the c1 technology platform making healthcare accessible ... · the chinese hamster ovary (cho) cell...

41
Investor Presentation NASDAQ: DYAI The C1 Technology Platform Making Healthcare Accessible & Affordable

Upload: others

Post on 02-Oct-2020

3 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Investor Presentation

NASDAQ: DYAI

The C1 Technology Platform

Making Healthcare Accessible & Affordable

Page 2: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION 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 March 31, 2019 Quarterly Report on

Form 10-Q filed with the SEC on May 9, 2019 and our December 31, 2018 Annual Report on

Form 10-K filed with the SEC on March 27, 2019, and our other filings with the SEC which are

available at the SEC's internet site (http://www.sec.gov). 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.

2

Page 3: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Biologics Development and Manufacturing Need Change

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

3

To further develop C1 into a safe and efficient gene expression systemto help speed up the development, lower production costs and improve the performance of biologic vaccines and drugs at flexible commercial scales.

Dyadic’sGoal

Gottlieb Slams Pharma, Launches Biosimilar Pathway, 7/19/2018

“Less than two percent of Americans use biologics, but they account for 40 percent of total spending on prescription drugs. They also represent 70 percent of the growth in drug spending from 2010 to 2015 and are expected to be the fastest growing segment of drug spending.”

Page 4: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Ticker: NASDAQ: DYAI

Share Price: $4.35(1)

52 Weeks Range: $1.40-$4.87(1)

Market Capitalization: ~$116.1 million(1)

Shares Outstanding: ~26.7 million(1)

Insider Ownership Percentage: 30.7% (2)

Debt: Zero

Warrants: Zero

Cash and Investment Grade Securities: ~$40.1 million(3)

Research coverage: Zacks Small Cap Research and Noble Capital

(1) As of 5/14/2019 (2) As of 04/29/2019, including Francisco Trust (3) Based on 3/31/2019 balance

Dyadic Highlight

4

Page 5: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATIONDYADIC INFORMATION 5

Dyadic Overview

HQ: Jupiter, FL

BD&L: London R&D Management: Budapest

R&D: Valladolid

R&D: Helsinki

20+ YEARS EXPERIENCE IN PHARMA / FUNGAL GENE EXPRESSION PLATFORMS

Page 6: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Arindam BoseDr. 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.

Barry BucklandDr. 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).

Michael P. TarnokMr. Tarnok (Dyadic chairman) 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 KeryxBiopharmaceuticals, Inc., where he also served as Chairman of the Board.

EXP

ERIE

NC

E

Biop

harm

aceu

tica

l M

arke

t O

ppor

tuni

ties • Strategic focus since

2016

• Recombinant Vaccines

• Biologics

• Biosimilars/Biobetters

• Human and Veterinary

Dyadic Board – Decades of Big Pharma Experience

Page 7: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

C1 Gene Expression Platform - Broad Applications

Funded On-going R&D

Collaborations with Top Tier

Pharm

Experienced Board Members

and Management

Team

Strong Cash Position and Zero Debt

Compelling Valuation and

NASDAQ Uplisted

Proven Technology for Industrial Use

Why Invest in Dyadic? (DYAI)

7

US$40.1M Cash &

Investment Grade

Securities (1)

No Debt or Warrants

Sold Industrial

Biotech Unit to DuPont for $75 Million in

2015

Form 10 Effective

Nasdaq Uplisted on April 17, 2019

(1) As of March 31, 2019

Page 8: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

2018 Achievements and Milestones

Signed More Than 100 Confidentiality Agreements & MTA’s

Sanofi – AventisFunded collaboration to use C1 technology to produce multiple types of biologic vaccines and drugs of interest for human health indications.

Mitsubishi Tanabe PharmaFunded collaboration to use C1 technology to produce two difficult-to-express vital therapeutic proteins for human health indications.

8

Three Collaborations with Top Tier Academic Institutions• Israel Institute for Biological Research (IIBR)• Structural Genomics Consortium (a part of the University of Oxford)• Fraunhofer USA Center for Molecular Biotechnology

Entered Into Nine New Collaborations:

Other Collaborations including two with Top 20 Pharma Companies• mAbs and Bi-specific antibodies• Fc Fusion and other therapeutic proteins• Primary metabolites• Animal biologics• Diagnostic enzymes

Page 9: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Q1-Q2 2019 Corporate Achievements and Milestones

9

Two Sublicensing Agreements• Luina Bio/Novovet: with equity stake and royalties to use C1 to develop biologic vaccines and drugs for

companion animals• Alphazyme: with equity stake, milestone payments, and royalties upon the commercialization of C1

