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

Transcription

1 C1, An Ultra-High Yielding, Game Changing Gene Expression Platform Dyadic (non-conf) BD Overview February, 2018

2 Safe Harbor Regarding Forward-Looking Statements 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, 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. DYADIC INFORMATION 2

3 Table of Contents 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 DYADIC INFORMATION 3

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

5 Platform Technology 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 DYADIC INFORMATION 5

6 Industrially Proven >100 g/l Yield & ~80% Purity Hyper Productive Enzyme Expression GRAS FDA Certified 500,000L Scale Production Industrial Licensees: DYADIC INFORMATION 6

7 Dyadic Leadership Team M. Emalfarb Founder, CEO T. Dubinski Vice President, CFO R. Tchelet, PhD Vice President, R&D M. Jones Commercial Officer DYADIC INFORMATION 7

8 Financial Overview LIQUIDITY >$110M C1 Related License Deals, Milestones & Equity $75M Deal with DuPont for Dyadic s Industrial Technology Business $19M Share Buyback Completed 2/2017 $5M Add l Share Buyback Initiated 8/2017 Fully Funded to Execute Business Plan FINANCIALS $51M Cash & Investment Grade Securities (1) $0 Debt $44M Market Cap OTC Markets Stock Exchange (OTCQX: DYAI) 28.7M Common Shares Outstanding (1) DYADIC INFORMATION 8

9 Dyadic Board Decades of Big Pharma Experience Arindam Bose, PhD Barry Buckland, PhD Michael P. Tarnok Chairman 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. 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. 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 of 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 9

10 Dyadic Launch's Biopharmaceutical Strategy for The C1 Gene Expression Platform DYADIC INFORMATION 10

11 Dyadic is Developing What the Industry Refers to As a CHO stopper 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 our 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. DYADIC INFORMATION 11

12 C1 Technology Platform Where to Play & How to Win 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 Penetration 1 $1.3 trillion spent on drugs currently, 18% or $235 billion is for biologics Biologics are the fastest growing segment of the pharmaceutical industry projected to grow at a CGAR of 10.9% over the period to $479.8 billion Global vaccines market projected to be $48.0 billion by 2021 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 DYADIC INFORMATION 12

13 Industry & Society Challenges Industry Problems Involves using enormous quantities of expensive growth medium Few advances in the protein production process during the past decade, particularly in the area of CHO cell improvement Therapeutic protein production is expensive Requires costly manufacturing facilities Current productivity is not adequate to meet future commercial manufacturing demand CHO Productivity Appears To Have Plateaued 1 4 g/l 0.1 g/l Current Industry Solution: Build more expensive manufacturing plants & operate 1 Estimated Industry Average CHO Yield for a day fermentation run, results vary by company. DYADIC INFORMATION 13

14 CHO Technology is Highly Capital Intensive and Costly Samsung Biologics plants in the Songdo district in Incheon, South Korea, Cost $740 million DYADIC INFORMATION 14

15 C1 Benefits: Lower Production Costs, Both CAPEX and OPEX Stainless Steel Multiuse 2 x12,000 liter Single Use Bioreactor 2,000 liter CHO C1 Annual Protein Demand in g 800, , ,000 Tank size in Liters 12,000 2,000 2,000 Productivity g/l % Yield 65% 75% 75% Batches per year Tank Output in g 624, , ,000 Tanks Needed % 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 15

16 C1 Production Host DYADIC INFORMATION 16

17 C1 The Science Unique Morphology High Purity - 80% of target protein secreted Wide operating conditions for ph and temperature Shorter Development & Production Cycle Higher Productivity Translates into better growth conditions Higher yields of secreted protein Lower viscosity Greater retention of 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 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 DYADIC INFORMATION 17

18 C1 for Biologics DYADIC INFORMATION 18

19 High Yield & Purity of C1 Expressed mab s We have expressed 100% of the mabs & FC-Fusions tested in our 3rd party research collaborations 1 6 The Binding Kinetics of C1 mab s are Virtually Identical To mab s expressed from CHO The mab genes are integrated specifically to a Hot spot in the C1 genome 2 5 The mab s are purified using Protein A The mabs are secreted to the media and are being properly folded 3 4 Levels of unoptimized expressed mab is > 1.5 g/l/d, Fc-fusion > 1.3 g/l/d DYADIC INFORMATION 19

20 C1 Advantages Over CHO System Faster genetic manipulation (cloning, growth and screening) Fast growing culture as yeast Higher stability (monoclonal culture, stable genome) Faster protein production rate 1.5 g/l/d (more than 10g/l in 7 days fermentation) High expression obtained by site specific integration Higher purity of protein achieved may decrease recovery time No need for induction. No need for virus clearance steps C1 1: Biomass Expansion 2: Protein Production 3: Protein Recovery* Duration of Steps in Production Production time reduced by >14 days CHO *Note: Protein Recovery may be faster due to higher purity of C1 production Week 1 Week 2 Week 3 Week 4 Batch Cycle time is reduced by >50% in comparison to CHO, freeing up capacity DYADIC INFORMATION 20

21 C1 Advantages for Vaccine Development & Production 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. Flexibility The relative simplicity of the production process of C1 enables the production of rvaccines at various scales and at different sites. 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 observations taken each day). 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. DYADIC INFORMATION 21

22 ZAPI Project 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 DYADIC INFORMATION 22

23 C1 Glycoengineering Glycoengineering of C1 strain will provide the formation of various glycan structures to evaluate immunogenicity C1 typical Glycan structure High mannose Core 5-25% GF2 Man 9 Man 8 Man 7 Man 6 Man 5 Man 3 C1 future Glycostructures Unlike most fungi and yeasts, C1 does not have high mannose (branched 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 DYADIC INFORMATION 23

24 C1 Glycoengineering Advantage of C1 over Yeast and CHO 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 observed with any of the modifications done Typical Yeast Glycan Structure Dyadic C1 Glycan Structure Targeted Mammalian Glycoform structuress Man Man 3-9 G0 G0F G2 G2F DYADIC INFORMATION 24

25 C1 mab s: Virtually Indistinguishable Binding Kinetics to CHO 25

26 C1 Technology Combat Emerging Diseases & Threats DYADIC INFORMATION 26

27 Biodefense, Combat Emerging Diseases & Threats Bioterrorism Agent Categories 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. The Top Four Bioterrorist Agents 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 27

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. DYADIC INFORMATION 28

29 IIBR Project 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 of 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 29

30 Advantages of Using C1 for the Development & Production of Biologics and Vaccines DYADIC INFORMATION 30

31 C1 Advantages for Developing & Producing Biologics 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 of 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 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 Cost in Million USD 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 Lower Cost: Lower Manufacturing Cost: C1 vs CHO Humira mab Defined, low-cost media based on glucose No Viruses eliminates associated costs DYADIC INFORMATION Annual OpEx Initial CapEx Investment C1-2,000L tank C1-10,000L tank CHO - 10,000L tank

32 Summary Higher protein yields Lower CapEx/OpEx Low Cost Media / No Viral Inactivation Shorter development & production cycles Higher purity & greater protein recovered 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 DYADIC INFORMATION 32

33 THANK YOU!