Vilya Announces New Publication in Science Validating Foundational Approach to Design of Novel Chemically Diverse Macrocycles
April 25 2024 - 2:00PM
VILYA, Inc. (Vilya), a biotechnology company creating a new class
of medicines that precisely targets disease biology, today
announced the publication of a new study in Science that validates
the company’s foundational drug discovery approach. The company’s
platform, which is based on an exclusive license to the technology
utilized in the study, leverages advanced computational approaches
to design macrocycles with atomic-level accuracy that enable
optimized drug-like properties.
“Macrocycles are promising drug-like compounds, but
incorporating diverse chemistries has historically been very
difficult. We have now shown that we can accurately identify,
design and synthesize small macrocycles using a new approach that
leverages conformational analysis and chemical diversity to predict
and construct macrocycles made out of a wide range of backbone
building blocks with high structural fidelity to their design
models,” said David Baker, Ph.D., Co-founder of Vilya, Director of
the IPD, Professor of Biochemistry at the University of Washington,
and publication co-author. “These findings indicate a promising
direction for the future of drug design in which exploring diverse
macrocycle structures could lead to the discovery of new
therapeutic macrocyclic compounds with enhanced efficacy and
specificity.”
In the published paper, titled “Expansive discovery of
chemically diverse structured macrocyclic oligoamides,” scientists
at the Institute for Protein Design (IPD) at the University of
Washington School of Medicine detailed a new proprietary
computational method to design and predict the structure of small
macrocycle compounds. This method significantly broadens the range
of macrocycle chemical structures available for drug discovery
beyond those found in nature. The study authors successfully
synthesized and tested several of these computationally designed
macrocycles, confirming that their actual structures closely match
the predicted models. The study illustrated the therapeutic
potential of these newly discovered macrocycles, which selectively
inhibited a protein target of current interest they were designed
to bind to. One of the three proteins designed against is the
enzyme histone deacetylase (HDAC) 6, which regulates various
cellular processes and has emerged as a therapeutic target involved
in several types of cancer and neurodegenerative disorders. Results
demonstrated that these designed macrocycles selectively and
potently inhibited this target. Researchers also successfully
applied this design approach to two other protein targets – mPro,
the main protease of SARS-CoV-2 that plays a crucial role in the
life cycle of the virus, and myeloid cell leukemia sequence 1
(MCL1), a protein that binds to BCL-2 antagonist/killer (BAK) and
prevents it from signaling cell death.
“This new study validates Vilya’s platform and is representative
of the ongoing work we are doing in the field of medicinal
chemistry to create small macrocycles, which are notable for their
potent biological activities,” said Patrick J. Salveson, Ph.D.,
Co-founder and Chief Technology Officer of Vilya and lead author of
the publication. “Our platform, which leverages our proprietary
computational design, rapidly generates both chemically and
structurally diverse drug-like macrocyclic compounds. In the short
time since Vilya was founded in 2022, we have built a team and
infrastructure to continue expanding our platform with increasing
efficiency and to develop our emerging pipeline of promising
macrocycles that could translate into revolutionary medicines.”
Overall, the authors identified 14.9 million macrocycles built
from a wide array of chemically diverse building blocks bonded
together to form complex structures, showcasing a wide spectrum of
drug-like macrocycles that could be used for novel bioactivities
and structure-based drug design. They then synthesized a focused
subset of 18 macrocycles and found the majority aligned closely to
their predicted models, thereby validating the computational design
approach. Nearly half of the macrocycles evaluated exhibited
membrane permeability, or the ability to diffuse across tissue
barriers and cell membranes. A majority also showed stability
against serum proteases, underscoring their potential for effective
pharmacokinetic profiles in vivo. Notably, the study authors
designed macrocycles against HDAC6, of which the vast majority
demonstrated potent inhibition, with select compounds achieving
100-fold to 1,000-fold selectivity over other HDACs. The
macrocycles developed against the two other protein targets – mPro
and MCL1 – highlight the generality of the developed methods.
“Vilya was launched to leverage the foundational research in
computational protein design pioneered by the team at the Institute
for Protein Design and apply it to the creation of new macrocycle
structures that could become transformative medicines for a variety
of diseases,” said Cyrus Harmon, Ph.D., Chief Executive Officer of
Vilya. “The publication in Science of the core capabilities of this
technology, which we have licensed and integrated into our own
proprietary platform, provides further validation of our approach.
We are excited to continue building on this foundation that we have
created over the past two years and advance several novel
macrocycles toward clinical development.”
About Vilya’s Proprietary PlatformVilya’s
proprietary platform, powered by advanced machine learning, taps
into uncharted chemical space to design de novo molecular
structures that are larger than most small molecules but much
smaller than antibodies. These molecules are designed to have
critical drug-like properties, including the ability to move
through biological membranes and disrupt protein-protein
interactions while being highly selective for their protein target.
These novel artificial molecules with customized biologic-like
properties can be leveraged for previously difficult-to-drug
therapeutic targets in a broad set of indications.
Vilya's computational design platform leverages advanced machine
learning and other computational approaches to explore an
exponentially larger chemical space than traditional discovery
methods and to design in desired drug-like pharmacokinetic
properties. The company’s ability to precisely design
membrane-permeable molecules with high structural accuracy could
lead to a new class of medicines that combine the advantages of
traditional small molecule drugs and larger protein-based
therapeutics. Vilya’s ability to create and screen a new class of
target-directed, structured molecules in silico could transform
drug discovery and development, potentially rendering
high-throughput screening obsolete.
About VilyaVilya is a computational
biotechnology company creating a novel class of medicines to
precisely target disease biology. The company’s proprietary
platform, powered by advanced machine learning, taps into uncharted
chemical space to design de novo molecular structures with enhanced
drug-like properties that range in size between small molecules and
antibodies. Vilya is leveraging its platform to focus on previously
difficult-to-drug therapeutic targets. Vilya was co-founded by a
team of scientists from the Institute of Protein Design (IPD), led
by David Baker, Ph.D., and ARCH Venture Partners. The company has
operations in Seattle and South San Francisco. To learn more,
visit https://www.vilyatx.com.
Contacts
For Vilya Media Inquiries Julie
Normartjnormart@realchemistry.com