have been approving biosimilars since 2010.
 Millions of patients have already received treatment in highly regulated markets with the same level
of safety and efficacy as the reference biologics.3
 The first biosimilar was approved in the United States in 2015.
 As biosimilars become more prevalent and accessible, experts predict savings to the U.S.
healthcare system could range from $44B to $250B through 2025.1
Accelerating Global Adoption of Biosimilars
24
3 Mulcahy AQ, Predmore Z, Mattke S. The cost savings potential of biosimilar drugs in the United States.
Available at: http://www.rand.org/content/dam/rand/pubs/perspectives/PE100/PE127/RAND_PE127.pdf. Accessed July 29th, 2015.

25. 20
Strong Global Pipeline Activity, especially for
Etanercept & Adalimumab Biosimilars
Biosimilars Congress Europe
SB2 (Samsung Bioepis)
GS071 (Aprogen)
Infliximab
PF-06438179 (Pfizer)
NI-071 (Nichiiko)
BOW15
(Epirus)
ABP 710 (Amgen)
BioXpress
Harvest Moon
Tocilizumab
BOW070 (Epirus)
Oncobiologics
Golimumab
Oncobiologics
Abatacept
BioXpress
M834 (Momenta)
Rituximab
PF-05280586 (Pfizer)
CT-P10 (Celltrion)
GP2013 (Sandoz)
BI 695500 (BI)
ABP 798 (Amgen)
MK-8808 (Merck)
Harvest Moon
BioXpress
AP052 (Aprogen)
MabionCD20 (Mabion)
Adalimumab
SB5 (Samsung)
ABP501 (Amgen)
Biocon
BI
GP2017 (Sandoz)
FKB327 (Kyowa Kirin)
Oncobiologics
PF-06410293 (Pfizer)
LBAL (LG Life)
CHS-1420 (Coherus)
Harvest Moon
BioXpress
(BOW050) Epirus
M923 (Momenta)
Etanercept
CHS-0214 (Coherus)
LBEC0101(LG Life)
Tunex (Mycenax )
GP2015 (Sandoz)
SB4 (Samsung Bioepis)
Biocon
(PRX-106) Protalix
BioXpress
Avasthagen
Filed
Late Phase
Early Phase
Preclinical
Molecule Filed
SB2 EU
SB4 EU
MabionCD20 Argentina
AP052 South Korea
BioXpress
Source: Alan Sheppard, IMS Health Thought Leadership, September 2015
As more Biosimilars reach the market, competition will grow and
drive down prices
25
Biosimilars market growth

26. EMA approved Biosimilars
26
Authorization
year
Product name Active substance Manufacturer/Company name
2006 Omnitrope somatropin Sandoz
2007 Abseamed epoetin alfa Medice Arzneimittel Pütter
2007 Binocrit epoetin alfa Sandoz
2007 Epoetin alfa Hexal epoetin alfa Hexal
2007 Retacrit epoetin zeta Hospira
2007 Silapo epoetin zeta STADA R & D
2008 Biograstim filgrastim CT Arzneimittel
2008 Ratiograstim filgrastim Ratiopharm
2008 Tevagrastim filgrastim Teva Generics
2009 Filgrastim Hexal filgrastim Hexal
2009 Zarzio filgrastim Sandoz
2010 Nivestim filgrastim Hospira
2013 Grastofil filgrastim Apotex
2013 Inflectra infliximab Hospira
2013 Ovaleap follitropin alfa Teva Pharma
2013 Remsima infliximab Celltrion
2014 Abasaglar (previously Abasria) insulin Eli Lilly/Boehringer
2014 Abasaglar (previously Abasria) glargine Ingelheim
2014 Accofil filgrastim Accord Healthcare
2014 Bemfola follitropin alfa Finox Biotech
(*) EMA - Generic and Biosimilars initiatives, Data collected on 12 May 2012, updated on 27 February 2015

27. Biological drugs on the market
27
Molecule Trade names Primary
Marketer
Type 2014
global
sales
2013
global
sales
EU
expiry
date
US
expiry
date
Glyco-
solation
Adalimumab Humira, Exemptia Abbott mAb $12.8bn $11.0b
n
2018 2016 Yes
Etanercept Enbrel Amgen/
Pfizer
Glycoprotein 8.8 8.7 2015 2028 Yes
Infliximab Remicade, Remsima,
Inflectra
J&J mAb 9.8 8.4 2014 2018 Yes
Insulin
Glargine
Landus, Toujeo,
Abasaglar, Basaglar
Sanofi Insulin 6.7 8.0 2014 2014 No
Rituximab Rituxan, MabThera,
Zytux
Roche/
Biogen
mAb 6.8 7.9 2013 2016 Yes
Trastuzumab Herclon, Herceptin Roche mAb 6.2 7.0 2014 2019 Yes
Pegfilgrastim Neulasta, Neulastim,
Imupeg
Amgen Glycoprotein 4.6 4.4 2017 2015 Yes
Ranibizumab Lucentis, etc. Roche mAb
fragment
4.1 4.3 2019 2019 No
Eyrthropoietin
(EPO)
Epogen, etc. Amgen Glycoprotein 2.4 3.4 2013 2015 Yes
Darbepoetin
alfa (Darbo)
Aranesp Amgen Glycoprotein 2.3 3.3 2016 2016 Yes
Therapeutic Biologic Drug Market to Soar at 10.1% CAGR till 2020,
~ $287 Billion

