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

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

Dyadic (non- c onf) BD Ove r vie w

F e brua ry, 2018

Safe Harbor Regarding Forward-Looking Statements

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Ce rta in sta te me nts c o nta ine d in this pre se nta tio n a re fo rwa rd-lo o king sta te me nts within the me a ning

• f

the fe de ra l se c uritie s la ws. T he se fo rwa rd-lo o king sta te me nts invo lve risks, unc e rta intie s a nd o the r fa c to rs tha t c o uld c a use Dya dic ’ s a c tua l re sults, pe rfo rma nc e o r a c hie ve me nts to b e ma te ria lly diffe re nt fro m a ny future re sults, pe rfo rma nc e o r a c hie ve me nts e xpre sse d o r implie d b y suc h fo rwa rd-lo o king sta te me nts. Any fo rwa rd-lo o king sta te me nts spe a k o nly a s o f the da te o f this pre se nta tio n a nd, e xc e pt a s re q uire d b y la w, Dya dic e xpre ssly disc la ims a ny inte nt o r o b lig a tio n to upda te o r re vise a ny fo rwa rd-lo o king sta te me nts to re fle c t a c tua l re sults, a ny c ha ng e s in e xpe c ta tio ns o r a ny c ha ng e in e ve nts. F a c to rs tha t c o uld c a use re sults to diffe r ma te ria lly a re disc usse d in Dya dic ’ s pub lic ly a va ila b le filing s, inc luding info rma tio n se t fo rth unde r the c a ptio n “Risk F a c to rs” in o ur De c e mb e r 31, 2016 Annua l Re po rt file d with OT C Ma rke ts o n Ma rc h 24, 2017. Ne w risks a nd unc e rta intie s a rise fro m time to time , a nd it is impo ssib le fo rus to pre dic t the se e ve nts o r ho w the y ma y a ffe c t us.

T itle and Safe Har bor Re gar ding F

• r

war d- L

• oking State me nts

1 T able of Conte nts 3 Dyadic Ove r vie w 4 C1 Comme r c ially Suc c e ssful in Industr ial Biote c h 7 C1 T e c hnology Platfor m - Whe r e to Play and How to Win 8 Biophar ma Industr y and Soc ie ty Challe nge s 11 C1 Pr

• duc tion Host

15 C1 F

• r

Biologic s 17 C1 T e c hnology Combat E me r ging Dise ase s and T hr e ats 22 Advantage s of using C1 for the De ve lopme nt & Pr

• duc tion of Biologic s and Vac c ine s

25 Summar y 28

Table of Contents

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Dyadic Overview

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4 1979 F OUNDE D 20+ YE ARS E XPE RIE NCE IN PHARMA / F UNGAL GE NE E XPRE SSION PL AT F ORMS HQ: Jupite r, F

L

BD&L : L

• nd o n

BD&L : Bud a pe st R&D: Spa in R&D: F

inla nd

Platform Technology

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C1: F ungal Ge ne E xpr e ssion Platfor m

fo r use in the De ve lo pme nt a nd Pro duc tio n o f Bio lo g ic s No ve l e ng ine e re d c e ll line (Myc e lio ptho ra the rmo phila )

>20 Pate nts

Value & Diffe r e ntiation:

De c re a se d De ve lo pme nt T ime L

• we r Pro duc tio n Co sts

I mpro ve d Bio lo g ic Pe rfo rma nc e Sig nific a ntCa pE x Sa ving s

Industrially Proven

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Industr ial L ic e nse e s: >100 g/ l Yie ld & ~80% Pur ity

Hype r Pro duc tive E nzyme E xpre ssio n

500,000L

Sc a le Pro duc tio n

GRAS F DA

Ce rtifie d

Dyadic Leadership Team

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• M. E

malfar b

F

• unde r, CE

O

• R. T

c he le t, PhD

Vic e Pre side nt, R&D

• M. Jone s

Comme rc ia l Offic e r

T . Dubinski

Vic e Pre side nt, CF O

Financial Overview

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$75M

De a l with DuPont for Dya dic ’s Industr ia l T e c hnolog y Busine ss

>$110M

C1 Re late d L ic e nse De als, Mile stone s & E quity

$19M Sha r

e Buyba c k Comple te d 2/ 2017

$5M Add’l Sha r

e Buyba c k Initia te d 8/ 2017

L IQUIDIT Y

F ully F unde d to E xe c ute Busine ss Plan

$51M

Cash & Inve stme nt Gr ade Se c ur itie s (1)

