Dyadic International, Inc. · NASDAQ:DYAI
Dyadic International — 6th Annual BFC Global Healthcare BD and Investment Conference (January 2023)
39 slides from Dyadic International's conference presentation, Jan 4, 2023
Slide 1: Next Generation Proteins for World Health
DYADIC” sive” Next Generation Proteins for World Health C1 Protein Production Platform 6th Annual BFC Global Healthcare BD and Investment Conference from January 8, 2023, San Francisco, CA USA Dyadic International, Inc. (Nasdaq:DYAI)
Slide 2: Safe Harbor Regarding Forward-Looking Statements
Safe Harbor Regarding For looking Ce ‘of the Securities Act of 1933 and Section 21€ of 1934, including . intentions, sti 1d beliefs pertaining ly those in the as a result of various important factors, including those described in Dyadic’s most recent fi filings with the SEC. Undue reliance should no
Slide 3: Dyadic's Mission: Proteins for World Health
Dyadic’s Mission: Proteins for World Health Transforming Biomanufacturing & Closing the Technology Gap Across the Globe Meeting the growing demand for proteins worldwide for human and animal health with highly productive scalable microbial biomanufacturing platforms. To improve how we feed, fuel, an
Slide 4: Over $100MM and Years of Commercial Engineering Invested in C1
Over $100MM and 30 Years of cial i ing i ted in C1 "C1" ( isan ly fungal strain Broad application of C1 has expanded through decades of commerci engineering 2005 2016 Today (> Enzyme library developed B, Ct strain discovered to yee Eee aeaiaa a valuable enzymes development for C I Faunch of C2 ep ht
Slide 5: Dyadic investing in validation of C1 Platform for human clinical trials
Dyadic investing in validation of C1 Platform for human clinical trials Bern ant -DYAI-100 CI log) EN) Regulatory -DYAI-100 1 trial (~ EARLY Q1 2023) loay -Developed full regulatory CMC technical package for Drug Product & Drug Substance, Submitted CTA -DYAI-100 fillfinish completed, product on long
Slide 6: Rapid, Stable, High Yield C1 Strain Development
DYADIC’ sive” RAPID, STABLE, HIGH YIELD C1 STRAIN DEVELOPMENT
Slide 7: Genetic toolbox for rapid, stable, high yield C1 strain development
Genetic toolbox for rapid, stable, high yield C1 strain development C1 advanced genetic toolkit for synthetic biology be HTP screening Precise gene targeting Change led to hyper- productivity and low viscosity. Reporter genes Se Gene integration
Slide 8: Extensive library of secretion and folding factors genes for the C1 platform
E: ive library of and folding factors genes for the C1 platform Selection of secretion and folding factors genes improves the productivity and stability Heterologous Secretion factors a (human) => C1 platform me oy Q Potentially enhance secretion andlor folding in C1 expression platform Q Factor gen
Slide 9: Rapid Generation of Highly Productive Stable C1 Cell Lines
Rapid Generation of Highly Productive Stable C1 Cell Lines Site Directed Integration: orpercenet) TMSBDHCEE —_pagional eget Genel) oe consis now ttt C1 genome Les 1 genome U dv J T T ‘The Target Genet) re dona! Target Genet) ae inogated ot genome Awook 3 wooks + The Genes are located in 1 Hot Spot g
Slide 10: Systematic deletion of proteases in C1 host to improve stability
y i ion of active pr in ct host to improve stability cell) 1 Pharma C1 — oses SS ae N . — reguiatoy mAbs stability is increased with proteases deletion Systematic deletion of proteases genes based on: Isolation and identification of extracellular proteases C1 protease library in Pichia pestis that a
Slide 11: Native C1 glycosylation pattern is more similar to human glycan structures than yeast
Native C1 glycosylation pattern is more similar to human glycan structures than yeast (C1 Humanized Proteins Relative response=~site occupancy uwotamab (€2) percentage is Man3-species » Several pio ccna steps: : si moval of detrimental activities . over amression of altearn once reference Opdivo
Slide 12: High Yield, Robust, Scalable C1 Biomanufacturing Process
HIGH YIELD, ROBUST, ST, C1 BIOMANUFACTURING PROCES:
Slide 13: C1 Fermentation - Upstream/Downstream Process
C1 Fer ion — Up/D: Pr and SSB/SUB fab production Fully defined low-cost medium. 11 to.500,0001 fermentation scale, stainless steel or PAPIPTET (2 Fed-batch technology with glucose feeding single use stirred tank fermenters, a ‘Wide range of conditions available pH: 5-8, Temp: 20-45 Process fermenter
