From The Editor | March 22, 2024

Why Fusion Pharma Is The Latest Billion Dollar Big Pharma Buy In Radiopharmaceuticals

Ben Comer_2022_1

By Ben Comer, Chief Editor, Life Science Leader

John Valliant_Fusion Pharma
John Valliant

AstraZeneca’s $2.4 billion acquisition of Fusion Pharmaceuticals is the third billion-plus dollar Big Pharma radiopharmaceuticals purchase announced in the last six months; Lilly completed its $1.4 billion acquisition of POINT Biopharma last December, and BMS completed its $4.1 billion acquisition of RayzeBio in February.

As I wrote in January, the field of radiopharmaceuticals is having a moment, due to new product science and isotope sources, improvements on the supply chain and manufacturing side, as well as growing clinical evidence (and growing sales figures for marketed drugs, such as Novartis’s Pluvicto) for a widening number of indications.

That growth has led to a radiopharmaceuticals expertise and capacity crunch, however, which can make outsourcing a challenge, as ARTBIO’s Conrad Wüller, director, strategy and operations, explained in a recent panel discussion.

It’s a problem that was cited by John Valliant, founder and CEO at Fusion Pharma, when I spoke with him in late January. People with the right science backgrounds, and the required nuclear safety qualifications, are in “tremendously short supply,” a fact exacerbated by current and predicted growth in the radiopharmaceutical sector. In 2022, the radiopharmaceuticals market (which includes both radiodiagnostics/imaging and radiotherapeutics/drugs) was worth over $7 billion, a 15% increase over 2021, according to MEDraysintell Nuclear Medicine Report & Directory Edition 2023. By 2032, the market is expected to reach $39 billion, according to the MEDraysintell forecast.

When I asked Valliant in January whether he was receiving (and answering) calls from Big Pharma about a potential acquisition, given the amount of deal activity in the space, he deftly deflected, noting that his “vision for the company has never changed; we have a platform, we have manufacturing [capable of producing 100,000 doses a year], and we want to be vertically integrated. We want to take multiple products all the way through to approval in different indications.”

He did, however, reference Fusion’s partnership with AstraZeneca, which began in 2020. “They are leaders in the antibody-drug conjugate space, so they’re really good at putting the actinium on, using our linker technology. And we co-own the drugs that come out of that,” he said. “For me, that’s the best of both companies coming together.”  

What’s Unique About Fusion Pharma

The emergence of targeted alpha therapies (TAT) is a key driver in the radiotherapeutics development space, and it served as the impetus for founding Fusion Pharma. As a chemistry professor at McMaster University in the early aughts, Valliant was conducting research focused on connecting medically useful isotopes to molecules, when “the potential of the field became clear,” he says. “There wasn’t the ability to move it out of academic labs and into industry … to have the manufacturing, the quality, and the ability to attract the investment needed to do big picture drug development and full-scale manufacturing.”

In 2008, Valliant founded and launched the Centre of Excellence for Commercialization and Research — now called the Centre for Probe Development and Commercialization — which specializes in radiopharmaceutical R&D and manufacturing. He ran that organization for over a decade, and realized that “to be commercially viable, you want to have an isotope with a long half-life, so that you can centrally manufacture products and ship them to the [patient delivery] sites.”

That insight led Valliant to focus on actinium-225, an alpha particle-emitting isotope with a 10-day half-life, which causes double-strand DNA breaks, a potent cancer cell killer. “The majority of currently approved [radio]therapies are based on beta particle emitters,” said Valliant. Beta particles cause single-strand DNA damage, but to really kill a tumor, “you need multiple single-strand breaks, which requires a lot of beta to cause the damage.” An Alpha particle is much larger in size by comparison, and it “destroys everything in its path,” says Valliant. “But it only travels a distance of one to three cells.” To kill cancer cells, it takes a lot less alpha than beta, or “one thousand times less radiation injected into a patient to cause that massive trauma to cancer cells.” In comparing the same delivery molecule, which directs the radioactive payload to the cancer cell, alpha particles drastically outperformed beta particles in terms of potency against solid tumors, said Valliant. “So we decided to create a company around that.”

Most radiopharmaceutical companies developing new therapies are shifting toward alpha emitters from beta, noted Valliant. Rayzebio, for example, is currently in Phase 3 clinical trials with a drug that also uses actinium-225 and is targeting gastroenteropancreatic neuroendocrine tumors. Fusion’s lead candidate (FPI-2265), which is moving into a Phase 2/3 registration trial, targets the same indication as Novartis’s Pluvicto: prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. However, Fusion is pursuing an indication for patients that fail on Pluvicto. “There are a significant number of patients who need another therapy [after Pluvicto], and we think that will be our first approval,” he says. “The nice part about that is, it will likely be [administered at] the same site, in the same position, and using the same process, making it super easy for a patient to get that therapy once it’s approved.”

Other Fusion pipeline products will explore different cancer types, an expansion on the prostate and neuroendocrine cancer indications that previously defined the field. “There is no reason why this technology shouldn’t have comparable impacts on breast cancer, colorectal cancer, pancreatic cancer … you’re putting a bomb inside a cell,” says Valliant. “We have three additional clinical programs taking this technology to other cancers. For me, it’s a huge whitespace, and we’re just scratching the surface of this field.”