Cullinan Oncology launches new subsidiary focused on collagen-binding cytokine treatment
Cullinan Oncology operates as both a biotech and an investment fund, housing each of its assets in subsidiaries under one large umbrella. A little over a month after its last launch, Cullinan has announced another such project.
The Cambridge-based company introduced Cullinan Amber on Wednesday morning, the ninth drug development enterprise in its portfolio, and has obtained an exclusive license from MIT to utilize collagen binding technology. Thanks to this tech, Cullinan Amber’s lead program will combine two antitumor cytokines, IL-12 and IL-2, with a collagen-binding domain to produce what CMO Jon Wigginton hopes are more localized cancer treatments.
“When you inject this molecule into the tumor,” Wigginton said, “it mediates significant antitumor activity, and by virtue of its collagen-binding domain, it binds the collagen in the tumor and is retained there better.”
Interleukins play a role in enhancing the body’s immune system, stimulating T and NK cell populations to attack tumor sites. But like many cancer immunotherapies, this can lead to high toxicity in healthy cells.
Cullinan Amber’s plan is to develop a single molecule that contains both IL-12 and IL-2, with the MIT tech providing a way to keep the immune response at the tumor site. Preclinical animal testing has shown that by injecting the compound directly into the tumor and binding to the tumor collagen, the cytokines stayed within the tumor environment. This tech was pioneered by MIT professor K. Dane Wittrup, who will be advising the Cullinan Amber team.
“What we’ve been able to show is not only do the animals gain weight over time, similar to the control group, but we essentially eviscerate their tumors,” CEO Owen Hughes said. “It’s really the advent of the collagen-binding domain that allows us to capitalize on what is very potent antitumor activity with these cytokines.”
Of course, collagen is present throughout the human body, and though early animal testing has encouraged Cullinan, the next challenge is to ensure such results translate to humans. This is the stage at which several companies previously abandoned their IL-12 and IL-2 projects, Wigginton said, because of the toxicity associated with the cytokines.
If some of the IL-12 and IL-2 were to spread outside the tumor environment in humans, side effects would be evident almost right away, Wigginton said. But thus far, the collagen-binding domain has proven quite effective and some testing has even shown signs of eliminating distant tumors.
“People historically have injected other agents like IL-12 into tumors, but those approaches have been limited by, in some cases, they haven’t shown the ability to generate systemic immunity,” Wigginton said. “We think that the agent will solve several historical challenges in the phase development of cytokines, and create the opportunity then to bring combinations together with much more favorable risk benefit.”
Targeting those off-site tumors will be the next step for Cullinan Amber as it moves into clinical stages. IND-enabling studies are expected to begin sometime before the end of 2020.
Though lots of tests remain, Wigginton hopes the compound can ultimately be safely used across a variety of solid tumor cancers.
“This is not a molecule that should necessarily be restricted to a specific tumor type,” Wigginton said. “We would start out with a Phase I trial with a mix of different tumor patients, guided by what we see from that and any translational studies, and probably pick a small number of cohort expansions to begin to characterize the antitumor activities and see how the molecule is safe and well-tolerated.”