Merck & Co. signaled its intent to become a leading presence in the scramble to develop COVID-19 drugs and vaccines through three initiatives it announced today: An agreement to acquire its Austrian collaboration partner in infectious disease and cancer therapeutics, Themis; a partnership with Ridgeback Therapeutics to develop its SARS-CoV-2 drug; and a new alliance with IAVI on a vaccine to prevent the virus.
Merck said it agreed to acquire privately-based Themis for an undisclosed price. Vienna-based Themis has built a pipeline of vaccine candidates and immune-modulatory therapies developed using its measles virus vector-based platform.
That platform is based on a vector originally developed by scientists at the Institut Pasteur and first licensed by Themis from the institution in 2010. Since then, the platform has been incorporated into vaccine development programs against infectious diseases that include SARS, Chikungunya, MERS, and Lassa fever.
In March, Themis expanded into COVID-19 when it joined the Institut Pasteur and The Center for Vaccine Research at the University of Pittsburgh to develop a vaccine candidate designed to prevent the disease by targeting SARS-CoV-2. That partnership has been funded by an initial $4.9 million from the Coalition for Epidemic Preparedness Innovations (CEPI).
In connection with the acquisition, Merck, Institut Pasteur, and CEPI have entered into a memorandum of understanding in which they agreed to address the COVID-19 pandemic by developing, manufacturing, and distributing the vaccine on a global basis, with “pricing that makes the vaccine both available around the world and accessible to those who need it, including low-income, middle-income and high-income countries based on the medical need when the vaccine may become available.”
“Building on the pioneering work of the Institut Pasteur, the Themis team has established specialized expertise that complements Merck’s own capabilities in the discovery, development, manufacturing and global distribution of vaccines,” Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, said in a statement. “We are eager to combine our strengths both to develop an effective COVID-19 vaccine in the near term and to build a pandemic preparedness capability directed toward emerging agents that pose a future epidemic threat.”
The companies’ COVID-19 vaccine candidate is in preclinical development, with clinical studies planned to start later in 2020, Merck added.
In August 2019, Merck and Themis agreed to collaborate on developing vaccine candidates based on Themis’ measles virus vector-based platform, through the Austrian biotech’s first-ever collaboration with a major biopharma. Speaking with GEN at the time, Themis CEO Erich Tauber, MD, would not disclose what indications the companies were focusing on.
“What I can say is the measles virus vector technology allows to exploit infectious diseases and cancer indications, and when it comes to infectious diseases, we use the measles virus to bring our specific antigens into the body. Those might be difficult to express in normal cell systems,” Tauber said. “Another advantage is we can use exactly the same manufacturing process for each new vaccine target.”
Through a subsidiary, Merck agreed to acquire all outstanding shares of Themis in exchange for an undisclosed cash payment. Upon completion of the deal Themis will become a wholly-owned subsidiary of Merck.
Closing of the acquisition deal is subject to the expiration or earlier termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, merger control clearance in Austria, and other customary conditions.
“We are excited for the next phase of our relationship with Merck and in the near-term look forward to focusing resources toward the development and global scale-up of our candidate SARS-CoV-2 vaccine,” Tauber stated today.
In a note to investors, Daina M. Graybosch, PhD, a Senior Research Analyst at SVB Leerink covering Immuno-Oncology, observed that Merck aims to mitigate scientific, scale, and safety platform risk by working with Themis and IAVI on recombinant viral vector vaccine programs—rather than programs based on RNA, where Merck has clinical experience though collaborations with Moderna.
“For a vaccine, we believe Merck is aiming for high antibody titers and durability with a single shot,” Graybosch wrote. “Though they are behind RNA-based vaccine programs from Moderna and BioNTech / Pfizer, we believe Merck’s reliance on more established technology and global clinical trial, manufacturing, and distribution capabilities could make it the tortoise in this race.”
Antiviral approach with Ridgeback
Merck also said it agreed to partner with Miami-based Ridgeback Therapeutics to develop EIDD-2801, an oral antiviral candidate now in a Phase I clinical trial against COVID-19.
EIDD-2801 is an orally bioavailable NHC-prodrug (Beta-D-N4 hydroxycytidine-5’-isopropyl ester), a direct acting anti-viral nucleoside analogue designed to inhibit replication of multiple RNA viruses including SARS-CoV2. EIDD-2801 was invented at Drug Innovations at Emory (DRIVE), a not-for-profit biotechnology company wholly owned by Emory University.
Ridgeback has been recruiting patients for the Phase I trial (NCT04392219), a randomized, double-blind, placebo-controlled, first-in-human study designed to evaluate the safety, tolerability, and pharmacokinetics of EIDD-2801 following oral administration to healthy volunteers. The trial began in April, has an estimated enrollment of 122 participants, and an estimated primary completion date of June 16.
