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We all remember the race for a COVID-19 vaccine during the pandemic a few years back. While the German company specializing in mRNA technology, CureVac, was a serious contender in the race with its first-generation COVID-19 vaccine, CVnCoV, it did not come first, and didn’t even finish the race.
Indeed, CureVac faced significant setbacks with its COVID candidates, allowing Moderna and BioNTech to come out as victors in the COVID mRNA vaccine race, and history is often written by the victors. However, like Biogen after it failed with its Alzheimer’s candidate, CureVac managed to turn things around. The company’s recent deal with GSK, worth up to $1.57 billion (€1.45 billion) , has marked a major turnaround and despite failing in 2021, CureVac is far from forgotten.
This article explores CureVac’s challenges, strategies, and the pivotal $1.57 billion deal that reshaped its future.
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The rise and fall of CureVac’s CVnCoV
CVnCoV, CureVac’s first-generation COVID-19 vaccine, was part of the global race to combat the pandemic. Developed rapidly in response to the emerging crisis, CureVac initiated the development of mRNA-based COVID-19 vaccine candidates in January 2020. CVnCoV utilized an optimized, non-chemically modified mRNA encoding the prefusion stabilized full-length spike protein of SARS-CoV-2, formulated within lipid nanoparticles (LNPs).
Early clinical trials began in mid-2020, with phase 1 and 2a trials showing that CVnCoV was generally well tolerated and induced strong antibody responses comparable to those seen in recovered COVID-19 patients. These promising results raised hopes that CVnCoV could be a viable option in the global effort to curb the pandemic.
Despite the promising early-stage data, the pivotal phase 2b/3 HERALD study revealed significant challenges. Conducted in an environment characterized by multiple circulating virus variants, the vaccine showed only 47% efficacy in its interim analysis. The final analysis confirmed a similar efficacy rate of 48%, which fell short of expectations, especially when compared to the highly effective vaccines from Moderna and BioNTech.
Dr. Franz-Werner Haas, CureVac’s chief executive officer (CEO) at that time, noted that the high diversity of variants presented a major challenge in demonstrating high efficacy, underscoring the need for next-generation vaccines to address emerging variants.
CureVac’s approach differed significantly from its competitors. “During the development of COVID vaccines, the main difference was that here at CureVac, we used unmodified or natural mRNA. Both Moderna and BioNTech used modified,” explained Alexander Zehnder, CureVac’s CEO.
However, this unmodified mRNA resulted in lower antibody titers compared to the modified mRNA used by Moderna and BioNTech, which allowed for higher doses and stronger antibody induction. “This unmodified mRNA may be less stable once in the body, leading to lower immunogenicity, and it is hypothesized that other changes the company made to non-coding regions may also affect immunogenicity,” added Meri Beckwith, co-founder of Lindus Health.
“During subsequent clinical evaluation, we found that applications such as vaccines for respiratory disease where primarily high antibody titers are required, favor the use of modified mRNA as it allows administration of higher doses and hence a stronger antibody induction. For therapeutic vaccines in cancer, for example, antibodies are less important, and a heightened T-cell response is more critical. For these applications, unmodified mRNA could be the preferred route,” said Zehnder.
“In the end, these phase 3 data were not enough to continue with development. Clearly, this was a huge disappointment during this time of global crisis, but CureVac already had a second-generation mRNA backbone,” said Zehnder.
CureVac’s response to the setback
Following the disappointing phase 3 results of its first-generation COVID-19 vaccine, CVnCoV, the German company discovered that while the vaccine induced strong immune responses in early trials, its efficacy against emerging variants was insufficient. This led to a comprehensive review of its mRNA technology, focusing on why antibody titers were lower compared to competitors using modified mRNA.
Zehnder, emphasized the importance of this analysis phase, which allowed the company to identify key areas for improvement. “Together with our partner GSK, we successfully extended our technology platform to the use of modified mRNA – a targeted improvement of our second-generation backbone to best address infectious diseases. This new mRNA backbone has now been validated in phase 2 clinical studies with vaccines targeting flu and COVID as part of our partnership with GSK.”
