Research programme: linear DNA based coronavirus vaccines - LineaRx/Takis
Alternative Names: 2019-nCoV coronavirus vaccine - LineaRx/Takis; LineaDNA™; Linear DNA based coronavirus vaccines - Takis/LineaRx; LinearDNA™ COVID-19 Vaccine-LinearRx/TakisLatest Information Update: 22 Jul 2020
At a glance
- Originator LineaRx; Takis
- Class COVID-19 vaccines; DNA vaccines
- Mechanism of Action Immunostimulants
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Preclinical COVID 2019 infections
Most Recent Events
- 17 Jul 2020 Positive immunogenicity data from preclinical studies in COVID-2019 infections released by Applied DNA Sciences and Takis
- 17 Jul 2020 Applied DNA Sciences and Takis Biotech plans a first in human clinical trials in December 2020
- 08 Jun 2020 Applied DNA Sciences and Takis plan additional toxicology studies with third-party (assuming positive results from ongoing dose-response studies) for COVID-2019 infections (Prevention) (Parenteral)
Development Overview
Introduction
Linear DNA based coronavirus vaccines are being developed by Takis/Evvivax (a spin-off of Takis and LineaRx (a wholly owned subsidiary of Applied DNA Sciences) for the prevention of COVID-2019 infections. The linear DNA vaccine candidates will be delivered via Takis' proprietary in vivo electro-gene-transfer technology. LineaRx will use its PCR methods for the production of linear DNA which is cleaner, faster and more easily modified in comparison with DNA produced using standard methods. Preclinical study is underway in the US and Italy.
Under this programme, five DNA vaccine candidates will be developed for preclinical animal testing. Takis will use the scaled-up LinearDNA™ synthetic genes produced by Applied DNA for each of the four putative vaccines to inoculate mice, whose sera will be tested for the presence of antibodies that bind to the purified spike proteins. The positive candidates that bind to spike will be tested for their ability to neutralize COVID-19 by preventing uptake of the virus in cells in culture and in animal models [1] .
A lead LinearDNA™ COVID-19 vaccine candidate is also being developed for veterinary use, which is beyond the scope of RDI, hence its development will not be covered [2] .
Company Agreements
In March 2020, LineaRx (subsidiary of Applied DNA Sciences) expanded its joint development agreement with Takis for COVID-19 vaccine development program to include a fifth vaccine candidate. Under the terms of the companies’ amended Joint Development Agreement, Takis will use the scaled-up LinearDNA synthetic genes produced by Applied DNA for each of the five putative vaccines to inoculate mice whose sera will be tested for the presence of antibodies that bind to the purified Spike proteins. Those positive candidates that bind to Spike will be tested for their ability to neutralize COVID-19 by preventing uptake of the virus in cells in culture and in animal models. Previously in February 2020, LineaRx expanded its joint development agreement with Takis for the preclinical development of a linear DNA vaccine against COVID-2019 infections. Earlier in September 2018, LineaRx entered into a joint development agreement with Takis for the discovery and development of DNA based anti-cancer vaccines. Under the terms of the agreement, both companies will jointly develop linear DNA expression vectors for two of Takis anticancer vaccine candidates using LineaRx's linear DNA technology. Linear DNA amplicons carrying the DNA sequences for Takis vaccine candidates will be delivered to preclinical animal models via Takis's proprietary electroporation technology for measurement of the antigen-specific immune responses. Further details of the agreement were not disclosed. [3] [1] [4]
Key Development Milestones
In May 2021, Applied DNA Sciences and Evvivax reported that following a booster injection delivered 30 days after the prime vaccination of the linearDNA coronoavirus vaccine candidate elicited average boost in SARS-CoV-2 neutralising antibody (NAb) levels (titers) by over 5-fold, and NAbs were induced in every cohort. These NAbs produced by feline, when tested against functional SARS-CoV-2 virus of the D614G lineage, demonstrated neutralising titers with a geometric mean titer for the cohort of 398 [5] .
