On June 16, 2025 Shasqi, Inc. ("Shasqi"), a biotech company whose mission is to make cancer drugs more effective with pre-targeting enabled by click chemistry, reported the publication of a manuscript detailing the preclinical development and translation of SQ3370 to a first-in-human dose-escalation clinical trial in patients with advanced solid tumors (Press release, Shasqi, JUN 16, 2025, View Source [SID1234653928]).

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The manuscript titled, Development of a first-in-class click chemistry-based cancer therapeutic, from preclinical evaluation to a first-in-human dose escalation clinical trial, was published today in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

"This groundbreaking clinical validation marks a paradigm shift in oncology—we’ve demonstrated for the first time that in vivo click chemistry can be used in humans to pre-target and concentrate therapeutics at tumor sites," said Dr. Sangeetha Srinivasan, Director of In-Vivo Biology at Shasqi. "By decoupling tumor targeting from the payload, our CAPAC platform enables delivery of 12-fold higher doses of doxorubicin per cycle compared to conventional approaches, while reducing systemic toxicity."

Shasqi’s Click Activated Protodrugs Against Cancer (CAPAC) platform is a pre-targeting technology composed of a tumor binding agent and a protodrug. Administered sequentially, these components are designed to only click with each other via a click chemistry reaction occurring directly at the tumor site. This releases high concentrations of cancer drugs at the tumor while sparing healthy tissues.

The manuscript describes the development and first-in-human study of SQ3370, an intratumorally injected biopolymer paired with a doxorubicin payload, and the first in vivo click chemistry based therapeutic to be tested in humans. In the study, 12x the standard dose of doxorubicin was administered per cycle with mild and manageable toxicities, including less than anticipated myelosuppression. The lack of immunosuppression and high drug doses enabled T-cell-dependent immune responses, including cytotoxic CD8 + T-cell expansion and activation in tumors and systemically.

"The significance of this work expands far beyond the current study, as it demonstrates that click chemistry can be harnessed inside the human body to redefine how therapeutics are activated in the body," said Carolyn Bertozzi, PhD, Professor of Chemistry at Stanford University, and winner of the Nobel Prize for Chemistry in 2022 for the development of click and biorthogonal chemistry. "This study shows that biorthogonal chemical groups and their reaction products are tolerated in humans, unlocking a new frontier for oncology innovation and beyond."

"This breakthrough study shows, for the first time, that click chemistry can be used inside the human body to activate cancer drugs at the tumor," said Jason S. Lewis, PhD, whose work as the Emily Tow Chair in Oncology and Deputy Director of Sloan Kettering Institute (OSET) at Memorial Sloan Kettering Cancer Center in New York is focused on pre-targeting radiopharmaceutical therapies using click chemistry. "This opens up new opportunities for targeted delivery of other cancer therapeutics such as radiopharmaceutical therapy."