august 10, 2016 (otcqx: dyai) - dyadic …...2016/08/10 · (3) global market study on biological...
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August 10, 2016(OTCQX: DYAI)
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
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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.
Strategic Opportunity (2): THE TECHNOLOGY
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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
Strategic Opportunity (3): THE OPPORTUNITY
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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
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
C1 Platform Technology
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Moscow State University
Scientific CollaborationsDyadic has a history of strong scientific collaborations
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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
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
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1992 1995 1997 2005 2009 2016
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
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
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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
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
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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
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C1HC
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
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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
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C1 Platform Technology Overview
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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
Vaccine Applications
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$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
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U.S. Vaccine Market
Global Vaccine Market
$32B
$100B
$0
$20
$40
$60
$80
$100
$120
2014 2025
Source: World Health Organization.
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
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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
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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
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Biologics Applications
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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%
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
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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
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Case Study: Generic Humira (Cont.)
In vitro stability of heavy chain against C1 fermentation culture filtrates
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0 4 8 24Single deletion
0 4 8 24Triple deletion
Hrs:
ΔproA ΔproA, ΔproB, ΔproC
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 $3.5B
in 2015 (2)
27(1) Human Insulin Market - Drugs Type, Brands, Delivery Devices, Applications - Forecasts to 2020(2) Global Lucentis Market – FierceBiotech August 8, 2016
C1 Platform Technology Advantages
Grows and expresses proteins over a wide range of pH levels and temperatures– Allows gene expression under conditions optimal for the activity and stability of a wide range of targets
Integrated gene expression system increases the likelihood of successful expression
C1 platform technology offers many advantages over current expression systems
Bacterial Fungal Mammalian E.coli Saccharomyces Pichia C1 CHO
Cost low low low low high
Growth rate high high high high low
Culture media and conditions simple simple simple simple complex
Post-translational modifications no some some some yes
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In the same amount of time, Dyadic’s C1 platform technology is expected to produce up to 20 times the g/L compared to CHO cells(1)
~CHO Cell Yield 2-10 g/L(2)
C1 Industrial Yield (Actual)
C1 Biopharmaceutical Yield (Expected in 2-3 years)
12-15 days
10-20 g/L 20-40 g/L
80 g/L 160 g/L
5-7 days
5-7 days
(1) C1 has a single cycle fermentation time of approximately 5-7 days compared to CHO single cycle fermentation time of 12-15 days.(2) Range based on approximate yield of Lonza and ThermoFisher CHO cell line expression systems.
5-7 days
5-7 days
Indicative Savings for Biosimilars with C1C1 productivity provides the potential to dramatically lower CapEx
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C1CHO
(1) Represents lower range of yield. Refer to page 15 for additional details.
500
100
0
50
100
150
200
250
300
350
400
450
500
2-10 G/L 20-40 G/L
DE
VE
LOP
ME
NT
CO
STS
($ 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
Conclusion: Commercially Proven
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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
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.
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Trial against former outside legal counsel remains set for January 6, 2017
Thank you. Q&A:
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