In July 2020, results from preclinical studies were released by Applied DNA Sciences [6]
In June 2020, Applied DNA Sciences reported that the linear DNA versions of the vaccine candidates manufactured by the company commenced preclinical dose-response trials. These studies were initiated on the heels of favourable results reported earlier in May 2020. The results had demonstrated the triggering of neutralising antibodies in test animals after the first injections of the Takis-developed plasmid-based DNA vaccine candidates against the Spike protein (product of the S gene) of the SARS-CoV-2 virus that causes COVID-2019 infections [7] [8] [1] .
In April 2020, LineaRx announced that it has completed qualification, production and shipment of five vaccine candidates to Takis Biotech in Italy. In March 2020, LineaRx and Takis Biotech had announced expansion of their COVID-2019 vaccine development program to include a fifth vaccine candidate. Along with the planned Takis animal trials, LineaRx plans to prepare for cGMP production of selected vaccine candidate(s) to support human trials scheduled to begin in fall [9] [4] .
In March 2020, Italian Ministry of Health approved to test the linear DNA based coronavirus vaccines in animal models. The preliminary examination to test the tolerability and efficacy will be conducted at the Spallanzani Institute [10] .
Financing information
In January 2021, Applied DNA Sciences announced closing of its previously announced registered direct offering with a group of institutional investors of 1,810,000 shares of common stock at a price of $8.30 per share, priced at-the-market under Nasdaq rules, resulting in total gross proceeds of approximately $15 million. This net proceeds will be utilized for general corporate purposes, including working capital, for research and development, and to advance the adoption of its LinearDNA™ manufacturing platform [11] .
In June 2020, Applied DNA sciences announced that it has secured a $US40,000 economic development grant from National Grid to support the pathway to manufacture the linear DNA based coronavirus vaccines for clinical trials [12] .
Drug Properties & Chemical Synopsis
- Route of administration Parenteral
- Formulation unspecified
- Class COVID-19 vaccines, DNA vaccines
- Mechanism of Action Immunostimulants
-
WHO ATC code
J07B-X (Other viral vaccines)
-
EPhMRA code
J7A9 (Other specified single component)
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | - | Prevention | Preclinical | Italy, USA | Parenteral / unspecified | LineaRx, Takis | 04 May 2020 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| LineaRx | Originator | USA |
| Takis | Originator | Italy |
| Takis | Owner | Italy |
| LineaRx | Owner | USA |
| The Lazzaro Spallanzani National Institute for Infectious Diseases | Collaborator | Italy |
Scientific Summary
Immunogenicity
Summary
Results from preclinical studies demonstrated that LineaDNA vaccine exhibited strong antibody and T-cell responses at very low doses. The vaccine provoked seroconversion in mice with all animals and produced IgG against the SARS-CoV-2 spike Protein by day 14 and exhibited significant enhanced responses by day 38. Titration studies showed that at dilutions of 1:50,000, antisera derived from mice vaccinated with linear DNA retained its binding activity. IgGs against SARS-CoV-2 spike could be readily identified in bronchoalveolar lavage, a wash of the lower respiratory system, suggesting that vaccination in mouse muscle would allow the consequent antibodies to fight the infection in the lower lung. T-cell responses to the linear vaccines were strongest for the linear construct that contained the sequence corresponding to an abbreviated form of the spike protein, specifically the portion of Spike that binds to the receptor on human cells that mediates viral uptake into the host’s epithelial cells in the respiratory system [6]
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2020 | Trial Update | Applied DNA Sciences and Takis Biotech plans a first in human clinical trials in December 2020 [6] | 22 Jul 2020 |
