making healthcare accessible & affordable · 9/14/2020 · hc wainwright investor...
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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
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
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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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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ADDRESSABLE MARKETS
C1 – Robust Technology Platform with Broad Application Potential
DYADIC FAVOURABLY ALIGNED WITH GLOBAL TRENDS
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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
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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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
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
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
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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DRIVING OPPORTUNISTIC & RETURN-FOCUSEDBUSINESS DEVELOPMENT PROCESS
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
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
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