$0

De bt

$44M

Ma rke t Ca p

OT C Mar ke ts Stoc k E xc hange (OT CQX: DYAI)

28.7M

Common Shar e s Outstanding (1)

F INANCIAL S

Dyadic Board – Decades of Big Pharma Experience

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Ar indam Bose , PhD

E XPE R IE NCE

• Dr. Bo se wo rke d a t Pfize r fo r 34

ye a rs a nd he ld le a de rship ro le s within b io pro c e ss de ve lo pme nt a nd c linic a l ma nufa c turing a nd is wide ly re c o g nize d a s a K e y T ho ug ht L e a de r in the b io pha rma c e utic a l industry.

Bar r y Buc kland, PhD

E XPE R IE NCE

• Dr. Buc kla nd wo rke d a t Me rc k fo r 29 ye a rs

whe re he se rve d in a numb e r o f se nio r R&D le a de rship ro le s fo c using o n fe rme nta tio n a nd b io pro c e ss de ve lo pme nt a nd the c o mme rc ia l ma nufa c turing o f b io lo g ic s a nd is wide ly re c o g nize d a s a K e y T ho ug ht L e a de r in the b io pha rma c e utic a l industry. Curre ntly,

• Dr. Buc kla nd is the E

xe c utive Dire c to r, NI I MBL (Na tio na l Institute fo r Inno va tio n in Ma nufa c turing Bio pha rma c e utic a ls) A pub lic -priva te c o nso rtium de dic a te d to a dva nc ing b io pha rma c e utic a l ma nufa c turing inno va tio n.

Mic hae l P. T ar nok Chair man

E XPE R IE NCE

• Mr. T

a rno k spe nt the ma jo rity o f his c a re e r a t Pfize r a nd is a se a so ne d fina nc e a nd o pe ra tio na l e xe c utive with e xte nsive e xpe rie nc e in the pha rma c e utic a l industry. Curre ntly a lso se rve s o n the Bo a rd o f the Glo b a l He a lth Co unc il, a nd Io ne tix, Inc . Prio r Bo a rd se rvic e inc lude s K e ryx Bio pha rma c e utic a ls, Inc ., whe re he a lso se rve d a s Cha irma n

• f the Bo a rd.

L AST POSIT ION

Vic e Pre side nt, Bio the ra pe utic s Pha rma c e utic a l Sc ie nc e s, E xte rna l Affa irs a nd Bio simila rStra te g y

L AST POSIT ION

Vic e Pre side nt, Bio pro c e ss R&D, Me rc k Re se a rc h L a b o ra to rie s

L AST POSIT ION

Se nio r Vic e Pre side nt in Pfize r’ s US Pha rma c e utic a l Divisio n

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

Dyadic is Developing What the Industry Refers to As a “CHO stopper”

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CHO sto ppe r? Bio g e n lo o ks to a lte rna tive c e ll line s fo r future o f b io pro duc tio n. T he Chine se ha mste r o va ry (CHO) c e ll line is no t the future fo r b io ma nufa c turing sa ys Bio g e n, MI T & Ga te s F

• unda tio n

Bio Pha rma Re po rte r Bio pro c e ssing surve y re po rt, 11/ 03/ 2017 “Ne a rly ha lf the re spo nde nts o f

• ur se c o nd sta te o f the g lo b a l

b io ma nufa c turing surve y b e lie ve we a re to o re lia nt o n Chine se Ha mste r Ova ry (CHO) e xpre ssio n syste ms.”

Dya dic ’s Goa l

T

• furthe r de ve lo p C1 into a sa fe a nd e ffic ie nt g e ne

e xpre ssio n syste m to he lp spe e d up the de ve lo pme nt, lo we r pro duc tio n c o sts a nd impro ve the pe rfo rma nc e o f b io lo g ic va c c ine s a nd drug s a t fle xib le c o mme rc ia l sc a le s.

