About Novavax
Novavax is a biotechnology company based in Maryland, USA. It was found in 1987 and has become known worldwide since its participation in the race to produce a vaccine against COVID-19. However, unlike other young biotech start-ups in the same race, such as Biontech and Moderna, the road Novavax took has been relatively tough. Let’s have a look at the technology, the products and the history of the company in this blog.
The technology used by Novavax
Novavax has a proprietary recombinant technology platform (Sf9/BV) for the production of antigens of vaccine that can induce immune responses.1 The two major components of the recombinant technology are baculovirus, a virus commonly attacked insects, and Sf9 moth cells.
Once the whole genome sequence of a pathogen has been identified, Novavax then identifies the genetic sequences that may trigger the immune responses in the host cells. Baculovirus used by the company is genetically engineered to carry the selected genetic sequence used to encode a vaccine antigen that can trigger an immune response. The recombinant baculovirus is then put into Sf9 moth cells by infection. Making use of the Sf9’s cellular post-transcriptional and post-translational machinery, the protein antigens expressed from the recombinant baculovirus are able to fold and modify themselves properly into their native forms. (Antigen in native configuration is necessary for optimized biologic immune responses for active immunity.) The Sf9 insect cell is like a manufacturing company which scales up production of antigens with native confirmation. The antigen produced is then harvested and purified as multimeric particles.1
Besides the antigen, Novavax also put its proprietary adjuvent, called Matrix-M, into its vaccine. Matrix-M is composed of 40-nanometer particles, based on saponin extracted from the Quillaja saponaria Molina bark, together with cholesterol and phospholipid.1 Matrix-M induces the influx of antigen presenting cells (APC), which enhance activated CD4+ and CD8+ T cells, long-lasting memory B cells, and APC populations. In general, Matrix-M generates potent, robust, and long-lasting protective immune responses. Therefore, the addition of Matrix-M in a vaccine can lower the dose of antigen required to achieve the desired immune response, and thus increases supply and manufacturing capacity using the same amount of antigens. Overall, the vaccine produced in this way is cheaper.
As the antigen in the vaccine is in protein form, which is more stable than the vaccine made of mRNA, Novavax’s vaccine is easier to transport and can be stored at room temperature for at least 24 hours.
Novavax has previous experience working with other coronaviruses, such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS). The two vaccine candidates demonstrated strong immunity and 100% protection in preclinical tests, but have never been put on the market for some reasons. This experience enabled the company to mobilize quickly against COVID-19.2
The hardship Novavax has gone through
Novavax has been established for more than 33 years. However, the biotech company has no single vaccine product being approved during these years. In January 2020, before the pandemic attacked the world, the company experienced a short interest which hit 30 percent of its share price. A year before that, Novavax was on the edge of closing, facing de-listing from Nasdaq. It had to lay off 120 manufacturing and quality-control staff, one-third of its staff.3
When we look back, Novavax has faced difficulties right at the beginning of its history. The company was founded in 1987 to develop “novazone” particles for vaccine delivery. But it soon changed its direction of the usage of the particles into hormone delivery. Its research and development in the women’s health business unfortunately had to be halted by 2005 due to unfavourable position in the competition market and concerns over the risk of breast cancer after oestrogen treatment.3
Since then, Novavax has been working on vaccines for SARS, MERS, Ebola, influenza, and Respiratory Syncytial Virus (RSV), a common virus that can be deadly for babies and older adults.2 This development of the vaccine to the RSV virus caused crisis after crisis in the company and almost drove the company to closure. In 2016, a Phase 3 clinical trial in older people failed due to not enough cases being available to reach a firm conclusion, and a diagnostic tool not widely available at the time. The company did not have enough funds to reinvent the Phase 3 trial and the company’s stock dropped 83 percent in one week. Later when the company was able to start a clinical trial of the RSV vaccine on pregnant women with the help of funding from the Gates Foundation, the trial failed and led to another financial crisis for the company in 2019 as mentioned above. In order to avoid being de-listed by Nasdaq, the company initiated a reverse stock split to lift its share price. It also had to sell its manufacturing facility in order to survive through the crisis.3,4
The promising products Novavax is developing
After surviving from the crisis, Novavax now has two promising vaccine candidates, other than the vaccine against COVID-19. One of them is NanoFlu™, a quadrivalent influenza nanoparticle vaccine. It is currently in a Phase 3 clinical trial to address key factors that can lead to the poor effectiveness of currently approved flu vaccines. Another one is ResVax™, the RSV vaccine that the company has long been developing. This is now in a Phase 3 clinical programme.2
Partnerships and manufacturing
Novavax sold its manufacturing facility in 2019 just before the company got funding from the US government to develop the COVID-19 vaccine. In order to fulfil the manufacturing capacity for clinical trials, the future vaccine supply, and rapid distribution across the world if and when its COVID-19 vaccine is approved for use, the company stretched itself in co-operating with many other pharmaceutical companies to produce the vaccine.
