C1, An Ultra-High Yielding, Game Changing Gene Expression Platform - - PowerPoint PPT Presentation

C1, An Ultra-High Yielding, Game Changing Gene Expression Platform

Dyadic (non-conf) BD Overview

February, 2018

Safe Harbor Regarding Forward-Looking Statements

DYADIC INFORMATION 2

Certain statements contained in this presentation are forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve risks, uncertainties and other factors 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. Any forward-looking statements speak only as of the date of this presentation and, except as required by law, Dyadic expressly disclaims any intent or obligation to update or revise any forward-looking statements to reflect actual results, any changes in expectations or any change in events. Factors that could cause 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 24, 2017. New risks and uncertainties arise from time to time, and it is impossible for us to predict these events or how they may affect us.

Title and Safe Harbor Regarding Forward-Looking Statements 1 Table of Contents 3 Dyadic Overview 4 C1 Commercially Successful in Industrial Biotech 7 C1 Technology Platform - Where to Play and How to Win 8 Biopharma Industry and Society Challenges 11 C1 Production Host 15 C1 For Biologics 17 C1 Technology Combat Emerging Diseases and Threats 22 Advantages of using C1 for the Development & Production of Biologics and Vaccines 25 Summary 28

Table of Contents

DYADIC INFORMATION 3

Dyadic Overview

DYADIC INFORMATION 4 1979 FOUNDED 20+ YEARS EXPERIENCE IN PHARMA / FUNGAL GENE EXPRESSION PLATFORMS HQ: Jupiter, FL BD&L: London BD&L: Budapest R&D: Spain R&D: Finland

Platform Technology

DYADIC INFORMATION 5

C1: Fungal Gene Expression Platform

for use in the Development and Production of Biologics Novel engineered cell line (Myceliopthora thermophila)

>20 Patents

Value & Differentiation:

Decreased Development Time Lower Production Costs Improved Biologic Performance SignificantCapEx Savings

Industrially Proven

DYADIC INFORMATION 6

Industrial Licensees: >100 g/l Yield & ~80% Purity

Hyper Productive Enzyme Expression

500,000L

Scale Production

GRAS FDA

Certified

Dyadic Leadership Team

DYADIC INFORMATION 7

• M. Emalfarb

Founder, CEO

• R. Tchelet, PhD

Vice President, R&D

• M. Jones

Commercial Officer

• T. Dubinski

Vice President, CFO

Financial Overview

DYADIC INFORMATION 8

$75M

Deal with DuPont for Dyadic’s Industrial Technology Business

>$110M

C1 Related License Deals, Milestones & Equity

$19M Share Buyback

Completed 2/2017

$5M Add’l Share

Buyback Initiated 8/2017

LIQUIDITY

Fully Funded to Execute Business Plan

$51M

Cash & Investment Grade Securities (1)

$0

Debt

$44M

Market Cap

OTC Markets Stock Exchange (OTCQX: DYAI)

28.7M

Common Shares Outstanding (1)

FINANCIALS

Dyadic Board – Decades of Big Pharma Experience

DYADIC INFORMATION 9

Arindam Bose, PhD

EXPERIENCE

• Dr. Bose worked at Pfizer for 34

years and held leadership roles within bioprocess development and clinical manufacturing and is widely recognized as a Key Thought Leader in the biopharmaceutical industry.

Barry Buckland, PhD

EXPERIENCE

• Dr. Buckland worked at Merck for 29 years

where he served in a number of senior R&D leadership roles focusing on fermentation and bioprocess development and the commercial manufacturing of biologics and is widely recognized as a Key Thought Leader in the biopharmaceutical industry. Currently,

• Dr. Buckland is the Executive Director,

NIIMBL (National Institute for Innovation in Manufacturing Biopharmaceuticals) A public-private consortium dedicated to advancing biopharmaceutical manufacturing innovation.

Michael P. Tarnok Chairman

EXPERIENCE

• Mr. Tarnok spent the majority of his

career at Pfizer and is a seasoned finance and operational executive with extensive experience in the pharmaceutical industry. Currently also serves on the Board of the Global Health Council, and Ionetix,

• Inc. Prior Board service includes

Keryx Biopharmaceuticals, Inc., where he also served as Chairman

• f the Board.