Additional Collaborations with Two Top 25 Pharma Companies• mAbs• Antigen

Corporate Achievements• Uplisted to NASDAQ: Initiated trading on April 17, 2019• Form 10 Effective on February 12, 2019

Serum Institute of India• Research and commercialization collaboration to develop and manufacture up to 12 antibodies and

vaccines using C1

Future Milestones and Pipelines• Expected additional collaborations throughout 2019• Expected scientific milestones and business development pipelines in 2019 and beyond

Page 10: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Dyadic and Serum Institute of India to Develop and Manufacture Globally Affordable and Accessible Antibody Products and Vaccines

10

Serum Institute of India – the world's largest vaccine manufacturer by number of doses produced and sold globally - the number of doses account to more than 1.3 billion.Serum supplies vaccines to more than 140 countries, 65 percent of all the children in the world receive at least one vaccine produced by Serum Institute (1).

Research and commercialization collaboration to develop and manufacture up to 12 antibodies and vaccines using Dyadic C1 Gene Expression Platform.

Adar Poonawalla, CEO, Serum Institute of India:

'Serum has a proven track record of more than 50 years of developing and delivering affordable vaccines and drugs globally and we are eager to incorporate Dyadic's industrially proven C1 gene expression platform into our antibody and vaccine development and manufacturing programs,'' said Adar Poonawalla, CEO, Serum Institute of India. He further stated that ''In recent years, monoclonal antibodies have emerged as preferred therapeutic candidates for the treatment of a multitude of disorders and diseases. These include a broad range of cancers, auto-immune diseases, microbial infections. Traditionally, antibody treatment is extremely costly and not widely affordable in the developed and developing worlds. We at Serum are committed to finding ways to speed the development, lower the cost and improve the performance of high quality, affordable antibodies and vaccines which have the potential to treat and prevent various diseases in India and across the globe. Dyadic's C1 gene expression platform has the potential to help us deliver on our commitment to bring down the cost of biologics in order to make them more accessible andaffordable to patients globally.''

(1) https://www.biospectrumindia.com/features/72/8523/biospectrum-ranking-survey-rank-1-serum-institute-of-india-.html

Potential to Receive Milestones & Royalties

Page 11: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

7.5% Ownership interest (2)

Pharma enzyme tools www.alpha-zyme.com

16.3% Ownership interest (1)

Virus like particles www.vlpbio.com

16.1% Ownership interest Animal & Human health www.bdibiotech.com

20% Ownership interest Biologic for Companion Animal www.novovet.com.au

Business Strategy to Sublicense C1 to Acquire Equity Interests in Biotech Companies

Dyadic C1 Technology

BDI Group

VLP Bio

NovovetLuinaBio

Alphazyme

FutureSublicensee Future

Sublicensee

FutureSublicensee

FutureSublicensee

(1) Dyadic’s equity in VLP is equivalent to 16.3 % (when including Dyadic’s equity stake in the BDI Group)(2) Subject to C1 Tech Transfer Successfully Completed

11

Page 12: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

Biopharmaceutical Markets

Page 13: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

“Market growth is primarily driven by the increasing demand for biosimilar drugs due to their cost-effectiveness, increasing incidences of chronic diseases, and strategic collaborations resulting in enhanced productivity and clinical trial activities. The rising incidence of blood disorders across the globe, low cost of biosimilars compared to biologics, and the rising pressure to reduce healthcare expenditure are major factors contributing to the growth of this segment.”

Global Biologic Drug Market To Be $ 479.8 Billion (2024)

(1) https://www.marketsandmarkets.com13

Page 14: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Healthcare is an inalienable right; Society is failing patients

FDA Commissioner Scott Gottlieb Slams Pharma,

Launches Biosimilar Pathway, 7/19/2018

“Less than two percent of Americans use biologics, but

they account for 40 percent of total spending on

prescription drugs. They also represent 70 percent of the

growth in drug spending from 2010 to 2015 and are

expected to be the fastest growing segment of drug

spending.”

14

Page 15: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Of the 350 million individuals worldwide infected with the hepatitis B virus, one-third reside in

China, with 130 million carriers and 30 million chronically infected. Every year, 300,000 people

die from HBV-related diseases in China, including 180,000 patients with HCC. (1)

• However, less than one in 50 patients in need of treatment receive it, with the biggest

barrier to treatment being affordability.

• Up to 10 million people in China could die from chronic hepatitis by 2030—urgent action

needed to bring an end to the ‘silent epidemic’.