28. THE C1 EXPRESSION
SYSTEM
28
Due to their complexity, biologics can only be manufactured in living cells.
C1, hyper productive living cells

29. C1 unique morphology
C1-propagules by scanning microscopy. Propagules instead of hyphae: low
viscosity, high productivity.
29
Morphology change: hyper productivity, low viscosity

30. Development of protein hyper-producing strains
Highcellulase, lowviscosity
(mycelialfragmentation)
C1
UV13-6
HCprt-
HC
NG7C-19
Wildtype
UVmutagenesis
Cellulaseover producer
De-repressedcellulase
production
UVmutagenesis
NTG* mutagenesis
esis
UVmutagenesis
Protease-deficient
Highcellulase, lowviscosity
(mycelialfragmentation)
HCprt-
Wildtype
genesis
Cellulaseover producer
De-repressedcellulase
production
genesis
utagenesis
UVmutagenesis
Protease-deficient
Viscosity Protein:Biomass Protein Yield
NG7C-19 (hi visc) UV18-25 (low visc) UV18-25 (optimized)
Viscosity Protein:Biomass Protein Yield
NG7C-19 (hi visc) UV18-25 (low visc) UV18-25 (optimi
NG7C-19 HC
Viscosity Protein
yield
Viscosity(cP)
100
200
300
400
500
Protein(g/L)
20
40
60
80
100
Viscosity Protein:Biomass Protein Yield
NG7C-19 (hi visc) UV18-25 (low visc) UV18-25 (optim
Development lineage of protein hyper-producing strains
30

31. The LC strain for protein production
Development high productivity low protease activity of host
strains for specific proteins productions
LCprt- with specific protease disruption
Protease deficient strain
De-repressed cellulase production
31
Cellulase over producer
Wild-type
High cellulase,
Low viscosity
Low cellulase,
Low viscosity

32. pH5.5
pH7.0
pH8.5
0
200
400
600
800
1000
LC LCprt- LCprt-Δalp1
ProteaseactivityU/ml
pH5.5
pH7.0
pH8.5
B
Protease activity
Host strains with low protease activity developed for heterologous
protein production
LC with low protease activity
32

33. 33
High yields, high purity, low cost
at industry leading scale
Two serendipitous mutations created the world class C1 expression system
100 g/L
80%
Purity
500,000
Liter scale
 Over 100 grams
per liter protein
 Up to 80% of
target protein has
been achieved
 Currently
produced in up to
500,000 liter
scale
Synthetic biology start-ups – large and
small – struggle with the reality of scaling
up microscopic cellular factories into
profitable business models
Dyadic’s patented & proprietary C1
expression system is being used to
produce biological products at very high
yields, low cost and in large commercial
fermenters.
World Class Productivity & Purity

34. LC expression of specific proteins
LC-1 LC-2 LC-3 LC-4
34
 Dyadic’s C1, LC strains
successfuly used for production
of single and multiple proteins
derived from fungal, bacteria,
bacterial-directed evolution,
mammalian, human and viral
strains.
 The expression reaches high
production levels of secreted
proteins – > 100 g/l with ~ 80%
purity of the targeted protein.
 The LC strain/s is fermented at
large commercial scale.
WT
LC
HC
The revolutionary C1 LC “White Strain”
C1 strain types
C1 LC “White Strains”
have very different
morphology than the C1
Wild Type Strains

35.  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
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 trails:
 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
Generally Recognized as Safe (GRAS) status
acknowledged by the FDA
35
C1 has an excellent safety profile

36. C1 Technology Overview
36

37. THE C1 EXPRESSION
SYSTEM FOR
BIOPHARMACEUTICALS

38. C1 expression system turns DNA into Biologic Medicines
38
Treatment options
for disabling & life-
threatening diseases
Dyadic Inside® Biologic Medicines
C1 Cells turns
genes into biologic
medicines
A template for
enzymes and other
proteins
Genes

39.  Expression was achieved of both: heavy and light chains
were obtained.
 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.
39
Heavy chain
Light chain
Peter Punt, TNO 2007
Produced biologically active monoclonal antibodies in C1
Expression of mAb in C1

