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C1 TECHNOLOGY PLATFORM MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE HC Wainwright Investor Presentation September 14, 2020

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Page 1: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

C 1 T E C H N O L O G Y P L AT F O R MM A K I N G H E A L T H C A R E A C C E S S I B L E & A F F O R D A B L E

HC Wainwright Investor Presentation

September 14, 2020

Page 2: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

Certain statements contained in this presentation are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including those regarding Dyadic’s expectations, intentions, strategies and beliefs pertaining to future events or future financial performance. Actual events or results may differ materially from those in the forward-looking statements as a result of various important factors, including those described in Dyadic’s most recent filings with the SEC. Undue reliance should not be placed on the forward-looking statements in this presentation, which are based on information available to us on the date hereof. Dyadic assumes no obligation to update publicly any such forward-looking statements, whether as a result of new information, future events or otherwise. For a more complete description of the risks that could cause our actual results to differ from our current expectations, please see the section entitled “Risk Factors” in Dyadic’s annual reports on Form 10-K and quarterly reports on Form 10-Q filed with the SEC, as such factors may be updated from time to time in Dyadic’s periodic filings with the SEC, which are accessible on the SEC’s website and at www.dyadic.com

SAFE HARBOR REGARDING FORWARD-LOOKING STATEMENTS

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Next Generation Protein Expression Biotech with Well-established Global Partners

Next-generation platform biotech company driving its proprietary C1 gene expression technology strategically aligned with global trends; significant runway for shareholder value creation

Disruptive protein expression technology to help accelerate drug development and improve productivity, reporting robust scientific data regarding protein expression yield, stability and purity

Partnered with well-established, global biological R&D organizations, top-tier animal and human health pharmaceutical companies, as well as governmental agencies

Opportunistic business development approach with emphasis on large and growing addressable human and animal health markets; many shots on goal

Strong financial position with $32.1 million in cash and investment securities, no debt and complemented by partner funded on-going R&D collaborations (1)

Highly experienced and energized management driving process and execution excellence

KEY TAKEAWAYS

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(1) As of June 30, 2020

Page 4: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

Ping RawsonCFO20+ years of finance/ accounting experience

Ronen TcheletVP of Research and Business Development15+ years in research/ pharmaceutical industry

Matthew JonesManaging Director, Business Development and Licensing20+ years life science & biopharma industry leadership

Dr. Arin BoseBoard Member34 years bioprocess development & clinical manufacturing | National Academy of Engineering

Dr. Barry BucklandBoard Member29 years R&D leadership | National Academy of Engineering

Michael TarnokChairman of the BoardSeasoned pharma industry finance/ operational executive

Highly Energized Team with Deep Industry Expertise – Driving Robust Portfolio and Pipeline of Opportunity

DYADIC LEADERSHIP

Mark EmalfarbFounder, CEOInventor 25+ U.S. and foreign biotechnology patents

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Page 5: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

Solid History with Growing Portfolio of High Value Collaborations

HISTORY

KEY FINANCIAL HIGHLIGHTS

SIGNIFICANT STRATEGIC RELATIONSHIPS

• Founded by Mark Emalfarb in 1979

• 1990’s - 2015 as an industrial biotech utilized C1 platform and other technologies to produce commercial quantities of enzymes for industrial products and applications

• Previously licensed C1 to leading industrial companies including Abengoa, BASF, Codexis and Shell Oil

• Retained co-exclusive rights to use C1 technology in human and animal pharma application to manufacture biopharmaceuticals and exclusive sublicensing rights through 12/31/2029

• Engaged with leading European research organizations ‒ VTT and BDI – to advance science and manage third-party projects

• Ongoing collaborations with human and animal health companies as well as research institutions globally

COMPANY HISTORY

• Sold industrial biotech business to DuPont for $75 million on December 31, 2015

• Generated >$100 million in product revenues from customers in 35 countries and received > $30 million for non-exclusive licenses

• Several hundred million dollars invested in C1 technology by Dyadic and its licensees

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Page 6: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

ADDRESSABLE MARKETS

Page 7: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

C1 – Robust Technology Platform with Broad Application Potential

DYADIC FAVOURABLY ALIGNED WITH GLOBAL TRENDS

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Page 8: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