This new backbone was engineered to optimize non-coding regions, thereby improving mRNA stability and translation efficiency. This development was crucial for generating stronger and more durable immune responses.
Zehnder explained a combination of factors helped maintain investor confidence when the company was bested by its competitors in 2021.
“As a pioneer in developing mRNA for therapeutic applications, our investors have always appreciated our strong scientific expertise, our end-to-end mRNA capabilities including manufacturing and the broad applicability of our technology in different therapeutic areas. By very quickly moving to our second-generation mRNA backbone and ensuring clinical validation, we were able to provide investors with valid reasons to remain confident. This was of course supported by the continued backing of our partner GSK.”
The collaboration with GSK was pivotal in CureVac’s strategic pivot. “Our partnership with GSK was instrumental in enabling the clinical development of promising late-stage mRNA vaccine candidates in flu and COVID leveraging our proprietary mRNA platform,” said Zehnder. Less than a month ago, the two companies restructured their deal.
CureVac building on a strong collaboration with GSK to restructure
“Earlier in 2024, we began a process of removing unnecessary residual pandemic infrastructure and better align our structure and resources to the size of our business and pipeline, while maintaining a strong focus on innovation and research and development (R&D),” said Zehnder.
On July 4, 2024, CureVac and GSK renewed the agreement that started in 2020. It included an upfront payment of $434 million, with potential milestones and royalties totaling up to $1.57 billion. This new agreement replaced all previous financial considerations from the prior collaboration between GSK and CureVac, providing a solid financial foundation for CureVac to advance its research and development initiatives.
“With this new agreement, we will apply GSK’s capabilities, partnerships, and intellectual property to CureVac’s technology to deliver these promising vaccines at pace,” stated Tony Wood, chief scientific officer of GSK in the press release.
GSK acquired full control over the development and commercialization of mRNA vaccines for flu and COVID-19. This deal not only validated CureVac’s technology but also ensured that these vaccine programs could be advanced with GSK’s extensive resources and expertise. The agreement included the development of seasonal and avian flu vaccines and flu/COVID-19 combination vaccines utilizing CureVac’s second-generation mRNA technology.
“Licensing the flu and COVID programs to GSK enables us to focus on building a strong R&D pipeline and advancing as a well-funded business in a less complex set-up. At the same time, important programs will be advanced by an established global pharma player – such as the program for avian flu, a virus which is considered a potential future pandemic threat, and which has sporadically crossed species from its original bird host to other animal hosts and humans,” explained Zehnder.
Zehnder added that CureVac’s efforts do not stop at this new deal with GSK. “We recently started further restructuring initiatives following the licensing agreement with GSK. While streamlining the business also includes a workforce reduction, we strongly believe the restructuring will allow for a stronger focus on high-value mRNA opportunities specifically in oncology but also other areas.”
One thing is certain, this deal brings substantial funds into CureVac’s operations. “The significant cash injection from the €400 million ($434 million) upfront payment, up to €1.05 billion ($1.57 billion) in milestones as well as tiered royalties, together with our restructuring, extends our case runway into 2028,” said Zehnder.
What lessons to learn from this journey?
CureVac’s journey highlights the importance of agility and resilience in biotech. After the disappointing phase 3 results of their first-generation COVID-19 vaccine, the company quickly pivoted by conducting analyses and focusing on improving their mRNA technology. This led to the development of a second-generation mRNA backbone aimed at enhancing the translation efficiency of mRNA into proteins, particularly for respiratory diseases.
“Drug development and the biotech industry are inherently challenging. Success in this business takes time and is never linear. So, it’s important to remain agile and react quickly to new data or circumstances,” summarize Zehnder.
Indeed, CureVac’s journey and its deals with GSK are examples of flexibility and reactivity. CureVac hit not two, but three birds with one stone. The deal allows the German company to focus on R&D while bringing financial stability and good odds for the flu and COVID programs licensed to GSK to reach the market.
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