DUBLIN – Themis Bioscience GmbH closed a €40 million (US$44.3 million) series D round that will enable it to complete an imminent phase III trial of a candidate vaccine for Chikungunya virus, MV-Chik, and to undertake its first clinical studies of its measles virus vector in oncology indications.
Almost a year after the Vienna-based firm pulled a €55 million IPO from the Euronext Exchange in Amsterdam, the company has found support from the private equity markets. "This is more or less the replacement transaction," Themis CEO Erich Tauber told BioWorld.
In addition, it has also secured funding commitments of $21 million for the phase III program from the Coalition for Epidemic Preparedness Innovations (CEPI), a public-private partnership established in 2016 by the governments of India and Norway, the Bill & Melinda Gates Foundation, the Wellcome Trust and the World Economic Forum, and from the European Union's Horizon 2020 research program. "We are now nicely financed to complete our phase III plans."
Themis will undertake the study in several thousand volunteers in the U.S., Latin America and Europe. Tauber would neither be drawn on the precise timing of the trial nor on its protocol, given the competitive dynamic introduced to Chikungunya virus vaccine development following the FDA's decision last year to add the Chikungunya infection to its priority list of tropical diseases. First to market will receive a tradable priority review voucher, which could be worth about $100 million. "It's our understanding that we are in the lead," Tauber said. A precise picture of the present state of play is not clear, however. "There's only so much we know about the competition."
Paxvax Inc., of San Diego, is about to start a second phase II trial of a Chikungunya virus-like particle vaccine, PXVX-0317, in collaboration with the Walter Reed Army Institute of Research. A phase II dose-and-formulation-finding study in 450 healthy volunteers is already underway. The second study will assess the safety and immunogenicity of an alum-adjuvanted formulation of the vaccine, which received FDA fast track designation in May 2018.
Valneva SE, of Lyon, France, is in phase I testing with VLA-1553, a single-dose live attenuated vaccine, which maintained a 100% seroconversion rate almost five months after immunization. It, too, has received CEPI funding. The vaccine, which received FDA fast track designation last December, is based on an attenuated infectious Chikungunya virus clone (CHIKV LR2006-OPY1). Themis received a similar designation in February.
Cambridge-based Moderna Inc. has completed a phase I trial with an mRNA-based vaccine, mRNA-1388, as part of a collaboration with the Defense Advanced Research Projects Agency (DARPA). It also reported phase I data this week for a second candidate therapy, mRNA-1944, which encodes an antibody directed against the virus.
First identified in Tanzania in the 1950s, Chikungunya virus is a mosquito-borne infection whose symptoms can be confused with those of Dengue virus and Zika virus. Given the sporadic, unpredictable and rapidly resolving nature of disease outbreaks, it is not feasible to conduct field studies of the virus. Developers need to demonstrate immunogenicity in healthy volunteers and then to establish correlates of protection through passive and active immunization studies in nonhuman primates. "We are very advanced in the regulatory discussion," Tauber said.
Cancer programs coming up
Meanwhile, the company is also embarking on its first clinical studies in oncology indications, using the same attenuated Schwarz strain of measles virus as a therapeutic vaccine. In cancer, Themis is not raising an immune response against selected tumor antigens but is exploiting the measles virus' affinity for CD46, an extracellular receptor whose expression is elevated in many different types of cancer.
Its first trial, in colorectal cancer, involves a version of the virus engineered to produce an enzyme that converts a prodrug of 5-fluorouracil to its active form. The idea is to generate high, localized concentrations of the chemotherapeutic agent within the tumor microenvironment. "As the virus will be applied directly into the tumor, the virus will replicate in the tumor," Tauber said.
That initial study is due to get underway either before year-end or early in 2020. Two other cancer programs, in glioblastoma and triple-negative breast cancer, are following. Each is engineered to produce an immunomodulatory protein. At least one should reach the clinic by around mid-2020, Tauber said.
Themis has now raised some €65 million in equity funding. The latest round was co-led by Farallon Capital and Hadean Ventures. Other new investors included Merck & Co. Inc., of Kenilworth, N.J. – as part of a recent licensing agreement – and Adjuvant Capital. Existing shareholders Global Health Investment Fund, AWS Gruenderfonds, Omnes Capital, Ventech and Wellington Partners Life Sciences, also participated. Hadean Ventures managing partner Walter Stockinger is joining the Themis board.