Hepatitis B: an Endemic in China

(1) Custer B, Sullivan SD, Hazlet TK, Iloeje U, Veenstra DL, Kowdley KV (2004). "Global epidemiology of hepatitis B virus". J. Clin. Gastroenterol. 38(2) DOI: https://doi.org/10.1016/S0140-6736(18)30499-9

15

Page 16: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

C1 Gene Expression Platform

Page 17: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION 17

C1, Myceliophthora Thermophila

C1 is a thermophilic fungus, Myceliophthora thermophila originally isolated from alkaline soil in Russia for its ability to produce neutral/alkaline cellulases for use in textiles, and later used to produce enzymes for biofuels, pulp & paper, biogas …

C1 has a unique morphology, led to better growth conditions & productivity.

Over 2 decades Dyadic & its licensees spent several hundred million dollars developing C1 into a industrially proven gene expression platform for producing low cost enzymes & other proteins at industrial scale with high productivity, purity and stability.o C1 genome fully sequenced and annotated

o Proprietary & Patented genetic elements (tool box) for use in engineering C1 strains to produce low cost biologic vaccines & drugs.

o C1 received a Generally Recognized As Safe (GRAS) designation from the US FDA (2009).

o Data shows C1 can speed development & lower costs of biopharmaceuticals

17

Page 18: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

CHO C1 White Strain 2.0

C1 – The Science

Unique Morphology

High Purity - 80% of target protein secreted

Wide operating conditions for pH and temperature

Shorter Development & Production Cycle

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 10 -14 days vs CHO Fermentation Cycle time 4-7 days

• 1/2 to 1/3rd the time of CHO

18

Page 19: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION 191

C1 (12 – 14 days) vs CHO (41-54 days) - FLOW

C1 CHOVS• C1: Higher Protein

Productivity• ½ the Cycle Time

• C1: Easier – Advanced Genetic Tool Box

• C1: Faster – Develop Initial Cell Line in c15 weeks

• Shorten development time• Lower Development &

Production Costs• Increased productivity • Smaller plants will be

required• Lower healthcare costs

Page 20: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

C1 Can Operate Successfully in Single Use Bioreactor

C1, a filamentous fungi, produces Certolizumab at Single Use bioreactor with the same performances than at Stainless Steel bioreactors

The productivity of 9.2 g/l is virtually identical to the productivity achieved in the Stainless Steel Bioreactor control that was based on an earlier C1 Certolizumab strain and process. The current yield in SSB is 14.5 g/l in 7 days fermentation

Results between batches are consistent, showing the robustness of the technology

Equipment: 50L XDR-50MO

Single Use GE bioreactor

Product protein:

Certolizumab

20

Page 21: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

C1 Broad Applications of Therapeutic Proteins

C1 to Help Overcome Difficult-to-Expressed Proteins

Page 22: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION 22

C1’s Broad Applications and High Yield Level

Fc-Fusion 12.2 g/l

144 Hours 1.74 g/l/day

Hemagglutinin (HA)

413 mg/l 137 Hours

72 mg/l/day

Bispecific1.04 g/l

144 Hours0.17 g/l/day

VLP300 mg/L112 Hours

64 mg/l/day

Therapeutic Proteins

Vaccines/Antigens/Virus Like Particles (VLP)

Antigen1,780 mg/L121 Hours

350 mg/l/day

mAbs 9 g/l

90 Hours 2.4 g/l/day

Fab (Certolizumab) 14.5 g/l

164 Hours 2.1 g/l/day

2015

Page 23: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Fermentation Results of ZAPI Antigen With C1 9xΔ Protease Strain

Seventeen (17X) The Initially Stated Target Expression Level

Affinity chromatography purification at small scale to determinate the production level

Baculovirus (30 - 50 mg/l)

ZAPI Antigen yield:

1,780 mg/l (time point 121h)

Fermentation analysis

Purification steps

23

Page 24: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Success In Bispecific Expression

In a few months work we have been able to express a bispecific antibody using C1 to a level of 1.04 g/L and

provide sufficient quantities of this antibody to our collaborator which they were not able to do previously

using other expression systems after two years of work.

