DUBLIN – Curevac AG has entered a global alliance with Bayer AG to accelerate its efforts to bring a third, desperately needed mRNA-based COVID-19 vaccine to market. The vaccine in question, CVnCoV, began a pivotal phase IIb/III trial on Dec. 14. The study has a recruitment target of 36,500 participants. Given the extraordinarily high levels of SARS-CoV-2 now circulating in many regions of the globe, hitting that target in a relatively short time frame should be feasible.

The company hopes the trial will log a sufficient number of infections to generate statistically significant data before the end of the first quarter. It then aims to submit a marketing authorization application early in the second quarter and could gain approval shortly after that, Curevac CEO Franz-Werner Haas told BioWorld. The file would be based on efficacy data and early safety data from the pivotal trial, as well as safety and efficacy data from a European phase I trial and a phase IIa trial in Panama and Peru, which completed recruitment of 670 volunteers in December.

Franz-Werner Haas, CEO, Curevac

It’s no great surprise that Tübingen, Germany-based Curevac has turned to a larger partner as it nears a potential rollout. Its choice of Leverkusen, Germany-based Bayer is surprising, however, given that Bayer has no track record in the development, production, registration or distribution of vaccines. Curevac entered a multiprogram alliance with London-based Glaxosmithkline plc, an established vaccine player, last July, but that agreement explicitly excluded CVnCoV.

“The clinical development path is quite clearly laid out,” Haas said. “We are pretty sure that this is safe and tolerable.” Curevac has partnered with Bayer to gain access to its global infrastructure and network. It will contribute its capabilities in clinical operations, regulatory affairs, pharmacovigilance, medical information and supply chain performance. “We are considering whether there can be a manufacturing component as well,” he said.

Financial terms were not disclosed. The agreement is global in scope, but the initial focus is on Europe, while Latin America and parts of Asia are also likely markets. The U.S. is not explicitly excluded, but it is not a priority given the wide range of purchase agreements the administration has already entered. “It’s well covered,” Haas said. Curevac will be the marketing authorization holder for the vaccine once it gains approval, while Bayer has options to become the authorization holder for selected markets outside of Europe.

The most pressing concern for all vaccine makers is the current uncertainty about whether their products will offer high levels of protection against newly emerging variants, such as the B1.1.1.7 and the 501.V2 variants identified in the U.K. and South Africa, respectively. If new vaccines are needed against those or other strains, a full development program may not be necessary – the development of novel seasonal influenza vaccines every year offers a precedent. “You’re not doing for each seasonal ‘flu vaccine a phase I, II, III clinical trial,” Haas said.

Curevac has in-house production capabilities at its Tübingen site but is also building a network of alliances to bring CVnCoV to market. So far, it has signed agreements with Munich-based Wacker Chemie AG and Luxembourg-based Fareva SA. Wacker will produce active substance at its vaccine production facility in Amsterdam, while Fareva is conducting fill-finish operations at two sites in France, Pau and Val de Reuil. The Wacker agreement entails 100 million doses per year initially, although there is scope for expansion. And more such agreements are to follow, Haas said. They will be based on cloning its existing GMP III facility.

The European Union could account for much of Curevac’s initial supply. Curevac entered an advance purchase agreement with the European Commission in November, which involves up to 225 million doses initially, with an option for a further 180 million doses.

Based on its present plans, which it set out in November, Curevac is still a second-tier player in volume terms, however. It plans to produce 300 million doses this year and another 600 million doses in 2022. The developers of the other two mRNA COVID-19 vaccines are scaling more aggressively. New-York-based Pfizer Inc. and Mainz, Germany-based Biontech SE plan to produce to up 1.3 billion doses this year, while Cambridge, Mass.-based Moderna Inc. will produce an estimated 600 million doses of its vaccine, COVID-19 Vaccine Moderna, this year but may be able to scale to 1 billion doses.

But Curevac is also actively considering how to scale production further, with Bayer and others. Curevac is itself building an in-house, large-scale GMP IV production facility, which will cover all steps from initial material to formulation. It will have annual capacity for 1 billion doses when it comes onstream in mid-2022.

Should it prove to be safe and efficacious, Curevac’s vaccine offers considerable production and distribution advantages over those two vaccines. It appears to be far more potent. The pivotal trial is testing a 2 x 12 mcg dose regimen, whereas the Moderna and Pfizer-Biontech vaccines entail 2 x 100-mcg and 2 x 30-mcg regimens, respectively. Curevac’s vaccine also boasts greater stability. The Pfizer-Biontech vaccine (BNT-162b2, tozinameran, Comirnaty) needs to be stored at -80°C to -60°C and is stable at ordinary refrigeration temperatures for up to five days. Moderna’s vaccine is stored at -25°C to -15°C but can be stored at ordinary refrigeration temperatures for up to 30 days. CVnCoV is generally stable at refrigeration temperature, which reduces logistical complications.