C1 Technology Platform– Where to Play & How to Win

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Bio lo g ic drug s ma ke up the fa ste st g ro wing se g me nt o f the pha rma industry a nd a re so me o f the mo st e xpe nsive tre a tme nts; the re fo re , the y a re pla c ing a n e no rmo us fina nc ia l b urde n o n b o th pa tie nts a nd the he a lthc a re syste ms g lo b a lly. T

• tal Addr

e ssable Mar ke t and Mar ke t Pe ne tr ation1

Dya dic is we ll positione d to pe ne tra te the ve ry a ttra c tive biolog ic s ma rke t for Drug s a nd Va c c ine s, both huma n a nd a nima l he a lth, with its unique ly powe rful a nd prove n te c hnolog y, the C1 Ge ne E xpre ssion Pla tform.

1 Data from market research published by MarketsandMarkets as of May 12, 2017 & Transparency Market Research published on Oct 6, 2016

Glo b a l va c c ine s ma rke t pro je c te d to b e $48.0 b illio n b y 2021 Bio lo g ic s a re the fa ste st g ro wing se g me nt o f the pha rma c e utic a l industry pro je c te d to g ro w a t a CGAR o f 10.9% o ve r the pe rio d 2016 – 2024 to $479.8 b illio n $1.3 trillio n spe nt o n drug s c urre ntly, 18%

• r $235 b illio n

is fo r b io lo g ic s

Industry & Society Challenges

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1 Estimated Industry Average CHO Yield for a 12-14 day fermentation run, results vary by company.

0.1 g/l 4 g/l CHO Produc tivity Appe a rs T

• Ha ve Pla te a ue d1

1985 1995 2005 2015 Cur r e nt Industr y Solution: Build mo re e xpe nsive ma nufa c turing pla nts & o pe ra te

Industry Proble ms

T he ra pe utic pro te in pro d uc tio n is e xpe nsive Invo lve s using e no rmo us q ua ntitie s o f e xpe nsive g ro wth me d ium Re q uire s c o stly ma nufa c turing fa c ilitie s F e w a d va nc e s in the pro te in pro d uc tio n pro c e ss d uring the pa st d e c a d e , pa rtic ula rly in the a re a o f CHO c e ll impro ve me nt Curre nt pro d uc tivity is no t a d e q ua te to me e t future c o mme rc ial ma nufa c turing d e ma nd

CHO Technology is Highly Capital Intensive and Costly

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Sa msung Bio lo g ic s pla nts in the So ng do distric t in I nc he o n, So uth K

• re a , Co st $740 millio n

C1 Benefits: Lower Production Costs, Both CAPEX and OPEX

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Sta inle ss Ste e l Multiuse 2 x12,000 lite r Sing le Use Biore a c tor 2,000 lite r

CHO C1 Annua l Pr

• te in De ma nd in g

800,000 800,000 800,000 T a nk size in L ite r s 12,000 2,000 2,000 Pr

• duc tivity g / l

4 10 15 % Yie ld 65% 75% 75% Ba tc he s pe r ye a r 20 40 40 T a nk Output in g 624,000 600,000 900,000 T a nks Ne e de d 2.0 2.0 1.0 % Ca pa c ity Utilize d 64% 67% 89%

C1 c a n lowe r CAPE X:

Sma lle r fa c ility fo o tprint a nd re la te d c o sts

C1 c a n lowe r OPE X:

• L
• w c o st me dia
• Hig h Yie ld / Pro duc e a t sma lle r sc a le

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C1 Production Host

C1 – The Science

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17 Unique Mor phology High Pur ity - 80% of tar ge t pr

• te in

se c r e te d Wide ope r ating c onditions for pH and te mpe r atur e Shor te r De ve lopme nt & Pr