Ridgeback and DRIVE announced their collaboration to rapidly advance EIDD-2801 into human trials in March. At the time, Ridgeback agreed to advance EIDD-2801 through clinical development and ensure that it is available during the pandemic.
Ridgeback’s COVID-19 activity is one of more than 90 efforts that GEN is “Keeping an Eye On” among the more than 200 candidates listed in the recently-launched COVID-19 DRUG & VACCINE CANDIDATE TRACKER, a comprehensive collection of news, milestones and more timely updates on more than 200 drug and vaccine candidates currently being developed for the COVID-19 pandemic.
Through the collaboration, Ridgeback has exclusively licensed EIDD-2801, which has shown broad spectrum activity against influenza, SARS, MERS, chikungunya, and equine encephalitis. On April 6, Timothy P. Sheahan, PhD, and Ralph Baric, PhD, both at The University of North Carolina at Chapel Hill, and colleagues from there, Emery, Vanderbilt University Medical Center, and the U.S. Centers for Disease Control and Prevention published a study in Science Translational Medicine reporting that both prophylactic and therapeutic administration of EIDD-2801 in mice infected with SARS-CoV or MERS-CoV improved pulmonary function, and reduced virus titer and body weight loss.
The study was published two weeks after the researchers disclosed their results in a preprint.
“Since preclinical studies demonstrate that EIDD-2801 has potent antiviral properties against multiple coronavirus strains including SARS-CoV-2, we are eager to advance the next phase of clinical studies as rapidly and responsibly as possible,” Perlmutter stated. “Clinical evaluation of EIDD-2801 in COVID-19 patients is just beginning, now that Phase I studies have demonstrated that the compound is well-tolerated,”
Through a subsidiary, Merck will gain exclusive worldwide rights to develop and commercialize EIDD-2801 and related molecules. Ridgeback Bio will receive an undisclosed upfront payment, specified milestones and a share of the net proceeds of EIDD-2801 and related molecules, if approved. Merck has agreed to oversee clinical development, regulatory filings and manufacturing.
Merck and Ridgeback said they committed to ensure that any medicines developed for SARS-CoV-2 “will be accessible and affordable globally.”
Vaccine collaboration with IAVI
Separately, Merck said it has launched a COVID-19 vaccine collaboration with IAVI, a nonprofit scientific research organization dedicated to addressing urgent, unmet global health challenges.
The vaccine candidate will use the recombinant vesicular stomatitis virus (rVSV) platform, which uses an attenuated strain of vesicular stomatitis virus, a common animal virus that has been modified to express proteins that stimulate an immune response. The rVSV platform is the basis for Merck’s Ebola Zaire virus vaccine, ERVEBO® (Ebola Zaire Vaccine, Live), the first rVSV vaccine approved for use in humans.
“We believe an rVSV-based vaccine strategy represents a promising approach to combating the novel coronavirus pandemic and look forward to implementing an accelerated development program, together with Merck, to evaluate the potential of our vaccine candidate against SARS-CoV-2,” IAVI President and CEO Mark Feinberg, MD, PhD, said. “The collaboration between Merck and IAVI represents an innovative partnership model and approach to utilize our joint capabilities in complementary and synergistic ways to address this difficult global health challenge.”
IAVI said its rVSV vaccine preclinical development, including work on the SARS-CoV-2 vaccine candidate, is being done by scientists at IAVI’s Design and Development Laboratory in Brooklyn, NY. The program is part of IAVI’s longstanding effort to develop rVSV vaccines for HIV as well as other emerging infectious diseases such as Lassa fever, Marburg, and Ebola Sudan disease, an effort led by Swati Gupta, DrPH, IAVI’s head of Emerging Infectious Diseases and Scientific Strategy.
Merck said it had signed an agreement with the Biomedical Advanced Research and Development Authority (BARDA), which disclosed that it agreed to provide the company and IAVI $38,033,570 in initial funding support.
“We are encouraged by the willingness of our private sector counterparts to come together as force multipliers to expedite vaccine development and to help save lives,” added BARDA Acting Director Gary Disbrow, PhD.
Until now, Merck’s COVID-19-related activity had been limited. The company’s Ivermectin–marketed under the names Stromectol® and Mectizan®, but also available as a generic drug—is under study by Monash Biomedicine Discovery Institute (BDI) and Peter Doherty Institute of Infection and Immunity. In April, they published a preprint study in Antiviral Research showing that Ivermectin essentially stopped the SARS-CoV-2 virus growing in cell culture within 48 hours, and reduced viral RNA significantly at 24 hours.
In March, Merck announced donations of 500,000 protective masks for New York City healthcare workers and first responders, and 300,000 masks for New Jersey’s Office of Homeland Security and Preparedness.