LAST POSITION Vice President, Biotherapeutics Pharmaceutical Sciences, External Affairs and Biosimilar Strategy LAST POSITION Vice President, Bioprocess R&D, Merck Research Laboratories LAST POSITION Senior Vice President in Pfizer’s US Pharmaceutical Division

DYADIC INFORMATION 10

Dyadic Launch's Biopharmaceutical Strategy for The C1 Gene Expression Platform

Dyadic is Developing What the Industry Refers to As a “CHO stopper”

DYADIC INFORMATION 11

CHO stopper? Biogen looks to alternative cell lines for future of bioproduction. The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation BioPharma Reporter Bioprocessing survey report, 11/03/2017 “Nearly half the respondents of

• ur second state of the global

biomanufacturing survey believe we are too reliant on Chinese Hamster Ovary (CHO) expression systems.” Dyadic’s Goal To further develop C1 into a safe and efficient gene expression system to help speed up the development, lower production costs and improve the performance of biologic vaccines and drugs at flexible commercial scales.

C1 Technology Platform– Where to Play & How to Win

DYADIC INFORMATION 12

Biologic drugs make up the fastest growing segment of the pharma industry and are some of the most expensive treatments; therefore, they are placing an enormous financial burden on both patients and the healthcare systems globally.

Total Addressable Market and Market Penetration1

Dyadic is well positioned to penetrate the very attractive biologics market for Drugs and Vaccines, both human and animal health, with its uniquely powerful and proven technology, the C1 Gene Expression Platform.

1 Data from market research published by MarketsandMarkets as of May 12, 2017 & Transparency Market Research published on Oct 6, 2016

Global vaccines market projected to be $48.0 billion by 2021 Biologics are the fastest growing segment of the pharmaceutical industry projected to grow at a CGAR of 10.9% over the period 2016 – 2024 to $479.8 billion $1.3 trillion spent on drugs currently, 18%

• r $235 billion

is for biologics

Industry & Society Challenges

DYADIC INFORMATION 13

1 Estimated Industry Average CHO Yield for a 12-14 day fermentation run, results vary by company.

0.1 g/l 4 g/l

CHO Productivity Appears To Have Plateaued1 1985 1995 2005 2015

Current Industry Solution: Build more expensive manufacturing plants & operate

Industry Problems

Therapeutic protein production is expensive Involves using enormous quantities of expensive growth medium Requires costly manufacturing facilities Few advances in the protein production process during the past decade, particularly in the area of CHO cell improvement Current productivity is not adequate to meet future commercial manufacturing demand

CHO Technology is Highly Capital Intensive and Costly

DYADIC INFORMATION 14

Samsung Biologics plants in the Songdo district in Incheon, South Korea, Cost $740 million

C1 Benefits: Lower Production Costs, Both CAPEX and OPEX

DYADIC INFORMATION 15

Stainless Steel Multiuse 2 x12,000 liter Single Use Bioreactor 2,000 liter

CHO C1 Annual Protein Demand in g 800,000 800,000 800,000 Tank size in Liters 12,000 2,000 2,000 Productivity g/l 4 10 15 % Yield 65% 75% 75% Batches per year 20 40 40 Tank Output in g 624,000 600,000 900,000 Tanks Needed 2.0 2.0 1.0 % Capacity Utilized 64% 67% 89%

C1 can lower CAPEX: Smaller facility footprint and related costs C1 can lower OPEX:

• Low cost media
• High Yield / Produce at smaller scale

DYADIC INFORMATION 16

C1 Production Host

C1 – The Science

DYADIC INFORMATION 17 Unique Morphology High Purity - 80% of target protein secreted Wide operating conditions for pH and temperature Shorter Development & Production Cycle

§ Translates into better growth conditions

• Higher yields of

secreted protein

• Lower viscosity

§ Greater retention

• f target secreted

protein through downstream processing § Requires only low cost synthetic media § No Viruses which eliminates 2 purification steps typical in CHO

• No Low pH

viral inactivation

• No Virus

nanofiltration § At scales ranging from laboratory shake flasks to 20,000l tanks and above § C1 has received GRAS (Generally Recognized as Safe) designation from FDA and is considered fit for human consumption § Develop g/l/d C1 cell lines in 15 weeks § From seed flask to fermenter

• Savings of

nearly 10 -14 days vs CHO § Fermentation Cycle time 4-7 days

• 1/2 to 1/3rd

the time of CHO § High Levels of expression

• mAbs > 1.5 g/l/d
• Fc-fusion > 1.3 g/l/d

Higher Productivity

DYADIC INFORMATION 18

C1 for Biologics

High Yield & Purity of C1 Expressed mAb’s

DYADIC INFORMATION 19 We have expressed 100% of the mAbs & FC-Fusions tested in our 3rd party research collaborations The mAb genes are integrated specifically to a “Hot spot” in the C1 genome The mAbs are secreted to the media and are being properly folded Levels of unoptimized expressed mAb is > 1.5 g/l/d, Fc-fusion > 1.3 g/l/d The mAb’s are purified using Protein A The Binding Kinetics of C1 mAb’s are Virtually Identical To mAb’s expressed from CHO

A) SDS-PAGE B) Western Blot

Controls C1+ mAb4 LC HC LC HC mAb4 Marker C1 PS C1+ mAb4 mAb4

(1) (2)

(*) Samples were taken from the 24-well plate culture.

