Candidates: VBI-2900 program consisting of two vaccines, VBI-2901 and VBI-2902
Types: VBI-2901 is a trivalent pan-coronavirus vaccine candidate expressing SARS-CoV-2, SARS-CoV (severe acute respiratory syndrome or SARS), and MERS-CoV (Middle East respiratory syndrome or MERS) spike proteins on the same particle. VBI-2902 is a monovalent vaccine candidate expressing the SARS-CoV-2 spike protein. The multivalent vaccine candidate program is based on VBI’s virus-like particle (eVLP) platform technology.
2021 Status: Positive Phase I Data–VBI on June 29 reported positive Phase I data from its adaptive Phase I/II trial of VBI-2902, adjuvanted with aluminum phosphate (NCT04773665)—the first of the company’s eVLP COVID-19 vaccine candidates—in healthy adults age 18-54 years of age.
After two doses, VBI-2902 induced neutralization titers in 100% of participants, with 4.3x the geometric mean titer (GMT) compared to convalescent sera. VBI-2902 also induced antibody binding titers in 100% of participants, with peak antibody binding GMT of 1:4,047 – 5.0x the GMT compared to convalescent sera. VBI-2902 was well-tolerated with no safety signals observed, and no increase in reactogenicity with subsequent doses.
As a result of the positive initial data, which VBI said validated its platform,as well as the increased circulation of COVID-19 variants, the company expects to begin the next phase of the Phase I/II study assessing VBI-2905, VBI’s eVLP vaccine candidate directed against the COVID-19 Beta variant, in the third quarter. During the first half of 2022, VBI expects to launch the first clinical study of VBI’s multivalent vaccine candidate (VBI-2901), designed to increase the breadth of protection against known and emerging variants of COVID-19.
Enrollment Initiated–VBI said March 9 that it initiated enrollment of participants in an adaptive Phase I/II trial of VBI-2902, adjuvanted with aluminum phosphate. The randomized, observer-blind, placebo-controlled study (NCT04773665) is designed to evaluate the safety, tolerability, and immunogenicity of adjuvanted VBI-2902 (VBI-2902a). The study’s Phase I portion will assess a one- and two-dose regimen of a 5µg dose of VBI-2902, and is set to enroll up to 60 healthy adults age 18-54. Based upon enrollment rate, initial Phase I data are expected by the end of the second quarter.
The trial’s Phase II portion is expected to be a dose-escalation extension study, assessing one- and two-dose regimens, that will enroll an expanded adult population across three age cohorts: 18-54, 55-65, and 65+. The study will be conducted at nine clinical sites in Canada, and is supported by up to CAD$56 million ($44 million) from Canada’s Strategic Innovation Fund.
VBI added that it anticipated launching a Phase I/II study of VBI-2901 “later in 2021.”
2020 Status: VBI Vaccines said August 27 that it selected VBI-2901 and VBI-2902—both of which have the potential to be one-dose vaccines—for study in an adaptive Phase I/II human clinical study that is expected to start “around year-end 2020,” subject to regulatory approval.
The selection followed positive results in preclinical mouse studies conducted to enable selection of optimized clinical candidates. the studies evaluated antibody binding titers and neutralizing antibody titers across a number of vaccine constructs, in order to assess the impact of VBI’s proprietary eVLP platform vs. recombinant vaccine candidates, differences in the conformation of the spike protein, and a variety of adjuvants.
VBI said the preclinical data showed neutralizing antibody (nAb) activity, with convalescent sera from 20 individuals who had contracted and recovered from COVID-19 collected for comparison. After a single dose, VBI’s eVLPs expressing a stabilized pre-fusion form of the COVID-19 spike protein elicited a nAb GMT that was 4x higher than the GMT of high-titer convalescent sera, which increased to 64x higher after a second dose
The data also showed antibody binding (Ab) activity, as the same eVLPs also induced, after one dose, an Ab binding GMT that was 10x higher than both the GMT of high-titer convalescent sera and the GMT induced with a stabilized prefusion recombinant spike protein, VBI said.
A variety of adjuvants tested further improved the induction of nAb titers approximately 5-fold, and promoted strong Th1-type antibody and T cell responses, while the trivalent eVLP vaccine construct induced Ab binding titers across COVID-19, SARS, and MERS spike proteins in addition to broadening reactivity to a seasonal human coronavirus not expressed in the vaccine, VBI added.
“If the clinical data reflects what we see preclinically and you have a single dose vaccine, that certainly would confer benefits relative to having to give individuals two doses and bring them back in. So that’s one potential advantage,” David E. Anderson, PhD, VBI’s Chief Scientific Officer, told GEN in September.
A second advantage, says VBI, is its vaccine platform, which is based on enveloped virus-like particles (eVLPs) that are designed to mimic the structure of viruses. According to the company, the structural similarity between viruses in nature and target proteins expressed in an eVLP enable eVLP vaccines to confer greater immunity compared with vaccines using the same recombinant target protein alone.
VBI has inked a manufacturing agreement with Therapure Biomanufacturing, the contract development and manufacturing organization (CDMO) division of Therapure Biopharma, for VBI’s coronavirus vaccine canddiates, Therapure said August 18. Therapure agreed to oversee the biomanufacturing of the vaccine drug substance as well as the aseptic fill of the drug product at the Therapure facility in Mississauga, ON, where the company is based. The value of the agreement was not disclosed.
Earlier in August, Variation Biotechnologies, the Ottawa-based wholly-owned Canadian subsidiary of VBI Vaccines, said August 5 it was awarded up to C$56 million ($42.5 million) from the Strategic Innovation Fund of the Government of Canada to support development of the company’s coronavirus program, VBI-2900, through Phase 2 clinical studies.
“This funding will help accelerate our vaccine candidates into and through clinical development, the first clinical studies for which are expected to initiate by the end of 2020,” Jeff Baxter, VBI’s President and CEO, said in a statement.
In March, VBI agreed to partner with the National Research Council (NRC), Canada’s largest federal research and development organization. The collaboration will combine VBI’s viral vaccine expertise, eVLP technology platform, and coronavirus antigens with the NRC’s COVID-19 antigens and assay development capabilities.
The NRC and VBI agreed to evaluate and select the optimal vaccine candidate. Following IND-enabling preclinical studies conducted at both the NRC’s core facilities and VBI’s research facility in Ottawa, ON, VBI said it believes clinical study materials could be available in the fourth quarter.
“We believe the trivalent construct could allow for the production of broadly reactive antibodies, which offer potential for protection from mutated strains of COVID-19 that may emerge over time,” stated Francisco Diaz-Mitoma, MD, PhD, VBI’s chief medical officer.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: