Dyadic International, Inc. · NASDAQ:DYAI
Dyadic International — WHO consultation on novel manufacturing technologies for monoclonal antibody production, 1 (September 2022)
28 slides from Dyadic International's conference presentation, Sep 13, 2022
Slide 1: Dyadic: Thermophilic Filamentous Fungus C1 Next-Gen Therapeutic Protein Production System
DYADIC" insioe” Thermophilic Filamentous Fungus, C1 Next-Gen Therapeutic Protein Production System ‘Speed development, increase access, affordability andindependence of biomanufacturing monoclonal antibodies and antigens for infectious and other diseases efficient low-cost monoclonal antib duction f
Slide 2: Safe Harbor Regarding Forward-looking Statements
Safe Harbor Regarding Forward-looking Statements Certain statements contained in this presentation are forward-looking statements within the meaning of Section27A of the Securities Act of 1933, ‘and Section2 1 of the Securities Exchange Act of 1934, including those regarding Dyadic’s expectations, i
Slide 3: Current costs of producing mAbs are too great to support independent production in LMICs
Current costs of producing mAbs are simply too great to support independent production in LMICs Access Challenges Affordability Chal Number of registered monoclonal antibodies in selected counties n-.es tosis
Slide 4: Dyadic's Mission: Proteins for World Health
Dyadic’s Mission: Proteins for World Health 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, and heal the world by utilizing modern biotechnology to revolutionize science,
Slide 5: Dyadic is already partnering on African and Indian Continents to improve local biomanufacturing
Dyadic is already partnering on African and Indian Continents to improve local biomanufacturing efforts ‘Submission of a Clinical Trial Application (CTA) with SA iPRA ‘South African Health Products Regulatory Authority (SAHPRA) to initiate @ Phase 1 study “We have veragedou inca proven ptr to bang a
Slide 6: Over $100MM and years of commercial engineering invested in C1
Over $100MM and 30 years of commercial engineering invested in C1 “C4” (Thermothelomyces heterothallica) is an exceptional genetically engineered fungal strain Broad application of C1 has expanded through decades of commercial engineering C1 strain discovered to produce commercially valuable enzymes
Slide 7: C1 technology directly addresses mAb production challenges for LMICs
C1 technology directly addresses mAb production challenges for LMICs Cost of infrastructure, media, and DSP to support current Affordability blomanufacturing platforms are prohibitive in LMICs Process Complexity Inherent chatenges Include time to produce stable cal ines, process ‘optimization, drug
Slide 8: Dyadic Investing In Validation of C1 Platform for Human Clinical Trials
Dyadic Investing In Validation of C1 Platform for Human Clinical Trials Platform Evaluation: -DYAr00 req aeesment permed by Paerl ih no signin delerie deed -DVAr100 EMC tec package pe-cnicalanina and ocoay suds eat by Pau Ercntt (PED BERRI? conctesondatapackage and suds suparte stbmison fica ia Appl
Slide 9: Genetic toolbox for rapid, stable, high yield C1 strain development
Genetic toolbox for rapid, stable, high yield C1 strain development sed genetic toolkit for synthetic biolog ee HTP screening =) -@- = S Change in morphology led to hyper- productivity and low viscosity.
Slide 10: Rapid Generation of Highly Productive Stable Monoclonal Antibody Cell Lines
Rapid Generation of Highly Productive Stable Monoclonal Antibody Cell Lines Site Directed Integration: vcnceenss) ME 26 agonal cenes) se Ct genome _It. _ = Ty. seroma ( i r r ‘Te Target Genes) ae ‘Aatona Target Gene(s) are intgralesto Ct genome. Integrateatoc genome Sweeks 1week 2 weeks Ei 1 week +
Slide 11: Library of secretion and folding factors genes
Library of secretion and folding factors genes Selection of secretion and folding factors genes improves the productivity and stability Q Potentially enhance secretion and/or folding in C1 expression platform Id/quality of mAb production in C4 ey i The factor genes of the library were selected based
Slide 12: Systematic deletion of active proteases in C1 host to improve stability
Systematic deletion of active proteases in C1 host to improve stability Ko proteases and main secreted proteins (15 genes ko) ste end mi seer pris (Spee te} Ko ‘Ny N adases eee regulator, mAbs stability is increased with proteases delation ‘Systematic deletion of proteases genes based on: d + Isolat
Slide 13: 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 > Native eycosyation pattern fromCt has been glycoengineeredto produce gvcan > Nearyall human-like N-lycans; over 99%, the remaining structures that resemble human structure corresponding to CHO percentageis Man3-s
Slide 14: C1 mAb Proof of Concept: Nivolumab
