May 2012
The C1 Expression System Reinventing Biologic Drug Production
(OTCQX: DYAI)
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.
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Dyadic overview
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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
C1, in use by industry giants
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Acquired by
C1 Platform, commercially proven
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.
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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
Biologics for Pharmaceuticals
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.
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What is a Biologic?
Biologics currently account for 21% of total global spending on medicines
and are expected to grow at 10.1% CAGR until 2020 to $287m
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Global pharmaceutical sales (US$ 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
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.htmlSource: RNCOS - http://www.insightpharmareports.com/Affiliated-Reports/RNCOS/Global-Biosimilar-Market-Outlook-2020/
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The C1 technology will be further developed to enable its use in the development & manufacturing of biologic drugs
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• 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
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4 3
Dyadic market projection
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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 withuniform Mannosestructures
• glycoproteinproduction withhumanization ofN-glycanstructures
New drug development
Regulatory approval
Glyco-engineering development
Vast screening development
Dyadic challenges
WHY RECOMBINANT VACCINES?AND WHY NOW?
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.
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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
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The vaccines market opportunity
CURRENT DYADIC VACCINE PROGRAMS
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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
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Sanofi partnership in drug development
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
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Expect a Go / No Go decision from Sanofi sometime in the later half of 2016.
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
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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
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WHY BIOSIMILARS?AND WHY NOW?
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.
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Biosimilars
As the aging population grows in developed and undevelopedcountries there is a growing need to deliver more medicinesand therapies to more people around the world faster, ingreater volumes and at lower cost
Investment into biosimilars is at an all-time high, with over 70biosimlar mAbs under development with over a dozen in PhaseI, Phase II and Phase III clinical trials
First biosimilar, Zarxio (filgrastim-sndz), was approved by theU.S. FDA in March 2015
Drug companies continue to invest heavily into makingincremental changes to their existing drugs, and manufacturingprocesses, such as developing and producing drugs using Chocells
“Global Biosimilar Market Outlook 2020”, the biosimilarmarket, was worth US$ 1.89 Billion (2014), expected to reachUS$25.53 Billion (2020), growing at a CAGR of 54.4%.3
There is little sign yet of any disruptive improvement in theefficiency of drug research translating into cheaper medicines.The health systems and insurers have little choice but to paythe drug companies whatever they are ask for.
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Growing Demand For Lower Cost Biologic Drugs
Biosimilar market growing at a CAGR of 54.4%, to reach $25 billion by 2020
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® – rituximab00
20
40
60
80
100
120
140
2014 2016 2018 2020 2022 2024
$140B
$120B
$100B
$80B
$60B
$40B
$20B
$0
Cost withoutBiosimilars
Cost withBiosimilars
FDA panel recommends first biosimilar approval, Zarxio a Novartis cancer drug as a biosimilaralternative to Amgen's Neupogen
The approval of Zarxio could save patients and payers as much as $5.7 billion over the next decade
$250BPotential saving
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$250 billion could be saved in next decade with 11 new biosimilars
Biosimilars saving
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SepAugJulyJunMarJan
Market trends
Regulatory
Market trends
Regulatory
Omnitrope sole subsidied somatropinfrom 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 Biosimilarapplication 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
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
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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.
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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
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Biosimilars market growth
EMA approved Biosimilars
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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
Biological drugs on the market
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Molecule Trade names Primary Marketer
Type 2014 globalsales
2013 global sales
EU expirydate
US expiry date
Glyco-solation
Adalimumab Humira, Exemptia Abbott mAb $12.8bn $11.0bn
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 mAbfragment
4.1 4.3 2019 2019 No
Eyrthropoietin(EPO)
Epogen, etc. Amgen Glycoprotein 2.4 3.4 2013 2015 Yes
Darbepoetinalfa (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
THE C1 EXPRESSION SYSTEM
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Due to their complexity, biologics can only be manufactured in living cells.
C1, hyper productive living cells
C1 unique morphology
C1-propagules by scanning microscopy. Propagules instead of hyphae: low viscosity, high productivity.
