An antibody drug is only as good as its ability to connect to its target. Sometimes a mutation at the binding point enables the target to escape, says Art Fratamico, CEO of startup Radiant Biotherapeutics. In other cases, the antibody might just fall off. Either way, without a strong connection to its target, a drug does not work.
Radiant’s technology imbues an antibody with more chances to bind to its target and maintain a connection. The startup is preclinical but it already has two big pharma partners and financial backing from the Bill & Melinda Gates Foundation. Radiant recently unveiled $35 million in financing to advance its research in cancer and infectious disease. In oncology, the company faces competition from other biotech companies also developing souped-up antibodies. Radiant aims to show how its approach could offer an edge.
A traditional monoclonal antibody is shaped like the letter “Y” with two arms called fragment antigen binding (Fab) fragments, regions that bind to a target antigen. Radiant, which splits its operations between Toronto and Philadelphia, is developing antibodies that are multivalent — they bind to more than one target. Whereas a traditional antibody has two Fabs, Radiant’s engineered antibodies have 24. The company calls its drugs Multabodies. With the ability for a Multabody to bind to more than one target, Fratamico says Radiant’s drugs can do things traditional antibodies can’t achieve. For one, these drugs offer better avidity, or binding strength, to their targets.
Sponsored Post
What Healthcare Can Learn from Costco
The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion.
By Jeff Bak, Imagine360 CEO and President
“I have multiple binding points, so once I grab it, it’s a better grip if you will,” Fratamico said. “With that comes improvement in efficacy and potency.”
Radiant’s technology is based on research from Jean-Philippe Julien, a senior scientist at The Hospital for Sick Children (SickKids) in Toronto and an associate professor in the department of immunology at the University of Toronto, and Bebhinn Treanor, a professor in the department of biological sciences at the U of T. Julien’s research focuses on antibody engineering. Fratamico said Julien was researching a multi-valent, multi-specific antibody platform. This platform is modular, enabling scientists to quickly find out early on in the drug discovery process whether a molecule is achieving the desired effect. At Radiant, this modular approach results in the company using the same scaffold, but placing Fabs on them from different antibodies to quickly test them to find which one to advance.
Julien aimed to develop treatments for infectious disease in underserved parts of the world. That research focus led to interactions with the Gates Foundation, which provided funding for his Covid-19 research. The foundation has interest in Radiant’s technology for potency improvement, Fratamico said. With Radiant’s platform, a molecule can go after multiple binding domains to deliver that improved potency. This capability could lead to antivirals capable of addressing elusive targets, such as HIV. The binding sites of this virus mutate, enabling it to escape traditional antibody approaches.
“With a Multabody, because we’re holding on, if there’s a mutation we’re still holding on and clearing virus,” Fratamico said.
Sponsored Post
The Future of Hospitals and Pharma Companies Will Depend on Strength of Healthcare Analytics Insights
PurpleLab® stands out from others in this sector by providing its data analytics services to several different groups of users across healthcare and pharma companies.
By pcallaghan
The HIV research is supported by $2 million in grant funding awarded by the Gates Foundation late last year. Much of Radiant’s new financing will support lead program 4-1BB, which takes its name from the receptor it is targeting on activated T cells and natural killer cells. Activating this receptor increases effector function, which is the way an immune cell interacts with a target of interest, Fratamico said. This increased function expands the cell and increases its ability to kill target cells. It also improves the function of immune cells that are exhausted.
Targeting and activating the 4-1BB receptor has been difficult to do safely and effectively with traditional antibodies. Earlier drug research efforts for this target stumbled in clinical trials due to either low efficacy or severe liver toxicity. Newer R&D efforts targeting 4-1BB with bispecific antibodies have reached early clinical development. Pieris Pharmaceuticals, I-Mab, and Aptevo Therapeutics are among the companies developing bispecifics. BioNTech’s acasunlimab combines PD-L1 checkpoint inhibition with 4-1BB stimulation. This drug candidate, made with antibody technologies from partner Genmab, is in Phase 1 testing for solid tumors.
Fratamico said a bispecific drug that addresses PD-L1 depends on a cancer to express that protein. Some cancers have high expression of that protein while others have low expression, which could lead to challenges in achieving efficacy. By contrast, a Multabody would not rely on PD-L1 expression to treat cancer. Radiant’s Multabody for cancer is monospecific — it only goes after 4-1BB. But it goes after that receptor with multiple Fabs. Fratamico said Radiant’s strategy is to demonstrate the company’s technology in the known biology of 4-1BB in a way that offers a first- or best-in-class approach. In time, Radiant could expand by developing drugs antibodies that offer multiple functions.
“As we continue to show the benefit of the platform, and it matures, then we’re open and wanting to take on more biology risk,” he said.
Radiant was formed in 2020 by Amplitude Ventures. In 2023, the startup emerged from stealth with $8 million in seed funding from Amplitude and two undisclosed big pharmaceutical company partners. Radiant has since revealed that those partners are GSK and Regeneron Pharmaceuticals, though the disease focus of each alliance remains undisclosed. Fratamico said he is not actively seeking more partners because the opportunity for Radiant to create value is by advancing its internal pipeline. The goal is to bring the 4-1BB program into the clinic in 2026. But Fratamico added that the startup could be open to new partnerships that offer the opportunity to create additional validation for Radiant’s technology and also bring non-dilutive funding.
The Gates Foundation and Amplitude co-led Radiant’s Series A financing. Other participants include new investors BDC Capital; the investment arm of the Business Development Bank of Canada, through its Thrive Venture Fund; and abrdn plc of Edinburgh, Scotland. Earlier investors FACIT, Alexandria Venture Investments, and Toronto Innovation Acceleration Partners also participated.