C1 mAb Proof of Concept: Nivolumab > Nivolumab strain development for high production level, high stability and Human glycan structure (( Productivity _} (__ Stability} (__N-Giycan _} Best productivity 22.3 g/Lin7 Protease activity days fermentation" “Sum w/ois | 100 Response wioiS | 10184384 Constr
Slide 15: C1 Fermentation - Up and Downstream Processes
C1 Fermentation —- Up and Downstream Processes Fully defined low-cost medium 11 to 500,000 fermentation scale, standard stainless Fed-batch technology with glucose feeding Fed-batch Wide range of conditions available pH:5-8, Temp: 20- asc (ters refer tothe supernatant Process Low viscosity culture d
Slide 16: Generic process flow chart for C1 is 12-14 days
Generic process flow chart for C1 is 12-14 days Inoculum expansion-bioreactors MN N-2740L scale | 'N-1"1000L scale Generic Process Flow Chart for CHO is 41 — 54 days =a ain
Slide 17: C1 platform: Increase mAb access
C1 platform: Increase mAb access C1 platform produces comparable therapeu! Devel and Production timeframe as one batch using CHO cells. folded mAbs that have binding and newtalizing properties similarto higher those produced fom CHO cells faster more affordably globally proteins as CHO wi le overcom
Slide 18: C1 produced antibodies perform like CHO mAbs to treat infectious diseases
C1 produced antibodies perform like CHO mAbs to treat infectious diseases + Flexibly Scalable Protein Based Product Manufacturing 4 . ’ Therapeutic treatments (mAbs) ‘ High Purities & Exceptional Yields/Stabilities Infectious Diseases
Slide 19: Similar structure of mAbs produced in C1 to CHO produced mAbs
Similar structure of mAbs produced in C1 to CHO produced mAbs [Peptide fingerprint | {Intact mass analysis (after de-N-glycosylation) eee
Slide 20: C1 manufactured monoclonal antibodies are stable and correctly folded
C1 manufactured monoclonal antibodies are stable and correctly folded Typically, stable mAbs production levels are between 5 ~ 10 g/Lin 5-7 days Best productivity at Amber system: © 24.5g/Lin7 days (3.5 g/I/day) Best productivity so far at 30L scale: © 20.6g/Lat 157 h (3.1g/L/day} sano — a. | mab co
Slide 21: CHO-like neutralization and binding, but faster and more affordable
CHO-like neutralization and binding, but faster and more affordable \SWANOV Newton cd ome + moves seroma = © ANDV-44 (C1 produced) = pel =< ee + cows ® baat "mons tn 25 EE of ‘mAb concantraton og, Maint) eee RIFT VALLEY. SARS-COV2 AS RVEV.268 C1 ve expi289F production al oy eens H 2 > 2 = conrare $a
Slide 22: Broad Neutralization of SARS-CoV-2 Variants of Concern C1 produced mAb
Broad Neutralization of SARS-CoV-2 Variants of Concern C1 produced mAb 2 2 = = Neutralization (%) C1 Expressed SARS-COV2 mAb Regeneron SARS-COV2 mAb 87G7 REGN10933 100. 100 = 06146 = “= Alpha 25 50. -~ Beta 22 50 =+ Gamma oe “+ Detta 38 Omicron 3 ° Zo 0+ 405 102 10% = 40°40 40# 405 107 407 40840 MAb
Slide 23: Manufacturing larger quantities of affordable cocktails of mAbs & antigen treatments / vaccines
Manufacturing larger quantities of affordable cocktails of mAbs & antigen treatments / vaccines as 87G7 mAb neutralize ALL CoV-2 variants through Omicron BA.2 sag TD © +» e [VariantCov-2mAbcanbe _| added to 8767 to develop mAb cocktail to neutralize BA.4/5 > The Cl recombinant protein production pla
Slide 24: C1 produced mAbs have virtually identical structure, properties and activities to CHO produced mAbs
C1 produced mAbs have virtually identical structure, properties and activities to CHO produced mAbs C1 platform produces comparable therapeu! i | ‘eo & 7) Binding proteins as CHO while overcoming key production limita CA. mAbs neutralize viruses virtually identical to CHO produced mAbs C1 produced m
Slide 25: C1 has capability to express bispecific antibodies, nanobodies, other therapeutic proteins
C1 has capability to express bispecific antibodies, nanobodies, other therapeutic proteins > The best production levels so far are: BispecificX at 7.62g/Lin7 days (unoptimized) > Mass spectrometry analysis indicates that vast majority of Bispecific X is correctly assembled MS Deconvoluted spectrum a
Slide 26: Rapid Commercial Manufacture of Affordable, High Value, Safe and Effective Protein Products
Rapid Commercial Manufacture of Affordable, High Value, Safe and Effective Protein Products HUMAN HEALTH ANIMAL HEALTH. High Yields and Purities for Therapeutic Proteins! Vaccine Antigen Glycoproteins & mAbs __ Total Yield___Yield per Day Fe-Fusion Products 15.3¢/L 2.58 g/t mAb Products 24.5 g/t aig
Slide 27: Peer Reviewed Scientific Publications
Peer Reviewed Scientific Publications To: ology Stud) + Toxicity and Local Tolerance of a Novel Spike Protein RBD Vaccine Against SARS-CoV-2, Produced Using the C1 Thermothelomyces Heterothallica Protein Expression Platform Journals: + Vaccines — The Highly Productive Thermothelomyces heterothallica
Slide 28: Dyadic
DYADIC Insioe” A Vaccine Or Drug That Is Unavailable Or Unaffordable Is 100% Ineffective Learn more at www.dyadic.com / info@dyadic.com