• duc tion

Cyc le

• T

r a nsla te s into be tte r g r

• wth c onditions
• Hig he r yie lds o f

se c re te d pro te in

• L
• we r visc o sity
• Gr

e a te r r e te ntion

• f ta r

g e t se c r e te d pr

• te in thr
• ug h

downstr e am pr

• c e ssing
• R

e quir e s only low c ost synthe tic me dia

• No Vir

use s whic h e limina te s 2 pur ific a tion ste ps typic a l in CHO

• No L
• w pH

vira l ina c tiva tio n

• No Virus

na no filtra tio n

• At sc a le s r

a ng ing fr

• m la bor

a tor y sha ke fla sks to 20,000l ta nks a nd a bove

• C1 ha s r

e c e ive d GR AS (Ge ne r a lly R e c og nize d a s Sa fe ) de sig na tion fr

• m F

DA a nd is c onside r e d fit for huma n c onsumption

• De ve lop g / l/ d C1

c e ll line s in 15 we e ks

• F

r

• m se e d fla sk to

fe r me nte r

• Sa ving s o f

ne a rly 10 -14 da ys vs CHO

• F

e r me nta tion Cyc le time 4- 7 da ys

• 1/ 2 to 1/ 3rd

the time o f CHO

• Hig h L

e ve ls of e xpr e ssion

• mAbs > 1.5 g / l/ d
• F

c - fusion > 1.3 g / l/ d

Highe r Pr

• duc tivity

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C1 for Biologics

High Yield & Purity of C1 Expressed mAb’s

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19 We have e xpr e sse d 100% of the mAbs & F C- F usions te ste d in our 3r d par ty r e se ar c h c ollabor ations

T he mAb g e ne s a re inte g ra te d spe c ific a lly to a “Ho t spo t” in the C1 g e no me T he mAb s a re se c re te d to the me d ia a nd a re b e ing pro pe rly fo ld e d

L e ve ls of unoptimize d e xpr e sse d mAb is > 1.5 g/ l/ d, F c - fusion > 1.3 g/ l/ d

T he mAb ’ s a re purifie d using Pro te in A

T he Binding Kine tic s of C1 mAb’s ar e Vir tually Ide ntic al T

• mAb’s

e xpr e sse d fr

• m CHO

1 2 3 4 5 6

C1 Advantages Over CHO System

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1 2 3 3 2 1

We e k 1 We e k 2 We e k 3 We e k 4

*No te : Pro te in Re c o ve ry may b e faste r due to hig he r purity

• f C1 pro duc tio n

Ba tc h Cyc le time is re duc e d by >50% in c ompa rison to CHO, fre e ing up c a pa c ity

1: Bio ma ss E

xpa nsio n

2: Pro te in Pro d uc tio n 3: Pro te in Re c o ve ry*

C1 CHO Produc tion time re duc e d by >14 da ys

Dur ation of Ste ps in Pr

• duc tion

F a ste r g e ne tic ma nipula tio n (c lo ning , g ro wth a nd sc re e ning ) Hig he r sta b ility (mo no c lo na l c ulture , sta b le g e no me ) Hig h e xpre ssio n o b ta ine d b y site spe c ific inte g ra tio n No ne e d fo r ind uc tio n. F a st g ro wing c ulture a s ye a st F a ste r pro te in pro d uc tio n ra te – 1.5 g / l/ d (mo re tha n 10g / l in 7 d a ys fe rme nta tio n) Hig he r purity o f pro te in a c hie ve d ma y d e c re a se re c o ve ry time No ne e d fo r virus c le a ra nc e ste ps

C1 Advantages for Vaccine Development & Production

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F le xibility– T

he re la tive simplic ity o f the pro duc tio n pro c e ss o f C1 e na b le s the pro duc tio n o f rVa c c ine s a t va rio us sc a le s a nd a t diffe re nt site s.

Adjuva nt e ffe c t – Re duc ing rVa c c ine s

• risk. Pre limina ry da ta indic a te s C1

po sse ss Adjuva nt pro pe rtie s. T hus, a ntig e n pro duc e d b y C1 ma y no t re q uire the a dditio n o f a rtific ia l Adjuva nts.

Immunog e nic ity – Antig e ns pro duc e d b y C1

de mo nstra te d e xc e lle nt immuno g e nic ity pro pe rtie s:

• Sa nofi Pr
• je c t: T

he full le ng th rHA fro m A/ Ne w Ca le do nia / 20/ 99 (H1N1) stra in sho we d e xc e lle nt immuno g e nic ity pro pe rtie s in mic e witho ut a djuva nt

• ZAPI Pr
• je c t: C1 pro duc e d a ntig e n

g e ne ra te d a n immune re spo nse in mic e tha t pro te c te d the mic e a nd did no t ha ve ne g a tive e ffe c ts o n the he a lth o f the mic e

Sa fe ty – Mic e te sts de mo nstra te d

tha t re c o mb ina nt pro te ins suc h a s HA pro duc e d in C1 did no t induc e a ny ne g a tive c linic a l sig ns in mic e .