1 2 3 4 5 6

C1 Advantages Over CHO System

DYADIC INFORMATION 20

1 2 3 3 2 1

Week 1 Week 2 Week 3 Week 4

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

• f C1 production

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

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

C1 CHO Production time reduced by >14 days

Duration of Steps in Production

Faster genetic manipulation (cloning, growth and screening) Higher stability (monoclonal culture, stable genome) High expression obtained by site specific integration No need for induction. Fast growing culture as yeast Faster protein production rate – 1.5 g/l/d (more than 10g/l in 7 days fermentation) Higher purity of protein achieved may decrease recovery time No need for virus clearance steps

C1 Advantages for Vaccine Development & Production

DYADIC INFORMATION 21

Flexibility– The relative simplicity of the production process of C1 enables the production of rVaccines at various scales and at different sites. Adjuvant effect – Reducing rVaccines

• risk. Preliminary data indicates C1

possess Adjuvant properties. Thus, antigen produced by C1 may not require the addition of artificial Adjuvants. Immunogenicity – Antigens produced by C1 demonstrated excellent immunogenicity properties: § Sanofi Project: The full length rHA from A/New Caledonia/20/99 (H1N1) strain showed excellent immunogenicity properties in mice without adjuvant § ZAPI Project: C1 produced antigen generated an immune response in mice that protected the mice and did not have negative effects on the health of the mice Safety – Mice tests demonstrated that recombinant proteins such as HA produced in C1 did not induce any negative clinical signs in mice. § No weight loss. § No negative clinical signs during the experiment (visual

• bservations taken each day).

Productivity – C1 is a highly productive strain that can produce rVaccines at very low cost. § Example: C1 can potentially produce levels of 1 g/L of HAs against seasonable Influenza virus(es) in 4 - 7 days fermentation 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.

ZAPI Project

DYADIC INFORMATION 22

ZAPI, is a research and development program sponsored by the EU with the goal of developing 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.

Three of the initial antigens, each one for a different virus, was expressed by C1 and secreted to the medium To date one of the C1 expressed antigens was tested in a very small mice test within the ZAPI project. Preliminary results indicated that the C1 produced antigen generated an immune response in mice that protected the mice, and did not have negative effects on the health of the mice We have initiated a C1 development program to express Virus like particles (VLP) for antigen expressions

C1 Glycoengineering

DYADIC INFORMATION 23

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

Man9 Man8 Man7 Man6 Man5 Man3 GF2 High mannose Core 5-25% C1 typical Glycan structure C1 future Glycostructures Unlike most fungi and yeasts, C1 does not have ‘high’ mannose (branched 30-50 mannose species), but rather has ‘oligo’ mannose and hybrid-type structure. The native C1 glycan pattern is relatively complex with high mannose type (Man3- Man9) and hybrid type (Man3HexNac- Man8HexNac) glycan forms So far, O-glycosylation was not identified in therapeutic proteins expressed in C1 but minor level is still possible Glycoengineering work is being applied to C1 strain to create a strain that produce proteins with defined human glycoforms

C1 Glycoengineering

DYADIC INFORMATION 24

Advantage of C1 over Yeast and CHO

Typical Yeast Glycan Structure Man30-50 Dyadic C1 Glycan Structure Man3-9 Targeted Mammalian Glycoform structuress G0 G0F G2 G2F

Dyadic’s C1’s glycan structure is more mammalian like than typical yeast § The native C1 glycan pattern is relatively complex with high mannose type (Man3- Man9) § O-glycosylation was not identified in therapeutic proteins expressed in C1 § Less engineering steps needed for C1 § Stable genome - defined glycan structure is stable from culture to culture and batch to batch The first steps of Glycoengineering C1 cells has begun and were successful No negative effects on cell viability have been

• bserved with any of

the modifications done

C1 mAb’s: Virtually Indistinguishable Binding Kinetics to CHO

25

DYADIC INFORMATION 26

C1 Technology Combat Emerging Diseases & Threats

Biodefense, Combat Emerging Diseases & Threats

DYADIC INFORMATION 27

Bioterrorism Agent Categories The “Top Four” Bioterrorist Agents

§ Category A – easily spread, cause public panic, high death rates- Bacillus anthracis, Clostridium botulinum. § Category B – moderately easy to spread, moderate illness rates and low death risk- Pseudomonas pseudo mallei. § Category C – easily available, easily produced and spread, potential for high mortality rates and major health impact- Lassa virus, Ebola viruses. § Yersini pestis, the bacterium that causes plague. § Variola virus, the virus that causes smallpox. §

• B. anthracis, the bacterium that

causes anthrax. § Botulinum toxin, a protein toxin produced by Clostridium botulinum, the bacterium that causes botulism.

