SOUTH SAN FRANCISCO, CA – (COMMERCIAL THREAD) – Twist Bioscience Corporation (Nasdaq: TWST) today announced that its internally discovered antibody candidate TB202-3 (CoVIC-094) has demonstrated potent binding to various variant mutations of SARS-CoV-2, including strains with E484K, N501Y, D614G, Y453F and K417N mutations in pseudovirus tests, indicating that this therapeutic antibody may be effective in treating many strains of COVID-19.
The Coronavirus Immunotherapy Consortium (CoVIC), a nonprofit academic-industry collaborative research effort, performed the blinded analysis, confirming that TB202-3 completely inhibits the SARS-CoV-2 spike protein to bind to human ACE2. The results were published in Science today
“CoVIC has analyzed more than 250 therapeutic antibodies from 46 groups, with the aim of identifying the most effective treatment approaches for patients with COVID-19,” said Erica Ollmann Saphire, Ph.D., director of CoVIC and professor at the La Jolla Institute for Immunology. “TB202-3 binds to a specific area (RBD-4) of the SARS-CoV-2 spike protein that has not been affected by most viral mutations. This makes it an important and viable candidate for clinical testing in combination with other therapeutic antibodies. ”
CoVIC used high throughput surface plasmon resonance analysis and cryo-EM structural determination, sorting the antibodies that react within the SARS-CoV-2 receptor binding domain (RBD) into 7 different “communities” ( RBD-1 to RBD-7). Antibodies from the RBD-4 community bind to the outer surface of RBD and may do so in the “high” or “low” RBD conformation. Monoclonal antibodies that target RBD-4 bind to the outer edge of the receptor binding motif and can block ACE2 binding on human cells, the entry point of the virus. Certain properties of RBD-4 antibodies indicate that they may have increased potency against the virus.
COVID-19 continues to evolve, causing mutations and additional viral strains. TB202-3 binds to the majority of known mutations, with the exception of the L452R mutation present in the Delta and Epsilon variants. Twist has developed a new single domain VHH antibody, TB339-031, with a structure and potency similar to TB202-3, which also binds and neutralizes the Delta and Epsilon variants, which are now progressing through discovery testing and testing. validation at an advanced stage.
SARS-CoV-2 is an RNA virus. Viruses survive by replicating in their target host, in the case of SARS-CoV-2, this is humans. During the replication process, there is often an error that causes the copy process, which is the definition of a mutation. Most of the time, mutations do not make a difference in the virus. Sometimes, however, a mutation makes the virus more transmissible or more deadly. Depending on the location of the mutation, it may reduce the effectiveness of therapeutic antibodies that bind to the mutated location. Therapeutic antibodies that bind to the virus in a location that is unaffected by the mutations can successfully treat the widest range of variant strains of COVID-19.
“By applying our proprietary drug discovery and optimization platform, we identified and advanced TB202-3 through preclinical studies and submitted this antibody to CoVIC for comprehensive testing against others,” said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. “With the continued emergence of variant strains of SARS-CoV-2, antibodies that bind to regions far from areas of frequent mutation will be critical to the ongoing global response. While broad spectrum is a term most often used in connection with antibiotics, it applies here to Twist antibodies, as they show efficacy in neutralizing a wide range of SARS-CoV-2 variants.
“These comprehensive results show that TB202-3 may be more resistant to receptor-induced selection pressure and that Twist antibodies can act therapeutically against emerging variants of SARS-CoV-2,” continued Dr Leproust. “In addition to their binding location and neutralization efficiency, due to their small size, selectivity and preclinical efficacy, Twist antibodies may offer an advantage over traditional antibodies as they can be an integral part of ‘a bispecific antibody or can be used with other antibodies. COVID-19 infection continues to spread around the world and new treatment options will be needed to treat emerging variants. ”
Previous studies of TB202-3, a single domain VHH ‘nanobody’, demonstrated protection against weight loss, a key indicator of disease severity, at the lowest dose of 1 mg / kg in a preclinical hamster challenge model. Conducted at the US Army Medical Research Institute of Infectious Diseases (USAMRIID), the immunocompromised animals received 1, 5 or 10 mg / kg each of the Twist antibodies and were assessed for weight loss. Animals treated with all doses of TB202-3 were protected against weight loss, while control animals lost an average of 11.7% of their body weight. Advanced validation and discovery studies are continuing for TB339-031.
