DUBLIN – Merck & Co. Inc. is placing two separate bets on recombinant viral vector technology in a broad effort to tackle COVID-19, in which it is also in-licensing a small-molecule antiviral drug. Kenilworth, N.J.-based Merck is acquiring Austrian vaccine developer Themis Bioscience GmbH in a move that propels the latter firm’s COVID-19 vaccine program to the front ranks of the industry pipeline. It is entering a COVID-19 vaccine development collaboration with the not-for-profit vaccine research organization IAVI. And it is collaborating with Ridgeback Biotherapeutics Inc. on the development of an oral antiviral drug, EIDD-2801, now in phase I development, which has previously exhibited in vivo efficacy against influenza virus.
Merck’s entry into the COVID-19 vaccine space is somewhat belated when compared with most of its big pharma peers, but it is noteworthy given its storied history in vaccine development and its considerable clinical development and manufacturing muscle. “This has greatly increased our chances of being successful with our vaccine,” Erich Tauber, CEO of Vienna-based Themis, told BioWorld. Financial terms are not being disclosed, but the consideration must surely be a multiple of the €65 million (US$71 million) in equity funding Themis raised during its 10 years as an independent company. Themis has also secured more than $100 million in grant and contract funding from the Oslo, Norway-based Coalition of Endemic Preparedness Innovations (CEPI), including $4.9 million to kickstart an effort in COVID-19 that also involves its long-time partner, The Pasteur Institute in Paris, as well as The Center for Vaccine Research at the University of Pittsburgh.
That effort involves the development of a vaccine based on a live attenuated measles virus (MV) vector, originally developed at The Pasteur Institute, which Themis has licensed for use across all of its programs. Merck has had visibility of that technology for some time, having entered a deal on an undisclosed program, worth up to $200 million, last August. Merck subsequently participated in Themis’s $44 million series D round, which was earmarked for a phase III trial of its candidate vaccine against Chikungunya virus (MV-Chik). That has been parked for now, but when Themis was seeking further support for its COVID-19 program, it “was, of course, logical to discuss it with them.”
Significantly, Merck has, in addition to the transaction agreement with Themis, signed a memorandum of understanding with Themis, CEPI and The Pasteur Institute setting out their joint commitment to making the vaccine available on a global basis, based on medical need and with pricing appropriate to the income levels of the countries involved. The clarity of that position is in sharp contrast to that of Paris-based Sanofi SA. The French government forced the latter firm to retract a statement from CEO Paul Hudson, who had earlier indicated that the U.S. would probably be the first in line to gain access to its COVID-19 vaccine, should it gain approval, because of the funding it received from the U.S. Biomedical Advanced Research and Development Authority (BARDA). “The Sanofi statement two weeks ago was, I believe, a shock for France,” Tauber said.
Merck’s collaboration with IAVI is also getting BARDA funding. It also involves a live, attenuated viral vector – a proven platform, with which it is already highly familiar. The recombinant vesicular stomatitis virus (VSV) vector, which will form the basis of their joint initiative in COVID-19, is the same technology underlying its Ebola Zaire virus vaccine, Ervebo, which has received approvals from the FDA, the European Union and from the regulatory authorities in Burundi, the Democratic Republic of the Congo, Ghana and Zambia.
Clinical trials this year
Ervebo was originally developed at the Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg. IAVI has itself been working with the technology for more than a decade and, prior to the emergence of SARS-CoV-2, it had VSV-based vaccine programs in preclinical development for Lassa virus, HIV and Marburg virus. The fact that the platform has a regulatory approval under its belt will aid development of a SARS-CoV-2 vaccine, Swati Gupta, vice president and head of emerging infectious diseases and scientific strategy at New-York-based IAVI, told BioWorld. “It allows us to leverage that information,” she said. Gupta has direct experience of Ervebo, having been involved in the development and deployment of the vaccine during the 2014-2016 Ebola epidemic in West Africa, during which time she was executive director at Merck Vaccines.
The COVID-19 vaccine is likely to have similarities and differences to its predecessor. “We envision it potentially as a one-dose vaccine, similar to Ervebo,” Gupta said. “We think that is one of the strong attractions of the program.” Ervebo is administered by intramuscular injection, whereas IAVI is evaluating an oral formulation as well as intramuscular injection, should shortages of needles or syringes arise. The biggest drawback with Ervebo is the need to store the vaccine at -80°C to -60°C. “We’re definitely looking to improve the cold-chain requirements,” Gupta said.
Both vaccines are still in preclinical development and are due to enter clinical trials later this year. Merck is also gearing up to take forward EIDD-2801, which is currently undergoing a phase I trial in 122 healthy volunteers. Recruitment is underway in the U.K., but has yet to start in the U.S. EIDD-2801, a ribonucleoside analogue, inhibits the replication of multiple RNA viruses. Merck’s move on EIDD-2801 validates a development program that became ensnared in the political controversy surrounding the recent ouster of former BARDA director Rick Bright, as reported by Science on May 13. Pending sight of phase I data, Bright had reportedly resisted pressure to provide BARDA funding for the program, which had already received $26 million in NIH and Department of Defense funding while still in development at Emory University’s Drug Innovations at Emory LLC arm.
Miami-based Ridgeback then licensed the molecule from Emory in March. Financial terms of the present deal were not disclosed, but Ridgeback will receive an up-front payment as well as potential milestones and sales royalties. EIDD-2801 is an orally available prodrug of beta-D-N4-hydroxycytidine (NHC; EIDD-1931), which, Timothy Sheehan, Ralph Baric and colleagues at the University of North Carolina, Chapel Hill and Emory University, recently reported exhibits in vitro activity against SARS-CoV-2 and activity in mice infected with a range of coronaviruses. The data appeared in Science Translational Medicine on April 29, 2020. Richard Plemper, of Georgia State University in Atlanta, and colleagues previously reported, in the Oct. 23, 2019, issue of the same journal that it had therapeutic effects in ferrets infected with influenza.