In June 2023, the click chemistry-focused startup Shasqi revealed a research pact with Johnson & Johnson Enterprise Innovation. More recently, the company announced that it had expanded the research alliance, furthering work on its intratumorally injected biopolymer, known as SQL70. The collaboration will also apply its clinically validated Click Activated Protodrugs Against Cancer (CAPAC) technology to the development of new cancer therapies through preclinical testing.
Inside the click chemistry Shasqi J&J alliance
Shasqi is working with an interventional oncology unit at J&J, which is aiming to take a holistic approach to cancer care that spans therapeutics and therapeutic approaches to meet unmet needs. “That completely matches with our view of the world,” said Dr. José M. Mejía Oneto, the founder and CEO of Shasqi.
The partnership with J&J will bolster research on Shasqi’s intratumorally injected biopolymer SQL70 but also support the development of an additional payload through preclinical testing.
“We’re now expanding beyond just biopolymers,” Oneto said. “We’re focusing on antigen targeting activators that can be infused into the body, which will bind to specific receptors and harness the power of click chemistry.”
The expanded collaboration with J&J is evidence of the growing traction of click chemistry. In 2022, click chemistry pioneers Carolyn R. Bertozzi, Morten Meldal, and K. Barry Sharpless won the Nobel Prize of Chemistry for their work in click chemistry and bioorthogonal chemistry.
Before that milestone, Oneto recalls having to “explain to people what click chemistry is.” But afterwards, people grasped its import. The partnership with J&J focused on click chemistry is further evidence of its evolving status.
Toward precision activation in cancer treatment
On Shasqi’s website, the company notes that a small percentage of drugs make it to their desired location in the body. “Imagine a world where cancer drugs are activated only where they are needed,” it reads. Oneto elaborated on this vision, stating, “Our goal is to create a world where drugs are activated exactly where you want them.” Drug developers may not be able to control how therapies get distributed, but “can you control where the activation of the powerful therapy that you want to give happens?” Oneto asked. “And so from our perspective, there’s multiple ways to enable that to happen. One is through a direct injection into a location in your body and the other one is through known receptors in a tumor.” Ultimately, the ability to selectively control where the activation occurs is “critical,” Oneto concluded, as it sets the stage for new possibilities in targeted cancer treatment.
A recent publication in ACS Central Science underscores the potential of Shasqi’s approach. The paper describes how Shasqi’s CAPAC platform used a click chemistry reaction between tetrazine and trans-cyclooctene to activate cancer drugs at specific tumor sites. This approach allowed for targeted activation either through intratumoral injection of a tetrazine-modified hyaluronate or by infusion of a tetrazine-modified HER2-targeting antigen-binding fragment. The study highlighted the efficacy of SQP22, a novel protodrug activated through click chemistry.
“That separation of the payload from targeting gives you an enormous amount of flexibility in terms of how you saturate those receptors,” Oneto said, referring to tumor-associated receptors such as HER2. Instead of the traditional approach where two agents are firmly tethered together, as in an antibody drug conjugate (ADC), the CAPAC platform uses click chemistry to activate drugs at specific tumor sites. By either intratumorally injecting a tetrazine-modified hyaluronate or infusing a tetrazine-modified HER2-targeting antigen-binding fragment, the method allows for receptors to first be targeted with a harmless agent that doesn’t carry the therapeutic component. “You can then follow up with the required payload dose. This enables activation where you want it.”