Initially, the company used a Maryland-based drug manufacturer, Emergent BioSolutions, to make initial doses for the clinical trials. Later, it partnered with different drug makers worldwide for production of vaccine if the vaccine candidate is approved: Serum Instititue of India Private Limited (SIIPL) for global production of the antigen component of its COVID-19 candidate;5,6 the National Research Council’s Biologics Manufacturing Centre for vaccine supply in Canada;7 FUJIFILM Diosynth Biotechnologies (FDB) manufacturing site in UK to manufacture the antigen component of its COVID-19 vaccine in the UK;8 Takeda for local manufacturing and commercialization in Japan;9 and SK Biosciences for the manufacturing of Novavax’s protein antigen for the supply in South Korea.10 In addition, Novavax recently acquired a factory, Praha Vaccines, in the Czech Republic, to provide extra annual capacity of over 1 billion doses of antigen for its COVID-19 vaccine candidate, starting in 2021.11
In the US, Novavax is co-operating with FUJIFILM Diosynth Biotechnologies (FDB) to manufacture bulk drug substances for its COVID-19 vaccine candidate. The manufactoring site of FDB in Morrisville has produced the first batch of the company’s COVID-19 candidate.12 The company itself is also expanding its campus to accommodate rapid growth. It has secured two additional properties in order to support its immediate need for additional laboratory and office space for manufacturing, R&D and business operations.13
Given the potential of its technology to manufacture millions of doses of vaccine quickly, Novavax received 1.6 billion US dollars from the US government early last year to expand its manufacturing capacity. Moreover, the company obtained additional funds from other sources since then.4 Hopefully the vaccine can get approval very soon in order to add supply to relieve the worldwide demand for COVID-19 vaccines.
References
1. Recombinant nanoparticle vaccine technology. Novavax website. https://www.novavax.com/our-unique-technology#recombinant-nanoparticle-vaccine-technology
2. Novavax advances development of novel COVID-19 vaccine. Novavax press release, Feb 26, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-advances-development-novel-covid-19-vaccine
3. Novavax closes in on Covid triumph after 33 years of failure. By Hannah Kuchler. Financial Times, March 1, 2021. https://www.ft.com/content/22d3805e-c304-4d95-ae32-f559ff34886a
4. How a struggling company won $1.6 billion to make a coronavirus vaccine. By Katie Thomas and Megan Twohey. New York Times, July 16, 2020. Updated Dec. 30, 2020. nytimes.com/2020/07/16/health/coronavirus-vaccine-novavax.html
5. “Hope to launch Covovax by September 2021”: Serum Institute’s Adar Poonawalla on second COVID vaccine. By Hannah Kuchler. New York. 1 March, 2021. https://www.livemint.com/news/india/hope-to-launch-covovax-by-september-2021-serum-institute-s-adar-poonawalla-on-2nd-covid-vaccine-11616830157066.html
6. Novavax announces COVID-19 vaccine manufacturing agreement with Serum Institute of India, increasing Novavax’ global production capacity to over 2 billion doses annually. Novavax press release, Sep 15, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-covid-19-vaccine-manufacturing-agreement-serum
7. Novavax announces memorandum of understanding to produce COVID-19 vaccine made in Canada. Novavax press release, Feb 02, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-memorandum-understanding-produce-covid-19
8. Novavax and UK government announce collaboration and purchase agreement for Novavax’ COVID-19 vaccine candidate. Novavax press release, Aug 14, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-and-uk-government-announce-collaboration-and-purchase
9. Novavax and Takeda finalize license agreement for Novavax’ COVID-19 vaccine candidate in Japan; Takeda initiates Phase 1/2 trial in Japan. Novavax press release, Feb 26, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-and-takeda-finalize-license-agreement-novavax-covid-19
10. Novavax announces expanded collaboration and license agreement with SK Bioscience for 40 million doses of COVID-19 vaccine for South Korea. Novavax press release, Feb 15, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-expanded-collaboration-and-license-agreement
11. Novavax expands large-scale global manufacturing capacity. Novavax press release, May 27, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-expands-large-scale-global-manufacturing-capacity
12. Novavax and FUJIFILM Diosynth Biotechnologies initiate large scale manufacturing of COVID-19 vaccine candidate. Novavax press release, Jul 23, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-and-fujifilm-diosynth-biotechnologies-initiate-large
13. Novavax announces facility expansion to support global vaccine development. Novavax press release, Nov 02, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-facility-expansion-support-global-vaccine
Novavax is a biotechnology company based in Maryland, USA. It was found in 1987 and has become known worldwide since its participation in the race to produce a vaccine against COVID-19. However, unlike other young biotech start-ups in the same race, such as Biontech and Moderna, the road Novavax took has been relatively tough. Let’s have a look at the technology, the products and the history of the company in this blog.
