large-scale pcr-based dna production · 2020. 1. 15. · company overview •one of the world’s...
TRANSCRIPT
Large-Scale PCR-Based DNA
Production
James Hayward, Ph.D.
CEO
The statements made by Applied DNA Sciences, Inc. (“the Company”, or “us”) in this presentation regarding the Company andits business may be forward-looking in nature and are made pursuant to the safe harbor provisions of the Private SecuritiesLitigation Reform Act of 1995. Forward-looking statements describe the Company’s future plans, projections, strategies andexpectations, including statements regarding future results of operations and financial position, business strategy, prospectiveproducts, timing and likelihood of success, and objectives of management for future operations, and are based on certainassumptions and involve a number of risks and uncertainties, many of which are beyond the control of the Company, including,but not limited to, the risks detailed in the Company’s Annual Report on Form 10-K for the fiscal year ended September 30,2019, and other reports filed by the Company with the Securities and Exchange Commission. Forward-looking statementsinclude all statements which are not historical facts, and can generally be identified by terms such as anticipates, believes,could, estimates, intends, may, plans, projects, should, will, would, or the negative of those terms and similar expressions.
Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted orquantified and may be beyond the Company’s control, you should not rely on these statements as predictions of future events.Actual results could differ materially from those projected due to the possibility of failure to make timely payment on itsoutstanding secured convertible notes and resulting enforcement by noteholders of remedies on collateral which includessubstantially all of the Company’s assets, the Company’s history of net losses, limited financial resources, limited marketacceptance, the uncertainties inherent in research and development, future clinical data and analysis, including whether any ofApplied DNA’s product candidates will advance further in the preclinical research or clinical trial process and whether andwhen, if at all, they will receive final approval from the U.S. FDA or equivalent foreign regulatory agencies, and various otherfactors detailed from time to time in Applied DNA’s SEC reports and filings. All forward-looking statements contained hereinspeak only as of the date hereof, and the Company undertakes no obligation to update any forward-looking statements,whether to reflect new information, events or circumstances after the date hereof or otherwise.
Forward Looking Statement
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Company Overview• One of the world’s largest polymerase chain reaction (PCR)-based, mass-producer of DNA
• PCR is a method used in molecular biology to make several-to-billions of copies of a specific DNA segment; essential in research and diagnosis but practiced in miniscule volumes (microliters). We have engineered to liters and continuous-flow.
• DNA molecular taggant to illuminate supply chains in large commercial ecosystems for authenticity and traceability
• Larger engineered amplicons and genes for biotherapeutics and diagnostics.
• Headquartered in Stony Brook, New York, with 55+ staff in the United States, United Kingdom, and India
• Central Testing Laboratory in Ahmedabad, India
• Distribution in US, Europe and Asia
• Over 125 issued patents and pending patent applications
• Large Global Markets
• Securing supply chains with small amplicons
• Large amplicons for therapeutics and diagnostics
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Corporate Structure
supply chain integrity / brand
protection
nucleic acid-based therapies utilizing
linear DNA
PCR Manufacturing
Methods
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Value Proposition Has Potential to Span Physical, Digital and Social Economies
5Sustainable Circular Economy
Claims Stay with
the Goods (enabling link
between digital transactions and physical assets)
Origin Provenance PurityAuthenticity
Proactive Proof for
Stakeholders &Activists
Brand Support
Recover counterfeit
market share
Recover Lost / Stolen Goods
Reduce Legal Risk
Application-specific In-Lab or In-Field Browser-based desktop or mobile
Information and Intelligence- Centralized | Blockchain | Enterprise -
T A G T E S T T R A C K
Cloud-based
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Global Commercialization and Diversification of Textiles Activities
Each circle signifies a partner or customer
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CertainT® Assurance for Textile MaterialsCommercial and Precommercial Products
(Covert fluorescence)
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Expanding The “Tagged Universe”Commercial and Precommercial Products
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Pharmaceutic ExcipientsSustainable Plastics and
Specialty Chemicals
Cannabis and Hemp Powders/Granules
Inks / Varnishes / Adhesives
Creams and Oils
LineaRx’s proprietary process enables large, gram-scale production of DNA through PCR for diagnostics and bio-
based therapeutics.
Focused on Adoptive Cell Therapies, DNA Vaccines (including Cancer),
CRISPR and other Nucleic Acid-based Therapies.
Pending IP for long term episomalpersistence, high translational
efficiency and non-viral transfection.
Active CMO/CRO business now supplying bulk GLP
DNA products; opportunity for cGMP validation.
Linear DNA does not require recombination;
hence, no need for virus.
No need for plasmids, reducing risks and unwanted DNA or
contaminants that need to be removed. Unique in that it can be centrally
scaled or operated remotely as licensed or managed service.
LineaRx – A New Paradigm in Diagnostics and Biotherapeutics – Gene-sized Amplicons and Larger
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Advantages of Linear DNA over Plasmids
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Path to Commerce
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Therapeutic Applications of Linear DNA
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Linear DNA Preclinical Pipeline• Cancer Vaccine – Partnership with Takis/Evvivax SRL
• PCR-produced linear DNA for Telomerase antigens produces strong immunogenic response in mice, clearing tumors in less than 10 days
• PCR-produced linear DNA cancer vaccine directed against neoantigens (more advanced, aggressive cancers) cleared disseminated cancers in mice in less than 30 days
• When an untreated human pancreatic cancer was transplanted into xenographic mice, and the human patient’s immune system reconstituted in the same mouse, the linear DNA vaccine for Telomerase resulted in the clearance of the pancreatic cancer.
