On September 9, 2025 Ridge Biotechnologies (Ridge Bio), a company pioneering enzyme and targeted drug design to power the next wave of precision medicines, reported to have emerged from stealth with an oversubscribed $25 million in seed financing (Press release, Ridge Bio, SEP 9, 2025, View Source [SID1234655903]). Sutter Hill Ventures (SHV) incubated Ridge Bio and led the round, with participation from Overlap Holdings among others.
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The Ridge Bio platform uses proprietary machine learning models informed by high-throughput, cell-free experimentation for a wide range of applications in antibody-drug conjugates (ADCs), in vivo CAR-T therapies, targeted nucleic acid delivery, small molecule biocatalysis, radiotherapies, and enzyme-based therapeutics. Weston Kightlinger, PhD, a serial entrepreneur and pioneer in the fields of cell-free synthesis and enzyme design, is co-founder and Chief Executive Officer of Ridge Bio. Dr. Kightlinger previously co-founded and served as Chief Technology Officer of SwiftScale Biologics, a leader in cell-free manufacturing 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," said Kightlinger, who built Ridge as an Entrepreneur-in-Residence at SHV where he remains a Strategic Advisor. "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 announced its collaboration with a leading ADC-focused biotech to leverage Ridge Bio’s ProTrigger and NativeLink product lines to design and precisely attach linker systems that deliver therapeutic payloads specifically to tumor tissue, sparing healthy cells.
Powering Enzyme and Conditionally Active Prodrug Design
Ridge Bio’s initial offerings include NativeLink enzymes and ProTrigger linkers. NativeLink enzymes are designer biocatalysts that enable drugmakers to site-specifically modify therapeutic proteins, augment them with diverse payloads, extend their half-lives, and add precision targeting systems, all without changing the protein sequence, cell lines, or any upstream manufacturing processes. Ridge Bio’s first product, the NativeLink — AXC enzyme provides homogeneous modification of native antibodies without altering glycans, disulfide bonds, or amino acid sequences, avoiding stability, manufacturing, and functional challenges common with the previous generations of ADC, antibody-oligonucleotide conjugate (AOC), and other antibody conjugate synthesis strategies. The versatile system can achieve user-defined drug to antibody ratios (DARs) and multiple payloads or even upgrade an existing ADC drug product directly into a dual payload ADC without additional process changes. ProTrigger linkers are AI-designed protease-cleavable prodrug systems that release or activate therapeutic payloads at targeted sites in the body. Initial applications of ProTrigger linkers include unlocking new ADC targets, enhancing safety by reducing off-tumor toxicity, and targeting the tumor microenvironment and stroma.
"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," said Mike Jewett, Professor of Bioengineering at Stanford University and Ridge Bio’s Academic Co-founder and Scientific Advisory Board Chair.
World-Class Investors and Leadership Team
Ridge Bio’s founding team brings together deep expertise across ML-driven protein engineering, cell-free systems, and bioconjugation, combining groundbreaking work in academia with proven experience in industry.
"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." Founded in 1962, some of Sutter Hill Ventures’ previous investments and incubations include NVIDIA, Snowflake, PureStorage, Corcept Therapeutics, GRAIL, and Forty Seven.
Ridge Bio’s distinguished advisory board includes Carolyn Bertozzi, PhD (Stanford University, 2022 Nobel Laureate in Chemistry); Sangeeta Bhatia, MD, PhD (MIT/HHMI); Michael Jewett, PhD (Stanford University); Gabe Kwong, PhD (Georgia Tech); Mandana Honu, PhD (Atommap and Protillion, formerly Resilience); Hans Wandall, PhD (University of Copenhagen); and Vesna Mitchell, PhD (formerly Codexis). Their founding scientific team includes Grant Landwehr, PhD (pioneered ML-accelerated cell-free enzyme engineering approaches at Stanford University); Antje Kruger, PhD (launched cell-free enabled offerings for drug developers at Resilience); Francesca Li, PhD (built AI-driven protein engineering methods with Frances Arnold, PhD and Yisong Yue, PhD at Caltech); and Josh Walker, PhD (developed novel bioconjugation and ADC platforms at Bolt Therapeutics and insitro).
"Ridge Bio is at the forefront of three key trends, next-generation bioconjugates, protein design, and enzymatic therapeutics," said Dr. Bertozzi, whose work on biorthogonal chemistry won her a Nobel Prize and has been pivotal in guiding the development of modern bioconjugates. "Their AI and experimental platform are very unique and its 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."