• No we ig ht lo ss.
• No ne g a tive c linic a l sig ns

during the e xpe rime nt (visua l

• b se rva tio ns ta ke n e a c h da y).

Pr

• duc tivity – C1 is a hig hly pro duc tive stra in tha t c a n pro duc e rVa c c ine s a t

ve ry lo w c o st.

• E

xa mple : C1 c a n po te ntia lly pro duc e le ve ls o f 1 g / L

• f HAs a g a inst

se a so na b le Influe nza virus(e s) in 4 - 7 da ys fe rme nta tio n the re fo re :

• In se a so na l Influe nza Va c c ine —to ta l do se s distrib ute d = 146M/ ye a r
• E

a c h 0.5 mL do se is fo rmula te d to c o nta in: 15 µg o f HA fo r e a c h stra in.

• T

hus, 3 X 1000L sc a le fe rme nta tio n runs will b e a b le to supply the a nnua l g lo b a l HA/ stra in ne e ds a g a inst Influe nza o f 2,175 g .

ZAPI Project

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ZAPI, is a r e se ar c h and de ve lopme nt pr

• gr

am sponsor e d by the E U with the goal of de ve loping a platfor m suitable for the r apid de ve lopme nt and pr

• duc tion of vac c ine s and

pr

• toc ols to fast-tr

ac k r e gistr a tion of de ve lope d pr

• duc ts to c ombat e pide mic Zoonotic

dise ase s that have the pote ntial to e ffe c t the human population.

T hre e o f the initia l a ntig e ns, e a c h o ne fo r a d iffe re nt virus, wa s e xpre sse d b y C1 a nd se c re te d to the me d ium T

• d a te o ne o f the C1 e xpre sse d a ntig e ns

wa s te ste d in a ve ry sma ll mic e te st within the ZAPI pro je c t. Pre limina ry re sults ind ic a te d tha t the C1 pro d uc e d a ntig e n g e ne ra te d a n immune re spo nse in mic e tha t pro te c te d the mic e , a nd d id no t ha ve ne g a tive e ffe c ts o n the he a lth o f the mic e We ha ve initia te d a C1 d e ve lo pme nt pro g ra m to e xpre ss Virus like pa rtic le s (VL P) fo r a ntig e n e xpre ssio ns

C1 Glycoengineering

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Glyc oe ng ine e ring

• f C1 stra in will provide

the forma tion of va rious g lyc a n struc ture s to e va lua te immunog e nic ity

Ma n9 Ma n8 Ma n7 Ma n6 Ma n5 Ma n3

GF 2

Hig h ma nno se Co re 5-25% C1 typic a l Glyc a n struc ture

C1 futur e Glyc ostr uc tur e s

Unlike mo st fung i a nd ye a sts, C1 d o e s no t ha ve ‘ hig h’ ma nno se (b ra nc he d 30-50 ma nno se spe c ie s), b ut ra the r ha s ‘ o lig o ’ ma nno se a nd hyb rid -type struc ture . T he na tive C1 g lyc a n pa tte rn is re la tive ly c o mple x with hig h ma nno se type (Ma n3- Ma n9) a nd hyb rid type (Ma n3He xNa c - Ma n8He xNa c ) g lyc a n fo rms So fa r, O-g lyc o syla tio n wa s no t id e ntifie d in the ra pe utic pro te ins e xpre sse d in C1 b ut mino r le ve l is still po ssib le

Glyc oe ngine e r ing wor k is be ing applie d to C1 str ain to c r e ate a str ain that pr

• duc e

pr

• te ins with de fine d

human glyc ofor ms

C1 Glycoengineering

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Adva nta g e of C1 ove r Ye a st a nd CHO

T ypic al Ye ast Glyc an Str uc tur e

Ma n30-50

Dyadic C1 Glyc an Str uc tur e

Ma n3-9

T ar ge te d Mammalian Glyc ofor m str uc tur e ss

G0 G0F G2 G2F Dya dic ’s C1’s g lyc a n str uc tur e is mor e ma mma lia n like tha n typic a l ye a st

