From the ground up with uPAR

Cancer Research UK invests in startup company’s novel cancer treatment

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LONDON—The world’s largest independent cancer research charity, Cancer Research UK, is placing a bet on a biopharma startup’s experimental cancer treatment. The organization has reached an agreement with Monopar Therapeutics to finance and coordinate preclinical development of an antibody that targets the cell surface protein uPAR.
“This target, uPAR, is overexpressed in some of the most deadly cancers, such as pancreatic, ovarian and glioblastoma,” Chandler Robinson, Monopar co-founder and CEO, tells DDNews. “The orthotopic models we’ve done seem to show that our antibody is as effective as currently available treatments, but what’s really intriguing are the very synergistic possibilities for it to be used in combination with other treatment for some of these extremely deadly cancers.”
The antibody to be developed, HuATN-658, was discovered by Monopar Chief Scientific Officer Andrew Mazar, an expert on the uPAR pathway. Promising findings from numerous studies of HuATN-658 led to the founding of Monopar in 2014 with a focus on the antibody’s development.
“When you see a drug with antitumor effectiveness in one or two mouse models, it can still be difficult to predict its potential,” says Robinson. “But when we started seeing effectiveness in five or more models—not just in Andrew’s hands, but also at leading labs—we began to realize that we might have a drug that could be quite impactful.”
The terms of the agreement call for Cancer Research UK’s Centre for Drug Development (CDD) to finance Phase 1 clinical trials of the experimental antibody in cancer patients with advanced solid tumors. The main goal of the trial will be to gauge the safety of the antibody, although the effectiveness of the drug will also be evaluated.
The trials will be managed and run by the CDD through the Experimental Cancer Medicine Centre (ECMC) network, a United Kingdom-wide initiative funded by Cancer Research UK, the National Institute for Health Research in England and the Departments of Health for Scotland, Wales and Northern Ireland.
Once the trials are over, Monopar will have the right to acquire the clinical data produced. If Monopar declines that option, Cancer Research Technology (CRT), a wholly owned subsidiary of Cancer Research UK, may continue the development and commercialization of HuATN-658 in exchange for giving Monopar a share of any future revenues that result from the drug. CRT is a specialist commercialization and development company focused on developing new cancer treatments.
Researchers have previously tested other approaches to targeting uPAR, the cell surface protein, but Robinson says that HuATN-658 offers a novel approach. “In the past, people have tried targeting uPAR and uPA, but that’s only one ligand interaction and it’s only half the story,” he tells DDNews. “So Andrew invented this antibody that hits a completely different domain on uPAR and seems to be affecting multiple of the ligand interactions and through them to have even more effective anticancer effects than previous approaches at targeting uPAR.”
Robinson says that the agreement will provide financing for the development of the antibody that would be difficult for an emerging company like Monopar to otherwise access. “While these are still the early days of the company, we have created a very strong team and development strategy,” he says. “The development partnership with Cancer Research UK allows Monopar to leverage a strong platform for the clinical advancement of this compound as it brings long-established clinical, regulatory and manufacturing expertise and resources that would be difficult for an emerging company to amass quickly.”
Nigel Blackburn, Cancer Research UK’s director of drug development, says that the partnership represents the latest collaboration through its Clinical Development Partnerships program, which aims to help progress promising treatments from drug company pipelines and bring them into early-phase trials sooner. “Thanks to this, six new treatments are now in clinical trials that may otherwise never have moved beyond the lab,” he says.

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