– Results Published in Science –
– Blinded Analysis Conducted through COVID
International Consortium –
Twist Bioscience Corporation (Nasdaq: TWST) today reported that
its internally-discovered antibody candidate TB202-3 (CoVIC-094),
demonstrated potent binding to diverse SARS-CoV-2 variant
mutations, including strains with the E484K, N501Y, D614G, Y453F
and K417N mutations in pseudovirus assays, indicating this
therapeutic antibody may be effective in treating many strains of
COVID-19.
The Coronavirus Immunotherapy Consortium (CoVIC), an
academic-industry, non-profit collaborative research effort,
performed the blinded analysis, confirming that TB202-3 completely
blocked SARS-CoV-2 spike protein from binding to human ACE2. The
results were published in Science today
“CoVIC analyzed over 250 therapeutic antibodies from 46 groups,
in an effort to identify 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 impacted by most viral
mutations. This makes it an important and viable candidate for
clinical testing in combination with other antibody
therapeutics.”
CoVIC used high-throughput surface plasmon resonance analysis
and cryo-EM structural determination, sorting antibodies that react
within the SARS-CoV-2 receptor binding domain (RBD) into 7
different “communities” (RBD-1 through RBD-7). Antibodies in the
RBD-4 community bind to the outer face of the RBD and can do so in
either the “up” or “down” RBD conformation. Monoclonal antibodies
that target RBD-4 bind towards the outer edge of the receptor
binding motif and can block binding to ACE2 on human cells, the
entry point for the virus. Select properties of RBD-4 antibodies
indicate they may have increased potency against the virus.
COVID-19 continues to evolve, spurring additional mutations and
viral strains. TB202-3 binds to a majority of known mutations, with
the exception of the L452R mutation present in the Delta and
Epsilon variants. Twist developed a new VHH single domain antibody,
TB339-031, with a similar structure and potency to TB202-3, which
also binds and neutralizes the Delta and Epsilon variants, that is
now advancing through late-stage discovery and validation
testing.
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 results in
the copying 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 efficacy of therapeutic antibodies that bind at the
mutated location. Therapeutic antibodies that bind to the virus in
a place that is not impacted by mutations can treat the widest
range of COVID-19 variant strains successfully.
“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 in comparison to others,” said Emily M. Leproust, Ph.D.,
CEO and co-founder of Twist Bioscience. “With the continuous
emergence of variant strains of SARS-CoV-2, antibodies that bind to
regions away from the areas of frequent mutation will be critical
to the ongoing global response. While broad-spectrum is a term used
most often in relation to antibiotics, it applies here to Twist’s
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-driven selection pressure and Twist
antibodies may work therapeutically against emerging SARS-CoV-2
variants,” continued Dr. Leproust. “In addition to binding location
and neutralization efficacy, due to its small size, selectivity and
preclinical efficacy, Twist antibodies may offer an advantage over
traditional antibodies as they can be an integral component of a
bispecific antibody or can be used with other antibodies. COVID-19
infection continues to spread throughout the world, and new
therapeutic options will be required 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 U.S. Army Medical
Research Institute of Infectious Diseases (USAMRIID),
immunosuppressed animals were given 1, 5 or 10 mg/kg of each of the
Twist antibodies and were assessed for weight loss. Animals treated
with all doses of TB202-3 were protected against weight loss,
whereas control animals lost a mean of 11.7% of their body weight.
Validation and late-stage discovery studies continue for
TB339-031.
About Twist Biopharma Antibodies
About 75 percent of the antibodies in the blood are IgGs. IgGs
are made up of two heavy protein chains and two light protein
chains that must pair together and cooperate to specifically
recognize a target, in this case the Spike Protein on SARS-CoV-2.
This specific targeting affords our immune systems “memory,”
allowing it to selectively and precisely eliminate pathogenic
threats.
Target recognition by VHH single domains, on the other hand,
requires just a single domain found on heavy chain only antibody.
With VHH-based antibodies able to exhibit pharmaceutically-relevant
properties comparable to IgGs, they are a promising therapeutic
with several advantages over their bulkier, more complex
counterparts. The small size of VHH antibodies means they can
squeeze into spaces and bind or block to parts of molecules that
would otherwise be inaccessible to human IgG antibodies. They are
also more thermally and chemically stable, making VHH-based
therapeutics good candidates to address respiratory infections,
administered by inhaler directly to the respiratory tract where the
infection is concentrated. In addition, the small size simplifies
manufacturing of VHH antibodies. In addition to SARS-CoV-2, Twist
Biopharma discovers and develops IgG and VHH antibodies to numerous
different targets for partners and internal development.
About The Coronavirus Immunotherapy Consortium
(CoVIC)
CoVIC is an academic-industry, non-profit collaborative research
effort that brought together scientists from around the world and
enabled them to share and evaluate candidate SARS-CoV-2 anti-S
protein antibodies side-by-side in a blinded, multidisciplinary
analysis. Together, they are identifying ideal therapeutic
combinations, the assays that best predict efficacy, and the
features that provide protection.
About Twist Bioscience Corporation
Twist Bioscience is a leading and rapidly growing synthetic
biology and genomics company that has developed a disruptive DNA
synthesis platform to industrialize the engineering of biology. The
core of the platform is a proprietary technology that pioneers a
new method of manufacturing synthetic DNA by “writing” DNA on a
silicon chip. Twist is leveraging its unique technology to
manufacture a broad range of synthetic DNA-based products,
including synthetic genes, tools for next-generation sequencing
(NGS) preparation, and antibody libraries for drug discovery and
development. Twist is also pursuing longer-term opportunities in
digital data storage in DNA and biologics drug discovery. Twist
makes products for use across 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 facts contained
herein, including but not limited to TB202-3’s role as an important
and viable candidate for clinical testing, its resistance to
receptor driven selection pressure, its ability to work
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 pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. Such
forward-looking statements involve known and unknown risks,
uncertainties, and other important factors that may cause Twist’s
actual results, performance, or achievements to be materially
different from any future results, performance, or achievements
expressed or implied by the forward-looking statements. Such risks
and uncertainties include, among others, the risks and
uncertainties of the duration, extent and impact of the COVID-19
pandemic, including any reductions in demand for our products (or
deferred or canceled orders) globally or in certain regions; the
ability to attract new customers and retain and grow sales from
existing customers; risks and uncertainties of rapidly changing
technologies and extensive competition in synthetic biology could
make the products Twist is developing obsolete or non-competitive;
uncertainties of the retention of a significant customer; supply
chain and other disruptions caused by the COVID-19 pandemic or
otherwise; risks of third party claims alleging infringement of
patents and proprietary rights or seeking to invalidate Twist’s
patents or proprietary rights; and the risk that Twist’s
proprietary rights may be insufficient to protect its technologies.
For a further description of the risks and uncertainties that could
cause actual results to differ from those expressed in these
forward-looking statements, as well as risks relating to Twist’s
business in general, see Twist’s risk factors set forth in Twist’s
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) on August 9, 2021 and subsequent filings
with the SEC. In addition, many of the foregoing risks and
uncertainties are, and could be, exacerbated by the COVID-19
pandemic and any worsening of global or regional business and
economic environment as a result. 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, results of operations
and cash flows. Any 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 statement, whether as a result of new information,
future events or otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20210923005235/en/
Angela Bitting 925- 202-6211 abitting@twistbioscience.com
Twist Bioscience (NASDAQ:TWST)
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