DUBLIN – The middle of a pandemic may not be the optimal time to launch an oncology-focused company, but Klosterneuburg, Austria-based Oncoone Research & Development GmbH unveiled a €13 million (US$14.1 million) series A round Wednesday, March 18, and laid out plans to develop several different approaches to targeting an immunologically distinct form of a ubiquitous inflammatory cytokine, which is unique to cancer cells and which is associated with a poor prognosis.
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which is involved in multiple aspects of immune regulation and which counters the anti-inflammatory actions of glucocorticoids. It is ubiquitously and constitutively expressed by healthy cells and has effects on other pro-inflammatory molecules, including tumor necrosis factor alpha (TNF-alpha), nitrous oxide and prostaglandin E2. It binds the CD74 receptor and induces both inflammation and cell proliferation by signaling through the nuclear factor kappa B (NF-kappaB), Erk1/2 and AP–1 (activator protein 1) pathways. It is elevated in many acute and chronic inflammatory conditions, including sepsis, rheumatoid arthritis, asthma, inflammatory bowel disease, psoriasis and systemic lupus erythematosus, as well as in cancer.
In their previous roles at Baxalta and later its acquirer Shire (both now part of Tokyo-based Takeda Pharmaceutical Co. Ltd.), the founding team at Oncoone led efforts to interrogate MIF biology. That included the discovery of an oxidized MIF isoform, dubbed oxMIF, which is found in the circulation of patients with inflammatory conditions and also in patients with colorectal, pancreatic, lung and ovarian cancers. It offers a potentially cleaner way of targeting MIF biology, without the likely toxicities associated with targeting a molecule that is present in healthy tissue. “I think a typical approach to neutralize MIF will not succeed,” Oncoone’s chief scientific officer and co-founder, Michael Thiele, told BioWorld. Shire did take such an antibody into the clinic in patients with colorectal cancer and other solid tumors, but it failed to progress.
Shortly after Shire exited cancer – it offloaded the oncology business it acquired through the Baxalta deal to Suresnes, France-based Les Laboratoires Servier SAS in a $2.4 billion sale – Oncoone’s founders came together to pick up the general theme of the work they had been doing, but with new approaches unconnected to their former employer. Its programs “are not a cut-and-paste” of what Baxalta/Shire had been doing, CEO and co-founder Randolf Kerschbaumer, who previously led oncology research at Shire, told BioWorld.
It has developed monoclonal antibodies that can selectively bind oxMIF without binding the “reduced” form of the cytokine – because the oxidation reaction triggers a conformational change that opens up new epitopes. “These antibodies have been very effective in models of inflammation and cancer,” said Thiele, who led the cell biology department in Shire’s oncology research unit. The company’s third co-founder is Chief Technology Officer Alexander Shinagl, a former research scientist at Shire.
But it has not yet disclosed what it plans to take forward as therapeutics. Oncoone plans to bring several biologic drug modalities to bear on oxMIF. It is working on three programs across the four key cancer indications it has identified. Shire was at least able to demonstrate target engagement in those indications with its program, so that offers some evidence to support the general strategy.
“Our current plan is our first candidate will be ready to enter the clinic in 2022,” Kerschbaumer said. It has not yet selected a lead indication – that will emerge from the preclinical studies and the completion of the company’s clinical strategy. The company aims to develop its therapies as monotherapies but also as combination partners for radiotherapy, chemotherapy and immuno-oncology agents. It is also conducting biomarker studies to identify likely responders.
What triggers the oxidation of MIF is still a mystery – as is whether the same mechanism is involved across different cancers. “I suspect there is a general mechanism which holds through for the different indications,” Thiele said.
The new cash will enable the company to complete preclinical development on whatever emerges as its lead program and take it up to the start of clinical trials. Participants in the present round included the Austrian Research Promotion Agency, the Austria Wirtschaftsservice Gesellschaft (AWS), a government development bank, and two undisclosed family offices.
“We started the discussion on the financing quite some time ago – way before the COVID-19 crisis,” Kerschbaumer said. “We hope and assume we will not be affected too much by the COVID-19 crisis,” he added. The company operates a hybrid research model – it conducts drug design and some in vitro and manufacturing work in-house but outsources animal work, formulation and production. It has eight employees, including the founding team, at present. A ninth hire starts work next month.