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Morphology change: hyper productivity, low viscosity
Development of protein hyper-producing strains
High cellulase, low viscosity (mycelial fragmentation)
Low cellulase, low viscosity
C1
UV13-6
HCprt-
HC
NG7C-19
LC
LCprt-
Wild type
UV mutagenesis
Cellulase over producer
De-repressed cellulase production
UV mutagenesis
NTG* mutagenesis
HCprt-Δalp1
LCprt-Δalp1
UV mutagenesis
UV mutagenesis
alp1 knock-out
alp1 knock-out
UV mutagenesis
HCprt- with major protease gene alp1 disrupted
LCprt- with major protease gene alp1 disrupted
Protease-deficient
Protease-deficient
High cellulase, low viscosity (mycelial fragmentation)
Low cellulase, low viscosity
C1
UV13-6
HCprt-
HC
NG7C-19
LC
LCprt-
Wild type
UV mutagenesis
Cellulase over producer
De-repressed cellulase production
UV mutagenesis
NTG* mutagenesis
HCprt-Δalp1
LCprt-Δalp1
UV mutagenesis
UV mutagenesis
alp1 knock-out
alp1 knock-out
UV mutagenesis
HCprt- with major protease gene alp1 disrupted
LCprt- with major protease gene alp1 disrupted
Protease-deficient
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 (optimized)NG7C-19 HC
Viscosity Proteinyield
Vis
cosi
ty (
cP)
100
200
300
400
500
Pro
tein
(g/
L)
20
40
60
80
100
Viscosity Protein:Biomass Protein Yield
NG7C-19 (hi visc) UV18-25 (low visc) UV18-25 (optimized)
Development lineage of protein hyper-producing strains
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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
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Cellulase over producer
Wild-type
High cellulase,Low viscosity
Low cellulase,Low viscosity
pH
5.5
pH
7.0
pH
8.5
0
200
400
600
800
1000
LC LCprt- LCprt-Δalp1
Pro
teas
e a
ctiv
ity
U/m
l pH 5.5
pH 7.0
pH 8.5
B
Protease activity
Host strains with low protease activity developed for heterologous protein production
LC with low protease activity
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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
LC expression of specific proteins
LC-1 LC-2 LC-3 LC-4
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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
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 toxigenicitydata: 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
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C1 has an excellent safety profile
C1 Technology Overview
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THE C1 EXPRESSION SYSTEM FOR BIOPHARMACEUTICALS
C1 expression system turns DNA into Biologic Medicines
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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
Expression was achieved of both: heavy and light chainswere obtained.
Heterodimeric antibody molecules were formed efficiently,allowing simple purification of the protein from the culturefluid using Protein A.
Cell-based bio-assays performed revealed almost completebioactivity.
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Heavy chain
Light chainPeter Punt, TNO 2007
Produced biologically active monoclonal antibodies in C1
Expression of mAb in C1
C1 CELL ENGINEERING PROGRAMS
40
Dyadic’s advanced genetic toolkit for manipulation of C1
C1 Genetics tools
41
MTP-based C1 fermentation property enables rapid screening of any new inserted protein
42
Library construction Screening Fermentation
Hit verification
Chromosome NotI NotI
NotI NotIC
BamHI BamHI
hTEL Pcbh TcbhpyrG insert AmpR pyrE hTEL
NotI NotIB
A
BamHI
pPinsT pyrE tel pyrG
Not I
pyrE
hTEL
I-CeuIhTEL
pyrGPcbh
insert DNA
Tcbh
AmpR
BamHI
Not I
Chromosome NotI NotI
NotI NotIC
BamHI BamHI
hTEL Pcbh TcbhpyrG insert AmpR pyrE hTEL
NotI NotIB
A
BamHI
pPinsT pyrE tel pyrG
Not I
pyrE
hTEL
I-CeuIhTEL
pyrGPcbh
insert DNA
Tcbh
AmpR
BamHI
Not I
RescreeningTransformation
2 M 4 M 6 M 8 M
Screening
Rapid screening
LC expression technology
Gene 1
Optimizing codon usageLibraries of efficient
strong promoter
Libraries of TF and signal peptides and / or carrier
proteins
Protease activity reduction LC
StrainAdjustment of post-
translational modification
Computational Biology for
Advanced genetic manipulation methodologies enable rapid and efficient cloning of heterologous genes
43
Protease deficient C1 host strains
44
C1(wt)
0
10
20
30
40
0 20 40 60 80 100
time (h)
pept
ide
bond
s (m
mol
)
UV18-25#100f
0
10
20
30
40
0 20 40 60 80 100
time (h)
pept
ide
bond
s (m
mol
)
Protease deficient strains were developedto improve the stability of expressedheterologous proteins.
Elimination of 3 specific active proteasesresulted in complete stable light and heavychain of IgG1 expressed in C1.
Protease
State of the art molecular engineering methods based on computationalbiology will enable us to eliminate specific proteases to stabilize biologicproteins.
C1 WT C1 Δ proteases
LC with low protease activity
C1 Glycans resemble human structure
40
C1 Glycans
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
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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
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C1 Expression System advantages
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
DYADIC'S C1 TECHNOLOGY POISED FOR SUCCESS
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50
Moscow State University
Dyadic has a history of strong scientific collaborations
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
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C1 is a developed host system that has high potential to be used forthe Biopharmaceutical market.
For vaccine production C1 system may offer rapid development timeand flexible production capacity at different sites.
The global Biosimilar market is growing steadily since the need forlower cost biologics among the developed and pharma emergingcountries 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 animpressive CAGR of 54.4%. 3
The increasing Biosimilar competition will eventually drive the costdown 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