• Anti-CD19b CAR T Adoptive Cell Therapy• Retroviral, plasmid format successful in limited human trials in China; 3 children with
Acute Lymphocytic Leukemia now in remission >12 months• Licensed from iCell in LineaRx format for North America• Transfection studies underway that will enable scale-up, FDA dialog, and production at
the point-of-care
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Human T Cells Transfected with Linear GFP DNA
Challenges of Chimeric Engineered Proteins
• Therapeutic engineered or chimeric proteins often under express or poorly express in hosts.
• Poor expression leads to poor presentation and therapeutic efficacy.
• Enhanced expression and stabilization leads to better therapeutic response.
• Chaperoning the engineered protein by a tag promotes compartmentalization.
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SUMO (small ubiquitin-like modifier)Fusion Technology
• SUMO enhances the quality and quantity of expressed engineered protein. Increased expression
• SUMO protects proteins from degradation
• Increased solubility• SUMO helps proteins to fold correctly
• SUMO fusion promotes compartmentalization • SUMO fusion help chaperone proteins to the right compartment
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“Applied DNA Subsidiary, LineaRx, Inc., Signs Licensing Agreement with LifeSensors, Inc.” (announced yesterday)
Error Mitigation PCR Workcell
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• Continuous PCR nucleic acid production that is unique in the ability to combine DNA origami assembly and error removal in one contiguous process for the production of long 100% error free nucleic acid assemblies
• The possibility to remove plasmid from the assembly and construction of long synthetic genes, expression vectors, and error mitigation within a large volume continuous PCR workcell
• This continuous-flow error-mitigated PCR-DNA origami process saves weeks of time in development in rapid high throughput scale up and large density screening of nucleic acid therapies
• Used in the production of homogeneous ssDNA, dsDNA, and RNA therapies
iCTC – Isolating Metastatic Cells in Blood
• A functional diagnostic assay that detects viable invasive circulating tumor cells (iCTCs) in blood (metastasis-initiating cells).
• Potential to detect cancers even before they can be imaged.
• Technical feasibility has been proven with 6,000+ blood samples supported by more than $7 million to-date from the National Cancer Institute.
• iCTC counts correlated with Prostate Cancer outcomes better than PSA.
• Opportunity to marry isolation of iCTCs to therapeutics using linear DNA.
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iCTC Technology• Functional metastatic cell isolation kit involving a specialized tube assay to isolate invasive
circulating tumor cells (iCTCs) from patient blood samples.
• Cell Adhesion Matrix coated surfaces emulate human tissue to capture tumor cells in blood.
iCTCs are captured based on their preferential
adhesion to CAM
CAM (Cell Adhesion Matrix)
Patient Samples are added to CAM coated
plates or tubes
CAM (Cell Adhesion Matrix) CAM (Cell Adhesion Matrix)
Captured iCTCs are labeled based on their integration of FTTC or
TRITC labeled CAM
Captured iCTCs are suspended for analysis
by flow or image cytometry or for gene
expression, gene mutation, or culture in
plates for growth inhibition with drugs or
other agents
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The iCTC Platform is Useful in Detecting Epithelial Cancers in Blood
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iCTCs Are Metastatic
• iCTCs were characterized using peritoneal and spontaneous metastasis models in vivo to evaluate their metastatic propensity and therapeutic response.
• 1,000-fold more metastatic propensity: Approximately 500 patient‐derived iCTCs recapitulated formation of iCTCs in mouse blood and formed micrometastases in the liver and/or lung, a degree of metastatic spread equivalent to the inoculation of 5 × 105 bulk tumor cells isolated from ascites and tumors.
Dong,H., et al 2019 Cancer Medicine
iCTCs in mouse blood
An iCTC in mouse lung metastases
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GFP+CAM+Bright Field
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GFP+CAM+Bright Field
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iCTCs respond to therapy and to patient status and can be used as a prognosticator.
• Surveillance screening of recurrence –iCTC™ assay was able to detect recurrences of ovarian cancer up to six months before conventional CT imaging and serum CA125 found evidence of recurrence.
• Monitoring therapy response –Increases in iCTCs (79.5%) were more sensitive than increases in CA125 (67.6%) to predict progressive disease or relapse.
Cited from: Pearl, ML 2014; 2015 Gyn. Oncol.
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iCTCs Are Good for Drug Development:iCTC-Tx® Drug Response (CDR) Blood Test to Screen Developing and Available (Standard-of-Care) Drugs
Blood draw at Clinic and Shipped to
Central Lab
Treating patient-derived iCTCs in culture with 3
doses of a panel of drugs.
CDR provides predictive information for drug
development and personalized treatment
decision-making.Within 48 hours
3 days
Flow cytometry analysis
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Summary Financial Highlights
For the 3 months ended
September 30,
For the 12 months ended
September 30,
2019 2018 2019 2018
Total Revenues $1.7 $1.2 $5.4 $3.9
Total Operating Expenses
$3.2 $4.4 $13.6 $14.3
Net Loss $(1.2) $(3.5) $(8.6) $(11.7)
Cash, cash equivalents ~$12.6*
Total Debt $1.5
*Includes gross proceeds of $12 million from an upsized underwritten public offering that closed subsequent to quarter-close.
($ in Millions)
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