• T

he na tive C1 g lyc a n pa tte rn is re la tive ly c o mple x with hig h ma nno se type (Ma n3- Ma n9)

• O-g lyc o syla tio n wa s no t ide ntifie d in

the ra pe utic pro te ins e xpre sse d in C1

• L

e ss e ng ine e ring ste ps ne e de d fo r C1

• Sta b le g e no me - de fine d g lyc a n struc ture is

sta b le fro m c ulture to c ulture a nd b a tc h to b a tc h

T he fir st ste ps of Glyc oe ng ine e r ing C1 c e lls ha s be g un a nd we r e suc c e ssful No ne g a tive e ffe c ts on c e ll via bility ha ve be e n

• bse r

ve d with a ny of the modific a tions done

C1 mAb’s: Virtually Indistinguishable Binding Kinetics to CHO

25

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C1 Technology Combat Emerging Diseases & Threats

Biodefense, Combat Emerging Diseases & Threats

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Biote rrorism Ag e nt Ca te g orie s T he “T

• p F
• ur” Biote rrorist Ag e nts
• Cate gor

y A – e a sily spre a d, c a use

pub lic pa nic , hig h de a th ra te s- Ba c illus a nthra c is, Clo stridium b o tulinum.

• Cate gor

y B – mo de ra te ly e a sy to

spre a d, mo de ra te illne ss ra te s a nd lo w de a th risk- Pse udo mo na s pse udo ma lle i.

• Cate gor

y C – e a sily a va ila b le , e a sily

pro duc e d a nd spre a d, po te ntia l fo r hig h mo rta lity ra te s a nd ma jo r he a lth impa c t- L a ssa virus, E b o la viruse s.

• Ye r

sini pe stis, the b a c te rium tha t

c a use s pla g ue .

• Var

iola vir us, the virus tha t c a use s

sma llpo x.

• B. anthr

ac is, the b a c te rium tha t

c a use s a nthra x.

• Botulinum toxin, a pro te in to xin

pro duc e d b y Clo stridium b o tulinum, the b a c te rium tha t c a use s b o tulism.

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How Can We Combat Bioterrorism?

“Improving na tion’s de fe nse s a g a inst biote rrorism is a ke y pa rt of the U.S. g ove rnme nt’s home la nd se c urity e ffort.”

– Natio nal I nstitute o f Alle rg y and I nfe c tio us Dise ase s (NI AI D).

Biode fe nse - the proc e dure s involve d in ta king de fe nsive me a sure s a g a inst a tta c ks using biolog ic a l a g e nts.

• Va c c ine s to immunize the pub lic a g a inst b io te rro r

a tta c ks.

• I

f a n a tta c k o c c urs, tre a tme nt in the fo rm o f a ntib o die s will b e ne e de d.

• Sto c kpile o f drug s a nd va c c ine s ne c e ssa ry fo r

e me rg e nc y c a se s

• Must b e a dministe re d b e fo re e xpo sure
• Dia g no stic T

e sts fo r first re spo nde rs a nd me dic a l pe rso nne l to he lp ide ntify e xpo sure a nd pro vide tre a tme nt.

• Pro visio n o f the ra py a va ila b le to infe c te d pe rso nne l to

he lp re c o ve ry a fte r infe c tio n.

IIBR Project

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Dyadic has e nte r e d into a R & D c ollabor ation with the Isr ae l Institute for Biologic al Re se ar c h (“IIBR”) to fur the r advanc e its C1 e xpr e ssion platfor m for the de ve lopme nt and manufac tur e

• f r

e c ombinant vac c ine s and ne utr alizing age nts c ompr ising tar ge te d antige ns and monoc lonal antibodie s, to c ombat e me r ging dise ase s and thr e ats. T he Isr ae l Institute for Biologic al Re se ar c h “IIBR” is a gove r nme ntal, applie d r e se ar c h institute spe c ializing in the fie lds of biology, me dic inal c he mistr y and e nvir

• nme ntal sc ie nc e s. Bac ke d by five

de c ade s of e xpe r ie nc e , IIBR c ombine s highly tr aine d pe r sonne l with c utting- e dge te c hnologie s and infr a- str uc tur e to c onduc t applie d r e se ar c h and de ve lopme nt in the fie lds of biology, me dic inal c he mistr y and e nvir

• nme ntal sc ie nc e s, in addition to basic r

e se ar c h studie s c lose ly r e late d to IIBR's applie d pr

• je c ts.