40. C1 CELL ENGINEERING
PROGRAMS
40

41. Dyadic’s advanced genetic toolkit for manipulation of C1
C1 Genetics tools
41

42. MTP-based C1 fermentation property enables rapid screening
of any new inserted protein
42
Library
construction Screening Fermentation
Hit
verification
Chromosome NotI NotI
NotI NotI
C
BamHI BamHI
hTEL Pcbh TcbhpyrG insert AmpR pyrE hTEL
NotI NotIB
A
BamHI
pPinsT pyrE tel pyrG
Not I
pyrE
hTEL
I-CeuI
hTEL
pyrG
Pcbh
insert DNA
Tcbh
AmpR
BamHI
Not I
Chromosome NotI NotI
NotI NotI
C
BamHI BamHI
hTEL Pcbh TcbhpyrG insert AmpR pyrE hTEL
NotI NotIB
A
BamHI
pPinsT pyrE tel pyrG
Not I
pyrE
hTEL
I-CeuI
hTEL
pyrG
Pcbh
insert DNA
Tcbh
AmpR
BamHI
Not I
RescreeningTransformation
2 M 4 M 6 M 8 M
Screening
Rapid screening

43. LC expression technology
Gene 1
Optimizing codon usage
Libraries of efficient
strong promoter
Libraries of TF and signal
peptides and / or carrier
proteins
Protease activity
reduction LC
Strain
Adjustment of post-
translational
modification
Computational
Biology for
Advanced genetic manipulation methodologies enable rapid and
efficient cloning of heterologous genes
43

44. Protease deficient C1 host strains
44
C1(wt)
0
10
20
30
40
0 20 40 60 80 100
time (h)
peptidebonds(mmol)
UV18-25#100f
0
10
20
30
40
0 20 40 60 80 100
time (h)
peptidebonds(mmol)
 Protease deficient strains were developed
to improve the stability of expressed
heterologous proteins.
 Elimination of 3 specific active proteases
resulted in complete stable light and heavy
chain of IgG1 expressed in C1.
Protease
 State of the art molecular engineering methods based on computational
biology will enable us to eliminate specific proteases to stabilize biologic
proteins.
C1 WT C1 Δ proteases
LC with low protease activity

45. C1 Glycans resemble human structure
40
C1 Glycans

46. C1 Glycoengineering for biosimilars and biobetters applications
G0
N-acetylglucosamine
Mannose
Fucose
Galactose
Sialic acid
G1
Important in ADCC.
Deleted forms have 10-
100x higher potency
1 or 3 additional
mannose may be
added.
G0: Simplest structure that
is human and yet still fully
functional. “Human neutral”
Terminal
Sialic acid not
necessary.
Dyadic will collaborate with several Biotechnology groups to use
state of the art technology for glyco-engineering C1 to resemble
human structure.
Glycoengineering C1 Cells
41

47. 47
 C1 genome sequenced and annotated
 Extensive molecular toolbox with high efficiency, stable integration
 Advantageous growth conditions with low cost defined media
 Track record of producing high protein yields, under low viscosity, at
varying scales, up to 500,000 liters
 Excellent safety record and Generally Recognized as Safe (GRAS) status
acknowledged by the FDA
Platform
technology
 Programmable to produce tailored “purer” proteins
 Effective homologous and heterologous gene expression
 Expressed proteins are secreted into the fermentation broth
 Serves as both a research and production host
Cost effective
product
development
Freedom to
operate
 No royalty stacking
47
C1 Expression System advantages

48. 48
When 10,000 liter production
fermenter can be reduced to
200 liter the saving is significant
in 3 ways:
1) Capital investment
required to build launch
capacity
2) factory with launch
capacity needs to be
constructed 24 month
before FDA approval,
or very costly CMO
3) FDA license easier for
small factory
C1 advantage in saving CapEx investment
20-
10-
300-
500-
20-
10-
300-
100-
2 g/l 20 g/l
C1 high productivity lowers development costs
Biosimilars saving with C1

49. DYADIC'S C1 TECHNOLOGY
POISED FOR SUCCESS
49

50. 50
Moscow State University
Dyadic has a history of strong scientific collaborations

51. 51
 The C1 White Strain 2.0 produces high levels of purer proteins
 Glycoengineering C1 cells to adapt it to the specific needs for broad
biopharmaceutical products
 Continued clean-up of the expression system background and further
improvements made to downstream purification process
Technology
improvements
 Sanofi project has continued into 2016
 New EU funded program (ZAPI) with Merial for animal vaccines
through 2018
Progress with
commercial
partners
Additional
resources
 Added two new Board members with significant pharmaceutical
industry experience
 Added additional resources and expertise to address technology
hurdles
 Strengthened Balance Sheet
 Focus on Biopharmaceuticals
We are well-positioned in the biologics market

52. 52
 C1 is a developed host system that has high potential to be used for
the Biopharmaceutical market.
 For vaccine production C1 system may offer rapid development time
and flexible production capacity at different sites.
 The global Biosimilar market is growing steadily since the need for
lower cost biologics among the developed and pharma emerging
countries is critical.
 “Global Biosimilar Market Outlook 2020”, reveals that the market, which was worth
US$ 1.89 Billion in 2014, is expected to reach US$ 25.53 Billion by 2020, growing at an
impressive CAGR of 54.4%. 3
 The increasing Biosimilar competition will eventually drive the cost
down to 45% and below.
 C1 high productivity system, for Vaccines, mAbs and other Biologics,
will offer significant saving in CapEx and operational cost.
Summary
Therapeutic Biologic Drug Market to Soar at 10.1% CAGR till
2020, ~ $287 Billion