DUBLIN – Abalos Therapeutics GmbH raised €12 million (US$13.2 million) in series A funding to advance a distinctive approach to harnessing viruses for immuno-oncology applications.

Although the Essen, Germany-based company fits into the broad category of oncolytic virus developers, its officials were at pains to point out that the arenavirus strains it is working with are not actually oncolytic. They preferentially infect cancer cells, but their replication within their host cells does not lead directly to cell lysis, but to prolonged immune activation. "Arenaviruses really replicate very well in tumor cells compared to other cell types and tissues," Jörg Vollmer, chief scientific officer of Abalos, told BioWorld. "Arenaviruses have the ability to persist somewhat longer in the body compared to oncolytic viruses."

As well as replicating within tumor cells, they also infect and replicate within antigen presenting cells, which leads to activation of pattern recognition receptors of the innate immune system, the induction of a type I interferon response, which results in the release of pro-inflammatory cytokines, antigen presentation and the recruitment of immune effector cells to the site of the tumor. Immunogenic tumor cell death follows, releasing a fresh repertoire of cancer epitopes, including neoepitopes, which can further extend the antitumor immune response.

Abalos is not genetically engineering these viruses, but it selects those that are best adapted to their host with its Fast Evolution platform, which enables the company effectively to tune the properties of a viral strain, according to parameters such as tumor cell tropism, infection rate and persistence, in order to generate an optimal immune response. "We let nature do its job, so to speak," Abalos CEO Marcus Kostka told BioWorld.

Its lead arenavirus candidate is a lymphocytic choriomeningitis virus (LCMV) strain. New-York-based Hookipa Pharma Inc. employs an attenuated, replication incompetent LCMV strain as a vector to deliver genes encoding viral or tumor antigens to patients' dendritic cells, in order to elicit a cytotoxic T-cell response. The key difference, Kostka said, is that Hookipa is taking a vaccination approach with an attenuated, genetically modified strain. "We are using non-attenuated lymphocytic choriomeningitis viruses," Vollmer added.

The shared focus on LCMV is not coincidental. Abalos' founders, brothers Karl and Philipp Lang, both conducted postdoctoral research in the lab of Rolf Zinkernagel, the 1996 Nobel laureate who is a co-founder of Hookipa. Karl Lang now holds the immunology chair in the medical faculty of the University of Duisburg-Essen, while Philipp Lang is director of the molecular medicine department at the University of Düsseldorf.

On the management side, CSO Vollmer has long experience in biotech R&D, most recently as CSO of Munich-based immuno-oncology firm Rigontec GmbH, which Kenilworth, N.J.-based Merck & Co. Inc. acquired for €115 million plus to €349 million in milestones. (See BioWorld, Sept. 7, 2017.)

His career also includes stints with Nexigen GmbH, Coley Pharmaceutical Group and, after the latter's acquisition by Pfizer Inc., he headed the pharma firm's oligonucleotide therapeutics unit in Dusseldorf. CEO Kostka has spent the duration of his career at Boehringer Ingelheim GmbH, most recently as venture fund partner at its venture capital arm BIVF. "After 23 years in pharma, I thought it was time to do something different," he said. BIVF is co-lead investor on the series A round, and Kostka was initially involved in putting the deal together until he jumped to the other side of the table to lead Abalos. His and Vollmer's paths previously crossed at Rigontec, where BIVF was also an investor – Kostka was a director of the company.

'A busy space'

Abalos is now funded for the next three years, during which it will pursue three main objectives, including additional validation and translational research on the optimized viruses it has in its portfolio, process development and IND-enabling studies. Safety will be a key issue, as several arenaviruses are known human pathogens, including Lassa virus, Junin virus and Machupo virus, among others. "Obviously this is something we will have a close look at," Vollmer said. LCMV has previously been tested in human cancer trials – as far back as the 1970s – with no ill effects, other than flu-like symptoms, he added. The company will decide on a lead indication at a later date.

The entry of Abalos into the virus-based immuno-oncology fray further extends an already lengthy list of contenders who hope to extend the scope and the power of the first generation of approved therapies. The commercial failure of Imlygic (talimogene laherparepvec; T-Vec), the first oncolytic virus to gain approval, has not been a deterrent to either startups or big pharma firms. "It's a busy space. It's an interesting space. There have been some successes," Kostka said.

Most of the successes have been commercial rather than clinical, as big pharma has snapped up several early stage contenders. For example, Merck acquired Sydney-based Viralytics Ltd. in a $394 million cash deal. Boehringer Ingelheim GmbH paid €210 million in total to acquire Viratherapeutics GmbH, which was developing a vesicular stomatitis virus strain pseudotyped with an LCMV glycoprotein. Johnson & Johnson paid $140 million up front with up to $900 million more to follow in milestones to acquire Benevir Biopharm Inc., whose T-Stealth platform is designed to cloak viruses from the immune system, to support extended persistence. Other transactions include large license deals between Bristol-Myers Squibb Co. and Psioxus Therapeutics Ltd. and between Abbvie Inc. and Turnstone Biologics Inc. (See BioWorld, Aug. 21, 2018.)

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