Swedish oncology firm Kancera AB is reorienting a drug development program originally conceived for multiple sclerosis toward cancer.

The Stockholm-based firm attended last week’s Bio-Europe Fall meeting in Munich to shop around a small molecule inhibitor of CX3CR1, a chemokine receptor, which has a potentially novel mode of action as an immuno-oncology agent.

The program is still over a year from the clinic. “We are currently filling the gaps in the preclinical package,” Kancera CEO Thomas Olin told BioWorld Today. “Our business model is to be able to find a partner to accelerate this program. This could receive a breakthrough designation if we can realize its potential.”

London-based Astrazeneca plc previously studied the same mechanism – and the same compound – in multiple sclerosis. The rationale underpinning this approach was to block central nervous system (CNS) infiltration of peripheral leukocytes expressing CX3CR1, namely subpopulations of T-lymphocytes and natural killer cells.

Company scientists reported last year that AZD8797 reduced paralysis, inflammation and central nervous system degeneration in an experimental autoimmune encephalomyelitis rat model. The data appeared in the April 8, 2014 issue of Proceedings of the National Academy of Sciences in a paper titled “Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis.”

Astrazeneca opted not to take the program any further, however, and Kancera has optioned the rights from Acturum Life Science, which has taken over the big pharma firm’s neuroscience R&D facilities at Södertälje, southwest of Stockholm, and more than a dozen research projects. “It was IND ready,” Olin said. “We believe we are first in class with a small molecule.”

What makes the target interesting in cancer is that its ligand, fractalkine (also called CX3CL1), is a negative predictor of response to anti-PD-L1 therapy. Indeed, elevated pre-treatment levels in tumors correlate with progression after anti-PD-L1 therapy, an observation that Genentech scientists and academic collaborators reported last year in a biomarker study involving 277 patients with advanced incurable cancer.

The data appeared in the Nov. 27, 2014 issue of Nature, in a paper titled “Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.” The finding was not expected, as fractalkine is associated with boosting immune cell infiltration, one of the overarching goals of immuno-oncology therapy.

In cancer, however, expression of CX3CR1 appears to be associated with the migration of cancer cells toward tissues that secrete high levels of fractalkine, including nerve tissue and bone. It is implicated in bone metastases of prostate and breast cancer, and with the development of neuropathic cancer pain, as tumor cells grow around nerve tissue.

The company has its roots in a drug discovery consultancy, Inovacia AB, which was spun out of Biovitrum AB (now Stockholm-based Swedish Orphan Biovitrum AB) in 2006. In 2010, this group pooled its expertise with scientists at the Karolinska Institute and a group of private investors and it went public on the junior First North Exchange in Stockholm in 2011. So far it has raised some SEK110 million (US$12.6 million) in funding, Olin said. (See BioWorld Asia, formerly International, Feb. 2, 2011.)