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Since this blog post was first published, Clover has announced positive efficacy data from its Phase 2/3 trial (September 2021), with the full dataset published in The Lancet.
We also expanded our partnership with Clover in November 2021 to support development of Clover's vaccine candidate for primary vaccination across all age groups (pediatric, adolescent, adults, and elderly) and development as a potential booster.
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Clover Biopharmaceuticals' COVID-19 vaccine candidate (SCB-2019) is the latest to join the growing COVAX portfolio of vaccines.
It follows in the footsteps of the CEPI-supported Oxford/AstraZeneca, Moderna, and Novavax COVID-19 vaccine programmes — of which contribute, or are set to contribute, hundreds of millions of doses of their candidates to our scheme to protect priority populations worldwide.
Through an agreement signed by COVAX co-lead, Gavi, Clover is set to make over 400 million doses of its vaccine candidate available for procurement in 2021 and 2022, pending Emergency Use Listing (EUL) from the World Health Organization (WHO). An initial 64 million doses of this vaccine are expected to be available by the end of 2021. The candidate could also be one of the first protein-based COVID-19 vaccines to be distributed through the global mechanism.
By investing early in the promising vaccine technology, and ‘baking in' access commitments into our contracts, CEPI has been able to catalyse the development of and equitable access to Clover's vaccine candidate.
In this blog, we take a closer look at CEPI's collaboration with Clover, some of the additional CEPI programmes it leverages, and the potential advantages of Clover's innovative vaccine technology, which could strengthen global efforts to end the acute phase of this devastating pandemic.
CEPI's rapid response to COVID-19
CEPI moved with urgency early on in the pandemic to accelerate the R&D needed to develop safe and effective COVID-19 vaccines, at speed.
Clover became the ninth COVID-19 vaccine developer to partner with CEPI in Spring, 2020, after submitting their proposal to CEPI's COVID-19 vaccine call launched earlier in the year.
CEPI's decision to invest in any COVID-19 vaccine candidate is based on scientific promise, and our core criteria of speed, scale, and access. We also worked to build a portfolio that is deliberately diverse, composed of different types of vaccine candidate—from mRNA and DNA vaccines to protein-based vaccines like that developed by Clover.
Within a month of the virus sequence becoming available in, January 2020, scientists at Clover had produced a vaccine candidate ready for testing, meeting CEPI's "speed" requirements. Clover also had in-house bio-manufacturing capabilities to rapidly scale-up the production of its vaccine, thereby satisfying our criterion for "scale". And both CEPI and Clover jointly recognised that the fast-spreading pandemic needed a global solution and were dedicated to enabling equitable access to future doses.
We knew from the outset of the fast-spreading outbreak that we needed a diverse portfolio if we were to have maximal chance of getting vaccines to licensure.
Clover ticked all the right boxes and its protein-based vaccine became an important addition within CEPI's COVID-19 toolbox. It was also an important project where we could not only provide funding and expertise, but also access to additional resources, through our other vaccine partnerships, to expedite the development process.
With the knowledge that the spike protein in SARS-CoV-2, and similar viruses, naturally occurs as a trimer (a molecule consisting of three identical parts), the S-Trimer vaccine uses Clover's innovative Trimer-Tag© technology to display the spike protein in its natural three-part form, leading to a potentially better immune response.
CEPI made its first investment in this technology in April, 2020, providing $3.5 million to support Phase 1 studies to assess the vaccine's safety.
An additional $66 million upfront funding was provided at-risk in July 2020 to expand the biotech's preclinical and clinical testing, and to prepare sites for a late-stage vaccine efficacy trial. This investment also increased Clover's manufacturing capacity to potentially allow for the production of hundreds of millions or even a billion doses per year.
While still under clinical development, the agreement between CEPI and Clover also recognised the expectation for vaccine output funded by CEPI's investment to be allocated through COVAX for global equitable distribution.
'Baking in' access agreements to our COVID-19 vaccine partnerships early on has been critical in now enabling fair allocation of these life-saving tools worldwide.
Follow-up investments
As promising preclinical and Phase I trial COVID-19 S-Trimer vaccine data became available, CEPI expanded the partnership in November, 2020 and again in November, 2021 to assess the potential vaccine candidate as a booster. To date, CEPI's total investments in Clover's COVID-19 vaccine is up to $397.5 million[1].
The new funding supports SPECTRA, Clover's global Phase II/III clinical trial to generate the necessary safety and efficacy data to support potential licensure of the vaccine.
The study is currently evaluating the vaccine's performance, as a two-dose regimen combining Clover's vaccine and two adjuvants, including Dynavax's CpG 1018 adjuvant, enabled through a separate CEPI partnership.
Named after the Latin word "adjuvare", meaning "to help" or "aid", adjuvants are substances which can be added to vaccines to enhance the immune response. They can also reduce the amount of drug substance required per dose, allowing for more vaccines to be produced and available for global distribution.
In total, SPECTRA is expected to enroll over 22,000 adult and elderly participants across Latin America, Asia, Europe, and Africa, with interim data anticipated in the coming months.
Access to populations worldwide
The new agreement between COVAX and Clover will further support low-income and middle-income countries so that they can protect the most vulnerable members of their societies against COVID-19.
Subject to receiving EUL, Clover's vaccine will be made available as a two-vial, two-dose programme. Mixing of the two vials (one including the drug substance and another including the adjuvant) will occur at vaccination sites, ahead of administration, as occurs for other vaccines.
All the vials being used by Clover have been secured through a partnership between CEPI and the Italian-based Stevanato Group, and can each hold up to 20 doses of COVID-19 vaccine.
Anticipating that the supply of glass vials would become limited, CEPI secured enough vials, back in June 2020, to store 2 billion doses of vaccines and has made these available to its vaccine-development partners.
Responding to variants and future pandemics
Given the emergence of SARS-CoV-2 variants, which threaten to impact the global vaccine rollout, Clover is also ready to adapt its technology to work against variants of concern, with the option for COVAX to access its variant-adapted vaccines.
As well as its potential to protect against COVID-19, Clover's innovative technology could also work as a targeted ‘plug-and-play' platform that can be quickly adapted to respond to known viruses, such as HIV and flu.
It could also be used against pathogens being prioritised by CEPI as part of our forward-looking $3.5 billion plan to prevent future epidemics and pandemics, like Lassa fever and Ebola, or even a future ‘Disease X'.
As part of its longer-term mission, CEPI aims to transform how the world responds to the next novel threat. By building on technological innovations technologies, like that of Clover, CEPI aims to significantly reduce global vulnerability to emerging infectious diseases and rapidly speed up vaccine development timelines.
Clover's collaboration with CEPI exemplifies the need for critical early-stage investments in R&D and manufacturing to speed up and enable access to life saving vaccines for the benefit of all.
This blog post is also available to read in Chinese.
Find out more about our partnership with Clover in this downloadable Case Study.
[1] In November 2020 CEPI announced an expanded partnership with investment of up to $328m. In June 2021 CEPI funding was increased by up to $32.8m to a total of up to $360.5m. This additional funding was approved to support additional CMC associated with the use of CpG and alum as an adjuvant. In November 2021, CEPI announced additional funding to develop Clover's vaccine candidate as a primary vaccination for all age groups (pediatric, adolescent, adults and elderly) and as a potential booster for previously-infected individuals and populations that have received the vaccine candidate as their primary vaccination.
CEPI statement: CEO welcomes Emergency Use Listing for NVX-CoV2373
CEPI and Clover expand partnership for COVID-19 vaccine to include evaluation as a booster
