Ridge Biotechnologies (Ridge Bio), a company focused on enzyme and targeted drug design to usher in the next era of precision medicines, has emerged from stealth mode with an impressive $25 million in oversubscribed seed financing. The funding round was led by Sutter Hill Ventures (SHV), which incubated Ridge Bio, with additional participation from Overlap Holdings and others.

The Ridge Bio platform employs proprietary machine learning models supported by high-throughput, cell-free experimentation for diverse applications including antibody-drug conjugates (ADCs), in vivo CAR-T therapies, targeted nucleic acid delivery, small molecule biocatalysis, radiotherapies, and enzyme-based therapeutics. Co-founder and CEO Weston Kightlinger, PhD, a seasoned entrepreneur and innovator in cell-free synthesis and enzyme design, previously co-founded SwiftScale Biologics, a leader in cell-free manufacturing that was acquired by Resilience.

“Drug development should never be limited by the complexity of molecules we can precisely construct, off-target toxicities, or binding-based mechanisms of action. Machine learning has dramatically expanded our ability to design enzymatic systems that can solve these problems, but unlocking their full potential requires massive experimental datasets. At Ridge Bio, we generate those datasets at unprecedented speed and scale —up to a million-fold more sequence-function data than conventional methods in a fraction of the time. We use custom-built ML models to apply this data to enzyme and conditionally active drug design, giving our partners powerful tools to create safer, more precise medicines,” Kightlinger stated. He added, “With the support of great investors and a world-class founding team, we are scaling operations, expanding our technology partnerships in bioconjugates, and advancing our discovery programs towards our longer-term goal of developing a new class of precision-designed therapeutic enzymes. The strong, early interest from leading biopharma companies and CDMOs validates our vision and inspires us to accelerate the delivery of breakthrough medicines that make a real difference for patients.”

Ridge Bio has also initiated a collaboration with a prominent ADC-focused biotech to leverage its ProTriggerTM and NativeLinkTM product lines for designing and precisely attaching linker systems that deliver therapeutic payloads directly to tumor tissue while protecting healthy cells.

The initial offerings from Ridge Bio encompass NativeLink enzymes and ProTrigger linkers. NativeLink enzymes serve as designer biocatalysts that allow drug manufacturers to modify therapeutic proteins site-specifically, augment them with various payloads, extend their half-lives, and integrate precision targeting systems without altering the protein sequence, cell lines, or upstream manufacturing processes. The first product, the NativeLink - AXC enzyme, enables homogeneous modification of native antibodies while avoiding stability, manufacturing, and functional issues typical of older ADC and antibody conjugate synthesis strategies. ProTrigger linkers represent AI-designed protease-cleavable prodrug systems that activate therapeutic payloads at targeted locations within the body, with initial applications focusing on unlocking new ADC targets and enhancing safety by minimizing off-tumor toxicity.

“What used to take years can now be done in weeks, thanks to the combination of cell-free experimentation and machine learning. Together, they have created a step-change in our ability to design and leverage enzymes and prodrugs with exquisite specificity. That specificity is at the heart of Ridge Bio’s technologies and the next generation of precisely designed therapeutics,” remarked Mike Jewett, Professor of Bioengineering at Stanford University and Ridge Bio’s Academic Co-founder and Scientific Advisory Board Chair.

Ridge Bio’s founding team possesses extensive expertise in ML-driven protein engineering, cell-free systems, and bioconjugation, merging groundbreaking academic research with practical industry experience. “Ridge Bio is the perfect example of our approach to building companies: back world-class founders and help them attract the incredible teams they need to solve tough technical problems and unlock huge markets. Ridge Bio’s capabilities across machine learning and wet lab bioengineering positions the company to build drugs that no one else can and enable a new class of precisely engineered enzyme-based therapeutics,” said Keith Loebner, PhD, Managing Director at SHV. “Each founding member of this team could have started something on their own, but they chose to join Ridge because they recognized that together they could do things no one else could do and, as a group, define the future of precision therapeutics.”

Ridge Bio’s advisory board includes notable figures such as Carolyn Bertozzi, PhD (Stanford University, 2022 Nobel Laureate in Chemistry); Sangeeta Bhatia, MD, PhD (MIT/HHMI); and Michael Jewett, PhD (Stanford University), among others. Their founding scientific team features experts like Grant Landwehr, PhD, who pioneered ML-accelerated cell-free enzyme engineering at Stanford, and Francesca Li, PhD, who developed AI-driven protein engineering methods at Caltech.

“Ridge Bio is at the forefront of three key trends, next-generation bioconjugates, protein design, and enzymatic therapeutics,” stated Dr. Bertozzi. “Their AI and experimental platform are very unique and it's already generating products that enable drug developers to differentiate themselves from competitors, not only through improved manufacturing but also through improved therapeutic indices while simultaneously unlocking the power of catalytic medicines.”