24

Purified samples of bispecific protein

• SE-HPLC• IEX-HPLC• SDS-PAGE (reducing/non-reducing)• Differential scanning fluorimetry (DSF)• Bioassay; cytotoxicity assay

Page 25: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Bispecific Produced in C1 and CHO Have Identical/Similar Activity

The function of C1-produced bispecific was compared to the CHO-produced control in a bioassayo C1-produced purified using only single chromatography step

o CHO-produced fully purified

Potency of C1-produced bispecific in the bioassay is comparable to the CHO-produced control

No negative effects of the C1-derived potential impurities in cellular assays

Blue – C1-produced bispecificRed – CHO-produced bispecific

25

Page 26: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Monoclonal Antibodies

• Antibody very stable

• Best productivity so far at 30L scale:

o mAb titer of 9 g/L at 90 h

o 2.4 g/L/day

26

Page 27: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

MAbY Binding Assay by Biacore T200

Studying the interaction of mAbs in real time

MAbY for which the ligand was commercially available was produced

in CHO (control Mab) and C1 (C1-produed mAb)

The binding properties of a pharma’s mAbs to the ligand were

compared in a Biacore T200 assay

The control mAbY and C1-produced MAbY showed virtually

indistinguishable binding kinetics.

Similar results were obtained with other mAb

27

mAb

Page 28: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

Dyadic C1 Biopharmaceutical Projects

Page 29: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Cimzia® Information

$1.4 B

M a r k e t v o l u m e

Certolizumab pegol, the drug substance of Cimzia® is a recombinant, humanized Fab' antibody.

It lowers inflammation in the body by blocking a protein called TNF (tumor necrosis factor).

Certolizumab Cimzia® is manufactured by UCB and used to treat Crohn’s disease, arthritis and other autoimmune disorders.

29

Page 30: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Success in Expressing Certolizumab (Fab) by C1

Successful expression of Certolizumab

No N glycosylation has been identified to date in Certolizumab O-glycosylation has recently been identified in Certolizumab, it will need to be reduced or removed

ELISA kit was used to measure and conform Certolizumab expression level (triplicates of samples were quantified)

The calculated expression level was 12.0 g/L, corresponding to 2.6 g/L/day production rate.

Initial result obtained from 7 days fermentation at 1L scale was 14.5 g/L, Corresponding to 2.1 g/L/day.

By further optimization of the fermentation process up to 7 days we would expect to see even higher expression levels

30

Page 31: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Roadmap for Biosimilar Certolizumab Development

Cell line develop-

ment

CMC develop-

ment

Biological activity

compari-son

Structural compari-

son

Non-clinical

compari-son

Clinical compari-

son

CMC development and batches production (GMP for clinical assays)Optimization of process & product quality attributes profile, cell line characterization & stability, formulation & product stability testing.

Generation of producing strain (1)

USP&DSP development

Analytics to compare the structural & physicochemical characteristics of product vs. commercial reference

In vitro assays to compare product mechanisms of action.

Primary: TNFαneutralization by binding and inhibition of cell signaling for proliferation

Secondary: activation of immune responses as CDC, ADCC….

In vitro PD studies to compare neutralization. activity, CDC, ADCC and apoptotic effects and cross-reaction with human tissues

In vivo PK studies to detect products in animal serum & to measure anti-products Ab concentration

In vivo toxicity & toxic kinetics assays

1 year Phase I trial to determine PK equivalence (mainly safety) in AS patients (250)

2 year Phase I pilot study for RA patients (19)

1 year Phase III trial to mainly determine therapeutic equivalence in RA patients (606)• Based on EMA assessment report for

approval of an Infliximab (anti-TNFα) biosimilar (2013)

• (1) O-glycosylation has recently been identified in Certolizumab, it will need to be reduced or removed.

In 30L bioreactor

14.5 g/l, (2.4 g/l/day) production rate

In Bench scale: using protein L Achieved: recovery

yields >90% and

Purities >85%

31

Year 1 Year 2 Year 3 – Year 6

Page 32: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Opdivo® Information

The immunotherapy drug Opdivo ® (nivolumab) is manufactured by Bristol Myers Squibb. Opdivo is approved for several cancers that are metastatic (such as lung cancer, melanoma, and

more), and has resulted in responses previously not seen with these advanced cancers. Opdivo, approved for both melanoma and lung cancer, is priced at $12,500 a month, or

about $150,000 for a year of treatment.