The technology used by Novavax
Novavax has a proprietary recombinant technology platform (Sf9/BV) for the production of antigens of vaccine that can induce immune responses.1 The two major components of the recombinant technology are baculovirus, a virus commonly attacked insects, and Sf9 moth cells.
Once the whole genome sequence of a pathogen has been identified, Novavax then identifies the genetic sequences that may trigger the immune responses in the host cells. Baculovirus used by the company is genetically engineered to carry the selected genetic sequence used to encode a vaccine antigen that can trigger an immune response. The recombinant baculovirus is then put into Sf9 moth cells by infection. Making use of the Sf9’s cellular post-transcriptional and post-translational machinery, the protein antigens expressed from the recombinant baculovirus are able to fold and modify themselves properly into their native forms. (Antigen in native configuration is necessary for optimized biologic immune responses for active immunity.) The Sf9 insect cell is like a manufacturing company which scales up production of antigens with native confirmation. The antigen produced is then harvested and purified as multimeric particles.1
Besides the antigen, Novavax also put its proprietary adjuvent, called Matrix-M, into its vaccine. Matrix-M is composed of 40-nanometer particles, based on saponin extracted from the Quillaja saponaria Molina bark, together with cholesterol and phospholipid.1 Matrix-M induces the influx of antigen presenting cells (APC), which enhance activated CD4+ and CD8+ T cells, long-lasting memory B cells, and APC populations. In general, Matrix-M generates potent, robust, and long-lasting protective immune responses. Therefore, the addition of Matrix-M in a vaccine can lower the dose of antigen required to achieve the desired immune response, and thus increases supply and manufacturing capacity using the same amount of antigens. Overall, the vaccine produced in this way is cheaper.
As the antigen in the vaccine is in protein form, which is more stable than the vaccine made of mRNA, Novavax’s vaccine is easier to transport and can be stored at room temperature for at least 24 hours.
Novavax has previous experience working with other coronaviruses, such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS). The two vaccine candidates demonstrated strong immunity and 100% protection in preclinical tests, but have never been put on the market for some reasons. This experience enabled the company to mobilize quickly against COVID-19.2
The hardship Novavax has gone through
Novavax has been established for more than 33 years. However, the biotech company has no single vaccine product being approved during these years. In January 2020, before the pandemic attacked the world, the company experienced a short interest which hit 30 percent of its share price. A year before that, Novavax was on the edge of closing, facing de-listing from Nasdaq. It had to lay off 120 manufacturing and quality-control staff, one-third of its staff.3
When we look back, Novavax has faced difficulties right at the beginning of its history. The company was founded in 1987 to develop “novazone” particles for vaccine delivery. But it soon changed its direction of the usage of the particles into hormone delivery. Its research and development in the women’s health business unfortunately had to be halted by 2005 due to unfavourable position in the competition market and concerns over the risk of breast cancer after oestrogen treatment.3
Since then, Novavax has been working on vaccines for SARS, MERS, Ebola, influenza, and Respiratory Syncytial Virus (RSV), a common virus that can be deadly for babies and older adults.2 This development of the vaccine to the RSV virus caused crisis after crisis in the company and almost drove the company to closure. In 2016, a Phase 3 clinical trial in older people failed due to not enough cases being available to reach a firm conclusion, and a diagnostic tool not widely available at the time. The company did not have enough funds to reinvent the Phase 3 trial and the company’s stock dropped 83 percent in one week. Later when the company was able to start a clinical trial of the RSV vaccine on pregnant women with the help of funding from the Gates Foundation, the trial failed and led to another financial crisis for the company in 2019 as mentioned above. In order to avoid being de-listed by Nasdaq, the company initiated a reverse stock split to lift its share price. It also had to sell its manufacturing facility in order to survive through the crisis.3,4
The promising products Novavax is developing
After surviving from the crisis, Novavax now has two promising vaccine candidates, other than the vaccine against COVID-19. One of them is NanoFlu™, a quadrivalent influenza nanoparticle vaccine. It is currently in a Phase 3 clinical trial to address key factors that can lead to the poor effectiveness of currently approved flu vaccines. Another one is ResVax™, the RSV vaccine that the company has long been developing. This is now in a Phase 3 clinical programme.2
Partnerships and manufacturing
Novavax sold its manufacturing facility in 2019 just before the company got funding from the US government to develop the COVID-19 vaccine. In order to fulfil the manufacturing capacity for clinical trials, the future vaccine supply, and rapid distribution across the world if and when its COVID-19 vaccine is approved for use, the company stretched itself in co-operating with many other pharmaceutical companies to produce the vaccine.