Slide 14: Generic Process Flow Chart for C1 vs. CHO
Generic Process Flow Chart for C1 of 12-14 days vs. CHO at 41-54 Days Generic Process Flow Chart for CHO is 41 - 54 days
Slide 15: Efficacy Enhancements Coupled with C1's Efficiencies
DYADIC’ sive” Efficacy Enhancements Coupled with C1’s Efficiencies (Speed, Yield, Cost) Next Generation C1 Antigens Designing biomolecules for better vaccine efficacy and durability * Ferritin Nanoparticles: Duke and Walter Reed have shown better durability and broader coverage * aMHCII: Targeting s
Slide 16: Advancing C1's capabilities to produce VLPs and ferritin nanoparticles
Advancing C1’s capabilities to Pp more C1 VLP’s a + VUP sie: 3000 kDa /25 nm diameter C1 Ferritin Nanoparticles a ressed secreted ferritin nanoparticles putative oligomerization forms wt Co ‘AILF10-R80 variants shows high esergnen) Ra ‘molecular weightbands under i oomeontha o> 07a non-reduced condi
Slide 17: C1 expressed ferritin nanoparticles keeping pace with advancing science
d ferritin ticles, | ing pace with advancing science Western blot from culture supernatants: F10-Wuhan F10-BA2 Delta. Fit QRED — gRBD gRBD gRBD FiOWuhan FIO-BA2 Deke red” RB oReD | Fermentation at higher scale shows clearly bands of the target proteins in Coomassie staining gels. Titers after 5 days
Slide 18: C1 Expressed Ferritin Nanoparticle
C1 Expressed Ferritin Nanoparticle F10-Wuhan-gRBD DYADIC CONFIDENTIAL INFORMATION
Slide 19: C1 gRBD Ferritin Nanoparticle Intramuscular Prime + Boosts
C1 gRBD Fi in Nanoparticle Intramuscular Prime + One or Two boosts (14 days apart) (TLR 7 & TLR 8 Cellular Adjuvant) Ferritin Nanoparticles (Cohort 1) W-36 (Rabbi, Antigens. Log, (MFRNT,, Titers to Delta Live Virus) ‘aan angen ooo. sndgun Cats. Bete ito cnn. ‘pions ‘Room nS cm ‘han ‘eet ‘aunt sepa r
Slide 20: C1 gRBD Ferritin Nanoparticle Data (14 days apart)
C1 GRBD Ferritin i Data (14 days apart) (TLR 7 & TLR 8 Cellular Adjuvant) Ferritin (Cohort 3) 12103722. VV-37 (Rabbit, . 12/17/22. W-37 (Rabbit, 100,00 ain 50988 Medan 125 asa 89 Log ,(MFRNT,, Titers to Delta Live Virus) 3 Log,,(MFRNT,, Titers to Deta Live Virus) DYADIC CONFIDENTIAL INFORMATION
Slide 21: Enhanced influenza efficacy with C1 produced aMHCII HA
Enhanced influenza efficacy with C1 produced aMHCll HA (protects against lethal dose) Influenza A/California Study » Mice were challenged with lethal dose of influenza A/California/4/2009 (H1N1) at wk 16 post vaccination + Monitored for weight + Mi ight loss of ot reaching, this endoint Weight loss
Slide 22: C1 aMHCII influenza antigens: high yield enabling more potent vaccines
C1 aMHCll ini High Pp yield enabling more potent influenza vaccines ELLA Assay IgG Titer through day 62 HEN2 lg6 250 30000. a ; wa FH 031399 .* a ta Boa H oe t > 2549 ° '~ = 5009 wu oy 0 “Ero ae rr oe ons eer ten > chart due to formatting. > Suggested Starting jose of ‘4ug for testing based on these
Slide 23: C1 aMHCII yield
C1 aMHCIl yield Hi coat HS coat HT coat Same: © Nach sa © NaCl ‘15000 © NaCl . =H “ =H ” oH +0000 os 10000 as 10000 as 7 me ome wo] + HUMST Mex seco TRISH a, + HIST Mc 0 vs o- EPL SS CP LSS & 3 3 Mice were vaccinated once intradermally with 1g of the indicated protein vaccines, mixed 1:1 with ASO3 a
Slide 24: C1 aMHCII-RBD COVID-19 prime elicits high neutralizing antibody titers
C1 aMHCII-RBD COVID-19 prime elicits high neutralizing antibody titers Total g6 ther Experiment 1 (32 mice)( ongoing, 11 weeks): roups: ‘sone “+ Naot A: NaCl saenees “® RBD, boost REO B: Prime with RBD, boost with RBD 7 betead ‘* aMHCI-RBD, boost RBD C: Prime with aMHCII-RBD, boost with RBD 2 2000 -
Slide 25: C1 expressed influenza and COVID-19 aMHCII antigens: next steps
C1 expressed influenza (HA, NA) and COVID-19 aMHCll antigens NEXT STEPS + Experiment 3 (32 mice): Groups: + A:NaCl + BraMHCILNA + C:aMHCII-NA + aMHClI-H1 + aMHCII-RBD- + D: aMHCI-NA + aMHCIL-H1/H5/H7 ‘Aim is to confirm that immunogenicity of NA is intact also when mixed with one or several HAS. Read
Slide 26: C1 expressed antigens can be made available for sampling