IIBR's r e se ar c h pr

• je c ts inc lude sponsor

ships by inte r national author itie s and institutions suc h as the US Public He alth Se r vic e s, Ce nte r for Dise ase Contr

• l, US Ar

my Me dic al Re se ar c h and De ve lopme nt Command, the Wor ld He alth Or ganization, US-Isr ae l Binational Sc ie nc e F

• undation,

National F

• undation of Canc e r Re se ar

c h and the Ge r man Ministr y for Sc ie ntific Re se ar c h and T e c hnology.

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

C1 Advantages for Developing & Producing Biologics

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Be tte r:

• Hig h Pro duc tivity Pro te in E

xpre ssio n: 20+ g / l (Ac hie ve d 80 g / l in Industria l a pplic a tio n)

• Hig h Purity Pro te in Se c re tio n (~80%)
• L
• w visc o sity
• Gre a te r Re te ntio n o f ta rg e t se c re te d pro te in

thro ug h do wnstre a m pro c e ssing

• C1 c urre nt de ve lo pe d stra in c a n b e use d a s

pro duc tio n pla tfo rm fo r no n-g lyc o syla te d pro te ins suc h a s F a b s, b i-spe c ific s a nd ne w drug s

• Glyc o e ng ine e ring wo rk is b e ing a pplie d to the

ho st pro duc tio n C1 stra in to a llo w fo r pro duc tio n

• f pro te ins with huma n de fine d g lyc o fo rms suc h

a s mAb s, F c -fusio ns a nd re c o mb ina nt va c c ine s

• Glyc o e ng ine e ring wo rk in C1 re q uire s le ss ste ps

tha n ye a st

• E

a sie r sta rting put sinc e C1 do e sn’ t ha ve hype r ma nno se struc ture

• No O-g lyc o syla tio n

E a sie r:

• Adva nc e d Ge ne tic T
• o l

Bo x

• Site spe c ific inte g ra tio n vs.

ra ndo m inte g ra tio n

• Wide o pe ra ting c o nditio ns

fo r pH a nd te mpe ra ture

• Simple C1 pro duc tio n

pro c e ss a llo ws fo r pro duc tio n o f b io lo g ic s a t va rio us sc a le s a nd a t diffe re nt site s

F a ste r:

• De ve lo p hig h yie ld g / l/ d C1 c e ll line s in 15 we e ks
• F

e d b a tc h te c hno lo g y – no ne e d fo r pe rfusio n

• No Viruse s e limina te s the ne e d fo r two

a dditio na l purific a tio n ste ps

• 4-7 da ys F

e rme nta tio n time (1/ 2 to 1/ 3rd le ss time tha n CHO)

• Ce ll Re pro duc tio n ra te (2x g re a te r tha n CHO)
• Initia l pro te in pro duc tio n ra te ~1.5x g re a te r tha n

CHO a nd e xpe c te d to inc re a se furthe r

L

• we r Cost:
• De fine d, lo w-c o st me dia

b a se d o n g luc o se

• No Viruse s e limina te s

a sso c ia te d c o sts

42 118 124 60 110 360

50 100 150 200 250 300 350 400

C1 - 2,000L tank C1 - 10,000L tank CHO - 10,000L tank Cost in Million USD

L

• we r

Manufac tur ing Cost: C1 vs CHO Humir a mAb Annua l OpE x Initia l Ca pE x Inve stme nt

Summary

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Sho rte r d e ve lo pme nt & pro d uc tio n c yc le s Hig he r pro te in yie ld s L

• we r Ca pE

x/ OpE x Hig he r purity & g re a te r pro te in re c o ve re d L

• w Co st Me d ia / No Vira l

Ina c tiva tio n No ne g a tive c linic a l sig ns in mic e stud ie s R&D Co lla b o ra tio ns L ic e nsing Arra ng e me nts Othe r Co mme rc ia l Oppo rtunitie s

Dya dic is looking for pa rtne rs in the biopha rma c e utic a l spa c e to e xploit the pote ntia l of C1. Conta c t mjone s@dya dic .c om

THANK YOU!