Anchor the drug.
Transform the medicine.
Our membrane-anchored drug design (MADD) platform links a pharmacophore to a membrane-mimicking kinetophore that lodges the molecule in the lipid bilayer, enabling unprecedented control of drug distribution and exceptional specificity for cell-surface targets—taming powerful pharmacophores for precise site of action and unlocking a new class of safer, more effective drugs.
Developing Novel drugs with Clinical Differentiation
Rezubio is a clinical-stage biotechnology company founded by scientists with decades of combined experience in small molecule and peptide drug discovery and development. Our leadership team brings deep expertise across medicinal chemistry, disease biology and pharmacology, CMC, and clinical development, with track records from global pharmaceutical organizations including Merck Sharp & Dohme, Novartis, and Roche.
Rezubio leverages its proprietary MADD platform to create gut-specific therapeutics against targets with proof-of-concept—such as GPCRs, transporters, and ion channels. By restricting drug action to the gut and minimizing systemic exposure, our platform can revive some targets that previously failed in clinical trials because of adverse effect caused by drugs in the systemic exposure. This approach opens new opportunities to develop safer, more effective medicines for metabolic, cardiometabolic, immune and inflammatory diseases.
GPR40 complex structure with full agonist AP8 (PDB: 5TZY)
Improved safety window
The kinetophore anchors the MADD molecule to the outer leaflet of the cell-membrane lipid bilayer in a specific orientation, and the molecule does not penetrate the membrane. MADD molecule consistently shows extremely low oral bioavailability (0.1–0.3%) and minimal systemic exposure—reducing risks of adverse effects.
Enhanced intrinsic potency
The membrane-anchoring feature enriches the molecule at the site of the target protein, resulting in higher local concentration and greater potency compared with the pharmacophore alone.
Optimized PK profile
The kinetophore stabilizes the molecule by keeping it non-penetrant, preventing intracellular enzymes from accessing and metabolizing it. As a result, our MADD molecules consistently show very low oral bioavailability, low clearance, and high gut distribution across multiple preclinical species.
Sustained effect for long-lasting efficacy
The MADD molecules have high affinity to cell membrane and long residence time in target tissue, allowing once-daily or even less frequent dosing.
Target GPR40 on EECs in the gut epithelium to induce secretion of incretins and non-incretin hormones for diabetes and obesity
Rezubio’s lead MADD therapeutic candidate, RZ-629, is a novel gut-targeted GPR40 agonist designed to deliver potent metabolic benefits with minimal systemic exposure. In multiple animal models, RZ-629 produced superior glucose lowering and body-weight reduction compared with the pharmacophore molecule alone, while avoiding the systemic liabilities—such as liver and pancreatic toxicities—that have limited prior GPR40 agonist programs.
A rat tissue-distribution study showed that nearly 100% of administered parent drug was recovered in feces, with biliary and urinary excretion each below 0.01% of dose, confirming that RZ-629 remains gut-restricted with negligible systemic exposure.
RZ-629 activates a broader, more physiological hormone response than current incretin-based GLP-1 receptor agonists. By stimulating endogenous secretion of GLP-1, GIP, PYY, and glucagon from the gut, RZ-629 mimics the body’s natural response to dietary fatty acids and shows synergy with food intake. Importantly, the induction of GIP and PYY is associated with significantly reduced gastrointestinal intolerance in rodent studies compared with GLP-1 receptor agonists, suggesting RZ-629 has a potentially more tolerable profile in patients.
Founders
Yusheng Xiong, CEO and co-founder
Yusheng Xiong is an industry-leading medicinal chemist with more than two decades of drug discovery experience at Merck, Sharp & Dohme (MSD). As Director of Medicinal Chemistry, he led the groundbreaking oral cyclic peptide PCSK9 program (MK-0616/enlicitide decanoate), which has completed multiple Phase 3 clinical trials and demonstrated best-in-class LDL-C reduction in humans. Throughout his career at the Merck Research Laboratory in New Jersey, Yusheng directed diverse discovery programs across metabolic, cardiovascular, and other therapeutic areas, advancing numerous candidates toward the clinic.
Yusheng earned his B.S. in Chemistry from Wuhan University and his Ph.D. in Organic Chemistry from UCLA funded by the US-China CGP program, followed by postdoctoral research at the University of Chicago.
Hong-Ping Guan, CSO and co-founder
Hong-Ping Guan is a translational scientist with deep expertise in diabetes and cardiometabolic diseases. During his more than seven years at MSD, he played key scientific roles in advancing multiple programs, including glucagon receptor antagonists, AMPK modulators, and MASH therapeutics. His work spans target biology, in vivo pharmacology, and mechanistic research that supported several clinical-stage assets.
Hong-Ping earned his Bachelor of Medicine from Beijing Medical University (Peking University Health Science Center) and his Ph.D. in Pharmacology from the University of Pennsylvania. He completed postdoctoral training at UT Southwestern Medical Center as a Pfizer Fellow of the Life Sciences Research Foundation.
R&D Pipeline
Program
RZ-629
RZ-520
RZ-858
Indication
Obesity & diabetes
Immune & inflammatory disease
Metabolic disease
Preclinical
IND
Phase 1
