A Johns Hopkins spinout building non-degrading macrocyclic molecular glues - and using them to reach the targets other drugs can't.
Rapafusyn Pharmaceuticals, on the Johns Hopkins School of Medicine campus in Baltimore - where a class of natural-product-like macrocycles first discovered in an academic lab is being engineered into medicines.
Rapafusyn Pharmaceuticals is a clinical-stage drug discovery company based in Baltimore, Maryland. It designs a specific kind of medicine - the molecular glue - and it has taken a deliberately different route than most of the field.
A molecular glue is a small molecule that brings two proteins into contact that would not otherwise meet. In recent years, the best-known glues have been degraders: they recruit a target protein to the cell's disposal machinery and mark it for destruction. Rapafusyn's glues are non-degrading. Rather than sending a target to the shredder, they hold it in place, forming a stable three-part complex that changes what the protein can do.
That distinction matters because it opens a different set of targets. Many disease-driving proteins are considered "undruggable" - they have no obvious pocket for a conventional small molecule to grab, and they sit inside the cell or span its membrane, out of reach of antibodies. Rapafusyn's macrocycles are built to be cell-permeable, which lets them work where those hard targets actually live: protein-protein interfaces, transcription factors, transporters, ion channels, and enzymes.
The company was founded in 2015 on discoveries from the laboratory of Dr. Jun O. Liu, a professor of pharmacology and molecular sciences at Johns Hopkins University and the director of the Johns Hopkins Drug Library. Rapafusyn licensed its foundational chemistry from the university and remains on the School of Medicine campus, drawing on that scientific and clinical ecosystem.
RapaGlue is the engine underneath everything Rapafusyn does - a discovery system for finding, ranking, and refining non-degrading molecular glues at scale.
At its core sits a proprietary DNA-encoded library (DEL) of more than eight billion compounds. Each molecule carries a short DNA "barcode," so the entire collection can be screened against a target in a single pooled experiment and the winners read out by sequencing. On top of that chemistry, the company layers machine learning to guide target selection and to optimize hits for the properties that decide whether a molecule ever becomes a drug: selectivity, potency, cell permeability, and how long it stays bound.
The result is a platform meant to feed a pipeline rather than a single product - the same approach that turned Rapafusyn's $44 million Series A into a bet on a method, not just a molecule.
A DNA-encoded library large enough to interrogate difficult targets against billions of chemical possibilities at once.
Machine learning steers target selection and hit optimization, narrowing an enormous search space to viable leads.
Natural-product-like rings engineered to cross the cell membrane and reach intracellular and transmembrane targets.
Modulates protein function by holding targets in a ternary complex - no protein destruction required.
How a non-degrading glue works: RAP-0001 binds the intracellular chaperone FKBP12 and ENT1, locking them into a single three-part complex.
Rapafusyn's lead program picks an unglamorous but pointed problem: acute kidney injury in patients undergoing cardiac surgery, a common complication with no approved preventive drug.
That program, RAP-0001, is a selective inhibitor of ENT1 - a nucleoside transporter. As a molecular glue, it binds the intracellular chaperone FKBP12 together with ENT1 to form a ternary complex. In preclinical models it has shown activity against ischemia-reperfusion injury, a major driver of acute kidney injury, and the company presented in vivo data at the American Society for Nephrology's Kidney Week in 2024. RAP-0001 is advancing toward IND-enabling studies.
Beyond the kidney, the RapaGlue platform is expected to feed programs across oncology, immunology and inflammation, and pain - each drawing on the same core ability to reach targets that conventional chemistry struggles to touch.
Pipeline stages shown are approximate, based on public statements; RAP-0001 is the most advanced program.
Molecular glues and targeted protein modulation have become one of the most active areas in drug discovery, with companies like Monte Rosa, Kymera, Nurix, Neomorph, and Arvinas building around protein degradation.
Rapafusyn's distinction is its non-degrading approach. Where degraders remove a protein entirely, Rapafusyn's glues change what a protein does while leaving it intact - a mechanism suited to targets you may want to inhibit or redirect rather than eliminate. Combined with macrocycle chemistry tuned for cell permeability and a DNA-encoded library measured in billions, it stakes out a lane that is adjacent to, but distinct from, the degrader crowd.
Commercially, Rapafusyn operates as a B2B biopharmaceutical company: it advances its own wholly owned programs while positioning the platform for partnerships, licensing, and co-development with larger pharmaceutical companies as candidates mature.
A small, science-led team pairing Johns Hopkins chemistry and biology with seasoned biopharma leadership.
Life-science industry veteran with 25+ years across strategy, drug and diagnostics development, and asset valuation. Previously built and ran clinical-stage biopharma Avotres.
Professor of Pharmacology & Molecular Sciences at Johns Hopkins; co-leads the Kimmel Cancer Center's chemical biology program and directs the Johns Hopkins Drug Library.
Leads the RapaGlue discovery platform.
Oversees the company's biology programs.
Leads macrocycle and medicinal chemistry.
Leads partnerships and corporate development.
Rapafusyn is established, licensing macrocycle molecular-glue technology from Dr. Jun O. Liu's laboratory at Johns Hopkins University.
The company presents in vivo data on its ENT1 inhibitor for acute kidney injury at the American Society for Nephrology's 2024 meeting.
A 25-year life-science industry veteran and former Avotres CEO takes the helm as President and CEO.
Rapafusyn closes a $44 million round - up from an initial $28M close - to advance RapaGlue and push RAP-0001 toward IND-enabling studies.
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