Twist Bioscience Corporation (Nasdaq: TWST) today announced
preclinical data for three of its proprietary antibodies against
the S1 protein in SARS-CoV-2, the virus that causes COVID-19. The
data show that TB202-3 and TB202-63, both single domain VHH
“nanobodies,” protect against weight loss, a key indicator of
disease severity, at the lowest dose of 1 mg/kg in a preclinical
hamster challenge model. In addition, TB181-36, an IgG antibody
discovered through Twist’s collaboration with Vanderbilt University
Medical Center (VUMC), was found to protect against weight loss at
5 mg/kg and 10 mg/kg.
“We are highly encouraged that the antibodies we discovered
using our proprietary platform demonstrated equivalent protection
against weight loss when compared to convalescent plasma in
preclinical studies,” said Emily M. Leproust, Ph.D., CEO and
co-founder of Twist Bioscience. “In addition to applicability in
traditional development pathways for therapeutics and diagnostics,
the small size, selectivity and active neutralization of our single
domain VHH antibodies could potentially enable new approaches to
treatment, prevention and diagnosis of COVID-19. We believe one
such opportunity would be a preventive daily nasal spray that would
block aerosolized particles of the SARS-CoV-2 virus from entering
the nasal passage and therefore the body.”
Preclinical studies of TB202-63, TB202-3 and TB181-36 were
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 TB202-63 and TB202-3 were
protected against weight loss, whereas control animals lost a mean
of 11.7% of their body weight. Animals treated with the higher two
doses of TB181-36 were protected against weight loss.
“With cases rising globally and a need for effective SARS-CoV-2
treatments, nanobodies, with their very small size, may offer an
advantage over traditional antibodies. For example, they could be
delivered intranasally to prevent infection or reduce transmission;
or they could be part of a more conventional therapeutic treatment
regimen,” commented Jay Hooper, Ph.D., chief of the molecular
virology branch at USAMRIID. “The preclinical data are supported by
live-virus neutralization testing we conducted, and we look forward
to working with Twist on next steps.”
TB202-63 and TB202-3 are single domain VHH “nanobody” candidates
identified by Twist Biopharma, a division of Twist Bioscience, by
screening its proprietary synthetic antibody discovery libraries
each containing more than 10 billion single domain antibody
sequences. These antibodies potently neutralize SARS-CoV-2 live
virus in vitro by binding the S1 receptor binding domain and
directly blocking its binding to ACE2 receptors found in humans and
other susceptible animals such as mink and cats.
TB181-36 is an IgG antibody based upon antibodies identified in
individuals who recovered from COVID-19 in a collaborative research
project with Vanderbilt University Medical Center researchers James
E. Crowe, Jr and Robert Carnahan in the Vanderbilt Vaccine Center.
The intellectual property covering such antibodies was later
licensed by Vanderbilt University to Twist Biopharma for use in
product development. Because the human immune system naturally
generates a variety of antibodies against specific foreign
invaders, including SARS-CoV-2, the virus that causes COVID-19,
antibodies from recovered individuals have the potential to treat
other people infected with the virus. Twist Biopharma built a
proprietary synthetic antibody discovery library based on these
sequences to identify the antibodies, one of which is TB181-36,
which also neutralizes live SARS-CoV-2 virus in vitro. Unlike our
single domain leads that directly block ACE2 binding, this antibody
binds a unique epitope on the N terminal domain of S1 and
neutralizes the virus through an alternate mechanism.
Twist intends to explore opportunities for further development
of all three antibodies both internally and potentially with
partners.
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 U.S. Army Medical Research Institute of Infectious
Diseases
For over 50 years, USAMRIID has provided leading edge medical
capabilities to deter and defend against current and emerging
biological threat agents. The Institute is the only laboratory in
the Department of Defense equipped to safely study highly hazardous
viruses requiring maximum containment at Biosafety Level 4.
Research conducted at USAMRIID leads to medical solutions –
vaccines, drugs, diagnostics, information, and training programs –
that benefit both military personnel and civilians. Established in
1969, the Institute plays a key role as the lead military medical
research laboratory for the Defense Threat Reduction Agency’s Joint
Science and Technology Office for Chemical and Biological Defense.
USAMRIID is a subordinate laboratory of the U.S. Army Medical
Research and Development Command. For more information, visit
www.usamriid.army.mil.
The information contained in this press release does not
necessarily reflect the position or the policy of the Government
and no official endorsement should be inferred.
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 the effectiveness of the
monoclonal antibody and VHH nanobody candidates identified by Twist
Biopharma as therapeutics for COVID-19, 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 12, 2020 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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Investor Contact: Argot Partners Maeve Conneighton 212-600-1902
maeve@argotpartners.com
Media Contact: Angela Bitting 925-202-6211
media@twistbioscience.com
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