While vaccines from big names such as Pfizer/BioNTech, Moderna and AstraZeneca are rolling out across the world, there are currently 64 vaccines in clinical development, according to the latest figures from the World Health Organization.
Phase 3 candidates from companies such as Johnson & Johnson and Curevac are well-known, but we take a look at some of the earlier-stage candidates coming through the pipeline.
Vaxart's tablet vaccine (VXA-COV2-1)
The vaccine: California-headquartered biotech Vaxart is working on an oral room temperature COVID-19 tablet.
Timeline: Vaxart has completed enrollment and expects to report top-line data for its Phase 1 clinical trial at the end of January. Following potentially positive results, Vaxart intends to initiate a Phase 2 trial in Q1 2021.
Point of difference: Vaxart highlights three key advantages of its vaccine: it doesn’t need needles; is room temperature stable; and could be easily modified to new strains.
“We believe that our vaccine holds the potential to solve the global distribution challenges facing current vaccines,” Sean Tucker, Ph.D., chief scientific officer of Vaxart, told this publication. “Cold-chain supply has proven to be a challenge even in developed countries like the US and has greatly hindered the ability to distribute approved vaccines effectively. Globally it could take years to reach a point where we could effectively break the chain of transmission and eradicate the virus. Our vaccine's advantages make it ideal for global rapid distribution as our vaccine does not require freezers or even a medical professional to administer.
“As the virus continues to spread, we have seen the emergence of novel strains that could potentially be resistant to current vaccines. Unlike the currently approved vaccines, which target the spike (S) proteins, our vaccine also targets the nucleocapsid (N) protein. The S protein is highly subject to mutations and we have already seen this with the new emerging strains. However, the N protein is largely conserved among coronaviruses and has historically been less likely to accrue mutations than the S protein. We believe that targeting the N could be key if the virus continues to change.
“Additionally, our vaccine platform technology is modular, meaning that if a resistant strain emerged, we could rapidly move a new clinical candidate into development.
“Another hurdle we are seeing as COVID-19 vaccine rollout ramps up worldwide is the fear of needles. According to the CDC, about a quarter of adults are afraid of needles, and an estimated 7% of adults avoid immunizations because of that fear which could hamper efforts to end this pandemic. We believe our oral tablet vaccine - which is no larger than an aspirin - could be the answer for those with ‘needle-phobia.’”
The vaccine: New York headquartered COVAXX (a subsidiary of United Biomedical Inc) is using a high precision, multi-antigen peptide platform approach to develop its vaccine: which could be the first multitope peptide-based vaccine for COVID-19. The UBITh Vaxxine Platform has previously been successfully used to develop a vaccine for hand, foot and mouth disease.
Timeline: COVAXX is completing Phase 1 clinical trials of its first COVID-19 vaccine candidate, UB-612, in Taiwan, and will begin Phase 2/3 clinical trials in the first quarter of 2021, in Asia, Latin America and the U.S.
Point of difference: UB-612 is composed of synthetic peptides designed to mimic biology, allowing COVAXX the ability to adapt the production peptide sequence quickly to new virus strains. The company announced this month that it has started preclinical work on a second vaccine candidate to address the latest mutations of the virus (specifically the mutations identified in South Africa – 501Y.V2 - and the UK).
“Furthermore, rather than focusing only on neutralizing antibodies, COVAXX’s vaccine is designed to activate both humoral and cellular immunity for greater efficacy," says the company. "As it is composed with synthetic peptides, rather than live virus, the UBITh Vaxxine Platform should pose no biohazard risk and is stable, allowing for a highly scalable manufacturing process. If approved, COVAXX plans to manufacture 100 million doses of UB-612 during early 2021 in Taiwan, and a billion doses by the end of 2021.”
“COVAXX vaccines are stable at 2-8 degrees C and can be delivered via existing distribution infrastructure and normal refrigeration.”
Codagenix's nasal vaccine (COVI-VAC)
The vaccine: New York headquartered Codagenix is developing an intranasal live attenuated vaccine
Timeline: The vaccine entered Phase 1 clinical trials in the UK this month.