DYADIC INFORMATION 28

How Can We Combat Bioterrorism?

“Improving nation’s defenses against bioterrorism is a key part of the U.S. government’s homeland security effort.” – National Institute of Allergy and Infectious Diseases (NIAID). Biodefense - the procedures involved in taking defensive measures against attacks using biological agents. § Vaccines to immunize the public against bioterror attacks.

• If an attack occurs, treatment in the form of

antibodies will be needed.

• Stockpile of drugs and vaccines necessary for

emergency cases

• Must be administered before exposure

§ Diagnostic Tests for first responders and medical personnel to help identify exposure and provide treatment. § Provision of therapy available to infected personnel to help recovery after infection.

ZAPI Project

DYADIC INFORMATION 29

Dyadic has entered into a R & D collaboration with the Israel Institute for Biological Research (“IIBR”) to further advance its C1 expression platform for the development and manufacture

• f recombinant vaccines and neutralizing agents comprising targeted antigens and

monoclonal antibodies, to combat emerging diseases and threats. The Israel Institute for Biological Research “IIBR” is a governmental, applied research institute specializing in the fields of biology, medicinal chemistry and environmental sciences. Backed by five decades of experience, IIBR combines highly trained personnel with cutting-edge technologies and infra-structure to conduct applied research and development in the fields of biology, medicinal chemistry and environmental sciences, in addition to basic research studies closely related to IIBR's applied projects. IIBR's research projects include sponsorships by international authorities and institutions such as the US Public Health Services, Center for Disease Control, US Army Medical Research and Development Command, the World Health Organization, US-Israel Binational Science Foundation, National Foundation of Cancer Research and the German Ministry for Scientific Research and Technology.

DYADIC INFORMATION 30

Advantages of Using C1 for the Development & Production of Biologics and Vaccines

C1 Advantages for Developing & Producing Biologics

DYADIC INFORMATION 31

Better:

§ High Productivity Protein Expression: 20+ g/l (Achieved 80 g/l in Industrial application) § High Purity Protein Secretion (~80%) § Low viscosity § Greater Retention of target secreted protein through downstream processing § C1 current developed strain can be used as production platform for non-glycosylated proteins such as Fabs, bi-specifics and new drugs § Glycoengineering work is being applied to the host production C1 strain to allow for production

• f proteins with human defined glycoforms such

as mAbs, Fc-fusions and recombinant vaccines § Glycoengineering work in C1 requires less steps than yeast

• Easier starting put since C1 doesn’t have

hyper mannose structure

• No O-glycosylation

Easier:

§ Advanced Genetic Tool Box § Site specific integration vs. random integration § Wide operating conditions for pH and temperature § Simple C1 production process allows for production of biologics at various scales and at different sites

Faster:

§ Develop high yield g/l/d C1 cell lines in 15 weeks § Fed batch technology – no need for perfusion § No Viruses eliminates the need for two additional purification steps § 4-7 days Fermentation time (1/2 to 1/3rd less time than CHO) § Cell Reproduction rate (2x greater than CHO) § Initial protein production rate ~1.5x greater than CHO and expected to increase further

Lower Cost:

§ Defined, low-cost media based on glucose § No Viruses eliminates associated costs

42 118 124 60 110 360 50 100 150 200 250 300 350 400 C1 - 2,000L tank C1 - 10,000L tank CHO - 10,000L tank Cost in Million USD

Lower Manufacturing Cost: C1 vs CHO Humira mAb

Annual OpEx Initial CapEx Investment

Summary

DYADIC INFORMATION 32 Shorter development & production cycles Higher protein yields Lower CapEx/OpEx Higher purity & greater protein recovered Low Cost Media / No Viral Inactivation No negative clinical signs in mice studies R&D Collaborations Licensing Arrangements Other Commercial Opportunities

Dyadic is looking for partners in the biopharmaceutical space to exploit the potential of C1. Contact mjones@dyadic.com

THANK YOU!