C1 expressed antigens can be made available for sampling SARS-CoV-2 $-RBD SARS-CoV-2 gRBD Ferritin Nanoparticles Alpha (B.1.1.7) * Wuhan gRBD Ferritin Nanoparticle + Beta (B.1.351) * Omicron gRBD Ferritin Nanoparticle * + Gamma (P.1) + Delta B.1.617.2 SARS-CoV-2 aMHCII Antigens + Omicron B.1.1.529 +
Slide 27: Record expression of an antigen for Livestock Viral Disease
Record expression of an antigen for Livestock Viral Disease > Record production of an antigen has been successfully expressed from C1 cells > Successful animal study demonstrated high Immunogenicity response Expression in CL 1 Increase in Antigen Production J Antigen | Yield inca ‘AntigenX 10.0 g/L/
Slide 28: In addition to the C1 platform, Dyadic is open to licensing its antigens
In addition to the C1 platform, Dyadic is open to li ing its anti &A Ra Robu C1 Platform Adaptable, and Scalable Platform ‘Antigens in higher yields and less time for more efficiency it 5, nanoparticies, Lower COGS provide enhanced pricing flexibility Regulatory approval of CTA submission and Phase
Slide 29: Appendix I: Monoclonal Antibodies
DYADIC’ Lessons Learned, US Army Supply Chain !: “we've had to carefully ration mAb supply in Region | throughout Delta, and the production timelines never quite caught up to demand until Omicron rendered our existing supply moot. That is an error that could have been extremely costly in lives, had
Slide 30: Human and Animal Therapeutic Proteins (mAbs)
Human and Animal Therapeutic Proteins (mAbs) Proof of Concept, Nivolumab High i in yield ion of mAbs (Ni have been obtained using novel genetic elements, Standard transformation in Dyadic microbial platforms: * Site directed integration into specific hot spots in the genome * One/two copies integrat
Slide 31: Strain & fermentation optimization of RM8671 and Imdevimab in C1
p & fer i ptimization of RM8671 and Imdevimab in C1 RM8671 productivity Imdevimab productivity “ : a - Ze atl tT . I ° Storm opt Gen 2 Gensferm opt* sedsermopt 24Gen Pcuten oe DYADIC CONFIDENTIAL INFORMATION ba
Slide 32: C1 vs CHO: Andes virus and Rift Valley fever mAbs
CHO- ANDES VIRUS \VSV-ANDV Neutralization ‘© IANDV-44 (ExpICHO produced) -e TANDV-44 (Ct produced) = DENv2022 ke neutralization and binding, but faster, ee quantities more affordably 9 Maan ot cael MAb conc logyo ( ngimL) +100 js “o MAST i102 94 my © BRIT LATTE OO) 0! © oss 25 mab ene tog10 aren RIF
Slide 33: Broad neutralization of SARS-CoV-2 variants of concern 87G7 / C1 expressed mAb
Broad neutralization of SARS-CoV-2 variants of concern 87G7 / C1 expressed mAb ai Neutralization (%) C1 Expressed SARS-COV2 mAb 87G7 1005 —~ D614G = Alpha 504 — Beta = Omicron Regeneron SARS-COV2 mAb REGN10933 1005 g i T 10+ 10° 102 107 10° 10" MAb concentration (g/ml) Live virus Neutralization (%)
Slide 34: 87G7 mAb produced from native C1 cells
87G7 mAb was p! from native ( gly ) C1-cells Effector function (ADCC) 40. «0. g 3 20. 30) = 20: 20. I i * Strong binding and high effector function (ADCC) from C1 407 104 109 10+ 109 107 10" “407 40" 4 tO" 10> 10F 10! Antibody (mg/ml) Dilution fol = Monocional C1 — Monoclonal human, Pre-pandemic = N
Slide 35: C1 87G7 mAb - Same safety & efficacy profiles as CHO mAb in animal studies
C1 87G7 mAb - Same safety & efficacy profiles as CHO mAb in animal studies 87G7 mAb was produced from native (non glycoengineered) C1-cells 87G7 mAb NHP Study 87G7mAb Hamster Study Challenge with 10° TCIDSO SARS-CoV-2 Delta VOC Body weight IRT-qPCR carried out on throat and nasal swab samples. ai +
Slide 36: Appendix II: Non-Animal Proteins
DYADIC’ Insive” APPENDIX Il: NON-ANIMAL PROTEINS
Slide 37: Alternative protein segment aligns with Dyadic's core strengths
¢ Alternative protein segment aligns with Dyadic’s core strengths CSE MLR GKCXM Reducing costs of recombinant proteins requires a highly product the high costs of recombinant proteins, low-cost expression system with commercial scale flexibility enzymes and growth factors. + Using pharma-grade produ
Slide 38: Alternative Proteins Expands Dyadic Product Range
¢ Alternative Proteins Expands Dyadic Ri Prod Research Grade > SMP crade Proteins and Enzymes uses: * Research and Diagnostic materials * Product and Clinical development materials
Slide 39: Dyadic International, Inc.
DYADIC Dyadic International, Inc. (Nasdaq:DYAI) IR@DYADIC.COM