About Twist Biopharma Antibodies
About 75 percent of the antibodies in the blood are IgG. IgGs are made up of two heavy protein chains and two light protein chains that must pair up and cooperate to specifically recognize a target, in this case the Spike Protein on SARS-CoV-2. This specific targeting gives our immune system a “memory”, allowing it to selectively and precisely eliminate pathogenic threats.
Target recognition by unique domains of VHH, on the other hand, requires only a single domain found on the heavy chain antibody only. With VHH-based antibodies capable of exhibiting pharmaceutically relevant properties comparable to IgG, they constitute a promising therapy with several advantages over their larger and more complex counterparts. The small size of VHH antibodies means that they can squeeze into spaces and bind or get stuck in parts of molecules that would otherwise be inaccessible to human IgG antibodies. They are also more thermally and chemically stable, making VHH-based treatments good candidates for treating respiratory infections, delivered by inhaler directly into the airways where the infection is concentrated. In addition, the small size simplifies the manufacture of VHH antibodies. In addition to SARS-CoV-2, Twist Biopharma discovers and develops IgG and VHH antibodies against many different targets for partners and internal development.
About the Coronavirus Immunotherapy Consortium (CoVIC)
CoVIC is a nonprofit academic-industry collaborative research effort that brought together scientists from around the world and enabled them to share and evaluate candidate antibodies to the anti-S SARS-CoV-2 protein side-by-side in a blind multidisciplinary analysis. . Together, they identify the ideal treatment combinations, the tests that best predict efficacy, and the characteristics that provide protection.
About Twist Bioscience Corporation
Twist Bioscience is a leading and growing synthetic biology and genomics company that has developed a disruptive DNA synthesis platform to industrialize the engineering of biology. The heart of the platform is proprietary technology that develops a new method of making synthetic DNA by “writing” DNA onto a silicon chip. Twist takes advantage of its unique technology to manufacture a wide range of DNA-based synthetics, including synthetic genes, tools for next-generation sequencing (NGS) preparation, and antibody libraries for discovery and drug development. Twist is also pursuing longer term opportunities in digital data storage in DNA and biological drug discovery. Twist manufactures products for many industries including healthcare, industrial chemicals, agriculture and academic research.
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Legal Notice Regarding Forward-Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical fact contained herein, including, but not limited to, the role of TB202-3 as an important and viable candidate for clinical testing, its resistance to pressure from receptor-induced selection, its ability to act therapeutically against emerging SARS-CoV-2 variants and its advantage over traditional antibodies, are forward-looking statements reflecting the current beliefs and expectations of management made in accordance with the provisions of the sphere of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve known and unknown risks, uncertainties, and other material factors that may cause Twist’s actual results, performance or achievements to be materially. different from the future results, performances or achievements expressed or implied by the declarations prospective ones. These risks and uncertainties include, among others, risks and uncertainties regarding the duration, extent and impact of the COVID-19 pandemic, including any reduction in demand for our products (or delayed or canceled orders) to globally or in certain regions; the ability to attract new customers and to retain and increase sales from existing customers; the risks and uncertainties associated with rapidly evolving technologies and intense competition in the field of synthetic biology could render the products developed by Twist obsolete or uncompetitive; the uncertainties of retaining a significant customer; supply chain and other disruptions caused by the COVID-19 pandemic or otherwise; the risks of claims by third parties alleging infringement of patents and proprietary rights or seeking to invalidate Twist’s patents or proprietary rights; and the risk that Twist’s property rights are insufficient to protect its technologies. For a more detailed description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as the risks associated with Twist’s business in general, see Twist’s risk factors set forth in the Twist’s quarterly report on Form 10 -Q filed with the Securities and Exchange Commission (SEC) on August 9, 2021 and subsequent SEC filings. In addition, many of the aforementioned risks and uncertainties are, and could be, exacerbated by the COVID-19 pandemic and any resulting deterioration in the global or regional business and economic environment. We cannot at this time predict the extent of the impact of the COVID-19 pandemic and any resulting business or economic impact, but it could have a material adverse effect on our business, financial condition, operating results and our cash flow. All forward-looking statements contained in this press release speak only as of the date hereof, and Twist Bioscience specifically disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events. or otherwise.