After several years incubating in the Centre for Probe Development and Commercialization (CPDC) at McMaster University in Hamilton, Ontario, Fusion Pharmaceuticals Inc. is hanging out its shingle. The company's formal launch was accompanied by a $25 million series A led by its founding venture investor, Johnson & Johnson (J&J) Innovation-JJDC Inc., joined by Healthcap, TPG Biotech, Genesys Capital and Fight Against Cancer Innovation Trust (FACIT).

Fusion, which will stay close to its CPDC roots, is developing targeted alpha-particle radiotherapeutics to treat cancer. Lead program FPX-01 is an antibody-targeted radiotherapy that seeks out insulin-like growth factor-1 receptor, or IGF-1R, a biomarker of resistance that's present on nearly all types of solid tumors, according to John Valliant, the company's founder and CEO. The technology is designed to selectively deliver actinium-225 to the tumor cells, using the emitted alpha particles to eradicate diseased tissue.

Valliant, a professor in the department of chemistry and chemical biology at McMaster, in 2008 founded the CPDC, a Centre of Excellence for Commercialization and Research funded by Canada's federal and provincial governments to propel intellectual property (IP) developed at the nation's academic institutions into the commercial sector. The CPDC, which is supported by the Ontario Institute for Cancer Research and other stakeholders, already has a global network of customers for its commercial GMP PET molecular imaging products and offers consulting services on the development of companion diagnostics. The segue into radiopharmaceuticals was a logical next step.

"The whole purpose of our center was basically to de-risk and enable the commercialization of academic IP – basically, to develop high-value materials and then spin them out into for-profit companies," Valliant told BioWorld Today.

The alpha therapeutic platform technology was moved into Fusion – a shell company at the time – in 2015, when the CPDC received seed financing from FACIT. The company then began to assemble a group of investors that would provide enough support to take the lead agent into the clinic.

Those efforts gained traction when the CPDC licensed the centyrin platform developed by J&J unit Janssen Biotech Inc. for exclusive use in combination with its radiopharmaceuticals to create nuclear imaging probes against immunotherapy drug targets. Centyrins are protein-targeting agents characterized by high selectivity and specificity combined with tunable pharmaceutical properties and efficient manufacturing. Behind FPX-01, Fusion has a centyrin-based targeting molecule in preclinical development that offers the potential to deliver isotopes to several cancer types.

'WE USE THE TARGET SIMPLY AS A SHUTTLE'

In general, radiotherapeutics are constructed using a targeting mechanism connected to an alpha particle-emitting medical isotope, which is designed to attack cancer cells and cause double-stranded DNA to break so the cells cannot easily repair themselves, reducing the chance of drug resistance. Fusion's therapeutic approach combines alpha particle-emitting technology with monoclonal antibodies to target cancer cells precisely, minimizing damage to normal tissues to limit side effects.

Alpha therapies are designed to deliver "a very lethal payload that actually only travels about the distance of a single cell," Valliant explained. "Differentiating these from other therapies is that resistance is highly improbable."

The amount of material needed for therapeutic activity also is less than with conventional drugs, such as antibodies or antibody-drug conjugates, "so you can go after targets that are less abundant or would not be considered druggable with other techniques," he added.

Fusion, whose name links the importance of nuclear science and chemistry with therapeutic development, will use the series A proceeds to move its lead candidate into an all-comers phase I study next year in patients with solid tumors. Although the study will focus primarily on safety and dose optimization, Fusion will apply another feature of its platform to identify patients most likely to benefit from the treatment so that it can move quickly into efficacy studies.

"One of the powers of our technique is that you can take the same molecule and, instead of inserting an alpha-emitting isotope, insert an alpha-imaging isotope," Valliant said. "We're actually able to use imaging to determine which patients have the target expressed in high concentration and most likely to respond to the therapy."

IGF-1R has been shown to be up-regulated in a variety of resistant solid tumors, including lung, colorectal, hepatic, gastric, prostate, breast, ovarian, endometrial and head and neck cancers. Although antibodies to IGF-1R have not shown clinical efficacy, Fusion's technology is more suited to their ability to engage the receptor and internalize.

"We use the target simply as a shuttle to move this alpha particle-emitting medical isotope into the cell," Valliant said. "That gives us a broad base of tumors to go after," with the prospect of creating a companion diagnostic with each candidate.

Emerging research also suggests that radiation-based therapies can stimulate the immune system, according to Valliant. Considering the preponderance of checkpoint inhibitors and similar immunotherapies in the clinic, "one area we'll be exploring in more detail is the synergy between alpha therapy and immunotherapy," he said.

Through the CPDC, Fusion already has access to manufacturing and distribution capabilities for its radiotherapeutics for trials and, ultimately, for the commercial market. That expertise represents another differentiator in the space, Valliant said.

Unlike first-generation radiotherapeutics, newer alpha particle-emitting agents like Fusion's offer improved handling features and can be administered in conventional treatment facilities, he added.

Although Fusion is an early entrant in the field of radiotherapeutics, it's not the first. Pioneers include companies such as Oslo, Norway-based Algeta ASA and Nordic Nanovector ASA – also portfolio companies of Sweden's Healthcap. Fusion will seek to leverage the expertise of its investor, which has "a tremendous track record in this field," Valliant said.

"We manufacture and distribute probes and molecules containing medical isotopes all across Canada, the U.S., Europe and Australia," he added. "Having strong relationships in Canada and the U.S. makes them lead sites to get started but we'll take a very global approach."

Fusion's team of approximately 20 scientists is led by Eric Burak, chief scientific officer, who previously held positions at the CPDC; privately held Theracos Inc., and antibiotics developer Rib-X Pharmaceuticals Inc.

In addition to Valliant, the company's board includes Asish Xavier of Johnson & Johnson Innovation-JJDC, Robert Sutherland from the CPDC, Eran Nadav of TPG Biotech, Healthcap's Johan Christenson and Damian Lamb of Genesys, who will serve as chairman.