$8.0 B (1)

M a r k e t v o l u m e

(1) Trefis team Analyst Opdivo Estimate for 2023

32

Page 33: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Model Glycosylated Monoclonal Antibody (mAb)

Successful expression of Nivolumab (mAb) by C1

Glycoengineering of the C1 host production cell is ongoing

Once we have the proper glycoengineered C1 cell line we will try and express nivolumab in that C1 cell. This will be a potential BioBetter, as the glycan structure is expected to be similar to

CHO produced nivolumab

Nivolumab (mAb)

G0 G0F G2 G2F

C1 strain

33

Page 34: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Sanofi Pasteur Mice Trial

Immunogenicity Study of HA/NC Produced by C1

HA/New Caledonia

The Recombinant Hemagglutinin

(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)

The HA/New Caledonia

produced in C1 showed

excellent immunogenic

properties in mice

Better protection than the

control HA/New Caledonia

produced by Baculovirus

C1 can produce high levels of HA (~1 g/L) as well as

other Antigens in 3 -7 days by using low cost

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.

34

Page 35: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Model Vaccine – Based on Sanofi Pasteur HA Data

Hemagglutinin (HA), (Develop C1 as a seasonal flu platform).• HI response after 2 IM immunizations in Mice: • Significant 2-fold difference in favor of HA derived from C1

Based on preliminary mice trial data C1 has the potential to produce HA at lower cost with potentially better immunogenicity. Also, C1 has the potential to speed the development time

HI Response after 1 IM immunizations in Mice.Percent of Responders (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)

https://www.dyadic.com/wp-content/uploads/2018/01/Sanofi-Pasteur-C1-Presentation.pdf

35

Page 36: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Exploring the use of C1 to produce AAV Vectors

Adeno – Associated Virus (AAV) Vectors New York Times, Nov 27, 2017: Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage

o Significant increase in gene therapy; Backlog for in the production of viruses

o Manufacturing disabled viruses (usually a disabled version of an adenovirus or a lentivirus) is costly and onerous

Recombinant AAV-based Vectors (AAVs)

o One of the most widely used vehicles for delivery in gene therapy

o Used in nearly 50% of the 483 currently ongoing gene therapy trials; Expected to increase over the next few years:

Lack of diseases associated with the wild-type virus

AAVs have the ability to transduce non-dividing, as well as dividing cells. A resulting long-term robust transgene expression isobserved in several Phase I and II trials.

Different AAV vector serotypes can be used to specifically target different tissues, organs, and cells, thus expanding the therapeutic application and commercial potential of AAV-based gene therapies.

Potential future larger production scale: Progress in gene therapy-based treatments for more common indications, such as Alzheimer’s, Parkinson’s, or Rheumatoid Arthritis

Global Opportunity Analysis and Industry Forecast, 2017-2023," the global gene therapy market accounted for $584 million in 2016, and is estimated to reach $4,402 million by 2023, registering a CAGR of 33.3% from 2017 to 2023.”

36

Page 37: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Applying C1 to Produce Metabolites

Primary metabolite Dyadic collaborated with a third party to develop C1 strain for a

high yield, low cost primary metabolite product Dyadic is using precise genetic manipulation that is based on

metabolic modeling and synthetic biology Funded by the third party

o Phase 1. Milestone achievedo Phase 2. & Potential continuation of project under

discussion

Secondary metabolite Project initiated by Dyadic

37

Metabolic model was developed to support PRECISE ENGINEERING

approach for Primary and Secondary metabolites production

Page 38: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

In Summary…

Page 39: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Proprietary Technology

C1: Fungal Gene Expression Platform

Success in Industrial Use

HQ: Jupiter, FL

BD&L: London & Budapest

R&D: Finland & Spain

Cash: $40.1 Mil (1)

Debt & Warrants: None

(1) Cash and Investment Grade Securities as of March 31, 2019

January 2019 Our40 Year Anniversary

>20 Patents

Over Two Decades Of Biotechnology Experience

&Several Hundred Million Dollars Spent on Developing C1 Platform

Leveraging C1’s Industrial Biotech Commercial Success

39

• Strategic focus since 2016

• Human and Veterinary• Recombinant Vaccines

• Biologics

• Metabolites

• AAV Vectors

Biopharmaceutical Market Opportunities

• Signed More Than 100 NDA’s & MTA’’s

9 - Deals in 20185 - Deals To Date 2019

Generated Data• High productivity

of multiple types & classes of vaccines & drugs

• C1 can be grown in single use bioreactors

• And more …

In 2 ½ Years

Page 40: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

DYADIC INFORMATION

Shorter development & production cycles

Higher protein yieldsLower CapEx/OpEx

Higher purity & greater protein recovered

Low cost media / No viral inactivation

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 [email protected]

C1 Business Benefits and Opportunities

40

Page 41: The C1 Technology Platform Making Healthcare Accessible ... · The Chinese hamster ovary (CHO) cell line is not the future for biomanufacturing says Biogen, MIT & Gates Foundation

THANK YOU !