ADDRESSABLE BIOPHARMACEUTICAL MARKET OPPORTUNITIES

Four of Top Four Animal Health CompaniesZAPI, BDI and othersRecombinant Vaccines for Animal healthMarket size – $8.6 Billion by 20221

Sanofi, and othersNew BiologicsmAbs, Bispecifics, FC-FusionsBioPharmaceutical Market size –$319 Billion by 20212

Cimzia, Opdivo®Biosimilars/Biobetters/Other Biologics Global Market size – $69 Billion by 20253

IIBR, ZAPI, UfoVax, Frederick National Lab Vaccines and drugs for CoronavirusPandemic and Epidemic zoonotic diseases and biologic threats

Serum, UfoVax and othersRecombinant vaccines for human healthMarket size – $58.4 Billion by 2024 4

In-house ProjectsPrimary and secondary metabolites

1 Source: https://tinyurl.com/y544yxg7. 2 Source: https://tinyurl.com/yyurkcml 3 Source: https://tinyurl.com/yxtfsm6y 4 Source: https://tinyurl.com/y2gg78ss

Global and Growing End Market Opportunities 8

Page 9: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

Strong Scientific and Financial Achievements

2020 – ACCOMPLISHMENTS

Fully-funded Research Collaboration with Top Animal Health Companies• Feasibility study for 2 proteins using C1 platform• Two additional collaborations for therapeutic proteins for companion and farm animal diseases with leading global animal health companies• Now working with all of the top four (4) animal health companies (global revenues)

University of Oslo Feasibility Study• Evaluate C1’s potential to express influenza virus antigen proteins

COVID-19 Initiatives• Selected by Frederick National Laboratory to engineer C1 cell lines to produce a number of COVID-19 vaccine candidates• Expanded Research Collaboration with the Israel Institute for Biological Research (IIBR)o Explore potential of C1 to express gene sequences and targets developed by IIBR

• UfoVax (Scripps Spinout)• Cr2o, Erasmus, Utrecht, TiHo Hannover• Submitted a number of proposals to various funding agencies and parties to develop SARS-CoV-2 vaccine candidates

• WuXi is a leading Contract Development Manufacturing Organization (CDMO)• Evaluating C1 in a cGMP facility and performing experiments to C1 cell lines• Funding supported by WuXiNew, Fully-Funded Collaboration with Another Top Five Global Pharmaceutical Company

WuXi Biologics Non-exclusive Research License

Scientific Achievements• Continued progress in glycoengineering C1 cells to impart human-like glycan structures • Excellent progress in reducing the extracellular protease background by 50 times in C1. The elimination of protease activity makes the C1 cell line more efficient

and stable, leading to even higher expression levels and lower cost

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Page 10: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

GROWTH OPPORTUNITIES

Acceleration of Glycoengineering Initiatives

Drive Opportunistic and Return Focused Development Process

Develop New Commercial Opportunities

Disciplined Capital Allocation

Execution on Key Partner RelationshipsGROWTH STRATEGY

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C1 GENE EXPRESSION PLATFORMCOMPETITIVE ADVANTAGES

Page 12: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

WHAT IS C1? THERMOTHELOMYCES HETEROTHALLICA

C1 is a thermophilic fungus originally isolated from alkaline soil in Russia; it has a unique morphology

allowing for hyper productivity and growth under low viscosity using a broad range of fermentation

conditions at flexible commercial scales

C1 initially engineered to produce enzymes for textiles, biofuels, pulp and paper, etc

C1 received a generally recognized as safe (GRAS) certification from the US FDA in 2009

Proprietary and patented genetic elements for use in engineered C1 strains

Proven low cost, high-yield, scalable, robust system with improved downstream benefits

C1 genome fully sequenced, annotated, and full set of genetic tools

Unique Morphology with Low Cost, High Yield and Scalable Benefits 12

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Glycoengineering - Advantage of C1 over Yeast and CHODialing Up Or Down C1 Glycan Structures For Improved Immunogenicity

