Harnessing Water Dynamics for Drug Design with Michael Crackower and Jason Burch
Aug 20, 2024
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Michael Crackower, Chief Scientific Officer at Ventus Therapeutics, and PhD researcher Jason Burch dive into the future of drug discovery. They unveil the ReSOLVE platform, designed to quickly iterate small molecular compounds for therapeutic use. The duo discusses the importance of water dynamics in protein interactions, machine learning's role in drug design, and their strides in targeting NLRP3 for neurodegenerative diseases. With groundbreaking data and a push to enter clinical trials, they highlight the rapid progress made from concept to investigational new drug.
Ventus Therapeutics' ReSOLVE platform revolutionizes drug design by treating water as a dynamic entity for better molecular interactions.
The company's strategic focus on the innate immune system opens doors to innovative therapies for aging-related and mitochondrial dysfunction diseases.
Deep dives
Innovations in Drug Discovery
Ventus Therapeutics focuses on leveraging the Resolve platform to transform drug discovery processes, particularly concerning small molecules. This platform enables more precise design and iteration of small molecular compounds for therapeutic use, aiming to increase the efficiency and speed of getting drugs into clinical testing. For instance, they discussed transitioning from initial drug candidates to Investigational New Drug (IND) status in record time, having achieved three such transitions within a single year, which is rare in the pharmaceutical industry. This approach marks a significant advancement from traditional methods, highlighting the potential of small molecules in addressing unmet health needs.
Harnessing the Innate Immune System
The strategic emphasis on addressing the innate immune system is a key differentiator for Ventus, with a focus on high-potential, previously underexplored targets. Leaders from the company emphasized the abundance of untapped opportunities in this area and the clinical validity of targeting innate immune pathways, particularly for diseases associated with aging and mitochondrial dysfunction. Their approach hinges on innovative technologies to develop therapeutics that could target diseases linked to aberrant immune responses. This includes promising initial candidates focused on conditions like neurodegenerative disorders and metabolic diseases.
The Role of Water in Drug Development
The innovative use of water dynamics in molecular modeling is central to the Resolve platform's functionality, enabling greater insight into how compounds can like bind to specific protein pockets. This method treats water as a dynamic entity rather than a static component, capturing its complex interactions during molecular simulations. This approach facilitates the identification of 'druggable' pockets that may not have been apparent through traditional modeling techniques. As a result, the platform not only informs compound design but also drives creativity in optimizing and discovering new therapeutic candidates.
Advancing Cure Potential through Collaboration
The collaboration between computational and medicinal chemistry teams is crucial to Ventus's success in drug development, merging advanced technology with human expertise and intuition. This synergy fosters a culture where computational insights encourage medicinal chemists to explore novel hypotheses and resolve challenges that standard approaches may overlook. For example, the C-GAS program demonstrated how dynamic modeling converted earlier failures into successful therapeutic candidates by inspiring the team to pursue unorthodox strategies. Through this teamwork, Ventus is positioned to quickly evolve its pipeline and deliver impactful new drugs that address challenging diseases.
Michael Crackower, PhD, Chief Scientific Officer of Ventus Therapeutics, and Jason Burch, PhD, join Vineeta Agarwala, MD, PhD, general partner at a16z Bio + Health.
Together, they talk about how Ventus approaches drug discovery and why they believe we’re in the early stages of small molecule innovation. Specifically, we’ll hear about the ReSOLVE platform, which enables the drug hunting team to more accurately design and iterate on small molecular compounds for therapeutic applications. They also talk about the current candidates in the pipeline and how they’re able to go from idea to IND in record time.
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