Ridge Biotechnologies Secures $25M Oversubscribed Seed Round Led by Nobel Laureate Carolyn Bertozzi to Advance AI-Designed Enzyme Therapeutics

On September 9, Palo Alto, California, Ridge Biotechnologies (Ridge Bio), a company pioneering enzyme and targeted drug design to power the next wave of precision medicines, announced the completion of a $25 millionOversubscriptionSeed Round Financing. Sutter Hill Ventures (SHV) incubated Ridge Bio and led this round of financing, with participation from companies such as Overlap Holdings.

Ridge Bio platform uses proprietary machine learning models informed by high-throughput cell-free assays for antibodyConjugationAntibody-drug conjugates (ADCs), in vivo CAR-T therapies, targeted nucleic acid delivery, small-molecule biocatalysis, radiotherapy, and enzyme-based therapies. Dr. Weston Kightlinger is a serial entrepreneur and a pioneer in cell-free synthesis and enzyme design, as well as the co-founder and CEO of Ridge Bio. Dr. Kightlinger co-founded and served as the Chief Technology Officer of SwiftScale Biologics, a leader in cell-free manufacturing that was acquired by Resilience.

Dr. Weston Kightlinger stated："Drug development should not be limited by the complexity of molecules we can precisely construct, off-target toxicity, or mechanism of action based on binding. Machine learning significantly expands our ability to design enzyme systems that can address these issues, but unleashing its full potential requires vast experimental datasets. At Ridge Bio, we generate these datasets at unprecedented speed and scale—producing a million times more sequence-function data in a short period than traditional methods. We apply this data to enzyme and conditionally active drug design using customized machine learning models, providing our partners with powerful tools to create safer and more precise medicines."KightlingerAs the resident entrepreneur of SHV, he founded Ridge Biotechnologies and remains a strategic advisor to SHV. With the support of great investors and a world-class founding team, the company is scaling operations, expanding technical partnerships in bioconjugates, and advancing.Ridge'sDiscovery Plan to Achieve the Long-term Goal of Developing a New Class of Precisely Designed Therapeutic Enzymes.

Strong early interest from leading biopharmaceutical companies and CDMOs validatesRidgeThe vision, and inspire the company to accelerate the delivery of breakthrough drugs that have a real impact on patients. Ridge Bio also announced a collaboration with a leading ADC-focused biotechnology company to leverage Ridge Bio's ProTrigger™ and NativeLink™ product lines for designing and precisely connecting linker systems that specifically deliver therapeutic payloads to tumor tissues while protecting healthy cells.

Driver Enzymes and Conditionally Active Prodrug Design

Ridge Bio's initial products include NativeLink enzymes and ProTrigger linkers. NativeLink enzyme is a designed biocatalyst that enables pharmaceutical manufacturers to modify therapeutic proteins at specific sites, enhancing them with different payloads, extending their half-life, and adding precise targeting systems, all without altering the protein sequence, cell line, or any upstream manufacturing process. Ridge Bio's first product, NativeLink-AXC enzyme, provides homogeneous modification of native antibodies without changing glycans, disulfide bonds, or amino acid sequences, avoiding stability, manufacturing, and functional challenges common to previous generations of ADCs, antibody-oligonucleotide conjugates (AOCs), and other antibody conjugate synthesis strategies. This versatile system allows for user-defined drug-to-antibody ratios (DAR) and multiple payloads, even enabling direct upgrading of existing ADC drug products into dual-payload ADCs without additional process changes. ProTrigger linkers are AI-designed protease-cleavable prodrug systems that release or activate therapeutic payloads at targeted sites in vivo. Initial applications of ProTrigger linkers include unlocking new ADC targets, improving safety by reducing off-tumor toxicity, and targeting the tumor microenvironment and stroma.

Mike Jewett, Professor of Bioengineering at Stanford University and Chairman of the Scientific Advisory Board and Co-Founder of Ridge Bio, stated:"Thanks to the combination of cell-free assays and machine learning, what used to take years can now be accomplished in weeks. Together, they have transformed our ability to design and harness enzymes and prodrugs with high specificity. This specificity is at the heart of Ridge Biotechnologies and the next generation of precisely engineered therapies."

Ridge Bio's founding team brings together deep expertise in machine learning-driven protein engineering, cell-free systems, and bioconjugation, combining groundbreaking academic work with industrial maturity.

Keith Loebner, Ph.D., Managing Director of SHV, stated:"Ridge Bio is the perfect example of our approach to building companies: supporting world-class founders and helping them attract the incredible teams needed to tackle tough technical problems and unlock massive markets. Ridge Bio’s capabilities in machine learning and wet-lab bioengineering enable the company to create drugs that others cannot make, delivering a new class of precision-engineered enzyme-based therapies. 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 achieve what others couldn’t, and as a team, define the future of precision medicine."

Sutter Hill Ventures, founded in 1962, has previously invested in and incubated projects including NVIDIA, Snowflake, PureStorage, Corcept Therapeutics, GRAIL, and Forty Seven.

Ridge Bio's distinguished advisory board includes Dr. Carolyn Bertozzi (Stanford University, 2022 Nobel Prize in Chemistry laureate); Dr. Sangeeta Bhatia (MIT/HHMI); Dr. Michael Jewett (Stanford University); Dr. Gabe Kwong (Georgia Institute of Technology); Dr. Mandana Honu (Atommap and Protillion, formerly Resilience); Dr. Hans Wandall (University of Copenhagen); and Dr. Vesna Mitchell (formerly Codexis). The founding scientific team includes Dr. Grant Landwehr (a pioneer in ML-accelerated cell-free enzyme engineering methods at Stanford University); Dr. Antje Kruger (who launched cell-free products for drug developers at Resilience); Dr. Francesca Li (who co-developed AI-driven protein engineering methods with Dr. Frances Arnold and Dr. Yisong Yue at Caltech); and Dr. Josh Walker (who developed novel bioconjugation and ADC platforms at Bolt Therapeutics and insitro).

Carolyn BertozziDr. said:"Ridge Bio is at the forefront of three key trends: next-generation bioconjugates, protein design, and enzyme therapies.""Their artificial intelligence and experimental platforms are highly unique, and the products they have generated enable drug developers to stand out from competitors—not only by improving manufacturing but also by enhancing therapeutic metrics, while unleashing the power of catalytic drugs."

Carolyn BertozziHer work in bioorthogonal chemistry earned her the Nobel Prize and played a key role in guiding the development of modern bioconjugates.

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