DUBLIN – Another big gun has entered the oncolytic virus fray. Prompted by positive progress in its collaboration with Viratherapeutics GmbH, Boehringer Ingelheim GmbH has exercised an option to buy the company outright in a deal worth €210 million (US$245 million) in total.
Part of the cash has already been handed over. Innsbruck, Austria-based Viratherapeutics received €20 million in up-front and research funding two years ago. The original agreement envisaged positive phase I data being the trigger, but Ingelheim, Germany-based Boehringer has decided that the data it has seen in a number of preclinical models are sufficiently good to justify the buyout. (See BioWorld Today, Sept. 29, 2016.)
Viratherapeutics, a spin-out from the Medical University of Innsbruck, is based on the work of professor of virology Dorothee von Laer, who developed a vesicular stomatitis virus (VSV) strain that she pseudotyped with a glycoprotein from lymphocytic choriomeningitis virus (LCMV). That maneuver eliminates the neurotoxicity associated with wild-type VSV GP, while at the same time avoiding complement activation, which helps to maintain high virus titers in the circulation.
"Here we have a very interesting virus biology, which is driven by the very fast replication potential of the virus," Knut Elbers, managing director and head of R&D at Viratherapeutics Center for Oncolytic Virus Research, told BioWorld. "We shield the virus a little bit from the immune system," he added. That opens up the possibility of repeat dosing.
Boehringer is keeping its clinical development strategy under wraps for now. "The virus biology and mechanism of action is driving our indication selection," Elbers said.
The choice of lead indication will also be influenced by input from regulatory authorities and cancer treatment centers. The company will also combine VSV-based constructs with other agents that act on immune targets. Those could include – but would also go beyond – classical checkpoint targets such as PD-1 and LAG-3. The company has a number of immuno-oncology agents in clinical development but a whole lot more coming up behind them with differing modes of action.
"We feel we have a rich pipeline of different modalities," Elbers said.
Its overarching strategy in immuno-oncology is to make "cold" tumors "hot" by disrupting the immune evasion strategies adopted by different cancers and ensuring that tumor antigens become visible to the immune system. It is pursuing various approaches, including cancer vaccines, bispecific T-cell engager (Bite) antibodies, as well as oncolytic viruses. Its in-house PD-1 inhibitor, BI 754091, is undergoing a range of combination trials.
Although PD-1 remains the target of choice for current combo regimens, that situation will not hold indefinitely. "In the long run it will get differentiated. You will see that different and more complex combinations will succeed," Elbers said.
Recent collaborations include a deal potentially worth more than $1.35 billion with Nantes, France-based OSE Immunotherapeutics SA on the development of an antibody targeting SIRP-alpha, a receptor expressed on myeloid-lineage cells, such as dendritic cells and tumor-associated macrophages. It is designed to disrupt an immune-inhibitory response that occurs when SIRP-alpha binds the cancer antigen CD47. (See BioWorld, April 5, 2018.)
The company's in-house immuno-oncology R&D effort is also growing. Originally that activity was based in Vienna only, but it currently has additional activity in Ridgefield, Conn., its main U.S. research site, in Biberach, Germany, and now in Innsbruck. The Viratherapeutics team is currently 19 strong, but Elbers said the company will further strengthen that unit, which is located in a research-rich environment.
Boehringer is a relatively late starter in the immuno-oncology game. As a private company, it does not feel the need to wave its flag too vigorously. But it is in this area for the long haul.
"We do not need to follow trends. We really can implement long-term strategies in certain areas," Elbers said. But it only moves in when the level of understanding of the field matures. "This is clearly the situation here in the oncolytic virus space."
Several other large pharma companies have been making similar moves of late. In May, New Brunswick, N.J.-based Johnson & Johnson put down $140 million and could pay another $900 million to acquire Benevir Biopharm Inc., of Gaithersburg, Md., the developer of an oncolytic virus engineering platform called T-Stealth, which is designed to overcome cancer's immune tolerance mechanisms. In February, Merck & Co. Inc., of Kenilworth, N.J., agreed to pay $394 million for Sydney-based Viralytics Ltd., the developer of Cavatak, a proprietary Coxsackievirus type A21 viral strain. Abbvie Inc., of North Chicago, and New-York-based Bristol-Myers Squibb Co. entered the field through partnering deals with Ottawa-based Turnstone Biologics, Inc., and Oxford, U.K.-based Psioxus Therapeutics Ltd., respectively. Woburn, Mass.-based Replimune Inc. raised $111 million in an IPO in July and entered a 50/50 shared-cost collaboration with Tarrytown, N.Y.-based Regeneron Pharmaceuticals, Inc., based around combinations of its second-generation engineered herpes simplex virus 1 (HSV-1) constructs and the latter's PD-1 inhibitor, cemiplimab.
Viratherapeutics' founders pioneered the first oncolytic virus, Imlygic (talimogene laherparepvec), for which its present owner, Amgen Inc., of Thousand Oaks, Calif., has yet to report any sales data. Imlygic is also an engineered HSV-1 strain, which has been modified to grow preferentially in cancer cells and to express granulocyte-macrophage colony-stimulating factor, an immunostimulatory cytokine. Its efficacy as a monotherapy is modest, but it has demonstrated real potential in combination regimens with immune checkpoint inhibitors such as Yervoy (ipilimumab). Those data, in particular, have sparked the present resurgence of interest. It will be some time yet, however, before Imlygic will have any competition.