| 30 Apr 2020 | Trial Update | Applied DNA Sciences and Takis Biotech plan Preclinical studies in COVID-2019 infections in late April 2020 [4] | 12 May 2020 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 17 Jul 2020 | Scientific Update | Positive immunogenicity data from preclinical studies in COVID-2019 infections released by Applied DNA Sciences and Takis [6] Updated 22 Jul 2020 |
| 17 Jul 2020 | Trial Update | Applied DNA Sciences and Takis Biotech plans a first in human clinical trials in December 2020 [6] Updated 22 Jul 2020 |
| 08 Jun 2020 | Trial Update | Applied DNA Sciences and Takis plan additional toxicology studies with third-party (assuming positive results from ongoing dose-response studies) for COVID-2019 infections (Prevention) (Parenteral) [7] Updated 11 Jun 2020 |
| 08 Jun 2020 | Trial Update | Applied DNA Sciences initiates preclinical dose-response trials of its linear-DNA vaccine candidates for COVID-2019 infections (Prevention) (Parenteral) [7] Updated 11 Jun 2020 |
| 04 May 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections (Prevention) in Italy (Parenteral) [8] Updated 12 May 2020 |
| 04 May 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections (Prevention) in USA (Parenteral) [8] Updated 12 May 2020 |
| 03 Apr 2020 | Licensing Status | LineaRx and Takis expands joint development agreement for linear DNA based coronavirus vaccines to include a fifth vaccine candidate [4] Updated 08 Apr 2020 |
| 03 Apr 2020 | Trial Update | LineaRX and Takis plan clinical trials for for Linear DNA based coronavirus vaccines in COVID-19 infections [4] Updated 08 Apr 2020 |
| 02 Apr 2020 | Trial Update | Applied DNA Sciences and Takis Biotech plan Preclinical studies in COVID-2019 infections in late April 2020 [4] Updated 12 May 2020 |
| 17 Mar 2020 | Regulatory Status | Italian Ministry of Health authorizes to conduct preclinical tests on animal models for Linear DNA based coronavirus vaccine in COVID-19 infections [10] Updated 20 Mar 2020 |
| 07 Feb 2020 | Licensing Status | LineaRx and Takis expands joint development agreement for preclinical development of linear DNA based coronavirus vaccine [1] Updated 12 Feb 2020 |
| 07 Feb 2020 | Phase Change | Early research in COVID-2019-infections (Prevention) in Italy (Parenteral) [1] Updated 12 Feb 2020 |
| 07 Feb 2020 | Phase Change | Early research in COVID-2019-infections (Prevention) in USA (Parenteral) [1] Updated 12 Feb 2020 |
References
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Applied DNA Sciences Subsidiary, LineaRx, and Takis Biotech Collaborate for Development of a Linear DNA Vaccine Candidate Against Wuhan Coronavirus 2019-nCoV.
Media Release -
Applied DNA, EvviVax, and GVS Receive Regulatory Approval to Conduct Veterinary Clinical Trial for Linear COVID-19 Vaccine Candidate.
Media Release -
LineaRx signs agreement with Takis/Evvivax to develop linear-DNA based anti-cancer vaccines.
Media Release -
Applied DNA and Takis Biotech Expand COVID-19 Vaccine Development Program to Include 5th Candidate.
Media Release -
Applied DNA and Evvivax Announce that LinearDNA(Tm) COVID-19 Vaccine Candidate Booster Yields 5-Fold Average Increase in Neutralizing Antibody Titers in Domestic Felines.
Media Release -
Applied DNA and Takis Report Positive Preclinical Results from LineaDNA(Tm) Vaccine Candidates for COVID-19.
Media Release -
Applied DNA Provides Update on Linear-DNA COVID-19 Vaccine Candidates Development Program.
Media Release -
Applied DNA and Takis Biotech Announce the Production of Neutralizing Antibodies Against SARS-CoV-2 After DNA Vaccination in Animals.
Media Release -
Applied DNA Ships COVID-19 LinearDNA(T) Vaccine Candidates to Italian Development Partner to Begin Preclinical Animal Testing.
Media Release -
Rome, 17 March 2020 - Takis, a biotech company in Castel Romano, Rome, announces that it is ready to test its Covid-19 vaccine on pre-clinical models.
Media Release -
Applied DNA Announces Closing of $15 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules.
Media Release -
Applied DNA Secures Grant from National Grid Partnered with the New York State MEP to Support Manufacture of COVID-19 Diagnostic Kits and Vaccine Candidates.
Media Release
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