Typical Yeast Glycan Structure

Man30-50

Dyadic C1 Native Glycan Structure C1 Engineered Glycoform Structures

The native C1 glycan structure is more mammalian-like than that of yeast Native C1 glycans are mostly high mannose type (Man3-Man9) including low amount of hybrid glycans We have successfully completed initial glycoengineering of C1 cells We now have Four (4) Novel C1 Cell Lines with different glycan patterns

(i) Man3-9 , (ii) Man3, (iii) G0 and (iv) G2

Man3-9 Man3 G2G0

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FAST & STABLE HIGH PRODUCING GENETICALLY STABLE C1 CELL LINE DEVELOPMENT

• Rapid Development Timelines

• High Productivity

• High Purity

• Robust Manufacturing Process

• Flexible Commercial Scales

• Low Cost

Rapid ResponseVery High # of

DosesFlexible Scalability

Affordability

C1 Site Directed Transformation Method Leads To Generating Genetically Stable C1 Cell Lines In ~ 2 months: • Plug & Play Site Directed Integration• We can integrate 1 or 2 genes into the same site. Two integration sites can also be used.• Speeds time to cGMP manufacturing • Addresses pandemics and other biological threats quickly

If the COVID-19 virus mutates and a second-generation SARS-CoV-2 antigen is needed, C1 can be used to rapidly develop and manufacture the antigen in larger quantities more affordably.

1 Integration site 2 Integration site

Episomes

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FLEXIBLE, SCALABLE, EASILY TECH TRANSFERRED TO EXISTING MICROBIAL PRODUCTION FACILITIES

Fed-batch process

• Fully defined low cost medium

• Fed-batch technology with glucose feeding

• Wide range of conditions available pH: 5-8, Temp: 20 - 45°C

• Low viscosity culture due to unique morphology in the fermenter

• (Typically) 4-7 day process

• 1L to 500,000L scale, stainless steel or single use stirred tank fermenters

• At the end 30-40% biomass, 60-70 % supernatant (titers refer to the supernatant)

• Protein production requires no inducer

• Protein is (typically) secreted to the media

From MTP to Large scale antigen, Fc-fusion, mAbs and other protein productivity

Antigens – up to ~ 350 mg/l/dayFc-fusion – up to ~ 1.8/g/l/dmAbs – up to ~ 3.5 g/l/d

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C1 – Robust Gene Expression Platform Superior to Existing Technology

C1 COMPETITIVE ADVANTAGE

Unique Morphology

Translates into better growth conditions

• Higher yields of secreted protein• Lower viscosity

High Purity of Target Protein Secreted

Greater retention of target secreted protein through downstream processing

More human glycan structures compared to yeast and typical fungi

Requires only low-cost synthetic media

No endotoxins, viruses or mycotoxins which simplifies processing compared to E.coli, CHO and other organisms

Wide Operating Conditions for pH and Temperature

Manufacturing can be done at flexible commercial scales ranging from laboratory shake flasks to 20,000l tanks and above

C1 has received GRAS (Generally Recognized as Safe) designation from FDA

No negative clinical effects seen in animal studies

Shorter Development & Production CycleDevelop genetically stable g/l/d C1 cell lines in ~ 8 weeks

• Savings of nearly 1-3 months over CHO

Fermentation Cycle time 5-7 days• 1/2 to 1/3rd the time of CHO

Higher productivity• Compared to CHO, yeast & baculovirus

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C1 Is A Versatile “Workhorse” That Expresses A Vast Range Of Proteins

C1 COMPETITIVE ADVANTAGE

Impressive Yield and Purity Demonstrated for Therapeutic Proteins

Proof of Principal for Antigen Classes Routinely Used in Vaccines

Fc-Fusion 18.1 g/l

168 Hours 2.58 g/l/day

Trispecific6.12 g/l

144 Hours1.02 g/l/day

mAbs24.5 g/l

168 Hours 3.1 g/l/day

Fab (Certolizumab) 14.5 g/l

164 Hours 2.1 g/l/day

Hemagglutinin (HA)413 mg/l

137 Hours 72 mg/l/day

Antigen1,780 mg/l121 Hours

350 mg/l/day

Virus-Like Particles2,200 mg/l110 Hours

500 mg/l/day

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Page 18: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