Initially, the company used a Maryland-based drug manufacturer, Emergent BioSolutions, to make initial doses for the clinical trials. Later, it partnered with different drug makers worldwide for production of vaccine if the vaccine candidate is approved: Serum Instititue of India Private Limited (SIIPL) for global production of the antigen component of its COVID-19 candidate;5,6 the National Research Council’s Biologics Manufacturing Centre for vaccine supply in Canada;7 FUJIFILM Diosynth Biotechnologies (FDB) manufacturing site in UK to manufacture the antigen component of its COVID-19 vaccine in the UK;8 Takeda for local manufacturing and commercialization in Japan;9 and SK Biosciences for the manufacturing of Novavax’s protein antigen for the supply in South Korea.10 In addition, Novavax recently acquired a factory, Praha Vaccines, in the Czech Republic, to provide extra annual capacity of over 1 billion doses of antigen for its COVID-19 vaccine candidate, starting in 2021.11
In the US, Novavax is co-operating with FUJIFILM Diosynth Biotechnologies (FDB) to manufacture bulk drug substances for its COVID-19 vaccine candidate. The manufactoring site of FDB in Morrisville has produced the first batch of the company’s COVID-19 candidate.12 The company itself is also expanding its campus to accommodate rapid growth. It has secured two additional properties in order to support its immediate need for additional laboratory and office space for manufacturing, R&D and business operations.13
Given the potential of its technology to manufacture millions of doses of vaccine quickly, Novavax received 1.6 billion US dollars from the US government early last year to expand its manufacturing capacity. Moreover, the company obtained additional funds from other sources since then.4 Hopefully the vaccine can get approval very soon in order to add supply to relieve the worldwide demand for COVID-19 vaccines.
References
1. Recombinant nanoparticle vaccine technology. Novavax website. https://www.novavax.com/our-unique-technology#recombinant-nanoparticle-vaccine-technology
2. Novavax advances development of novel COVID-19 vaccine. Novavax press release, Feb 26, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-advances-development-novel-covid-19-vaccine
3. Novavax closes in on Covid triumph after 33 years of failure. By Hannah Kuchler. Financial Times, March 1, 2021. https://www.ft.com/content/22d3805e-c304-4d95-ae32-f559ff34886a
4. How a struggling company won $1.6 billion to make a coronavirus vaccine. By Katie Thomas and Megan Twohey. New York Times, July 16, 2020. Updated Dec. 30, 2020. nytimes.com/2020/07/16/health/coronavirus-vaccine-novavax.html
5. “Hope to launch Covovax by September 2021”: Serum Institute’s Adar Poonawalla on second COVID vaccine. By Hannah Kuchler. New York. 1 March, 2021. https://www.livemint.com/news/india/hope-to-launch-covovax-by-september-2021-serum-institute-s-adar-poonawalla-on-2nd-covid-vaccine-11616830157066.html
6. Novavax announces COVID-19 vaccine manufacturing agreement with Serum Institute of India, increasing Novavax’ global production capacity to over 2 billion doses annually. Novavax press release, Sep 15, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-covid-19-vaccine-manufacturing-agreement-serum
7. Novavax announces memorandum of understanding to produce COVID-19 vaccine made in Canada. Novavax press release, Feb 02, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-memorandum-understanding-produce-covid-19
8. Novavax and UK government announce collaboration and purchase agreement for Novavax’ COVID-19 vaccine candidate. Novavax press release, Aug 14, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-and-uk-government-announce-collaboration-and-purchase
9. Novavax and Takeda finalize license agreement for Novavax’ COVID-19 vaccine candidate in Japan; Takeda initiates Phase 1/2 trial in Japan. Novavax press release, Feb 26, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-and-takeda-finalize-license-agreement-novavax-covid-19
10. Novavax announces expanded collaboration and license agreement with SK Bioscience for 40 million doses of COVID-19 vaccine for South Korea. Novavax press release, Feb 15, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-expanded-collaboration-and-license-agreement
11. Novavax expands large-scale global manufacturing capacity. Novavax press release, May 27, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-expands-large-scale-global-manufacturing-capacity
12. Novavax and FUJIFILM Diosynth Biotechnologies initiate large scale manufacturing of COVID-19 vaccine candidate. Novavax press release, Jul 23, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-and-fujifilm-diosynth-biotechnologies-initiate-large
13. Novavax announces facility expansion to support global vaccine development. Novavax press release, Nov 02, 2020. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-facility-expansion-support-global-vaccine
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