ZW800-1: The 1st Zwitterionic NIR Fluorophore for Cancer Imaging & Ureter Mapping - Image-guided surgery using invisible near-infrared (NIR) fluorescent light is here to stay. Multiple
commercial imaging systems from Stryker, Olympus, Medtronic, and Intuitive Surgical are now available for
human surgery. However, only innovative NIR fluorophores will solve major clinical problems.
Curadel has invented a novel family of NIR fluorophores termed “zwitterionic,” or more precisely,
geometrically-balanced, electrically-neutral, polyionic polymethine indocyanines. Zwitterionic NIR fluorophores,
such as ZW800-1, exhibit ultralow non-specific binding and uptake in normal tissues and organs, as well as
100% renal clearance and elimination into urine.
Within 1-10 min after a low (≤ 2.5 mg) dose intravenous (IV) injection, the ureters become highly NIR
fluorescent for up to 3.6 h, thus providing surgeons with the ability to avoid them during all abdominopelvic
cancer surgeries. In fact, in most cases ZW800-1 eliminates the need to surgically dissect, identify, and isolate
the ureters altogether, saving over 20 min of OR time, reducing anesthesia time, and reducing the risk of
complications, such as adhesions. Currently, ureter damage is quite common in cancer surgery and leads to
enormous cost ($1.35B annually in the USA alone) and high patient morbidity.
Because of its clinical potential, ZW800-1 was deemed a high value asset by the NCI’s Experimental
Therapeutics (NExT) Program and was accepted into the first-in-human tract. Two-species toxicity, as well as
genotoxicity and mutagenicity, were extraordinarily low. Curadel used a Direct-to-Phase II SBIR grant (NCI
5R44-CA-210820-02) to scale-up cGMP production, qualify impurities, and optimize aseptic fill-finish, while
collaborators in Europe performed a Phase 1 trial on human volunteers and a Phase 2 trial on patients
undergoing abdominopelvic surgery for cancer resection. The results of the Phase 1 and 2 trials presented
herein are exceptional and validate our hypothesis that ZW800-1 is an ideal contrast agent for ureter mapping.
A single low dose permitted ureter mapping for hours on FLARE®, Olympus®, and Da Vinci® NIR fluorescence
imaging systems, and could be repeated if needed for longer cases.
ZW800-1 is now poised to complete the remaining steps of market approval where we anticipate
widespread adoption in abdominopelvic cancer surgery. Innovative aspects of our application include a cGMP
synthesis and aseptic fill-finish strategy that does not require excipients or other additives yet results in a final
drug product with > 5 years of stability, and a commercialization plan that requires only ≈ $8M to get to NDA
submission yet results in a commercial product with >93% gross margin and a $100M+ annual market. Our
competitive position is also unusually strong because of issued patent claims for ZW800-1 in USA, Europe,
Japan, and Australia, and unique pharmacokinetics that no other competing NIR fluorophore can match.
Our long-term goal is to solve the problem of ureter mapping during cancer surgery once and for all.