DRIVING OPPORTUNISTIC & RETURN-FOCUSEDBUSINESS DEVELOPMENT PROCESS

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OPPORTUNISTIC & RETURN-FOCUSED BUSINESS DEVELOPMENT

External ProgramsDyadic develops and advances its C1 platform technology at little or no cost to the Company

Big Pharma• Funded proof of concept collaborations for specific therapeutic agents• Up front access fees, milestones and royalty paymentsSmaller Biotech• Equity, milestones and royalty paymentsGrant• Governmental and agency grants

Internally Funded Programs

Dyadic funds programs where its C1 gene expression technology can overcome barriers of existing platforms or where it can have a meaningful technological or commercial impact

• Glycoengineering• Protease deletion• Biosimilars and Biobetters• Metabolites • COVID-19, Influenza other Infectious Diseases

Aligned with Global Leaders and Driving Internal Growth Initiatives 19

Page 20: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

COVID–19: Reinforcing C1’s Broad Application Potential 20

INFECTIOUS DISEASE COMMERCIALIZATION OPPORTUNITIES

COVID - 19

• Israel Institute for Biological Research (IIBR)

• ZAPI

• UfoVax (Scripps Spinout Company)

• Cr2o, Utrecht, TiHo Hannover (Select ZAPI Scientists / Institutes)

• Vaccine Clinical Materials Program, Frederick National Laboratory

• Additional Ongoing Collaborations & Discussions

C1 is a robust platform which has the potential to produce large quantities of affordable recombinant vaccines, drugs and reagents for infectious diseases, including the COVID-19 pandemic.

Rapidly developed a C1 cell line which produces large amounts of a SARS-CoV-2 Vaccine Candidate which the Israel Institute for Biological Research (“IIBR”), European collaborators and others are advancing towards animal trials.

Dyadic was selected by the Frederick National Laboratory to engineer its patented and proprietary C1 cell lines to produce a number of COVID-19 vaccine candidates which will be utilized by the Vaccine Research Center (VRC) part of the National Institute of Allergy and Infectious Diseases (NIAID), at the National Institutes of Health.

Our previous work with existing collaborators has provided new opportunities:

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PRODUCTION OF RBD SARS-CoV-2 PROTEIN IN C1

In 2 months we developed cell line expressing the Receptor Binding Domain (23kDa) of SARS-CoV-2 spike protein C1 stable cell line expressed the RBD at a level of ~ 1 g/L was developed – no need for transient stage C1 fermentation is based on Fed-batch technology with glucose feeding and cGMP synthetic media Fermentation was run for 5 days in the Ambr250 system and in 5L fermentor scale The RBD antigen was secreted to the media – no need for induction Ongoing fermentation process optimization is likely to lead to even greater productivity aiming to reach 1.5 g/L or higher

C1 cell line in Ambr250 fermenter system Purified C1-RBD after 5L scale fermentation

Days of fermentation

1 2 3 4 5

Marker

C1 RBD strain was run in Ambr250 for 5 days

WB analysis off fermentation broth

Marker Supernatant Purified Marker

RBD-CTag C1 RBD strain was run in 5L scale fermentationThe RBD was purified twice with CaptureSelect™ C-tag 10ml column.

98% purity70% recovery

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EVALUATION OF RBD PRODUCED BY C1

Biomolecular Binding Kinetics Assays: The equilibrium dissociation constant (KD) of C1 SARS-CoV-2-RBD-Ctag binding to recombinant hACE2 was calculated to be 4.9 Nm, which is comparable to that of the CHO SARS-CoV-2-RBD: 5.11 Nm.

Biosensor

hACE2 receptorRBD Antigen

Biosensor

hACE2 receptor

RBD Antigen

OCTET assay: RBD antigen binding assay. A ACE2 receptor is immobilized on the biosensor, followed by the binding of the RBD antigen. The binding coefficient is measured by the Biosensor

In addition, all RBD neutralizing mAbs (that bind to different RBD epitopes) that were identified in patients infected by SARS-CoV-2 were efficiently bounded to C1 RBD-Ctag. This binding clearly demonstrates that C1-RBD was properly folded and has high potential to generate immune response and protection against the SARS-CoV-2.

