LONDON – A veteran of the European vaccines industry has brought together three companies in three countries, in what is described as an ultra-fast-track COVID-19 vaccine development program.
From a standing start less than three months ago, the three biotechs, Reithera Srl in Rome, Leukocare AG in Munich, Germany, and Univercells SA in Brussels, Belgium, have advanced to GMP manufacturing, with first-in-human studies due to start in June.
The collaboration was fostered by Jean-Paul Prieels, former head of Glaxosmithkline plc’s vaccine division in Rixensart, Belgium. During more than 23 years at the company he was instrumental in the introduction of modern adjuvants and the development of several marketed vaccines, including Synflorix for the prevention of pneumococcal infections and Rotarix, which protects against rotavirus infections.
“We have not worked together before,” said Michael Scholl, CEO of Leukocare. “The link, as is often the case, is one single person – Jean-Paul Prieels. He is on the board of all three companies,” Scholl told BioWorld.
The three have come together to develop an adenoviral vector vaccine delivering the genetic code for the spike protein though which SARS-CoV-2 infects host cells.
Leukocare’s role is in developing a stable liquid formulation based on its platform of established excipients and artificial intelligence tools, while Univercells will adapt and scale up GMP production using its Nevoline process intensification technology.
“We are now preparing GMP material for the first clinical trial. The next stage is toxicology and preclinical research,” Scholl said.
Reithera is in discussions with contract research organizations on the design and conduct of the study, to be carried out in Italy, one of the countries most badly affected by the pandemic, with 184,000 confirmed cases and 24,648 deaths. The Italian government is supporting the trial.
At the same time as moving toward the clinic, the consortium will start manufacturing the vaccine at pilot scale. Approximately 6 million doses will be available by early 2021, if it is found to be safe and immunogenic in the phase I/II study, and an emergency use program will be set up to vaccinate at-risk people, such as health care professionals.
To date, the companies have funded the work themselves, but Scholl said they are now looking for backing from bodies such as the Gates Foundation, the Coalition for Epidemic Preparedness Innovation, national governments and the EU.
“The three partners decided to fund the work internally for the first steps because we didn’t want to wait for external funding,” Scholl said. “In parallel, we are talking to different organizations. We’re pretty optimistic we’ll find funds, the feedback is positive.”
Reithera’s proprietary gorilla adenoviral vector has been evaluated in phase I and phase II trials in oncology indications and also in respiratory syncytial virus infection, where it was strongly immunogenic. Based on that, the aim is to develop a single-dose vaccine.
The management team at Reithera has been involved in the field of viral-vectored vaccines since 2002. In 2007, they formed Okairos AG, which Glaxosmithkline acquired in 2013 for $321 million.
That expertise and the positive preclinical and clinical data on its adenoviral vaccine “allows us to react to this unprecedented situation in a prompt and timely [way],” said Stefano Colloca, chief technology officer.
mRNA vaccines ‘particularly suited’
In another example of the remarkable speed with which COVID-19 vaccines are reaching the clinic, Biontech SE announced the German regulator the Paul Ehrlich Institute has approved the phase I/II program for its mRNA vaccine candidates. That is a mere 12 weeks since the start of the program on Jan. 29, and just 11 days after applying for permission on April 9. FDA approval also is imminent.
In the phase I/II, Biontech will test four different candidates, each using different mRNA formats and target antigens.
Two of the four have nucleoside modified mRNA, another has a uridine containing mRNA, while the fourth uses a self-amplifying mRNA construct. The first three will be administered in two doses, the fourth in a single dose. All four are lipid nanoparticle formulations.
The chemical modifications prevent the immune system from recognizing the introduced mRNA as foreign and blocking production of the antigens which it encodes.
The modification technology, developed by Drew Weissman, an immunologist at the University of Pennsylvania, is intended to overcome one of the key barriers that have held back use of mRNA in infectious diseases, opening the door to benefits including faster and cheaper manufacture and the ability to elicit a potent and long-lasting immune response.
“We and many others believe that mRNA is particularly suited for pandemic vaccines,” said Ugur Sahin, CEO and co-founder of Mainz, Germany-based Biontech.
In addition to different chemical modifications, the candidate vaccines will deliver different mRNA sequences, with two carrying the code for the spike protein via which SARS-CoV-19 invades the host cell, and two carrying the sequence for the smaller receptor binding domain of the spike protein.
The dose-escalation phase will include 200 healthy subjects, ages 18 to 55, and will use a dose range of 1 mcg to 100 mcg.
“We are using established mRNA technologies, validated for immunogenicity and safety in oncology indications,” said Sahin. The goal is the induction of a long-term immune response, he told listeners of a teleconference held to discuss the trial.
In preclinical development, all three double-dose candidates generated a strong antibody and CD8 and CD4 T-cell response.
The self-amplifying mRNA construct, which uses replicase to catalyze replication of RNA, elicited very strong antibody and T-cell responses at doses 60 times lower that the uridine-modified candidate. Unlike the three other candidates, the self-amplifying product has not been in clinical studies before.
Sahin said all four candidates will be tested in the phase I/II study. It is possible that two, or even three could be taken forward if the results are positive.
“The decision will be based on overall observations. In principle, we are open to continuing with [more than one]. We may get different responses, for example in elderly people,” he said.
Sahin declined to discuss timelines, saying it is not appropriate at this stage. “We have first of all to see if the vaccine is safe. We know how fast we can move ahead, but we don’t know the requirement for applying it yet.”
Similarly, he declined to comment on the commercial prospects if the company gets a vaccine through to approval.
Biontech has signed commercialization deals with Pfizer Inc. and Fosun Pharmaceuticals Ltd. for the COVID-19 vaccine program, receiving a total of $250 million up front. With the partners responsible for most of the development costs, Biontech has sufficient near-term funding for the clinical program. However, Ryan Richardson, chief strategy officer, said the company is planning to “address the [capital expenditure] needs” to scale up manufacturing.