Shasqi has achieved a groundbreaking milestone in cancer therapeutics by successfully demonstrating the first-in-human use of click chemistry to deliver targeted cancer treatments. The biotechnology company published results from its landmark clinical trial of SQ3370 in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), marking a paradigm shift in oncology drug delivery.
Revolutionary Click Chemistry Platform Shows Clinical Promise
The study represents the clinical translation of Shasqi's Click Activated Protodrugs Against Cancer (CAPAC®) platform, a pre-targeting technology that uses Nobel Prize-winning click chemistry to concentrate therapeutics at tumor sites. The platform consists of two components administered sequentially: a tumor binding agent and a protodrug that only react with each other via click chemistry directly at the tumor site.
"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."
Exceptional Safety Profile Enables Higher Drug Doses
The first-in-human dose-escalation clinical trial tested SQ3370, an intratumorally injected biopolymer paired with a doxorubicin payload, in patients with advanced solid tumors. Remarkably, the study demonstrated that 12 times the standard dose of doxorubicin could be administered per cycle with mild and manageable toxicities, including less than anticipated myelosuppression.
The reduced systemic toxicity and lack of immunosuppression from the high drug doses enabled T-cell-dependent immune responses, including cytotoxic CD8+ T-cell expansion and activation both in tumors and systemically. This immune activation represents an additional therapeutic benefit beyond the direct cytotoxic effects of the concentrated chemotherapy.
Nobel Laureate Validates Breakthrough Significance
Carolyn Bertozzi, PhD, Professor of Chemistry at Stanford University and winner of the 2022 Nobel Prize for Chemistry for developing click and biorthogonal chemistry, emphasized the broader implications of this achievement. "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," Bertozzi stated. "This study shows that biorthogonal chemical groups and their reaction products are tolerated in humans, unlocking a new frontier for oncology innovation and beyond."
Expanding Applications Beyond Current Study
The successful clinical validation opens new possibilities for targeted cancer therapeutics beyond traditional chemotherapy. Jason S. Lewis, PhD, Emily Tow Chair in Oncology and Deputy Director of Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center, highlighted the broader potential applications.
"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," Lewis said. "This opens up new opportunities for targeted delivery of other cancer therapeutics such as radiopharmaceutical therapy."
Addressing Limitations of Current Targeted Therapies
The CAPAC platform is designed to address key limitations of existing targeted therapies, particularly antibody drug conjugates (ADCs) and targeted radiopharmaceutical approaches. By eliminating catabolic activation—a process where normal tissues clear unbound ADCs and break linkers, causing toxicity in healthy tissues—the platform aims to expand the scope of potential targets and widen the therapeutic window.
Shasqi, founded in 2014 by CEO Jose Meija Oneto, MD, PhD, has positioned itself as the first company to translate click chemistry technology into human clinical applications. The company's mission centers on answering the fundamental question: "What if we could tell drugs where to go in the body?"
The successful clinical translation of click chemistry represents a significant advancement in precision oncology, offering a new approach to maximize therapeutic efficacy while minimizing systemic toxicity—a long-standing challenge in cancer treatment.
