– Company creating de novo designed macrocycles with enhanced efficacy that precisely target disease biology
– Vilya’s privileged macrocycles have the potential to be applied across broad therapeutic areas, addressing large unmet medical needs
SEATTLE, April 25, 2024 (GLOBE NEWSWIRE) -- 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 Platform
Vilya’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 Vilya
Vilya 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 Normart
jnormart@realchemistry.com