Recently – mice study confirmed that RBD antigen produced by C1 induced the production of neutralizing antibodies against the SARS-CoV-2 in mice. More studies are on the way.

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ANIMAL TRIALS WITH C1 EXPRESSED SARS-CoV-2 RBD VACCINE CANDIDATES

IIBR conducted mice study with RBD that was produced by C1. They injected C1 RBD-C-tag 3 times (a prime and 2 boosts) to 10 mice with an adjuvant 1.

Currently, they are evaluating the last blood samples that were taken at day 50 and the final analysis of the results will beready in a week or ten days.

Notably, the interim results show excellent immunogenicity responses with very high titers. In addition, plaque reduction neutralization test (PRNT) confirmed that the RBD induced neutralizing antibodies against the virus.

No adverse effects were observed to any of the mice. Based on the promising results in terms of the efficacy, the IIBR are planning to initiate an animal study using transgenic

mice expressing the Human Ace2 instead of hamsters.

UPCOMING EXPECTED EU (Former ZAPI Scientists) ANIMAL TRIAL:

The immunogenicity and efficacy of certain C1 expressed RBD vaccine candidates will be assessed in the established Syrian golden hamster model. To this end, groups of hamsters will be used to assess the immunogenicity and protective efficacy upon challenge 2.

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INFECTIOUS DISEASE ANTIGENS and mAbs SUCCESSFULLY EXPRESSED FROM C1

SARS-CoV-2 Receptor Binding Domain (RBD) Antigen SARS-CoV-2 Nucleocapsid Antigen SARS-CoV-2 mAb Protein

RVFV Antigen H1N1 (HA) Protein SBV Antigen

Page 25: MAKING HEALTHCARE ACCESSIBLE & AFFORDABLE · 9/14/2020  · HC Wainwright Investor Presentation. September 14, 2020. ... • Previously licensed C1 to leading industrial companies

C1 EXPRESSED HEMAGGLUTINEN, ANOTHER EXAMPLE OF THE POTENTIAL OF C1

Seasonal Flu

University of Oslo consortium HA study • Ongoing to determine viability of C1 to express APC-targeted Influzena virus antigen proteins

• Expression of HA was successful, analytics ongoing.

• C1 previously successfully tested in an immunogenicity study of Recombinant Hemagglutinin (HA) from the A/H1N1/New Caledonia/20/99 strain conducted by Sanofi Pasteur demonstrated that:

• (1) C1 was safe and well-tolerated in mice; and • (2) the C1 strain produced by Dyadic was at least as immunogenic as the baculovirus-rHA in mice.

EXPRESSION SYSTEM

DOSE OF RHA1 U/G

DOSE OF RHA3.3 U/G

DOSE OF RHA10 U/G

DOSE OF RHA30 U/G

C1 50% (4/8) 57% (4/7) 100% (8/8) 100% (8/8)

Baculovirus 62% (5/8) 12% (1/8) 50% (4/8) 75% (6/8)

25Dyadic Has And Continues To Gain Knowledge & Generate Data From Various Pharma R&D Collaborations

Sanofi Pasteur (HA) Mice Study Results

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KEY TAKEAWAYS

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Next Generation Protein Expression Biotech with Well-established Global Partners

Next-generation platform biotech company driving its proprietary C1 gene expression technology strategically aligned with global trends; significant runway for shareholder value creation

Disruptive protein expression technology to help accelerate drug development and improve productivity, reporting robust scientific data regarding protein expression yield, stability and purity

Partnered with well-established, global biological R&D organizations, top-tier animal and human health pharmaceutical companies, as well as governmental agencies

Opportunistic business development approach with emphasis on large and growing addressable human and animal health markets; many shots on goal

Strong financial position with $32.1 million in cash and investment securities, no debt and complemented by partner funded on-going R&D collaborations (1)

Highly experienced and energized management driving process and execution excellence

KEY TAKEAWAYS

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(1) As of June 30, 2020