Point of difference: As well as avoiding the use of needles, Codagenix believes a nasal vaccine is a good fit against SARS-CoV-2 because of the virus' airborne transmission."A nasal drop, such as what COVI-VAC employs, allows the vaccine to be administered directly to the nasal mucosa, which is where the initial SARS-CoV-2 virus infection occurs. Thus, COVI-VAC offers the potential to elicit an immune response at the point of virus entry, which could help to minimize the ability of SARS-CoV-2 to initially replicate," a spokesperson told this publication.
"As a live attenuated vaccine, COVI-VAC has the potential to provide a broader immune response in comparison to other COVID-19 vaccines that target only a portion of the virus, which could prove critical as new variants of SARS-CoV-2 have begun to emerge.
"Additionally, we believe COVI-VAC can address potential gaps in supplying the global immunization effort against COVID-19, especially in developing countries.”
Valneva's inactivated candidate (VLA2001)
The vaccine: France’s Valneva is working on VLA2001: which consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018. It uses the same tech as the company’s FDA/EMA approved Japanese encephalitis vaccine.
Timeline: VLA2001 entered Phase 1/2 clinical studies in December 2020 and Valneva expects to report initial safety and immunogenicity data in April 2021. Upon analysis of the data, Valneva will select the best dose and commence the second part of the Phase 1/2 clinical development. If clinical development is successful, an initial approval may be granted in the second half of 2021.
Point of difference: Valneva champions a ‘tried and tested’ approach with its inactivated candidate: the only vaccine of its type being advanced in Europe and the US. Valneva highlights that an inactivated vaccine candidate has the potential to be used in certain vulnerable patient populations; whereas vaccines using new tech are not being administered to such groups because of lack of data. And it says the reduced distribution complexity is another advantage of inactivated vaccines (the candidate is expected to conform with standard cold chain requirements of 2 degrees to 8 degrees Celsius).
Arcturus Therapeutics eyes up single dose (ARCT-021/LUNAR-COV19)
The vaccine: California’s Arcturus Therapeutics is developing ARCT-021: which combines self-transcribing and replicating mRNA (using the company’s STARR tech) with LUNAR lipid-mediated delivery technology, which is designed to enhance and extend antigen expression, enabling vaccination at lower doses.
Timeline: A Phase 2 study in the US and Singapore is expected to produce interim data early this year, with the company targeting a Phase 3 global study to start in Q2 2021. This could allow application for emergency use in H2 2021.
Point of difference: Phase 1/2 studies indicate ACT-021 could be effective as a single dose, which would differentiate it from many other vaccines in development (The Phase 2 study explores both single dose and two dose regimens).
Akston Biosciences's room temperature stable vaccine (AKS-452)
The vaccine: The adjuvanted COVID-19 vaccine candidate, AKS-452, is the most advanced COVID-19 specific Fc fusion protein vaccine in commercial development. Massachusetts company Akston Biosciences drew on tech from its work with insulin engineering to create the vaccine.
Timeline: Phase 3 studies could start in late March / early April: with the company hoping to apply for emergency use in Europe as soon as the first Phase 3 readouts are available in April/May. It is following a similar path in the US, albeit with a slight delay.
Point of difference: As a vaccine that is shelf-stable for weeks at up to 37˚ C (95˚ F) – far above most candidates which require refrigerated conditions - the candidate does not require complicated or expensive storage and transportation. It is also inexpensive to produce - a single facility could produce up to 1 billion doses a year, according to company estimates - and would also be suitable for repeated dosing if immunity fades.
Clover Biopharmaceuticals (SCB-2019)
The vaccine: China headquartered Clover Biopharmaceuticals is developing two protein-based COVID-19 S-Trimer vaccine candidates: one with an adjuvant from GSK and another with adjuvant from Dynavax.
Timeline: Having announced Phase 1 data in December, both vaccines are set for Phase 2/3 clinical trials in the first half of this year.
Point of difference: Preliminary studies showed the vaccines are stable 2-8o C for at least six months and stable at room temperature and 40 degrees C for at least one month, in line with the adjuvants tested. “Thus, the ability of Clover’s COVID-19 vaccine candidates to be stored in standard refrigeration temperatures makes them suitable for broad global distribution based on current results.”